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Compulsivity is associated with alterations in the structure and the function of parallel and interacting brain circuits involved in emotional processing (involving both the reward and the fear circuits), cognitive control, and motor functioning. These brain circuits develop during the pre-natal period and early childhood under strong genetic and environmental influences. In this review we bring together literature on cognitive, emotional, and behavioral processes in compulsivity, based mainly on studies in patients with obsessive-compulsive disorder and addiction. Disease symptoms normally change over time. Goal-directed behaviors, in response to reward or anxiety, often become more habitual over time. During the course of compulsive disorders the mental processes and repetitive behaviors themselves contribute to the neuroplastic changes in the involved circuits, mainly in case of chronicity. On the other hand, successful treatment is able to normalize altered circuit functioning or to induce compensatory mechanisms. We conclude that insight in the neurobiological characteristics of the individual symptom profile and disease course, including the potential targets for neuroplasticity is an unmet need to advance the field.

Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5.

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.

We examined the role of placebo response in acute mania trials. Specifically, whether placebo response: (1) predicts treatment effect, (2) can be predicted by patient and study characteristics, and (3) can be predicted by a parsimonious model. We performed a meta-analysis of individual patient data from 10 registration studies (n=1019) for the indication acute manic episode of bipolar disorder. We assessed the effect of 14 determinants on placebo response. Primary outcome measures were mean symptom change score (MCS) on the Young Mania Rating Scale (YMRS) and response rate (RR), defined as ≥50% YMRS symptom improvement from baseline to endpoint. The overall placebo response was 8.5 points improvement on the YMRS (=27.9%) with a RR of 32.8%. Placebo response was significantly associated with the overall treatment response. Five determinants significantly (p

Generalizability of efficacy results from medication trials across geographic regions is disputed. Geographic differences in factors such as patient characteristics, treatment practices and disease definitions might lead to differences in effect sizes across regions. This study examined geographic variation in efficacy results of schizophrenia trials with atypical antipsychotics using individual-patient data meta-analysis. Twenty-two studies including in total 5233 patients from three regions (North America, Europe, and the rest of the world) were included in the random effects meta-analysis. The effect size in North American patients was smaller in terms of mean change from baseline and in terms of responders (Hedge׳s G=0.37, 95% CI 0.28–0.46; OR 1.71, 95% CI 1.35–2.17) as compared to patients in Europe (Hedge׳s G=0.56, 95% CI 0.34–0.79; OR 2.25, 95% CI 1.62–3.12) and the rest of the world (Hedge׳s G=0.53, 95% CI 0.12–0.75; OR 2.61, 95% CI 1.66–4.17). The differences were not statistically significant. The observed differences remained when the confounding effect of unequal distribution of compounds was controlled for by analyzing separately the compounds that were studied across all three regions. Based on these results it cannot be excluded that there are differences in efficacy results of atypical antipsychotics trials across geographic regions. The observed trend towards differential efficacy across geographic regions warrants further examination of the determinants of these differences.

Introduction Obsessive compulsive disorder (OCD) is a chronic and disabling condition, often showing an early onset (1). OCD has been extensively studied in adults, adolescents, and children, but a critial gap remains in the clinical characterization of older patients (2). The present study was aimed to assess prevalence of geriatric OCD (G-OCD ≥ 65 years) and associated sociodemographic and clinical correlates of geriatric OCD in a large international sample of OCD patients. Methods Data of 416 outpatients recruited by different OCD Clinics worldwide, participating in the International College of Obsessive-compulsive Spectrum Disorders (ICOCS) network (3), were assessed and first categorized into 2 groups, age Results Patients with G-OCD represented a significant minority of the overall sample (n=24, 6% of the total sample vs age When the whole sample was divided on the basis of the median age (age Conclusions The present international multicenter study revealed a significantly lower rate of patients with age ≥ 65 years compared to patients younger than 65 years. Patients with G-OCD showed a significantly higher age at onset and rate of adult onset compared to non-geriatric patients. Moreover, in G-OCD patients CBT was less frequently utilized. Subgroups divided on the basis of the median age of the sample showed that the age ≥ 42 years group had a significantly later onset of illness and higher rate of adult onset and female gender.

