Cortical profiles of numerous psychiatric disorders and normal development share a common pattern.

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.

Correction: Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.

[This corrects the article DOI: 10.1371/journal.pone.0260952.].

Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955.

Correlation between brain function and ADHD symptom changes in children with ADHD following a few-foods diet: an open-label intervention trial.

Research into the effect of nutrition on attention-deficit hyperactivity disorder (ADHD) in children has shown that the few-foods diet (FFD) substantially decreases ADHD symptoms in 60% of children. However, the underlying mechanism is unknown. In this open-label nutritional intervention study we investigated whether behavioural changes after following an FFD are associated with changes in brain function during inhibitory control in 79 boys with ADHD, aged 8-10 years. Parents completed the ADHD Rating Scale before (t1) and after the FFD (t2). Functional magnetic resonance imaging (fMRI) scans were acquired during a stop-signal task at t1 and t2, and initial subject-level analyses were done blinded for ARS scores. Fifty (63%) participants were diet responders, showing a decrease of ADHD symptoms of at least 40%. Fifty-three children had fMRI scans of sufficient quality for further analysis. Region-of-interest analyses demonstrated that brain activation in regions implicated in the stop-signal task was not associated with ADHD symptom change. However, whole-brain analyses revealed a correlation between ADHD symptom decrease and increased precuneus activation (pFWE(cluster) = 0.015 for StopSuccess > Go trials and pFWE(cluster) < 0.001 for StopSuccess > StopFail trials). These results provide evidence for a neurocognitive mechanism underlying the efficacy of a few-foods diet in children with ADHD.

Brain responses to anticipating and receiving beer: Comparing light, at-risk, and dependent alcohol users.

Impaired brain processing of alcohol-related rewards has been suggested to play a central role in alcohol use disorder. Yet, evidence remains inconsistent and mainly originates from studies in which participants passively observe alcohol cues or taste alcohol. Here, we designed a protocol in which beer consumption was predicted by incentive cues and contingent on instrumental action closer to real life situations. We predicted that anticipating and receiving beer (compared with water) would elicit activity in the brain reward network and that this activity would correlate with drinking level across participants. The sample consisted of 150 beer-drinking males, aged 18 to 25 years. Three groups were defined based on alcohol use disorders identification test (AUDIT) scores: light drinkers (n = 39), at-risk drinkers (n = 64), and dependent drinkers (n = 47). fMRI measures were obtained while participants engaged in the beer incentive delay task involving beer- and water-predicting cues followed by real sips of beer or water. During anticipation, outcome notification and delivery of beer compared with water, higher activity was found in a reward-related brain network including the dorsal medial prefrontal cortex, orbitofrontal cortex, and amygdala. Yet, no activity was observed in the striatum, and no differences were found between the groups. Our results reveal that anticipating, obtaining, and tasting beer activates parts of the brain reward network, but that these brain responses do not differentiate between different drinking levels.

Brain responses and approach bias to social alcohol cues and their association with drinking in a social setting in young adult males.

Alcohol is mainly consumed in social settings, in which people often adapt their drinking behaviour to that of others, also called imitation of drinking. Yet, it remains unclear what drives this drinking in a social setting. In this study, we expected to see stronger brain and behavioural responses to social compared to non-social alcohol cues, and these responses to be associated with drinking in a social setting. The sample consisted of 153 beer-drinking males, aged 18-25 years. Brain responses to social alcohol cues were measured during an alcohol cue-exposure task performed in an fMRI scanner. Behavioural responses to social alcohol cues were measured using a stimulus-response compatibility task, providing an index of approach bias towards these cues. Drinking in a social setting was measured in a laboratory mimicking a bar environment. Specific brain responses to social alcohol cues were observed in the bilateral superior temporal sulcus and the left inferior parietal lobe. There was no approach bias towards social alcohol cues specifically; however, we did find an approach bias towards alcohol (versus soda) cues in general. Brain responses and approach bias towards social alcohol cues were unrelated and not associated with actual drinking. Thus, we found no support for a relation between drinking in a social setting on the one hand, and brain cue-reactivity or behavioural approach biases to social alcohol cues on the other hand. This suggests that, in contrast to our hypothesis, drinking in a social setting may not be driven by brain or behavioural responses to social alcohol cues.

