[Show abstract][Hide abstract] ABSTRACT: Importance:
Abnormal reward processing is suggested to underlie the formation of psychotic symptoms, likely driven by elevated ventral striatal (VS) dopamine levels. Functional magnetic resonance imaging studies reveal alterations of VS activity during reward processing in patients with chronic psychosis and first episode of psychosis, as well as individuals at high risk for psychosis, but findings are inconclusive, conflicting, and difficult to subject to meta-analysis without introducing bias because several studies reported that findings were not statistically significant but did not report statistics.
To assess the differences between patients with schizophrenia spectrum disorders and healthy controls in VS activation during reward processing.
Web of Knowledge database (incorporating Web of Science and MEDLINE) until July 2015, including references of eligible articles and reviews.
Functional magnetic resonance imaging studies comparing VS activity during monetary reward processing between patients with schizophrenia spectrum disorders or clinical or genetic high-risk state for psychosis and healthy controls.
Data extraction and synthesis:
Statistics and thresholds related to the main outcome measures and potential moderators were independently retrieved by 2 investigators. Effect sizes were analyzed using MetaNSUE, a random-effects method that enables the unbiased inclusion of nonstatistically significant unreported effects.
Main outcomes and measures:
Effect size of the group differences in VS activity, and correlation between VS activity and negative and positive symptom scores in patients.
The meta-analysis included 23 studies (917 patients) for reward anticipation, 9 studies (358 patients) for reward feedback, and 8 studies (314 patients) for reward prediction error. We found significant bilateral VS hypoactivation during reward anticipation (23 studies, n = 917) in patients compared with healthy controls (left/right Cohen d, -0.50/-0.70; P < .001). Left VS abnormality was more severe in patients with high scores of negative symptoms during reward anticipation (r = -0.41; P < .001). Patients also showed hypoactivation during reward feedback (left/right d, -0.57/-0.56; P < .001). Simulations showed that exclusion of studies with nonstatistically significant unreported effects was associated with a strong bias (d bias = 0.22), whereas estimations using MetaNSUE were unbiased even when statistics were seldom reported (d bias < 0.001).
Conclusions and relevance:
This meta-analysis provides evidence that patients with psychosis demonstrate VS hypoactivation during reward anticipation. The assessment of VS prediction errors seems to be promising, but more studies are needed to draw valid conclusions.
[Show abstract][Hide abstract] ABSTRACT: The processing of emotional faces is an important prerequisite for adequate social interactions in daily life, and might thus specifically be altered in adolescence, a period marked by significant changes of social emotional processing. Previous research has shown that the Cannabinoid Receptor CB1R is associated with longer gaze duration and increased brain responses in the striatum to happy faces in adults, yet, for adolescents, is it not clear whether an association between CBR1 and face processing exists. In the present study we investigated genetic effects of the two CB1R polymorphisms, rs1049353 and rs806377 on the processing of emotional faces in healthy adolescents. They participated functional magnetic resonance imaging during the Faces Task where participants watched blocks of video clips with angry and neutral facial expressions, and completed the Morphed Faces Task in the laboratory where they watched different facial expressions that switched from anger to fear/sadness or from happiness to fear/sadness and labelled them according to these four emotional expressions. A-allele versus GG-carriers in rs1049353 displayed earlier recognition of facial expressions changing from anger to sadness/fear, but not for expressions changing from happiness to sadness/fear, and higher brain responses to angry, but not to neutral faces in the amygdala and insula. For rs806377 no significant effects emerged. This suggests that rs1049353 is involved in the processing of anger-related negative facial expressions with relation to anger in adolescents. These findings add to our understanding of social emotion-related mechanisms in adolescents. This article is protected by copyright. All rights reserved.
