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Recovery is a multidimensional construct that can be defined either from a clinical perspective or from a consumer-focused one, as a self-broadening process aimed at living a meaningful life beyond mental illness. We aimed to longitudinally examine the overlap and mutual distinctions between clinical and personal recovery. Of 1239 people with schizophrenia consecutively recruited from the FondaMental Advanced Centers of Expertise for SZ network, the 507 present at one-year did not differ from those lost to follow-up. Clinical recovery was defined as the combination of clinical remission and functional remission. Personal recovery was defined as being in the rebuilding or in the growth stage of the Stages of Recovery Instrument (STORI). Full recovery was defined as the combination of clinical recovery and personal recovery. First, we examined the factors at baseline associated with each aspect of recovery. Then, we conducted multivariable models on the correlates of stable clinical recovery, stable personal recovery, and stable full recovery after one year. At baseline, clinical recovery and personal recovery were characterized by distinct patterns of outcome (i.e. better objective outcomes but no difference in subjective outcomes for clinical recovery, the opposite pattern for personal recovery, and better overall outcomes for full recovery). We found that clinical recovery and personal recovery predicted each other over time (baseline personal recovery for stable clinical recovery at one year; P = .026, OR = 4.94 [1.30-23.0]; baseline clinical recovery for stable personal recovery at one year; P = .016, OR = 3.64 [1.31-11.2]). In short, given the interaction but also the degree of difference between clinical recovery and personal recovery, psychosocial treatment should target, beyond clinical recovery, subjective aspects such as personal recovery and depression to reach full recovery., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Bipolar disorder (BD) is a chronic, lifelong condition, associated with increased risk of obesity, cognitive impairment, and suicidal behaviors. Abdominal obesity and a higher risk of violent suicide attempt (SA) seem to be shared correlates with older age, BD, and male sex until middle age when menopause-related female body changes occur. This study aimed at assessing the role of abdominal obesity and cognition in the violent SA burden of individuals with BD., Methods: From the well-defined nationwide cohort FACE-BD (FondaMental Advanced center of Expertise for Bipolar Disorders), we extracted data on 619 euthymic BD patients that were 50 years or older at inclusion. Cross-sectional clinical, cognitive, and metabolic assessments were performed. SA history was based on self-report., Results: Violent SA, in contrast to non-violent and no SA, was associated with higher waist circumference, abdominal obesity and poorer California Verbal Learning Test short-delay free recall (CVLT-SDFR) (ANOVA, p < .001, p = .014, and p = .006). Waist circumference and abdominal obesity were associated with violent SA history independently of sex, BD type and anxiety disorder (Exp(B) 1.02, CI 1.00-1.05, p = .018; Exp(B) 2.16, CI 1.00-4.64, p = .009, accordingly). In an exploratory model, waist circumference and CVLT-SDFR performance mediated the association between male sex and violent SA., Limitations: Cross-sectional design and retrospective reporting., Conclusions: Violent SA history was associated with abdominal obesity and poorer verbal memory in older age BD patients. These factors were interlinked and might mediate the association between male sex and violent SA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Treatment-resistant depression (TRD) is a disabling psychiatric condition characterized by the failure of two antidepressants (ADs). Since the occurrence of side effects (SEs) appears to be one of the main determinants of early discontinuation of pharmacological treatments contributing to a pseudo-resistance, the purpose of this study was to determine the parameters associated with the occurrence of SEs under ADs in a cohort of patients with TRD. Methods: An observational, cross-sectional, multicentre study was carried out using data from the French network of Expert Centers for TRD. For the 108 patients enrolled in the study, the statistical analyses focused on the overall occurrence and on the profile of the SEs (9 categories, 32 items). Results: SEs were influenced by age and sex and were positively associated with the intensity of anxious, depressive and suicidal symptoms, a history of childhood trauma (sexual abuse, emotional abuse and neglect), and negatively associated with self-esteem, and assessment of overall functioning. Conclusion: Using variables accessible in common practice, these results fall within the dynamic of a more tailored approach to medicine that could allow, through integrated pharmacological management, the continuation of antidepressant treatments, and therefore limit the risk of therapeutic failure., Competing Interests: AY received speaker's honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka, Servier and carried out clinical studies in relation to the development of medicine Janssen and Lundbeck medicine unrelated to this work. J-BG received a speaker's honorarium from Servier. P-ML received grants, honoraria, and consulting fees from Allergan, Gedeon Richter, Janssen- Cilag, Lundbeck, Otsuka, Recordati, Sanofi-Aventis, and Teva. RRi received a speaker's honorarium from Janssen Cilag. FS received honoraria from Otsuka. EH acted in advisory capacities, carried out clinical studies in relation to the development of a medicine, received personal researches, studies, or travel allowance, gave presentations at meetings, and received remuneration for input from the following pharmaceutical organizations: AstraZeneca, BMS, Cellgene, Euthérapie-Servier, Janssen, Elli Lilly, Lundbeck, LivaNova, Otsuka, Pfizer, Sanofi. WE-H received speaker's honoraria from Chugai, Eisai, Lundbeck, Janssen-Cilag, Otsuka, and UCB unrelated to this work. BA received speaker's honoraria and/or a travel allowance from Lundbeck, Sanofi, Janssen-Cilag, and Eli Lilly. He has served on the advisory board of Janssen-Cilag. BE received honoraria for consulting activities for Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Levy, El-Hage, Bennabi, Allauze, Bouvard, Camus, Courtet, Dorey, Etain, Fond, Genty, Holtzmann, Horn, Leboyer, Llorca, Meyrel, Molière, Nguon, Petrucci, Rey, Richieri, Stephan, Vaiva, Walter, Haffen, Aouizerate and Yrondi.)