Acceleration of drinking pace throughout the evening among frequently drinking young adults in the Netherlands.

BACKGROUND AND AIMS: Previous studies have found that in some countries 'drinking pace' (number of drinks consumed per hour) increases during the course of an evening. We aimed to provide evidence of this acceleration from a culture in which binge drinking is prevalent and to test whether this is consistent across gender, day of week and in high-risk drinkers. DESIGN: Event-level data collected on Thursday, Friday and Saturday evenings over 5 consecutive weeks. SETTING: The Netherlands. PARTICIPANTS: A total of 197 young adult frequent drinkers (48.7% women, mean age = 20.8). MEASUREMENTS: High-risk drinking (assessed by the Alcohol Use Disorders Identification Test) and gender were measured at baseline, and questionnaires were sent to participants' smartphones every hour between 9 p.m. and 1 a.m. A total of 7185 questionnaires during 1589 evenings were used for the analyses. FINDINGS: Multi-level latent growth curve models revealed an acceleration in drinking on days of the week tested [throughout all evenings; b = 0.430, standard error (SE) = 0.045, P < 0.001], which stabilized as the evening progressed (b = -0.072, SE = 0.008, P < 0.001). The temporal pattern did not differ between the days or gender, but men started with a higher number of drinks at the beginning of the evening (b = 0.465, SE = 0.099, P < 0.001). High-risk drinking was related to more alcoholic drinks at the beginning of an evening (b = 0.032, SE = 0.011, P = 0.003) and a steeper acceleration during the subsequent hours (b = 0.021, SE = 0.009, P = 0.024). CONCLUSIONS: Young adults in the Netherlands appear to show an increase in drinking pace during the course of an evening's drinking, with high-risk drinkers showing a greater increase.

Young adults do not catch up missed drinks when starting later at night-An ecological momentary assessment study.

Drinking heavily in a short period is associated with significant health risks. However, little is known about when heavy drinking occurs during an evening. Recently, research found that individuals increase their drinking pace across the evening, speeding up their drinking. The current study examines whether this speeding up is different depending on when individuals start to drink in the evening. Data on alcohol consumption were collected among 197 young adults in the Netherlands (48.7% female, Mage = 20.8 SD = 1.7) on Thursday, Friday and Saturday evenings for 5 consecutive weeks using questionnaires send to participants' smartphone every hour between 9 p.m.-1 a.m. The final sample consisted of 10,144 questionnaires across 2,781 evenings. On evenings when individuals started to drink early (between 8 and 9 p.m.), more alcohol was consumed in the first drinking hour, yet no increase in acceleration was found compared to evenings when individuals started later. Moreover, starting later resulted in a lower overall evening consumption and less binge-drinking episodes compared to starting earlier. The results indicate that when individuals start drinking later in the evening they do not tend to catch up the "missed" drinks, that is they do not increase their drinking faster when starting later in the evening, and they drink less heavily. Therefore, motivating young adults to postpone their first drink in the evening could help heavy drinking young adults to drink less on weekend evenings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cognitive Biases for Social Alcohol-Related Pictures and Alcohol Use in Specific Social Settings: An Event-Level Study.

BACKGROUND: Alcohol use occurs mainly among friends, in social contexts, and for social reasons. Moreover, cognitive biases, such as attentional and approach biases, have repeatedly been associated with alcohol use. This study aimed to test whether nondependent drinkers display cognitive biases for social alcohol-related (SA) pictures and whether these biases are associated with alcohol use in social drinking contexts. METHODS: The visual dot probe task and stimulus-response compatibility tasks were used to measure attentional and approach biases for alcohol-related pictures at baseline. Event-level alcohol use was measured using Ecological Momentary Assessments via personal smartphones. One hundred and ninety-two young adults (51.6% men; Mage  = 20.73) completed the study, resulting in 11,257 assessments conducted on Thursday, Friday, and Saturday evenings for 5 consecutive weeks. RESULTS: While no overall attentional bias for alcohol-related pictures was found, young adults showed an approach bias for both social and nonsocial alcohol-related pictures. Multilevel models revealed no direct association between cognitive biases for alcohol-related pictures and alcohol use. However, higher levels of attentional bias for SA pictures were associated with more drinking when individuals were surrounded by a greater number of friends of opposite gender. Higher levels of an approach bias for SA pictures were associated with more drinking in women surrounded by a greater number of friends of the same gender. CONCLUSIONS: In a nondependent sample, cognitive biases for SA pictures could not be associated with drinking directly. However, a cognitive bias for SA pictures moderated the association between alcohol use and number of friends present. As most observed effects were gender and situation specific, replication of these effects is warranted.