European Journal of Neuroscience 11/2015; DOI:10.1111/ejn.13118 · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Contemporary psychiatry faces major challenges. Its syndrome-based disease classification is not based on mechanisms and does not guide treatment, which largely depends on trial and error. The development of therapies is hindered by ignorance of potential beneficiary patient subgroups. Neuroscientific and genetics research have yet to affect disease definitions or contribute to clinical decision making. In this challenging setting, what should psychiatric research focus on? In two companion papers, we present a list of problems nominated by clinicians and researchers from different disciplines as candidates for future scientific investigation of mental disorders. These problems are loosely grouped into challenges concerning nosology and diagnosis (this Personal View) and problems related to pathogenesis and aetiology (in the companion Personal View). Motivated by successful examples in other disciplines, particularly the list of Hilbert's problems in mathematics, this subjective and eclectic list of priority problems is intended for psychiatric researchers, helping to re-focus existing research and providing perspectives for future psychiatric science.
The Lancet Psychiatry 11/2015; DOI:10.1016/S2215-0366(15)00361-2
[Show abstract][Hide abstract] ABSTRACT: This is the second of two companion papers proposing priority problems for research on mental disorders. Whereas the first paper focuses on questions of nosology and diagnosis, this Personal View concerns pathogenesis and aetiology of psychiatric diseases. We hope that this (non-exhaustive and subjective) list of problems, nominated by scientists and clinicians from different fields and institutions, provides guidance and perspectives for choosing future directions in psychiatric science.
The Lancet Psychiatry 11/2015; DOI:10.1016/S2215-0366(15)00360-0
[Show abstract][Hide abstract] ABSTRACT: 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.
Frontiers in Psychology 10/2015; 6. DOI:10.3389/fpsyg.2015.01683 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of the present longitudinal study was the psychometric evaluation of the Substance Use Risk Profile Scale (SURPS).
We analyzed data from N = 2,022 adolescents aged 13 to 15 at baseline assessment and 2 years later (mean interval 2.11 years). Missing data at follow-up were imputed (N = 522). Psychometric properties of the SURPS were analyzed using confirmatory factor analysis. We examined structural as well as convergent validity with other personality measurements and drinking motives, and predictive validity for substance use at follow-up.
The hypothesized 4-factorial structure (i.e., anxiety sensitivity, hopelessness, impulsivity [IMP], and sensation seeking [SS]) based on all 23 items resulted in acceptable fit to empirical data, acceptable internal consistencies, low to moderate test-retest reliability coefficients, as well as evidence for factorial and convergent validity. The proposed factor structure was stable for both males and females and, to lesser degree, across languages. However, only the SS and the IMP subscales of the SURPS predicted substance use outcomes at 16 years of age.
The SURPS is unique in its specific assessment of traits related to substance use disorders as well as the resulting shortened administration time. Test-retest reliability was low to moderate and comparable to other personality scales. However, its relation to future substance use was limited to the SS and IMP subscales, which may be due to the relatively low-risk substance use pattern in the present sample.
Alcoholism Clinical and Experimental Research 10/2015; DOI:10.1111/acer.12886 · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Cyberpsychology, Behavior, and Social Networking 10/2015; DOI:10.1089/cyber.2015.0140 · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In alcohol dependence, individual prediction of treatment outcome based on neuroimaging endophenotypes can help to tailor individual therapeutic offers to patients depending on their relapse risk. We built a prediction model for prospective relapse of alcohol-dependent patients that combines structural and functional brain images derived from an experiment in which 46 subjects were exposed to alcohol-related cues. The patient group had been subdivided post hoc regarding relapse behavior defined as a consumption of more than 60 g alcohol for male or more than 40 g alcohol for female patients on one occasion during the 3-month assessment period (16 abstainers and 30 relapsers). Naïve Bayes, support vector machines and learning vector quantization were used to infer prediction models for relapse based on the mean and maximum values of gray matter volume and brain responses on alcohol-related cues within a priori defined regions of interest. Model performance was estimated by leave-one-out cross-validation. Learning vector quantization yielded the model with the highest balanced accuracy (79.4 percent, p < 0.0001; 90 percent sensitivity, 68.8 percent specificity). The most informative individual predictors were functional brain activation features in the right and left ventral tegmental areas and the right ventral striatum, as well as gray matter volume features in left orbitofrontal cortex and right medial prefrontal cortex. In contrast, the best pure clinical model reached only chance-level accuracy (61.3 percent). Our results indicate that an individual prediction of future relapse from imaging measurement outperforms prediction from clinical measurements. The approach may help to target specific interventions at different risk groups.
