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General intelligence has a substantial genetic background in children, adolescents, and adults, but environmental factors also strongly correlate with cognitive performance as evidenced by a strong (up to one SD) increase in average intelligence test results in the second half of the previous century. This change occurred in a period apparently too short to accommodate radical genetic changes. It is highly suggestive that environmental factors interact with genotype by possible modification of epigenetic factors that regulate gene expression and thus contribute to individual malleability. This modification might as well be reflected in recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events.
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.
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.
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.
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.
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.
Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24-30 years) and 25 older (aged 60-75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.
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.
Cities and Mental Health
(2017)
Background: More than half of the global population currently lives in cities, with an increasing trend for further urbanization. Living in cities is associated with increased population density, traffic noise and pollution, but also with better access to health care and other commodities. Methods: This review is based on a selective literature search, providing an overview of the risk factors for mental illness in urban centers. Results: Studies have shown that the risk for serious mental illness is generally higher in cities compared to rural areas. Epidemiological studies have associated growing up and living in cities with a considerably higher risk for schizophrenia. However, correlation is not causation and living in poverty can both contribute to and result from impairments associated with poor mental health. Social isolation and discrimination as well as poverty in the neighborhood contribute to the mental health burden while little is known about specific inter actions between such factors and the built environment. Conclusion: Further insights on the interaction between spatial heterogeneity of neighborhood resources and socio-ecological factors is warranted and requires interdisciplinary research.
The interruption of learning processes by breaks filled with diverse activities is common in everyday life. This study investigated the effects of active computer gaming and passive relaxation (rest and music) breaks on auditory versus visual memory performance. Young adults were exposed to breaks involving (a) open eyes resting, (b) listening to music, and (c) playing a video game, immediately after memorizing auditory versus visual stimuli. To assess learning performance, words were recalled directly after the break (an 8:30 minute delay) and were recalled and recognized again after 7 days. Based on linear mixed-effects modeling, it was found that playing the Angry Birds video game during a short learning break impaired long-term retrieval in auditory learning but enhanced long-term retrieval in visual learning compared with the music and rest conditions. These differential effects of video games on visual versus auditory learning suggest specific interference of common break activities on learning.
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.
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.
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.
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.
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.
Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward.
Psychiatrische Stationen sind ein wichtiges Element in der psychiatrischen Versorgung von Menschen mit akuter Eigen- oder Fremdgefährdung. Leider kommt es in diesem Rahmen immer wieder auch zu Aggression, Gewalt (Konflikten) sowie zur Anwendung von Zwang (Eindämmung). Als entscheidender Faktor für den sachgemäßen Umgang mit diesen Situationen wird sowohl die Quantität als auch die Qualität der Mitarbeitenden angesehen. Vor diesem Hintergrund beschäftigt sich die vorliegende Untersuchung mit der Versorgungssituation auf akutpsychiatrischen Stationen. Die Hypothese lautet, dass sowohl die Größe der akutpsychiatrischen Station als auch die Anzahl der Pflegenden einen Einfluss auf das Vorkommen konflikthafter Situationen haben. Hierfür sind Daten in 6 Kliniken auf insgesamt 12 psychiatrischen Stationen erfasst worden. Als Erfassungsinstrument diente die Patient Staff Conflict Checklist – Shift Report (PCC-SR). Insgesamt konnten 2026 Schichten (Früh‑, Spät- und Nachtschicht) erfasst und ausgewertet werden. Die personelle Besetzung der Stationen mit Pflegepersonal variierte erheblich. Die Ergebnisse zeigen, dass sowohl die Stationsgröße als auch die Anzahl der Pflegepersonen auf akutpsychiatrischen Stationen einen signifikanten Einfluss auf das Vorkommen von Konflikten haben. In den Ergebnissen zeigt sich weiterhin, dass sich die Inzidenz des konflikthaften Verhaltens von Patienten sowohl im Hinblick auf die untersuchten Stationen der beteiligten Krankenhäuser als auch im Hinblick auf die betrachteten Dienstzeittypen unterscheiden. Darüber hinaus zeigt sich, dass das Ausmaß der Schließung einer Akutstation und die Größe einer Station einen negativen Einfluss auf die Inzidenz von Konflikten im stationär akutpsychiatrischen Kontext haben. Das Auftreten konflikthaften Verhaltens kann zur Fremd- oder Selbstgefährdung und zu einer Vielzahl deeskalierender und eindämmender Maßnahmen führen. Hierfür sind entsprechende personelle Ressourcen erforderlich.