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Background
Postoperative delirium is a common disorder in older adults that is associated with higher morbidity and mortality, prolonged cognitive impairment, development of dementia, higher institutionalization rates, and rising healthcare costs. The probability of delirium after surgery increases with patients’ age, with pre-existing cognitive impairment, and with comorbidities, and its diagnosis and treatment is dependent on the knowledge of diagnostic criteria, risk factors, and treatment options of the medical staff. In this study, we will investigate whether a cross-sectoral and multimodal intervention for preventing delirium can reduce the prevalence of delirium and postoperative cognitive decline (POCD) in patients older than 70 years undergoing elective surgery. Additionally, we will analyze whether the intervention is cost-effective.
Methods
The study will be conducted at five medical centers (with two or three surgical departments each) in the southwest of Germany. The study employs a stepped-wedge design with cluster randomization of the medical centers. Measurements are performed at six consecutive points: preadmission, preoperative, and postoperative with daily delirium screening up to day 7 and POCD evaluations at 2, 6, and 12 months after surgery. Recruitment goals are to enroll 1500 patients older than 70 years undergoing elective operative procedures (cardiac, thoracic, vascular, proximal big joints and spine, genitourinary, gastrointestinal, and general elective surgery procedures.
Discussion
Results of the trial should form the basis of future standards for preventing delirium and POCD in surgical wards. Key aims are the improvement of patient safety and quality of life, as well as the reduction of the long-term risk of conversion to dementia. Furthermore, from an economic perspective, we expect benefits and decreased costs for hospitals, patients, and healthcare insurances.
Trial registration
German Clinical Trials Register, DRKS00013311. Registered on 10 November 2017.
Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
Background
Postoperative delirium is a common disorder in older adults that is associated with higher morbidity and mortality, prolonged cognitive impairment, development of dementia, higher institutionalization rates, and rising healthcare costs. The probability of delirium after surgery increases with patients’ age, with pre-existing cognitive impairment, and with comorbidities, and its diagnosis and treatment is dependent on the knowledge of diagnostic criteria, risk factors, and treatment options of the medical staff. In this study, we will investigate whether a cross-sectoral and multimodal intervention for preventing delirium can reduce the prevalence of delirium and postoperative cognitive decline (POCD) in patients older than 70 years undergoing elective surgery. Additionally, we will analyze whether the intervention is cost-effective.
Methods
The study will be conducted at five medical centers (with two or three surgical departments each) in the southwest of Germany. The study employs a stepped-wedge design with cluster randomization of the medical centers. Measurements are performed at six consecutive points: preadmission, preoperative, and postoperative with daily delirium screening up to day 7 and POCD evaluations at 2, 6, and 12 months after surgery. Recruitment goals are to enroll 1500 patients older than 70 years undergoing elective operative procedures (cardiac, thoracic, vascular, proximal big joints and spine, genitourinary, gastrointestinal, and general elective surgery procedures.
Discussion
Results of the trial should form the basis of future standards for preventing delirium and POCD in surgical wards. Key aims are the improvement of patient safety and quality of life, as well as the reduction of the long-term risk of conversion to dementia. Furthermore, from an economic perspective, we expect benefits and decreased costs for hospitals, patients, and healthcare insurances.
Trial registration
German Clinical Trials Register, DRKS00013311. Registered on 10 November 2017.
IntroductionPostoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. MethodsBetween November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. ResultsPOD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). ConclusionPreoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients.
Background: First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other "criterion A' symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.
Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 % of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 %. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.
Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.
Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.
Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).
Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.
Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002).
Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.
Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.
One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex.
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.
Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus–action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian–instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.
Background Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders.
Methods Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP).
Results The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: & beta; = -0.35; NVS: & beta; = 0.39; CS: & beta; = -0.12; SP: & beta; = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association.
Limitations The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for.
Conclusion Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.
Pavlovian cues can influence ongoing instrumental behaviour via Pavlovian-to-instrumental transfer (PIT) processes. While appetitive Pavlovian cues tend to promote instrumental approach, they are detrimental when avoidance behaviour is required, and vice versa for aversive cues. We recently reported that susceptibility to interference between Pavlovian and instrumental control assessed via a PIT task was associated with risky alcohol use at age 18. We now investigated whether such susceptibility also predicts drinking trajectories until age 24, based on AUDIT (Alcohol Use Disorders Identification Test) consumption and binge drinking (gramme alcohol/drinking occasion) scores. The interference PIT effect, assessed at ages 18 and 21 during fMRI, was characterized by increased error rates (ER) and enhanced neural responses in the ventral striatum (VS), the lateral and dorsomedial prefrontal cortices (dmPFC) during conflict, that is, when an instrumental approach was required in the presence of an aversive Pavlovian cue or vice versa. We found that a stronger VS response during conflict at age 18 was associated with a higher starting point of both drinking trajectories but predicted a decrease in binge drinking. At age 21, high ER and enhanced neural responses in the dmPFC were associated with increasing AUDIT-C scores over the next 3 years until age 24. Overall, susceptibility to interference between Pavlovian and instrumental control might be viewed as a predisposing mechanism towards hazardous alcohol use during young adulthood, and the identified high-risk group may profit from targeted interventions.
Theories of decision-making and its neural substrates have long assumed the existence of two distinct and competing valuation systems, variously described as goal-directed vs. habitual, or, more recently and based on statistical arguments, as model-free vs. model-based reinforcement-learning. Though both have been shown to control choices, the cognitive abilities associated with these systems are under ongoing investigation. Here we examine the link to cognitive abilities, and find that individual differences in processing speed covary with a shift from model-free to model-based choice control in the presence of above-average working memory function. This suggests shared cognitive and neural processes; provides a bridge between literatures on intelligence and valuation; and may guide the development of process models of different valuation components. Furthermore, it provides a rationale for individual differences in the tendency to deploy valuation systems, which may be important for understanding the manifold neuropsychiatric diseases associated with malfunctions of valuation.
Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
No association of goal-directed and habitual control with alcohol consumption in young adults
(2017)
Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model-free habitual over model-based goal-directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model-based goal-directed and model-free habitual control in 188 18-year-old social drinkers in a two-step sequential decision-making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model-free and model-based decision-making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model-free nor model-based decision weights nor the trade-off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model-free or model-based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole-brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model-free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model-based goal-directed and model-free habitual control might rather not be a trait marker of alcohol intake per se.
A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects.
Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity.
In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects.
We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability.
Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting.
To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.
Background:
Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making.
Methods:
127 subjects performed the two Step task and completed the blatant and subtle prejudice scale.
Results:
By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices.
Conclusion:
These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.
This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.
Mobile data collection of cognitive-behavioral tasks in substance use disorders: Where are we now?
(2022)
Introduction: Over the last decades, our understanding of the cognitive, motivational, and neural processes involved in addictive behavior has increased enormously. A plethora of laboratory-based and cross-sectional studies has linked cognitive-behavioral measures to between-subject differences in drinking behavior. However, such laboratory-based studies inevitably suffer from small sample sizes and the inability to link temporal fluctuations in task measures to fluctuations in real-life substance use. To overcome these problems, several existing behavioral tasks have been transferred to smartphones to allow studying cognition in the field. Method: In this narrative review, we first summarize studies that used existing behavioral tasks in the laboratory and self-reports of substance use with ecological momentary assessment (EMA) in the field. Next, we review studies on psychometric properties of smartphone-based behavioral tasks. Finally, we review studies that used both smartphone-based tasks and self-reports with EMA in the field. Results: Overall, studies were scarce and heterogenous both in tasks and in study outcomes. Nevertheless, existing findings are promising and point toward several methodological recommendations: concerning psychometrics, studies show that - although more systematic studies are necessary - task validity and reliability can be improved, for example, by analyzing several measurement sessions at once rather than analyzing sessions separately. Studies that use tasks in the field, moreover, show that power can be improved by choosing sampling schemes that combine time-based with event-based sampling, rather than relying on time-based sampling alone. Increasing sampling frequency can further increase power. However, as this also increases the burden to participants, more research is necessary to determine the ideal sampling frequency for each task. Conclusion: Although more research is necessary to systematically study both the psychometrics of smartphone-based tasks and the frequency at which task measures fluctuate, existing studies are promising and reveal important methodological recommendations useful for researchers interested in implementing behavioral tasks in EMA studies.
BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.
Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.
Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).
Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.
Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002).
Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.
Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.
Background: Demographic changes are leading to growing care needs of older people and creating a challenge for healthcare systems worldwide. Nursing homes (NHs) need to provide care for growing numbers of residents while ensuring a high-quality care. We aimed to examine an innovative NH in Germany and apply a theory of change (ToC) approach to develop a best practice model (BPM) for therapeutic care in NHs.
Methods: A multimethod qualitative study conducted from February to July 2021 in Germany involved interviews with 14 staff members of an innovative NH and 10 directors and care managers of other NHs. The interview guidelines included questions on nursing practices, infrastructure, resources, interprofessional collaboration, and working culture. Additional material on the participating NH (website, promotion videos, newsletters, care documentation) were collected. Contextual literature on NH culture and therapeutic care in Germany, ToC methodology, and NH culture change were reviewed. Following a question-focused analysis of all material, we generated a ToC model towards a BPM of therapeutic care and meaningful living in NHs.
Results: were verified in interdisciplinary team meetings, with study participants and other stakeholders to establish consensus. Results The participating NH's care concept aims to improve residents' functional abilities and wellbeing as well as staff members' job satisfaction. Central components of their approach include therapeutic elements such as music and movement in all nursing activities, multidisciplinary collaboration, a broad therapy and social activity offer, the continuation of therapy in everyday activities, a focus on individual life history, values, needs, and skills, social integration into the regional community, and the creation of a meaningful living environment for residents and staff.
Conclusion: The BPM we developed shows how a meaningful living environment can be created through therapeutic care and integrative activities. The ToC sheds light onto the contextual factors and cultural values which should be considered in the development of NH interventions. Research on not only biomedical aspects, but also psychosocial dynamics and narrative co-constructions in nursing practice should inform NH innovations. The ToC also highlights the importance of developing adequate political frameworks and infrastructures for implementing such innovative practices on a larger scale.
Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping on- going thought and behavior. The influence of Pavlovian stimuli on on-going behavior is paradigmatically measured by Pavlovian-to-instrumental-transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol
dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent, and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced Pavlovian-Instrumental transfer.
Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. The task involved both Pavlovian stimuli associated with monetary rewards and losses, and images of drinks.
Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs.
Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol- dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
Background Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown. Methods To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations. Results Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms. Conclusion Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.
Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.
Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [F-18]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction.
We investigated the efficacy of reminiscence therapy (RT) on symptoms of depression in patients with mild to moderate dementia. Out of 227 patients with mild to moderate dementia from a specialized physician’s office, 27 pairs (N = 54; mean age 79.04 ± 6.16 years) who had either received treatment as usual (TAU) or TAU combined with RT, were matched retrospectively according to age as well as cognitive and depressive symptom scores. After controlling for age and sex, symptoms of depression significantly decreased over time in the RT group compared to TAU (F1,52 = 4.36; p < .05). RT is a promising option for the treatment of depression in mild to moderate dementia. Larger randomized-controlled trials are needed.
Timing and magnitude of surface uplift are key to understanding the impact of crustal deformation and topographic growth on atmospheric circulation, environmental conditions, and surface processes. Uplift of the East African Plateau is linked to mantle processes, but paleoaltimetry data are too scarce to constrain plateau evolution and subsequent vertical motions associated with rifting. Here, we assess the paleotopographic implications of a beaked whale fossil (Ziphiidae) from the Turkana region of Kenya found 740 km inland from the present-day coastline of the Indian Ocean at an elevation of 620 m. The specimen is similar to 17 My old and represents the oldest derived beaked whale known, consistent with molecular estimates of the emergence of modern straptoothed whales (Mesoplodon). The whale traveled from the Indian Ocean inland along an eastward-directed drainage system controlled by the Cretaceous Anza Graben and was stranded slightly above sea level. Surface uplift from near sea level coincides with paleoclimatic change from a humid environment to highly variable and much drier conditions, which altered biotic communities and drove evolution in east Africa, including that of primates.
Background: Infection with human immunodeficiency virus (HIV) affects muscle mass, altering independent activities of people living with HIV (PLWH). Resistance training alone (RT) or combined with aerobic exercise (AE) is linked to improved muscle mass and strength maintenance in PLWH. These exercise benefits have been the focus of different meta-analyses, although only a limited number of studies have been identified up to the year 2013/4. An up-to-date systematic review and meta-analysis concerning the effect of RT alone or combined with AE on strength parameters and hormones is of high value, since more and recent studies dealing with these types of exercise in PLWH have been published. Methods: Randomized controlled trials evaluating the effects of RT alone, AE alone or the combination of both (AERT) on PLWH was performed through five web-databases up to December 2017. Risk of bias and study quality was attained using the PEDro scale. Weighted mean difference (WMD) from baseline to post-intervention changes was calculated. The I2 statistics for heterogeneity was calculated.
Results: Thirteen studies reported strength outcomes. Eight studies presented a low risk of bias. The overall change in upper body strength was 19.3 Kg (95% CI: 9.8±28.8, p< 0.001) after AERT and 17.5 Kg (95% CI: 16±19.1, p< 0.001) for RT. Lower body change was 29.4 Kg (95% CI: 18.1±40.8, p< 0.001) after RT and 10.2 Kg (95% CI: 6.7±13.8, p< 0.001) for AERT. Changes were higher after controlling for the risk of bias in upper and lower body strength and for supervised exercise in lower body strength. A significant change towards lower levels of IL-6 was found (-2.4 ng/dl (95% CI: -2.6, -2.1, p< 0.001). Conclusion: Both resistance training alone and combined with aerobic exercise showed a positive change when studies with low risk of bias and professional supervision were analyzed, improving upper and, more critically, lower body muscle strength. Also, this study found that exercise had a lowering effect on IL-6 levels in PLWH.
Age-related decline in executive functions and postural control due to degenerative processes in the central nervous system have been related to increased fall-risk in old age. Many studies have shown cognitive-postural dual-task interference in old adults, but research on the role of specific executive functions in this context has just begun. In this study, we addressed the question whether postural control is impaired depending on the coordination of concurrent response-selection processes related to the compatibility of input and output modality mappings as compared to impairments related to working-memory load in the comparison of cognitive dual and single tasks. Specifically, we measured total center of pressure (CoP) displacements in healthy female participants aged 19–30 and 66–84 years while they performed different versions of a spatial one-back working memory task during semi-tandem stance on an unstable surface (i.e., balance pad) while standing on a force plate. The specific working-memory tasks comprised: (i) modality compatible single tasks (i.e., visual-manual or auditory-vocal tasks), (ii) modality compatible dual tasks (i.e., visual-manual and auditory-vocal tasks), (iii) modality incompatible single tasks (i.e., visual-vocal or auditory-manual tasks), and (iv) modality incompatible dual tasks (i.e., visual-vocal and auditory-manual tasks). In addition, participants performed the same tasks while sitting. As expected from previous research, old adults showed generally impaired performance under high working-memory load (i.e., dual vs. single one-back task). In addition, modality compatibility affected one-back performance in dual-task but not in single-task conditions with strikingly pronounced impairments in old adults. Notably, the modality incompatible dual task also resulted in a selective increase in total CoP displacements compared to the modality compatible dual task in the old but not in the young participants. These results suggest that in addition to effects of working-memory load, processes related to simultaneously overcoming special linkages between input- and output modalities interfere with postural control in old but not in young female adults. Our preliminary data provide further evidence for the involvement of cognitive control processes in postural tasks.
Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination.
Background: Given the well-established association between perceived stress and quality of life (QoL) in dementia patients and their partners, our goal was to identify whether relationship quality and dyadic coping would operate as mediators between perceived stress and QoL.
Methods: 82 dyads of dementia patients and their spousal caregivers were included in a cross-sectional assessment from a prospective study. QoL was assessed with the Quality of Life in Alzheimer's Disease scale (QoL-AD) for dementia patients and the WHO Quality of Life-BREF for spousal caregivers. Perceived stress was measured with the Perceived Stress Scale (PSS-14). Both partners were assessed with the Dyadic Coping Inventory (DCI). Analyses of correlation as well as regression models including mediator analyses were performed.