[Show abstract][Hide abstract] ABSTRACT: The new edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) by the American Psychiatric Association (Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, Washington, DC, 2013) has sparked considerable debate. Allen Frances (Saving normal: an insider’s revolt against out-of-control psychiatric diagnosis, DSM-5, Big Pharma, and the medicalization of ordinary life, 1st edn. William Morrow, New York, 2013) and others (Heinz A, Friedel E, Der Nervenarzt 85:571–577, 2014) have argued that this revision may increase the risk to inadequately pathologize socially unwanted behavior and to defocus psychiatric treatment. An undesirable result can be that more severely ill patients will not be adequately provided with services, while an abundance of problems of everyday life in modern societies receives a medical label. This may cause the ambivalent consequence that psychotherapeutic aid can be provided, but that social problems are individualized and isolated from their context instead of being open to social rather than medical or psychotherapeutic interventions. These concerns will be discussed with respect to three topics: firstly, it will be described how the general definition of mental disorders underwent a slight change with nevertheless considerable consequences; secondly, it will be exemplified how a loss of psychopathological traditions and a new definition of core symptoms in schizophrenia together with a lack of consideration of neurological disorders have widened the schizophrenia category to a degree that it may do more harm than good to patients; and thirdly, it will be discussed by way of example how the merging of the previously distinct categories of harmful substance use and substance dependence combines a diagnostically unreliable (harmful substance use) and a diagnostically reliable (substance dependence) clinical category resulting in a socially potentially abusive and poorly defined new category of “substance use disorders.” It is argued that the underlying changes would have deserved a more profound discussion of their philosophical as well as social implications.
Handbook of the Philosophy of Medicine, Edited by Thomas Schramme, Steven Edwards, 10/2015: pages 1-15; Springer Netherlands., ISBN: 9789401787062
[Show abstract][Hide abstract] ABSTRACT: Gaze direction and especially direct gaze is a powerful nonverbal cue that plays an important role in social interactions. Here we studied the neural mechanisms underlying the privileged access of direct gaze to visual awareness. We performed functional magnetic resonance imaging in healthy human volunteers who were exposed to faces with direct or averted gaze under continuous flash suppression, thereby manipulating their awareness of the faces. A gaze processing network comprising fusiform face area (FFA), superior temporal sulcus, amygdala, and intraparietal sulcus showed overall reduced neural responses when participants reported to be unaware of the faces. Interestingly, direct gaze elicited greater responses than averted gaze when participants were aware of the faces, but smaller responses when they were unaware. Additional between-subject correlation and single-trial analyses indicated that this pattern of results was due to a modulation of the relationship between neural responses and awareness by gaze direction: with increasing neural activation in the FFA, direct-gaze faces entered awareness more readily than averted-gaze faces. These findings suggest that for direct gaze, lower levels of neural activity are sufficient to give rise to awareness than for averted gaze, thus providing a neural basis for privileged access of direct gaze to awareness.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 09/2015; 35(39):13287-13299. DOI:10.1523/JNEUROSCI.0815-15.2015 · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70) of 14-year olds with a history of cannabis use to a group (n = 70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood.