Introduction Half of all patients with obsessive compulsive disorder (OCD) have their disease onset in childhood and adolescence of which up to 40 percent shows persistence of symptoms into adulthood [1]. In addition to their clinical symptoms, patients also show an underperformance in neurocognitive functioning that may hamper the efficacy of cognitive behavioral therapy (CBT) [2]. Previous studies showed changes after CBT in prefrontal cortex function and cognitive performance in pediatric OCD [3]. It remains unknown whether these changes are short lasting or persistent during a period of brain maturation. Here, we investigated the long-term effects of CBT on planning performance and brain function in pediatric OCD using a longitudinal design. Methods Fifteen pediatric OCD patients and sixteen matched healthy controls ranging from the ages of 8-18 years performed the Tower of London planning paradigm during functional magnetic resonance imaging (fMRI) at three time points; before treatment, after 16 sessions of CBT and after two years of naturalistic follow up. The task consisted of six conditions: a baseline condition and five planning conditions with increasing difficulty. Weighted contrasts for each subject for the effect of all planning moves versus baseline and for the linear effect of the increasing task load were computed. Voxel-wise statistical tests were family wise error (FWE) rate corrected (P Results Pediatric OCD patients performed the planning task significantly slower than healthy controls at baseline (pre-treatment), but with the same accuracy. After two years of follow up, reaction times were at the level of healthy controls. Imaging results at baseline showed that increasing task difficulty was associated with stronger recruitment of the left inferior frontal gyrus, middle frontal gyrus and anterior insula in patients than controls. With increasing age, activity in the left insula and right cingulum decreases, opposed to increasing activity in the parietal lobe. Normalization of the anterior insula and inferior frontal gyrus that occurred shortly after CBT continued during the two-year follow-up. Conclusion Pediatric OCD patients showed longer reaction times and additional recruitment of frontal brain regions during planning complexity compared with healthy controls. These differences tended to normalize after CBT and the process continued during two years of follow-up. This longitudinal study shows long-lasting changes in cognitive performance and prefrontal cortex function after CBT during a period of ongoing brain maturation. In addition, the temporary effects of this longitudinal study suggest that modest planning dysfunction in pediatric OCD is a state rather than a trait characteristic of the disorder.

Background The genetic architecture of psychiatric disorders is characterized by a large number of small-effect variants located primarily in non-coding regions, suggesting that the underlying causal effects may influence disease risk by modulating gene expression. Methods We provide comprehensive analyses using transcriptome data from an unprecedented collection of tissues to gain pathophysiological insights into the role of the brain, neuroendocrine factors (adrenal gland) and gastrointestinal systems (colon). Results Among significant (FDR Discussion Our analyses highlight the importance of multi-tissue approaches as 70% of the genes were detected only in inaccessible tissues.

Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) both are neuropsychiatric disorders associated with abnormalities in dopamine neurotransmission. Aims of this study were to quantify striatal D2/3 receptor availability in TS and OCD, and to examine dopamine release and symptom severity changes in both disorders following amphetamine challenge. Changes in [(11)C]raclopride binding potential (BP(ND)) were assessed using positron emission tomography before and after administration of d-amphetamine (0.3 mg kg(-1)) in 12 TS patients without comorbid OCD, 12 OCD patients without comorbid tics, and 12 healthy controls. Main outcome measures were baseline striatal D2/3 receptor BP(ND) and change in BP(ND) following amphetamine as a measure of dopamine release. Voxel-based analysis revealed significantly decreased baseline [(11)C]raclopride BP(ND) in bilateral putamen of both patient groups vs. healthy controls, differences being more pronounced in the TS than in the OCD group. Changes in BP(ND) following amphetamine were not significantly different between groups. Following amphetamine administration, tic severity increased in the TS group, which correlated with BP(ND) changes in right ventral striatum. Symptom severity in the OCD group did not change significantly following amphetamine challenge and was not associated with changes in BP(ND). This study provides evidence for decreased striatal D2/3 receptor availability in TS and OCD, presumably reflecting higher endogenous dopamine levels in both disorders. In addition, it provides the first direct evidence that ventral striatal dopamine release is related to the pathophysiology of tics.