Results: We found negative correlations between stress and QoL in both partners (QoL-AD: r = -0.62; p < 0.001; WHO-QOL Overall: r = -0.27; p = 0.02). Spousal caregivers had a significantly lower DCI total score than dementia patients (p < 0.001). Dyadic coping was a significant mediator of the relationship between stress and QoL in spousal caregivers (z = 0.28; p = 0.02), but not in dementia patients. Likewise, relationship quality significantly mediated the relationship between stress and QoL in caregivers only (z = -2.41; p = 0.02).
Conclusions: This study identified dyadic coping as a mediator on the relationship between stress and QoL in (caregiving) partners of dementia patients. In patients, however, we found a direct negative effect of stress on QoL. The findings suggest the importance of stress reducing and dyadic interventions for dementia patients and their partners, respectively.
Background: Continuous treatment is an important indicator of medication adherence in dementia. However, long-term studies in larger clinical settings are lacking, and little is known about moderating effects of patient and service characteristics.
Methods: Data from 12,910 outpatients with dementia (mean age 79.2 years; SD = 7.6 years) treated between January 2003 and December 2013 in Germany were included. Continuous treatment was analysed using Kaplan-Meier curves and log-rank tests. In addition, multivariate Cox regression models were fitted with continuous treatment as dependent variable and the predictors antidementia agent, age, gender, medical comorbidities, physician specialty, and health insurance status.
Results: After one year of follow-up, nearly 60% of patients continued drug treatment. Donezepil (HR: 0.88; 95% CI: 0.82-0.95) and memantine (HR: 0.85; 0.79-0.91) patients were less likely to be discontinued treatment as compared to rivastigmine users. Patients were less likely to be discontinued if they were treated by specialist physicians as compared to general practitioners (HR: 0.44; 0.41-0.48). Younger male patients and patients who had private health insurance had a lower discontinuation risk. Regarding comorbidity, patients were more likely to be continuously treated with the index substance if a diagnosis of heart failure or hypertension had been diagnosed at baseline.
Conclusions: Our results imply that besides type of antidementia agent, involvement of a specialist in the complex process of prescribing antidementia drugs can provide meaningful benefits to patients, in terms of more disease-specific and continuous treatment.
Background: Dementia is a psychiatric condition the development of which is associated with numerous aspects of life. Our aim was to estimate dementia risk factors in German primary care patients.
Methods: The case-control study included primary care patients (70-90 years) with first diagnosis of dementia (all-cause) during the index period (01/2010-12/2014) (Disease Analyzer, Germany), and controls without dementia matched (1:1) to cases on the basis of age, sex, type of health insurance, and physician. Practice visit records were used to verify that there had been 10 years of continuous follow-up prior to the index date. Multivariate logistic regression models were fitted with dementia as a dependent variable and the potential predictors.
Results: The mean age for the 11,956 cases and the 11,956 controls was 80.4 (SD: 5.3) years. 39.0% of them were male and 1.9% had private health insurance. In the multivariate regression model, the following variables were linked to a significant extent with an increased risk of dementia: diabetes (OR: 1.17; 95% CI: 1.10-1.24), lipid metabolism (1.07; 1.00-1.14), stroke incl. TIA (1.68; 1.57-1.80), Parkinson's disease (PD) (1.89; 1.64-2.19), intracranial injury (1.30; 1.00-1.70), coronary heart disease (1.06; 1.00-1.13), mild cognitive impairment (MCI) (2.12; 1.82-2.48), mental and behavioral disorders due to alcohol use (1.96; 1.50-2.57). The use of statins (OR: 0.94; 0.90-0.99), proton-pump inhibitors (PPI) (0.93; 0.90-0.97), and antihypertensive drugs (0.96, 0.94-0.99) were associated with a decreased risk of developing dementia.
Conclusions: Risk factors for dementia found in this study are consistent with the literature. Nevertheless, the associations between statin, PPI and antihypertensive drug use, and decreased risk of dementia need further investigations.
The aim was to analyze the risk of hip fracture in German primary care patients with dementia. This study included patients aged 65-90 from 1072 primary care practices who were first diagnosed with dementia between 2010 and 2013. Controls were matched (1:1) to cases for age, sex, and type of health insurance. The primary outcome was the diagnosis of hip fracture during the three-year follow-up period. A total of 53,156 dementia patients and 53,156 controls were included. A total of 5.3% of patients and 0.7% of controls displayed hip fracture after three years. Hip fracture occurred more frequently in dementia subjects living in nursing homes than in those living at home (9.2% versus 4.3%). Dementia, residence in nursing homes, and osteoporosis were risk factors for fracture development. Antidementia, antipsychotic, and antidepressant drugs generally had no significant impact on hip fracture risk when prescribed for less than six months. Dementia increased hip fracture risk in German primary care practices.
Background: The goal of this study was to estimate the prevalence of and risk factors for diagnosed depression in heart failure (HF) patients in German primary care practices.
Methods: This study was a retrospective database analysis in Germany utilizing the Disease Analyzer (R) Database (IMS Health, Germany). The study population included 132,994 patients between 40 and 90 years of age from 1,072 primary care practices. The observation period was between 2004 and 2013. Follow-up lasted up to five years and ended in April 2015. A total of 66,497 HF patients were selected after applying exclusion criteria. The same number of 66,497 controls were chosen and were matched (1:1) to HF patients on the basis of age, sex, health insurance, depression diagnosis in the past, and follow-up duration after index date.
Results: HF was a strong risk factor for diagnosed depression (p < 0.0001). A total of 10.5% of HF patients and 6.3% of matched controls developed depression after one year of follow-up (p < 0.001). Depression was documented in 28.9% of the HF group and 18.2% of the control group after the five-year follow-up (p < 0.001). Cancer, dementia, osteoporosis, stroke, and osteoarthritis were associated with a higher risk of developing depression. Male gender and private health insurance were associated with lower risk of depression.
Conclusions: The risk of diagnosed depression is significantly increased in patients with HF compared to patients without HF in primary care practices in Germany.
There is evidence for cortical contribution to the regulation of human postural control. Interference from concurrently performed cognitive tasks supports this notion, and the lateral prefrontal cortex (lPFC) has been suggested to play a prominent role in the processing of purely cognitive as well as cognitive-postural dual tasks. The degree of cognitive-motor interference varies greatly between individuals, but it is unresolved whether individual differences in the recruitment of specific lPFC regions during cognitive dual tasking are associated with individual differences in cognitive-motor interference. Here, we investigated inter-individual variability in a cognitive-postural multitasking situation in healthy young adults (n = 29) in order to relate these to inter-individual variability in lPFC recruitment during cognitive multitasking. For this purpose, a oneback working memory task was performed either as single task or as dual task in order to vary cognitive load. Participants performed these cognitive single and dual tasks either during upright stance on a balance pad that was placed on top of a force plate or during fMRI measurement with little to no postural demands. We hypothesized dual one-back task performance to be associated with lPFC recruitment when compared to single one-back task performance. In addition, we expected individual variability in lPFC recruitment to be associated with postural performance costs during concurrent dual one-back performance. As expected, behavioral performance costs in postural sway during dual-one back performance largely varied between individuals and so did lPFC recruitment during dual one-back performance. Most importantly, individuals who recruited the right mid-lPFC to a larger degree during dual one-back performance also showed greater postural sway as measured by larger performance costs in total center of pressure displacements. This effect was selective to the high-load dual one-back task and suggests a crucial role of the right lPFC in allocating resources during cognitivemotor interference. Our study provides further insight into the mechanisms underlying cognitive-motor multitasking and its impairments.
The interruption of learning processes by breaks filled with diverse activities is common in everyday life. We investigated the effects of active computer gaming and passive relaxation (rest and music) breaks on working memory performance. Young adults were exposed to breaks involving (i) eyes-open resting, (ii) listening to music and (iii) playing the video game “Angry Birds” before performing the n-back working memory task. Based on linear mixed-effects modeling, we found that playing the “Angry Birds” video game during a short learning break led to a decline in task performance over the course of the task as compared to eyes-open resting and listening to music, although overall task performance was not impaired. This effect was associated with high levels of daily mind wandering and low self-reported ability to concentrate. These findings indicate that video games can negatively affect working memory performance over time when played in between learning tasks. We suggest further investigation of these effects because of their relevance to everyday activity.
Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and
their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes.