[Show abstract][Hide abstract] ABSTRACT: The field of neuroimaging has truly become data rich, and novel analytical
methods capable of gleaning meaningful information from large stores of imaging
data are in high demand. Those methods that might also be applicable on the
level of individual subjects, and thus potentially useful clinically, are of
special interest. In the present study, we introduce just such a method, called
nonlinear functional mapping (NFM), and demonstrate its application in the
analysis of resting state fMRI from a 242-subject subset of the IMAGEN project,
a European study of adolescents that includes longitudinal phenotypic,
behavioral, genetic, and neuroimaging data. NFM employs a computational
technique inspired by biological evolution to discover and mathematically
characterize interactions among ROI (regions of interest), without making
linear or univariate assumptions. We show that statistics of the resulting
interaction relationships comport with recent independent work, constituting a
preliminary cross-validation. Furthermore, nonlinear terms are ubiquitous in
the models generated by NFM, suggesting that some of the interactions
characterized here are not discoverable by standard linear methods of analysis.
We discuss one such nonlinear interaction in the context of a direct comparison
with a procedure involving pairwise correlation, designed to be an analogous
linear version of functional mapping. We find another such interaction that
suggests a novel distinction in brain function between drinking and
non-drinking adolescents: a tighter coupling of ROI associated with emotion,
reward, and interoceptive processes such as thirst, among drinkers. Finally, we
outline many improvements and extensions of the methodology to reduce
computational expense, complement other analytical tools like graph-theoretic
analysis, and allow for voxel level NFM to eliminate the necessity of ROI
[Show abstract][Hide abstract] ABSTRACT: The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of "dynamic network neuroscience" to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the "n-back" task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes "network flexibility," employs transient and heterogeneous connectivity between frontal systems, which we refer to as "integration." Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia.
Proceedings of the National Academy of Sciences 08/2015; 112(37). DOI:10.1073/pnas.1422487112 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cannabis use during adolescence is known to increase the risk for schizophrenia in men. Sex differences in the dynamics of brain maturation during adolescence may be of particular importance with regard to vulnerability of the male brain to cannabis exposure.
To evaluate whether the association between cannabis use and cortical maturation in adolescents is moderated by a polygenic risk score for schizophrenia.
Observation of 3 population-based samples included initial analysis in 1024 adolescents of both sexes from the Canadian Saguenay Youth Study (SYS) and follow-up in 426 adolescents of both sexes from the IMAGEN Study from 8 European cities and 504 male youth from the Avon Longitudinal Study of Parents and Children (ALSPAC) based in England. A total of 1577 participants (aged 12-21 years; 899 [57.0%] male) had (1) information about cannabis use; (2) imaging studies of the brain; and (3) a polygenic risk score for schizophrenia across 108 genetic loci identified by the Psychiatric Genomics Consortium. Data analysis was performed from March 1 through December 31, 2014.
Cortical thickness derived from T1-weighted magnetic resonance images. Linear regression tests were used to assess the relationships between cannabis use, cortical thickness, and risk score.
Across the 3 samples of 1574 participants, a negative association was observed between cannabis use in early adolescence and cortical thickness in male participants with a high polygenic risk score. This observation was not the case for low-risk male participants or for the low- or high-risk female participants. Thus, in SYS male participants, cannabis use interacted with risk score vis-à-vis cortical thickness (P = .009); higher scores were associated with lower thickness only in males who used cannabis. Similarly, in the IMAGEN male participants, cannabis use interacted with increased risk score vis-à-vis a change in decreasing cortical thickness from 14.5 to 18.5 years of age (t137 = -2.36; P = .02). Finally, in the ALSPAC high-risk group of male participants, those who used cannabis most frequently (≥61 occasions) had lower cortical thickness than those who never used cannabis (difference in cortical thickness, 0.07 [95% CI, 0.01-0.12]; P = .02) and those with light use (<5 occasions) (difference in cortical thickness, 0.11 [95% CI, 0.03-0.18]; P = .004).
Cannabis use in early adolescence moderates the association between the genetic risk for schizophrenia and cortical maturation among male individuals. This finding implicates processes underlying cortical maturation in mediating the link between cannabis use and liability to schizophrenia.