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Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Difficulties with sociability include a tendency to avoid social contacts and activities, and to prefer being alone rather than being with others. While sociability is a continuously distributed trait in the population, decreased sociability represent a common early manifestation of multiple neuropsychiatric disorders such as Schizophrenia (SCZ), Bipolar Disorder (BP), Major Depressive Disorder (MDD), Autism Spectrum Disorders (ASDs), and Alzheimer’s disease (AD). We aimed to investigate the genetic underpinnings of sociability as a continuous trait in the general population. In this respect, we performed a genome-wide association study (GWAS) using a sociability score based on 4 social functioning-related self-report questions in the UK Biobank sample (n=342,461) to test the effect of individual genetic variants. This was followed by LD score analyses to investigate the genetic correlation with psychiatric disorders (SCZ, BP, MDD, ASDs) and a neurological disorder (AD) as well as related phenotypes (Loneliness and Social Anxiety). The phenotypic data indeed showed that the sociability score was decreased in individuals with ASD, (probable) MDD, BP and SCZ, but not in individuals with AD. Our GWAS showed 604 genome-wide significant SNPs, coming from 18 independent loci (SNP-based h2=0.06). Genetic correlation analyses showed significant correlations with SCZ (rg=0.15, p=9.8e-23), MDD (rg=0.68, p=6.6e-248) and ASDs (rg=0.27, p=4.5e-28), but no correlation with BP (rg=0.01, p=0.45) or AD (rg=0.04, p=0.55). Our sociability trait was also genetically correlated with Loneliness (rg=0.45, p=2.4e-8) and Social Anxiety (rg=0.48, p=0.002). Our study shows that there is a significant genetic component to variation in population levels of sociability, which is relevant to some psychiatric disorders (SCZ, MDD, ASDs), but not to BP and AD.

The adaptive regulation of the trade-off between pursuing a known reward (exploitation) and sampling lesser-known options in search of something better (exploration) is critical for optimal performance. Theory and recent empirical work suggest that humans use at least two strategies for solving this dilemma: a directed strategy in which choices are explicitly biased toward information seeking, and a random strategy in which decision noise leads to exploration by chance. Here we examined the hypothesis that random exploration is governed by the neuromodulatory locus coeruleus-norepinephrine system. We administered atomoxetine, a norepinephrine transporter blocker that increases extracellular levels of norepinephrine throughout the cortex, to 22 healthy human participants in a double-blind crossover design. We examined the effect of treatment on performance in a gambling task designed to produce distinct measures of directed exploration and random exploration. In line with our hypothesis we found an effect of atomoxetine on random, but not directed exploration. However, contrary to expectation, atomoxetine reduced rather than increased random exploration. We offer three potential explanations of our findings, involving the non-linear relationship between tonic NE and cognitive performance, the interaction of atomoxetine with other neuromodulators, and the possibility that atomoxetine affected phasic norepinephrine activity more so than tonic norepinephrine activity.

Obsessive-compulsive and related disorders (O-CRDs) are highly disabling psychiatric illnesses of early-onset. They are responsible for considerable morbidity and socioeconomic burden. Existing treatments are usually only partially successful and there is an urgent need to understand the aetiological factors and neurobiological bases of the disorders in order to develop new and more effective strategies for prevention, early detection and effective treatment. Emerging data from the neurosciences supports the reconceptualisation of obsessive-compulsive disorder as a spectrum disorder, related to but different from the anxiety disorders and closely aligned with other less well understood psychiatric disorders characterised by compulsive acts such as body dysmorphic disorder, trichotillomania, skin-picking disorder, hoarding disorder; and possibly extending to tic disorders and other neurodevelopmental disorders such as autism. A new, O-CRDs research network, supported by the Networks Initiative of the European College of Neuropsychopharmacology and comprising leading figures in preclinical and clinical research, has been established. It aims to provide a European perspective on the current debate around internationally-accepted diagnostic criteria and treatment strategies for O-CRDs. Its objectives include; (1) identifying the key outstanding research questions that depend upon cross-centre collaborative investigation, (2) setting a research agenda that is likely to produce an impact on health-outcomes, and (3) strengthening existing projects and collaborative enterprises with these objectives in mind. This paper reviews some of these critical research priorities. By establishing shared multinational databases, collaborative research networks, multicentre studies and joint publications, it is hoped that progress will be achieved.

Contains fulltext : 110321.pdf (Publisher’s version ) (Open Access) BACKGROUND: Clinicians need to be well informed about staging and profiling so that they can divide patients with anxiety disorders into groups according to the phase and severity of their illness. The group to which the patient is assigned determines the types of treatment he or she receives. AIM: To investigate ways in which clinicians can be helped to apply staging and profiling procedures to patients with anxiety disorders. METHOD: We searched the literature for articles about the staging and profiling of anxiety disorders. RESULTS: There seems to be practically no literature relating to the staging and profiling of anxiety disorders. However, in daily practice clinicians do attempt to classify their patients and use forms of staging when deciding on special types of treatment for their patients and when assessing the length of treatment required. The revised Dutch guidelines on anxiety disorders include a generalised form of staging, called 'stepped care’. These revisions have been made on the basis of consensus decisions reached by the guideline committee. CONCLUSION: The revised guidelines on anxiety disorders assist clinicians with the application of staging in their daily practice. However, because of the lack of scientific data, our article closes with the presentation of a research agenda.

Rationale Cannabis users often claim that cannabis has the potential to enhance their creativity. Research suggests that aspects of creative performance might be improved when intoxicated with cannabis; however, the evidence is not conclusive. Objective The aim of this study was to investigate the acute effects of cannabis on creativity. Methods We examined the effects of administering a low (5.5 mg delta-9-tetrahydrocannabinol [THC]) or high (22 mg THC) dose of vaporized cannabis vs. placebo on creativity tasks tapping into divergent (Alternate Uses Task) and convergent (Remote Associates Task) thinking, in a population of regular cannabis users. The study used a randomized, double-blind, between-groups design. Results Participants in the high-dose group (n = 18) displayed significantly worse performance on the divergent thinking task, compared to individuals in both the low-dose (n = 18) and placebo (n = 18) groups. Conclusions The findings suggest that cannabis with low potency does not have any impact on creativity, while highly potent cannabis actually impairs divergent thinking.

BACKGROUND: Both genetics and neuroimaging have developed rapidly in the past few years. Recently the two methods have been combined in a new technique called genetic neuroimaging. AIM: To provide an overview of the backgrounds and the possibilities of genetic neuroimaging. METHOD: In this review we first discuss genetic and neuroimaging research methods that are currently in use and then discuss their synergistic combination. Finally we analyse two recent cases in which genetic neuroimaging was used to study an individual's vulnerability to affective and psychotic symptoms. results Results are very promising, particularly with regard to research into vulnerability to psychiatric disorders. It is expected that the use of genetic neuroimaging procedures will increase. Genetic and neuroimaging methods are often exceedingly complex, which means they cannot be easily accessed by the general public. CONCLUSION: Genetic neuroimaging is an important method to study the relation between candidate genes and variations in cognitive and emotional functioning and the vulnerability to psychiatric disorders