Background
Depression is one of the key factors contributing to difficulties in one’s ability to work, and serves as one of the major reasons why employees apply for psychotherapy and receive insurance subsidization of treatments. Hence, an increasing and growing number of studies rely on workability assessment scales as their primary outcome measure. The Work and Social Assessment Scale (WSAS) has been documented as one of the most psychometrically reliable and valid tools especially developed to assess workability and social functioning in patients with mental health problems. Yet, the application of the WSAS in Germany has been limited due to the paucity of a valid questionnaire in the German language. The objective of the present study was to translate the WSAS, as a brief and easy administrable tool into German and test its psychometric properties in a sample of adults with depression.
Methods
Two hundred seventy-seven patients (M = 48.3 years, SD = 11.1) with mild to moderately severe depression were recruited. A multistep translation from English into the German language was performed and the factorial validity, criterion validity, convergent validity, discriminant validity, internal consistency, and floor and ceiling effects were examined.
Results
The confirmatory factor analysis results confirmed the one-factor structure of the WSAS. Significant correlations with the WHODAS 2–0 questionnaire, a measure of functionality, demonstrated good convergent validity. Significant correlations with depression and quality of life demonstrated good criterion validity. The WSAS also demonstrated strong internal consistency (α = .89), and the absence of floor and ceiling effects indicated good sensitivity of the instrument.
Conclusions
The results of the present study demonstrated that the German version of the WSAS has good psychometric properties comparable to other international versions of this scale. The findings recommend a global assessment of psychosocial functioning with the sum score of the WSAS.
In recent years digital technologies have become a major means for providing health-related services and this trend was strongly reinforced by the current Coronavirus disease 2019 (COVID-19) pandemic. As it is well-known that regular physical activity has positive effects on individual physical and mental health and thus is an important prerequisite for healthy aging, digital technologies are also increasingly used to promote unstructured and structured forms of physical activity. However, in the course of this development, several terms (e.g., Digital Health, Electronic Health, Mobile Health, Telehealth, Telemedicine, and Telerehabilitation) have been introduced to refer to the application of digital technologies to provide health-related services such as physical interventions. Unfortunately, the above-mentioned terms are often used in several different ways, but also relatively interchangeably. Given that ambiguous terminology is a major source of difficulty in scientific communication which can impede the progress of theoretical and empirical research, this article aims to make the reader aware of the subtle differences between the relevant terms which are applied at the intersection of physical activity and Digital Health and to provide state-of-art definitions for them.
Research within the framework of Basic Psychological Need Theory (BPNT) finds strong associations between basic need frustration and depressive symptoms. This study examined the role of rumination as an underlying mechanism in the association between basic psychological need frustration and depressive symptoms. A cross-sectional sample of N = 221 adults (55.2% female, mean age = 27.95, range = 18–62, SD = 10.51) completed measures assessing their level of basic psychological need frustration, rumination, and depressive symptoms. Correlational analyses and multiple mediation models were conducted. Brooding partially mediated the relation between need frustration and depressive symptoms. BPNT and Response Styles Theory are compatible and can further advance knowledge about depression vulnerabilities.
Exercise is known for its beneficial effects on preventing cardiometabolic diseases (CMDs) in the general population. People living with the human immunodeficiency virus (PLWH) are prone to sedentarism, thus raising their already elevated risk of developing CMDs in comparison to individuals without HIV. The aim of this cross-sectional study was to determine if exercise is associated with reduced risk of self-reported CMDs in a German HIV-positive sample (n = 446). Participants completed a self-report survey to assess exercise levels, date of HIV diagnosis, CD4 cell count, antiretroviral therapy, and CMDs. Participants were classified into exercising or sedentary conditions. Generalized linear models with Poisson regression were conducted to assess the prevalence ratio (PR) of PLWH reporting a CMD. Exercising PLWH were less likely to report a heart arrhythmia for every increase in exercise duration (PR: 0.20: 95% CI: 0.10–0.62, p < 0.01) and diabetes mellitus for every increase in exercise session per week (PR: 0.40: 95% CI: 0.10–1, p < 0.01). Exercise frequency and duration are associated with a decreased risk of reporting arrhythmia and diabetes mellitus in PLWH. Further studies are needed to elucidate the mechanisms underlying exercise as a protective factor for CMDs in PLWH.
The concurrent performance of cognitive and postural tasks is particularly impaired in old adults and associated with an increased risk of falls. Biological aging of the cognitive and postural control system appears to be responsible for increased cognitive-motor interference effects. We examined neural and behavioral markers of motor-cognitive dual-task performance in young and old adults performing spatial one-back working memory single and dual tasks during semitandem stance. On the neural level, we used EEG to test for age-related modulations in the frequency domain related to cognitive-postural task load. Twenty-eight healthy young and 30 old adults participated in this study. The tasks included a postural single task, a cognitive-postural dual task, and a cognitive-postural triple task (cognitive dual-task with postural demands). Postural sway (i.e., total center of pressure displacements) was recorded in semistance position on an unstable surface that was placed on top of a force plate while performing cognitive tasks. Neural activation was recorded using a 64-channel mobile EEG system. EEG frequencies were attenuated by the baseline postural single-task condition and demarcated in nine Regions-of-Interest (ROIs), i.e., anterior, central, posterior, over the cortical midline, and both hemispheres. Our findings revealed impaired cognitive dual-task performance in old compared to young participants in the form of significantly lower cognitive performance in the triple-task condition. Furthermore, old adults compared with young adults showed significantly larger postural sway, especially in cognitive-postural task conditions. With respect to EEG frequencies, young compared to old participants showed significantly lower alpha-band activity in cognitive-cognitive-postural triple-task conditions compared with cognitive-postural dual tasks. In addition, with increasing task difficulty, we observed synchronized theta and delta frequencies, irrespective of age. Taskdependent alterations of the alpha frequency band were most pronounced over frontal and central ROIs, while alterations of the theta and delta frequency bands were found in frontal, central, and posterior ROIs. Theta and delta synchronization exhibited a decrease from anterior to posterior regions. For old adults, task difficulty was reflected by theta synchronization in the posterior ROI. For young adults, it was reflected by alpha desynchronization in bilateral anterior ROIs. In addition, we could not identify any effects of task difficulty and age on the beta frequency band. Our results shed light on age-related cognitive and postural declines and how they interact. Modulated alpha frequencies during high cognitive-postural task demands in young but not old adults might be reflective of a constrained neural adaptive potential in old adults. Future studies are needed to elucidate associations between the identified age-related performance decrements with task difficulty and changes in brain activity.
Basic psychological needs theory postulates that a social environment that satisfies individuals’ three basic psychological needs of autonomy, competence, and relatedness leads to optimal growth and well-being. On the other hand, the frustration of these needs is associated with ill-being and depressive symptoms foremost investigated in non-clinical samples; yet, there is a paucity of research on need frustration in clinical samples. Survey data were compared between adult individuals with major depressive disorder (MDD; n = 115; 48.69% female; 38.46 years, SD = 10.46) with those of a non-depressed comparison sample (n = 201; 53.23% female; 30.16 years, SD = 12.81). Need profiles were examined with a linear mixed model (LMM). Individuals with depression reported higher levels of frustration and lower levels of satisfaction in relation to the three basic psychological needs when compared to non-depressed adults. The difference between depressed and non-depressed groups was significantly larger for frustration than satisfaction regarding the needs for relatedness and competence. LMM correlation parameters confirmed the expected positive correlation between the three needs. This is the first study showing substantial differences in need-based experiences between depressed and non-depressed adults. The results confirm basic assumptions of the self-determination theory and have preliminary implications in tailoring therapy for depression.
The aim was to analyze the risk of hip fracture in German primary care patients with dementia. This study included patients aged 65-90 from 1072 primary care practices who were first diagnosed with dementia between 2010 and 2013. Controls were matched (1:1) to cases for age, sex, and type of health insurance. The primary outcome was the diagnosis of hip fracture during the three-year follow-up period. A total of 53,156 dementia patients and 53,156 controls were included. A total of 5.3% of patients and 0.7% of controls displayed hip fracture after three years. Hip fracture occurred more frequently in dementia subjects living in nursing homes than in those living at home (9.2% versus 4.3%). Dementia, residence in nursing homes, and osteoporosis were risk factors for fracture development. Antidementia, antipsychotic, and antidepressant drugs generally had no significant impact on hip fracture risk when prescribed for less than six months. Dementia increased hip fracture risk in German primary care practices.
