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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.
Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. (C) 2016 Published by Elsevier Ltd.
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 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.
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.
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.