The role of social stimuli content in neuroimaging studies investigating alcohol cue-reactivity.

INTRODUCTION: Cue-reactivity is thought to play a fundamental role in the maintenance of addiction. The incentive sensitization theory proposes that conditioned responses are related to increased sensitivity of the reward-related dopaminergic pathways in the brain. However, neuroimaging studies on alcohol cue-reactivity show inconsistent results. METHODS: Stimuli content of 26 alcohol cue-reactivity studies was systematically reviewed. RESULTS: No differences were found between alcoholic beverage stimuli and non-alcoholic beverage stimuli in human display and brand factors; however, alcoholic beverage stimuli were more likely to display social interaction compared to non-alcoholic beverage stimuli. CONCLUSIONS: Given that processing of social information activates brain areas that partly overlap with reward-related brain areas associated with cue-reactivity, such differences between conditions can introduce noise in the findings. We therefore suggest matching stimuli sets on the reviewed factors carefully to improve reliability of neuroimaging studies investigating alcohol-related cue-reactivity.

Drinking Motives Moderate the Effect of the Social Environment on Alcohol Use: An Event-Level Study Among Young Adults.

OBJECTIVE: The purpose of this study was to test (a) whether drinking motives predict event-level drinking on weekend evenings; (b) whether the number of friends present in social situations was associated with drinking on weekend evenings; and (c) whether drinking motives moderate the association between friends present and drinking. METHOD: We linked individual-level drinking motives (measured at baseline) to event-level data assessed every Thursday, Friday, and Saturday evening over 5 weeks. The number of drinks and male and female friends present in the situation were assessed at 9 p.m., 10 p.m., 11 p.m., midnight, and 1 a.m. In total, 197 young adults (51.3% male) completed 11,516 event-level assessments. RESULTS: Multilevel models by gender revealed that higher enhancement motives predicted a greater number of drinks consumed in a given moment, but only among women. The higher the number of male and female friends present in a situation, the more drinks consumed by both genders. Last, drinking motives moderated the association between the number of friends present and the number of drinks. For women, higher enhancement motives predicted more drinks in situations with more male friends. For men, higher coping motives predicted more drinks in situations with no friends and in situations with more female friends. Lower coping motives predicted more drinks with more male friends. Higher conformity motives predicted fewer drinks with more female friends. CONCLUSIONS: Drinking motives appear to moderate event-level factors rather than directly predict drinking on weekend evenings. Depending on the motives for drinking, event-level factors (e.g., friends present in a situation) have a strong effect on an individual's drinking.

Relation between structural and functional connectivity in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is characterized by abnormalities in both brain structure and function within a frontolimbic network. However, little is known about the relation between structural and functional abnormalities in MDD. Here, we used a multimodal neuroimaging approach to investigate the relation between structural connectivity and functional connectivity within the frontolimbic network. METHODS: Eighteen MDD and 24 healthy control subjects were included, of which the integrity of the uncinate fasciculus was assessed that connects the subgenual anterior cingulate cortex (ACC) to the medial temporal lobe (MTL) with diffusion tensor imaging. Furthermore, we assessed the functional connectivity between these brain regions with functional magnetic resonance imaging. RESULTS: The results showed that white matter integrity of the uncinate fasciculus was reduced and that functional connectivity between the subgenual ACC and MTL was enhanced in MDD. Importantly, we identified a negative correlation between uncinate fasciculus integrity and subgenual ACC functional connectivity with the bilateral hippocampus in MDD but not in healthy control subjects. Moreover, this negative structure-function relation in MDD was positively associated with depression severity. CONCLUSIONS: These findings suggest that structural abnormalities in MDD are associated with increased functional connectivity between subgenual ACC and MTL and that these changes are concomitant with severity of depressive symptoms. This association indicates that structural abnormalities in MDD contribute to increased functional connectivity within the frontolimbic network.