Cognitive resources contribute to balance control. There is evidence that mental fatigue reduces cognitive resources and impairs balance performance, particularly in older adults and when balance tasks are complex, for example when trying to walk or stand while concurrently performing a secondary cognitive task.
We conducted a systematic literature search in PubMed (MEDLINE), Web of Science and Google Scholar to identify eligible studies and performed a random effects meta-analysis to quantify the effects of experimentally induced mental fatigue on balance performance in healthy adults. Subgroup analyses were computed for age (healthy young vs. healthy older adults) and balance task complexity (balance tasks with high complexity vs. balance tasks with low complexity) to examine the moderating effects of these factors on fatigue-mediated balance performance.
We identified 7 eligible studies with 9 study groups and 206 participants. Analysis revealed that performing a prolonged cognitive task had a small but significant effect (SMDwm = −0.38) on subsequent balance performance in healthy young and older adults. However, age- and task-related differences in balance responses to fatigue could not be confirmed statistically.
Overall, aggregation of the available literature indicates that mental fatigue generally reduces balance in healthy adults. However, interactions between cognitive resource reduction, aging and balance task complexity remain elusive.
Background
The metabolic syndrome (MetS) is a risk cluster for a number of secondary diseases. The implementation of prevention programs requires early detection of individuals at risk. However, access to health care providers is limited in structurally weak regions. Brandenburg, a rural federal state in Germany, has an especially high MetS prevalence and disease burden. This study aims to validate and test the feasibility of a setup for mobile diagnostics of MetS and its secondary diseases, to evaluate the MetS prevalence and its association with moderating factors in Brandenburg and to identify new ways of early prevention, while establishing a “Mobile Brandenburg Cohort” to reveal new causes and risk factors for MetS.
Methods
In a pilot study, setups for mobile diagnostics of MetS and secondary diseases will be developed and validated. A van will be equipped as an examination room using point-of-care blood analyzers and by mobilizing standard methods. In study part A, these mobile diagnostic units will be placed at different locations in Brandenburg to locally recruit 5000 participants aged 40-70 years. They will be examined for MetS and advice on nutrition and physical activity will be provided. Questionnaires will be used to evaluate sociodemographics, stress perception, and physical activity. In study part B, participants with MetS, but without known secondary diseases, will receive a detailed mobile medical examination, including MetS diagnostics, medical history, clinical examinations, and instrumental diagnostics for internal, cardiovascular, musculoskeletal, and cognitive disorders. Participants will receive advice on nutrition and an exercise program will be demonstrated on site. People unable to participate in these mobile examinations will be interviewed by telephone. If necessary, participants will be referred to general practitioners for further diagnosis.
Discussion
The mobile diagnostics approach enables early detection of individuals at risk, and their targeted referral to local health care providers. Evaluation of the MetS prevalence, its relation to risk-increasing factors, and the “Mobile Brandenburg Cohort” create a unique database for further longitudinal studies on the implementation of home-based prevention programs to reduce mortality, especially in rural regions.
Trial registration
German Clinical Trials Register, DRKS00022764; registered 07 October 2020—retrospectively registered.
Satisfaction and frustration of the needs for autonomy, competence, and relatedness, as assessed with the 24-item Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), have been found to be crucial indicators of individuals’ psychological health. To increase the usability of this scale within a clinical and health services research context, we aimed to validate a German short version (12 items) of this scale in individuals with depression including the examination of the relations from need frustration and need satisfaction to ill-being and quality of life (QOL). This cross-sectional study involved 344 adults diagnosed with depression (Mage (SD) = 47.5 years (11.1); 71.8% females). Confirmatory factor analyses indicated that the short version of the BPNSFS was not only reliable, but also fitted a six-factor structure (i.e., satisfaction/frustration X type of need). Subsequent structural equation modeling showed that need frustration related positively to indicators of ill-being and negatively to QOL. Surprisingly, need satisfaction did not predict differences in ill-being or QOL. The short form of the BPNSFS represents a practical instrument to measure need satisfaction and frustration in people with depression. Further, the results support recent evidence on the importance of especially need frustration in the prediction of psychopathology.
(1) Background: People with HIV (PWH) may perform more than one type of exercise cumulatively. The objective of this study is to investigate recreational exercise and its association with health-related quality of life (HRQOL) and comorbidities in relation to potential covariates. (2) Methods: The HIBES study (HIV-Begleiterkrankungen-Sport) is a cross-sectional study for people with HIV. The differences between non-exercisers versus exercisers (cumulated vs. single type of exercises) were investigated using regression models based on 454 participants. (3) Results: Exercisers showed a higher HRQOL score compared to non-exercisers (Wilcox r = 0.2 to 0.239). Psychological disorders were identified as the main covariate. Participants performing exercise cumulatively showed higher scores in duration, frequency, and intensity when compared to participants performing only one type of exercise. The mental health summary score was higher for the cumulated and single type of exercise if a psychological disorder existed. Duration and intensity were associated with an increase of HRQOL, whilst a stronger association between psychological disorders and exercise variables were evident. Exercise duration (minutes) showed a significant effect on QOL (standardized beta = 0.1) and for participants with psychological disorders (standardized beta = 0.3), respectively. (4) Conclusions: Psychological disorders and other covariates have a prominent effect on HRQOL and its association with exercise. For PWH with a psychological disorder, a stronger relationship between HRQOL with exercise duration and intensity emerged. However, differentiation of high-HRQOL individuals warrants further investigation by considering additional factors.
The concurrent performance of cognitive and postural tasks is particularly impaired in old adults and associated with an increased risk of falls. Biological aging of the cognitive and postural control system appears to be responsible for increased cognitive-motor interference effects. We examined neural and behavioral markers of motor-cognitive dual-task performance in young and old adults performing spatial one-back working memory single and dual tasks during semitandem stance. On the neural level, we used EEG to test for age-related modulations in the frequency domain related to cognitive-postural task load. Twenty-eight healthy young and 30 old adults participated in this study. The tasks included a postural single task, a cognitive-postural dual task, and a cognitive-postural triple task (cognitive dual-task with postural demands). Postural sway (i.e., total center of pressure displacements) was recorded in semistance position on an unstable surface that was placed on top of a force plate while performing cognitive tasks. Neural activation was recorded using a 64-channel mobile EEG system. EEG frequencies were attenuated by the baseline postural single-task condition and demarcated in nine Regions-of-Interest (ROIs), i.e., anterior, central, posterior, over the cortical midline, and both hemispheres. Our findings revealed impaired cognitive dual-task performance in old compared to young participants in the form of significantly lower cognitive performance in the triple-task condition. Furthermore, old adults compared with young adults showed significantly larger postural sway, especially in cognitive-postural task conditions. With respect to EEG frequencies, young compared to old participants showed significantly lower alpha-band activity in cognitive-cognitive-postural triple-task conditions compared with cognitive-postural dual tasks. In addition, with increasing task difficulty, we observed synchronized theta and delta frequencies, irrespective of age. Taskdependent alterations of the alpha frequency band were most pronounced over frontal and central ROIs, while alterations of the theta and delta frequency bands were found in frontal, central, and posterior ROIs. Theta and delta synchronization exhibited a decrease from anterior to posterior regions. For old adults, task difficulty was reflected by theta synchronization in the posterior ROI. For young adults, it was reflected by alpha desynchronization in bilateral anterior ROIs. In addition, we could not identify any effects of task difficulty and age on the beta frequency band. Our results shed light on age-related cognitive and postural declines and how they interact. Modulated alpha frequencies during high cognitive-postural task demands in young but not old adults might be reflective of a constrained neural adaptive potential in old adults. Future studies are needed to elucidate associations between the identified age-related performance decrements with task difficulty and changes in brain activity.
Dimensional psychiatry
(2014)
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.
We used functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task to study the functional correlates of reward anticipation across major psychiatric disorders in 184 subjects, with the diagnoses of alcohol dependence (n = 26), schizophrenia (n = 44), major depressive disorder (MDD, n = 24), bipolar disorder (acute manic episode, n = 13), attention deficit/hyperactivity disorder (ADHD, n = 23), and healthy controls (n = 54). Subjects' individual Beck Depression Inventory-and State-Trait Anxiety Inventory-scores were correlated with clusters showing significant activation during reward anticipation.
During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.
Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
Purpose
To test whether the negative relationship between perceived stress and quality of life (Hypothesis 1) can be buffered by perceived social support in patients with dementia as well as in caregivers individually (Hypothesis 2: actor effects) and across partners (Hypothesis 3: partner effects and actor-partner effects).