Atypical antipsychotics are increasingly used for treatment of anxiety disorders, either in mono- or combination therapy. This is the first review reporting on the use of atypical antipsychotics in monotherapy or augmentation in patients with primary anxiety disorders or anxiety (disorders) comorbid to schizophrenia, bipolar disorder (BPD) and major depressive disorder (MDD). We included 49 open-label trials, 32 randomized, placebo-controlled trials (RCTpls) and five randomized controlled trials without placebo arm with almost 6000 patients (open-label: 1710, randomized: 4145). An increasing number of RCTpls show promising results in 27-71% of patients with primary or comorbid anxiety disorders who were treated with monotherapy atypical antipsychotics or augmentation therapy. However, methodological flaws of included studies may limit conclusions of this review and larger placebo-controlled trials are warranted comparing standard treatment with monotherapy and augmentation therapy of atypical antipsychotics and placebo. In addition, higher dropout rates and side effects from treatment with atypical antipsychotics may limit the use of atypical antipsychotics in patients with anxiety disorders.

Background A large number of studies have reported the high prevalence of problematic internet use (PIU) among adolescents and students (13-50%)1, and PIU has been associated with many psychiatric symptoms2. In contrast, only a few studies have investigated its prevalence among the adult population. To the best of our knowledge, there have been no studies investigating the prevalence and comorbidity of PIU in a psychiatric population although psychiatric symptoms might either induce PIU in patients with psychiatric illnesses, or PIU might induce or aggravate psychiatric symptoms. The aims of this study are to investigate the prevalence of PIU and psychiatric co-morbidity among adult psychiatric patients. Methods Three hundred thirty-three adult psychiatric patients with internet access were recruited at the outpatient clinic of psychiatry at the University Hospital, Kyoto Prefectural University of Medicine over a three-month period. Two hundred thirty-one of them completed the survey (response rate: 69.4%; Male/Female/Transgender: 90/139/2; mean age = 42.2). We divided participants into “normal internet users” and “problematic internet users” using a combination of Young’s Internet Addiction Test (IAT) and the Compulsive Internet Use Scale (CIUS), using established cut-off values. Demographic data and comorbid psychiatric symptoms were compared between the two groups, using self-rating scales measuring insomnia (Athens Insomnia Scale, AIS), depression (Beck Depression Inventory, BDI), anxiety (State-trait Anxiety Inventory, STAI), attention deficit hyperactivity disorder (ADHD) (Adult ADHD Self-report Scale, ASRS), autism (Autism Spectrum Quotient, AQ), obsessive-compulsive disorder (OCD) (Obsessive-Compulsive Inventory, OCI), social anxiety disorder (SAD) (Liebowitz Social Anxiety Scale, LSAS), alcohol abuse, and impulsivity (Barratt Impulsive Scale, BIS). Results Of our 231 respondents, 58 (25.1%) were defined as problematic internet users, as they scored high on either the IAT (40 or more) or CIUS (21 or more). The age of problematic internet users was significantly lower than that of normal internet users (35.9 vs 43.6, p Conclusions The prevalence of PIU among adult psychiatric patients is relatively high (25%). As previous studies reported in the general population, PIU among adult psychiatric patients was associated with lower age and higher psychiatric comorbidity. Longitudinal research is needed to determine any causal relations between problematic internet use and psychopathological illnesses.