Panic disorder in the elderly is an understudied disorder, despite being associated with substantial functional impairment, a diminished quality of life and an increased suicide risk in this population. This disorder is likely to be underdiagnosed and sometimes inadequately treated due to the absence of national and international guidelines for this vulnerable population. Few therapeutic trials have specifically focused on the efficacy and tolerability of pharmacological and psychotherapy treatments for panic disorder in the elderly and current approaches to detect and manage this disorder are mainly based on expert opinions or extrapolation from data available on younger adults. This report aims to provide a summary of current knowledge on pharmacological and psychotherapeutic treatments for panic disorder in the elderly and to propose a medical treatment algorithm, which should be viewed as a tool that may contribute to the choice of treatment, especially for treatment-resistant older patients with panic disorder. The main results here are the emphasis on antidepressant treatment, such as selective serotonin reuptake inhibitor (SSRI), restricted benzodiazepine usage, awareness of drug interactions and the importance of psychotherapy such as cognitive behavioural therapy (CBT).

The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ») was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment., (Copyright © 2021. Published by Elsevier B.V.)

The interest in social cognition in schizophrenia is justified by the relationship between deficits in these skills and negative functional outcomes. Although assessment batteries have already been described, there is no consensus about which measures are useful in predicting patient functioning or quality of life (QoL). We investigated a set of five measures of recognition of facial emotions, theory of mind (ToM), and empathy in a cohort of 143 patients with schizophrenia or schizoaffective disorder at inclusion and, amongst whom 79 were reassessed 1 year later. The distribution was satisfactory for the TREF (Facial Emotion Recognition Task), V-SIR (Versailles-Situational Intention Reading), and QCAE (Questionnaire of Cognitive and Affective Empathy). Internal consistency was satisfactory for the TREF, V-SIR, V-Comics (Versailles Intention Attribution Task), and QCAE. Sensitivity to change was acceptable for the TREF. The TREF and V-SIR showed a cross-sectional relationship with functioning beyond the clinical symptoms of schizophrenia but not beyond neurocognition. Moreover, the TREF and V-SIR at inclusion could not predict functioning one year later, whereas most neurocognitive and clinical dimensions at inclusion could. Finally, only affective QCAE showed a significant cross-sectional, but not longitudinal, association with QoL. In conclusion, the TREF had satisfactory psychometric properties and showed a cross-sectional, but not longitudinal, association with objective outcome measures, thus appearing to be reliable in clinical practice and research. The V-SIR also showed promising psychometric properties, despite a possible weakness to detect change. However, these measures should be interpreted within the context of the good predictive power of the neurocognitive and clinical status on the outcome.