Method
A total of 108 couples (N = 216 individuals) comprised of one individual with early-stage dementia and one caregiving partner were assessed at baseline and one month apart. Moderation effects were investigated by applying linear mixed models and actor-partner interdependence models.
Results
Although the stress-quality of life association was more pronounced in caregivers (beta = -.63, p<.001) compared to patients (beta= -.31, p<.001), this association was equally moderated by social support in patients (beta = .14, p<.05) and in the caregivers (beta =.13, p<.05). From one partner to his or her counterpart, the partner buffering and actor-partner-buffering effect were not present.
Conclusion
The stress-buffering effect has been replicated in individuals with dementia and caregivers but not across partners. Interventions to improve quality of life through perceived social support should not only focus on caregivers, but should incorporate both partners.
Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
Objective: To test the effect of a complex guideline-based intervention on agitation and psychotropic prescriptions.
Design, Setting, Participants: Cluster randomized controlled trial (VIDEANT) with blinded assessment of outcome in 18 nursing homes in Berlin, Germany, comprising 304 dementia patients.
Intervention: Training, support, and activity therapy intervention, delivered at the level of each nursing home, focusing on the management of agitation in dementia. Control group nursing homes received treatment as usual.
Measurements: Levels of agitated and disruptive behavior (Cohen-Mansfield agitation inventory [CMAI]) as the primary outcome. Number of neuroleptics, antidepressants, and cholinesterase inhibitors (ChEIs) prescribed in defined daily dosages (DDDs).
Results: Of 326 patients screened, 304 (93.3%) were eligible and cluster-randomized to 9 intervention (n = 163) and 9 control (n = 141) nursing homes. Data were collected from 287 (94.4%) patients at 10 months. At 10 months, compared with controls, nursing home residents with dementia in the intervention group exhibited significantly less agitation as measured with the CMAI (adjusted mean difference, 6.24; 95% CI 2.03-14.14; P = .009; Cohen's d = 0.43), received fewer neuroleptics (P < .05), more ChEIs (P < .05), and more antidepressants (P < .05).
Conclusion: Complex guideline-based interventions are effective in reducing agitated and disruptive behavior in nursing home residents with dementia. At the same time, increased prescription of ChEIs and antidepressants together with decreased neuroleptic prescription suggests an effect toward guideline-based pharmacotherapy.
Apathy in nursing home residents with dementia: Results from a cluster-randomized controlled trial
(2015)
Purpose: Here we evaluate an interdisciplinary occupational and sport therapy intervention for dementia patients suffering from apathy.
Subjects and methods: A prospective, controlled, rater-blinded, clinical trial with two follow-ups was conducted as part of a larger cluster-randomized trial in 18 nursing homes in Berlin. n = 117 dementia patients with apathy, defined as a score of 40 or more on the apathy evaluation scale (AES) or presence of apathy on the Neuropsychiatric Inventory (NPI), were randomly assigned to intervention or control group. The intervention included 10 months of brief activities, provided once a week. The primary outcome measure was the total score on the AES scale measured directly after the intervention period and again after 12 months.
Results: We found significant group differences with respect to apathy during the 10 month intervention period (F-2,F-82 = 7.79, P < 0.01), which reflected an increase in apathy in the control group, but not in the intervention group. Within one year after the intervention was ceased, the treatment group worsened and no longer differed significantly from the control group (P = 0.55).
Conclusions: Our intervention was effective for the therapy of apathy in dementia, when applied, but not one year after cessation of therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.
Age-related decline in executive functions and postural control due to degenerative processes in the central nervous system have been related to increased fall-risk in old age. Many studies have shown cognitive-postural dual-task interference in old adults, but research on the role of specific executive functions in this context has just begun. In this study, we addressed the question whether postural control is impaired depending on the coordination of concurrent response-selection processes related to the compatibility of input and output modality mappings as compared to impairments related to working-memory load in the comparison of cognitive dual and single tasks. Specifically, we measured total center of pressure (CoP) displacements in healthy female participants aged 19–30 and 66–84 years while they performed different versions of a spatial one-back working memory task during semi-tandem stance on an unstable surface (i.e., balance pad) while standing on a force plate. The specific working-memory tasks comprised: (i) modality compatible single tasks (i.e., visual-manual or auditory-vocal tasks), (ii) modality compatible dual tasks (i.e., visual-manual and auditory-vocal tasks), (iii) modality incompatible single tasks (i.e., visual-vocal or auditory-manual tasks), and (iv) modality incompatible dual tasks (i.e., visual-vocal and auditory-manual tasks). In addition, participants performed the same tasks while sitting. As expected from previous research, old adults showed generally impaired performance under high working-memory load (i.e., dual vs. single one-back task). In addition, modality compatibility affected one-back performance in dual-task but not in single-task conditions with strikingly pronounced impairments in old adults. Notably, the modality incompatible dual task also resulted in a selective increase in total CoP displacements compared to the modality compatible dual task in the old but not in the young participants. These results suggest that in addition to effects of working-memory load, processes related to simultaneously overcoming special linkages between input- and output modalities interfere with postural control in old but not in young female adults. Our preliminary data provide further evidence for the involvement of cognitive control processes in postural tasks.
There is evidence for cortical contribution to the regulation of human postural control. Interference from concurrently performed cognitive tasks supports this notion, and the lateral prefrontal cortex (lPFC) has been suggested to play a prominent role in the processing of purely cognitive as well as cognitive-postural dual tasks. The degree of cognitive-motor interference varies greatly between individuals, but it is unresolved whether individual differences in the recruitment of specific lPFC regions during cognitive dual tasking are associated with individual differences in cognitive-motor interference. Here, we investigated inter-individual variability in a cognitive-postural multitasking situation in healthy young adults (n = 29) in order to relate these to inter-individual variability in lPFC recruitment during cognitive multitasking. For this purpose, a oneback working memory task was performed either as single task or as dual task in order to vary cognitive load. Participants performed these cognitive single and dual tasks either during upright stance on a balance pad that was placed on top of a force plate or during fMRI measurement with little to no postural demands. We hypothesized dual one-back task performance to be associated with lPFC recruitment when compared to single one-back task performance. In addition, we expected individual variability in lPFC recruitment to be associated with postural performance costs during concurrent dual one-back performance. As expected, behavioral performance costs in postural sway during dual-one back performance largely varied between individuals and so did lPFC recruitment during dual one-back performance. Most importantly, individuals who recruited the right mid-lPFC to a larger degree during dual one-back performance also showed greater postural sway as measured by larger performance costs in total center of pressure displacements. This effect was selective to the high-load dual one-back task and suggests a crucial role of the right lPFC in allocating resources during cognitivemotor interference. Our study provides further insight into the mechanisms underlying cognitive-motor multitasking and its impairments.
Working memory load-dependent brain response predicts behavioral training gains in older adults
(2014)
In the domain of working memory (WM), a sigmoid-shaped relationship between WM load and brain activation patterns has been demonstrated in younger adults. It has been suggested that age-related alterations of this pattern are associated with changes in neural efficiency and capacity. At the same time, WM training studies have shown that some older adults are able to increase their WM performance through training. In this study, functional magnetic resonance imaging during an n-back WM task at different WM load levels was applied to compare blood oxygen level-dependent (BOLD) responses between younger and older participants and to predict gains in WM performance after a subsequent 12-session WM training procedure in older adults. We show that increased neural efficiency and capacity, as reflected by more "youth-like" brain response patterns in regions of interest of the frontoparietal WM network, were associated with better behavioral training outcome beyond the effects of age, sex, education, gray matter volume, and baseline WM performance. Furthermore, at low difficulty levels, decreases in BOLD response were found after WM training. Results indicate that both neural efficiency (i. e., decreased activation at comparable performance levels) and capacity (i. e., increasing activation with increasing WM load) of a WM-related network predict plasticity of the WM system, whereas WM training may specifically increase neural efficiency in older adults.
Satisfaction and frustration of the needs for autonomy, competence, and relatedness, as assessed with the 24-item Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS), have been found to be crucial indicators of individuals’ psychological health. To increase the usability of this scale within a clinical and health services research context, we aimed to validate a German short version (12 items) of this scale in individuals with depression including the examination of the relations from need frustration and need satisfaction to ill-being and quality of life (QOL). This cross-sectional study involved 344 adults diagnosed with depression (Mage (SD) = 47.5 years (11.1); 71.8% females). Confirmatory factor analyses indicated that the short version of the BPNSFS was not only reliable, but also fitted a six-factor structure (i.e., satisfaction/frustration X type of need). Subsequent structural equation modeling showed that need frustration related positively to indicators of ill-being and negatively to QOL. Surprisingly, need satisfaction did not predict differences in ill-being or QOL. The short form of the BPNSFS represents a practical instrument to measure need satisfaction and frustration in people with depression. Further, the results support recent evidence on the importance of especially need frustration in the prediction of psychopathology.
The primary aim of the current study was to examine the unique contribution of psychological need frustration and need satisfaction in the prediction of adults’ mental well-being and ill-being in a heterogeneous sample of adults (N = 334; Mage = 43.33, SD = 32.26; 53% females). Prior to this, validity evidence was provided for the German version of the Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS) based on Self-Determination Theory (SDT). The results of the validation analyses found the German BPNSFS to be a valid and reliable measurement. Further, structural equation modeling (SEM) showed that both need satisfaction and frustration yielded unique and opposing associations with well-being. Specifically, the dimension of psychological need frustration predicted adults’ ill-being. Future research should examine whether frustration of psychological needs is involved in the onset and maintenance of psychopathology (e.g., major depressive disorder).
When local poverty is more important than your income: Mental health in minorities in inner cities
(2015)
Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying F-18-fallypride positron emission tomography (F-18-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.
During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.
Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
Objectives: To investigate the efficacy of animal-assisted therapy (AAT) on symptoms of agitation/aggression and depression in nursing home residents with dementia in a randomized controlled trial. Previous studies have indicated that AAT has beneficial effects on neuropsychiatric symptoms in various psychiatric disorders but few studies have investigated the efficacy of AAT in patients suffering from dementia. Methods: Of 65 nursing home residents with dementia (mean [standard deviation] age: 81.8 [9.2] years; mean Mini-Mental State Examination score: 7.1 [0.7]), 27 matched pairs (N = 54) were randomly assigned to either treatment as usual or treatment as usual combined with AAT, administered over 10 weekly sessions. Blinded raters assessed cognitive impairment with the Mini-Mental State Examination, presence of agitation/aggression with the Cohen-Mansfield Agitation Inventory, and depression with the Dementia Mood Assessment Scale at baseline and during a period of 4 weeks after AAT intervention. Results: In the control group, symptoms of agitation/aggression and depression significantly increased over 10 weeks; in the intervention group, patients receiving combined treatment displayed constant frequency and severity of symptoms of agitation/aggression (F-1,F-48 = 6.43; p <0.05) and depression (F-1,F-48 = 26.54; p <0.001). Symptom amelioration did not occur in either group. Conclusions: AAT is a promising option for the treatment of agitation/aggression and depression in patients with dementia. Our results suggest that AAT may delay progression of neuropsychiatric symptoms in demented nursing home residents. Further research is needed to determine its long-time effects.
Depression is the most prevalent psychiatric disorder in the general population. Despite a large demand for efficient treatment options, the majority of older depressed adults does not receive adequate treatment: Additional low-threshold treatments are needed for this age group. Over the past two decades, a growing number of randomized controlled trials (RCT) have been conducted, testing the efficacy of physical exercise in the alleviation of depression in older adults. This meta-analysis systematically reviews and evaluates these studies; some subanalyses testing specific effects of different types of exercise and settings are also performed. In order to be included, exercise programs of the RCTs had to fulfill the criteria of exercise according to the American College of Sports Medicine, including a sample mean age of 60 or above and an increased level of depressive symptoms. Eighteen trials with 1,063 participants fulfilled our inclusion criteria. A comparison of the posttreatment depression scores between the exercise and control groups revealed a moderate effect size in favor of the exercise groups (standardized mean difference (SMD) of –0.68, p < .001). The effect was comparable to the results achieved when only the eleven trials with low risk of bias were included (SMD = –0.63, p < .001). The subanalyses showed significant effects for all types of exercise and for supervised interventions. The results of this meta-analysis suggest that physical exercise may serve as a feasible, additional intervention to fight depression in older adults. However, because of small sample sizes of the majority of individual trials and high statistical heterogeneity, results must be interpreted carefully.
Background: The aim of the present study was to investigate the psychometric characteristics of the Perceived Stress Scale (PSS) in a sample of dementia patients and their spousal caregivers. Methods: We investigated the reliability and validity of the 14-item PSS in a sample of 80 couples, each including one spouse who had been diagnosed with mild to moderate dementia (mean age 75.55, SD = 5.85, 38.7% female) and one spousal caregiver (mean age 73.06, SD = 6.75, 61.3% female). We also examined the factor structure and sensitivity of the scale with regard to gender differences. Results: Exploratory factor analysis of the PSS revealed a two-factor solution for the scale; the first factor reflected general stress while the second factor consisted of items reflecting the perceived ability to cope with stressors. A confirmatory factor analysis verified that the data were a better fit for the two-factor model than a one-factor model. The two factors of the PSS showed good reliability for patients as well as for caregivers ranging between alpha = 0.73 and alpha = 0.82. Perceived stress was significantly positively correlated with depressive symptomatology in both caregivers and patients. Mean PSS scores did not significantly differ between male and female patients nor did they differ between male and female caregivers. Conclusion: The present data indicate that the PSS provides a reliable and valid measure of perceived stress in dementia patients and their caregivers.
In recent years digital technologies have become a major means for providing health-related services and this trend was strongly reinforced by the current Coronavirus disease 2019 (COVID-19) pandemic. As it is well-known that regular physical activity has positive effects on individual physical and mental health and thus is an important prerequisite for healthy aging, digital technologies are also increasingly used to promote unstructured and structured forms of physical activity. However, in the course of this development, several terms (e.g., Digital Health, Electronic Health, Mobile Health, Telehealth, Telemedicine, and Telerehabilitation) have been introduced to refer to the application of digital technologies to provide health-related services such as physical interventions. Unfortunately, the above-mentioned terms are often used in several different ways, but also relatively interchangeably. Given that ambiguous terminology is a major source of difficulty in scientific communication which can impede the progress of theoretical and empirical research, this article aims to make the reader aware of the subtle differences between the relevant terms which are applied at the intersection of physical activity and Digital Health and to provide state-of-art definitions for them.
Sedentarism is a risk factor for depression and anxiety. People living with the human immunodeficiency virus (PLWH) have a higher prevalence of anxiety and depression compared to HIV-negative individuals. This cross-sectional study (n = 450, median age 44 (19-75), 7.3% females) evaluates the prevalence rates and prevalence ratio (PR) of anxiety and/or depression in PLWH associated with recreational exercise. A decreased likelihood of having anxiety (PR=0.57; 0.36-0.91; p = 0.01), depression (PR=0.41; 0.36-0.94; p=0.01), and comorbid anxiety and depression (PR = 0,43; 0.24-0.75; p=0.002) was found in exercising compared to non-exercising PLWH. Recreational exercise is associated with a lower risk for anxiety and/or depression. Further prospective studies are needed to provide insights on the direction of this association.
Evaluation of technology-based interventions for informal caregivers of patients with dementia
(2019)
Objective: The aim of this study was to estimate the efficacy of technology-based interventions for informal caregivers of people with dementia (PWD). Methods: PubMed, PsycINFO, and Cochrane Library databases were searched in August 2018, with no restrictions in language or publication date. Two independent reviewers identified 33 eligible randomized controlled trials (RCTs) conducting a technology-based intervention for informal carers of PWD. Meta-analyses for the outcome measures caregiver depression and caregiver burden were conducted with subgroup analyses according to mode of delivery (telephone, computer/web-based, combined interventions). To assess methodologic quality, the Cochrane risk-of-bias assessment was rated. Results: Meta-analyses revealed a small but significant postintervention effect of technology-based interventions for caregiver depression and caregiver burden. Combined interventions showed the strongest effects. Conclusion: Technology-based interventions have the potential to support informal caregivers of PWD. Because of advantages such as high flexibility and availability, technology-based interventions provide a promising alternative compared with "traditional services," e.g., those for people living in rural areas. More high-quality RCTs for specific caregiver groups are needed.
Effects of Aerobic and Resistance Exercise on Cardiovascular Parameters for People Living With HIV
(2019)
People living with HIV (PLWH) have limited exercise capacity because of anemia, neuromuscular disorders, and pulmonary limitations. We used a meta-analysis to examine the effect of aerobic and resistance exercise alone and in combination on cardiovascular parameters. Subgroup meta-analyses were conducted and long-term effects of exercise were investigated. A systematic literature search was conducted up to July/August 2017. The Physiotherapy Evidence Database-scale was used to rate quality and assess the risk of bias on the papers. Standardized mean differences (SMDs) were calculated to assess the effect of exercise. Posttreatment comparison between the exercise and control groups revealed moderate and large effect sizes in favor of the intervention group for VO2max (SMD50.66, p < .0001) and the 6-minute walk test (SMD = 1.11, p = .0001). Exercise had a positive effect on cardiovascular parameters in PLWH. Exercise can be a prevention factor for PLWH dealing with multiple comorbidities.
As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12 sessions (45 min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75 years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks suggest that transfer to other cognitive tasks remains possible in aging. (C) 2016 Elsevier Inc. All rights reserved.
Objective: To estimate the prevalence and type of antidepressant medication prescribed by German primary care physicians for patients with depression and osteoporosis. Methods: This study was a retrospective database analysis conducted in Germany utilizing the Disease Analyzer (R) Database (IMS Health, Germany). The study population included 3,488 female osteoporosis patients aged between 40 and 90 years recruited from 1,179 general practitioner practices and who were initially diagnosed with depression during the index period (January 2004 to December 2013). Follow-up lasted up to 12 months and was completed in August 2015. Also included in this study were 3,488 nonosteoporosis controls who were matched (1 : 1) to osteoporosis cases on the basis of age, health insurance coverage, severity of depression, and physician carrying out the diagnosis. Results: After 12 months of followup, 30.1% of osteoporosis and 29.9% of nonosteoporosis patients with mild depression (p = 0.783), 52.4% of osteoporosis and 48.0% of non-osteoporosis patients with moderate depression (p = 0.003), and 39.4% of osteoporosis and 35.1% of nonosteoporosis patients with severe depression (p = 0.147) were being treated with antidepressants. Osteoporosis patients with moderate depression had a higher chance of being prescribed antidepressant therapy at the initial diagnosis (hazard ratio (HR): 1.12, p = 0.014). No differences were found between osteoporosis and nonosteoporosis patients regarding the proportion of patients receiving selective serotonin reuptake inhibitors (SSRI)/serotonin-noradrenaline reuptake inhibitors (SNRI), tricyclic antidepressant (TCA), or other antidepressants. Osteoporosis patients were more often referred to hospitals or psychiatrists for consultation. Conclusion: Osteoporosis patients are more often treated initially with antidepressants than non-osteoporosis patients, especially within the groups of patients with moderate or severe depression. TCA was the most frequently used antidepressant therapy class on initial diagnosis in both patient groups. Osteo-porosis patients receive referrals to hospitals or psychiatrists more often than patients without osteoporosis.
Background: Despite extensive research in the past decades, the influence of genetics on cognitive functions in schizophrenia remains unclear. Dystrobrevin-binding protein 1 (DTNBP1) is one of the most promising candidate genes in schizophrenia. An association of DTNBP1 with cognitive dysfunction, particularly memory impairment, has been reported in a number of studies. However, the results remain inconsistent. The aim of this study was to measure the association between DTNBP1 polymorphisms and cognitive domains in a well-characterized sample. Methods: Ninety-one clinically stable schizophrenia outpatients underwent a battery of cognitive tests. Six single nucleotide polymorphisms (SNPs) of DTNBP1 were genotyped in all participants. Statistical and multivariate analyses were performed. Results: Factor analysis revealed 4 factors corresponding to distinct cognitive domains, namely sustained attention, set-shifting, executive functioning, and memory. We found a significant association of the rs909706 polymorphism with attention (p = 0.030) and a nonsignificant trend for set-shifting (p = 0.060). The other SNPs and haplotypes were not associated with cognitive function. Discussion: Replication of this finding in a larger sample is needed in order to confirm the importance of this particular polymorphism in the genetics of schizophrenia, particularly the distinct cognitive domains. In conclusion, the present study supports the involvement of DTNBP1 in the regulation of cognitive processes and demonstrates association in particular with sustained attention and set-shifting in schizophrenia patients. (C) 2016 S. Karger AG, Basel
The Summary Thirty-five thousand four hundred eighty-three female osteoporosis patients were compared with 35,483 patients without osteoporosis regarding the incidence of depression. The risk of depression is significantly increased for patients with osteoporosis compared with patients without osteoporosis in primary care practices within Germany. Introduction The objectives of the present study were to analyze the incidence of depression in German female patients with osteoporosis and to evaluate the risk factors for depression diagnosis within this patient population. Methods This study was a retrospective database analysis conducted in Germany utilizing the Disease Analyzer (R) Database (IMS Health, Germany). The study population included 70,966 patients between 40 and 80 years of age from 1072 primary care practices. The observation period was between 2004 and 2013. Follow-up duration was 5 years and was completed in April 2015. A total of 35,483 osteoporosis patients were selected after applying exclusion criteria, and 35,483 controls were chosen and then matched (1:1) to osteoporosis patients based on age, sex, health insurance coverage, depression diagnosis in the past, and follow-up duration after index date. The analyses of depression-free survival were carried out using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models (dependent variable: depression) were used to adjust for confounders. Results Depression diagnoses were presented in 33.0% of the osteoporosis group and 22.7% of the control group after the 5-year follow-up (p < 0.001). Dementia, cancer, heart failure, coronary heart disease, and diabetes were associated with a higher risk of developing depression (p < 0.001). Private health insurance was associated with a lower risk of depression. There was no significant effect of fractures on depression risk. Conclusion The risk of depression is significantly increased for patients with osteoporosis in primary care practices within Germany.
AIM To determine the prevalence of depression and its risk factors among patients with coronary heart disease (CHD) treated in German primary care practices. METHODS Longitudinal data from nationwide general practices in Germany (n = 1072) were analyzed. Individuals initially diagnosed with CHD (2009-2013) were identified, and 59992 patients were included and matched (1: 1) to 59992 controls. The primary outcome measure was an initial diagnosis of depression within five years after the index date among patients with and without CHD. Cox proportional hazards models were used to adjust for confounders. RESULTS Mean age was equal to 68.0 years (SD = 11.3). A total of 55.9% of patients were men. After a five-year follow-up, 21.8% of the CHD group and 14.2% of the control group were diagnosed with depression (P < 0.001). In the multivariate regression model, CHD was a strong risk factor for developing depression (HR = 1.54, 95% CI: 1.49-1.59, P < 0.001). Prior depressive episodes, dementia, and eight other chronic conditions were associated with a higher risk of developing depression. Interestingly, older patients and women were also more likely to be diagnosed with depression compared with younger patients and men, respectively. CONCLUSION The risk of depression is significantly increased among patients with CHD compared with patients without CHD treated in primary care practices in Germany. CHD patients should be routinely screened for depression to ensure improved treatment and management.
Persistence with antidepressant drugs in patients with dementia: a retrospective database analysis
(2016)
Background: The aims of the present study are to determine what proportion of patients with dementia receives antidepressants, how long the treatment is administered, and what factors increase the risk of discontinuation. Methods: The study was based on Disease Analyzer database and included 1,203 general practitioners (GP) and 209 neurologists/psychiatrists (NP). 12,281 patients with a diagnosis of dementia and an initial prescription of an antidepressant drug between January 2004 and December 2013 were included. The main outcome measure was antidepressant discontinuation rates within 6 months of the index date. Results: After 6 months of follow-up, 52.7% of dementia patients treated with antidepressants had stopped medication intake. There was a significantly decreased risk for treatment discontinuation for patients using selective serotonin reuptake inhibitors (SSRRIs) or serotonin and norepinephrine reuptake inhibitors (SSNRIs) compared to tricyclic antidepressants. There was a significantly increased risk of treatment discontinuation for older patients and patients treated in NP practice. Comorbidity of diabetes or history of stroke was associated with a decreased risk of treatment discontinuation. Conclusion: The study results show insufficient persistence in antidepressant treatment in dementia patients in a real world setting. The improvement must be achieved to ensure the treatment recommended in the guidelines.