Background: Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles., Methods: This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters., Results: Four groups were identified among the 1795 included patients: group 1 ("heterogeneous" n = 1099), group 2 ("lithium" n = 265), group 3 ("valproate" n = 268), and group 4 ("lamotrigine" n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales., Limitations: The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder., Conclusions: Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Neuropsychiatric symptoms are frequent in obese individuals. Mounting evidence suggests that adiposity-related inflammation contributes to this effect. This study assessed the relationship between adiposity, neuropsychiatric symptom dimensions and systemic inflammation in subjects stratified by body-mass-index (BMI)., Methods: The study included 165 subjects, of whom 70 were very severely obese (BMI ≥ 40 kg/m 2 ), 50 severely obese (BMI: 35-39.99 kg/m 2 ), 21 overweight or moderately obese (BMI: 25-34.9 kg/m 2 ), and 24 lean (BMI < 25 kg/m 2 ). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mini-International Neuropsychiatric Interview (MINI). Fatigue and general neurobehavioral symptoms were assessed using the Multidimensional Fatigue Inventory (MFI) and Neurotoxicity Rating Scale (NRS) respectively. Serum levels of the inflammatory markers, high-sensitive (hs) CRP and hsIL-6, were determined by ELISA., Results: Severely obese subjects exhibited higher MADRS, MFI and NRS scores and were more frequently afflicted with current diagnosis of major depression than lean participants. Scores on psychometric scales were also increased in very severely obese subjects, although to a lesser extent. Alterations in neuropsychiatric dimensions were highly inter-related. HsCRP was significantly increased in subjects with severe or very severe obesity, while hsIL-6 was augmented in all obese groups. Overall, increased neuropsychiatric comorbidity was associated with greater systemic inflammation, notably hsCRP., Conclusion: Obesity is characterized by an increased prevalence of inter-related neuropsychiatric symptoms together with low-grade systemic inflammation augmenting with adiposity. The association between adiposity, systemic inflammation and neuropsychiatric alterations supports the contribution of adiposity-related inflammatory processes to neuropsychiatric comorbidities in obesity. These data suggest that consideration of adiposity characteristics may help identifying subjects at increased risk for neuropsychiatric comorbidity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample., Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres., Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect., Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms., Competing Interests: Antoine Yrondi received speaker’s honoraria (AstraZeneca, Janssen, Lundbeck, Otsuka, Servier), and carried out clinical studies in relation to the development of a medicine (Janssen, Lundbeck) unrelated to this work. Christophe Arbus received honoraria (Janssen, Lundbeck, Otsuka) and carried out clinical studies in relation to the development of a medicine (Janssen). Olivier Doumy received honoraria from Lilly, Astra-Zeneca, Janssen, Servier and Lundbeck. Jean Baptiste Genty received speaker’s honoraria from Servier. Pierre Michel Llorca received grants, honoraria, and consulting fees from Allergan, Gedeon Richter, Janssen-Cilag, Lundbeck, Otsuka, Recordati, Sanofi-Aventis and Teva. Raphael Rachieri received speaker’s honoraria from Janssen Cilag. Ludovic Samalin received grants, honoraria, and consulting fees from Janssen-Cilag, Lundbeck, and Otsuka. Florian Stephan received honoraria from Otsuka. Guillaume Vaiva received speaker’s honoraria from Otsula/Lundbeck (Annual participation at the reception day for new professors of psychiatry). Emmanuel Haffen: acted in an advisory capacity, carried out clinical studies in relation to the development of a medicine, received personal research, study or travel allowances, gave presentations at meetings, and received remuneration for input from the following pharmaceutical organisations: AstraZeneca, BMS, Cellgene, Euthérapie - Servier, Janssen, Elli Lilly, Lundbeck, LivaNova, Otsuka, Pfizer and Sanofi. He also held a managerial position at the FondaMental Foundation (Créteil) and the French Association of Biological Psychiatry and Neuropsychopharmacology. Wissam El-Hage has received speaker’s honoraria from Chugai, Eisai, Lundbeck, Janssen-Cilag, Otsuka, and UCB unrelated to this work. Bruno Aouizerate received speaker’s honoraria and a travel allowance from Lundbeck, Janssen-Cilag, and Eli Lilly. He has served on the advisory board of Janssen-Cilag. Our compeing interest does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Bipolar disorder (BD) is a chronic and severe mental illness. It requires a non-discontinued pharmacological treatment to prevent mood recurrences but nonadherence to medication is frequent. To this date, medication adherence in BD has been mostly evaluated in cross-sectional studies and often considered as a stable trait. We aimed to study medication adherence using a prospective person-oriented approach., Methods: 1627 BD patients were followed on a 2 years period and assessed every 6 months. Medication adherence was evaluated at each visit with the Medication Adherence Rating Scale (MARS). A latent class mixed model (LCMM) was used to identify trajectory classes of adherence over time. Regression analyses and linear mixed model were used to search for predictors and covariables of the trajectories., Results: Three distinct and robust trajectories of medication adherence have been identified: one that starts poorly and keeps deteriorating (4.8%), one that starts poorly but improves (9%) and one that starts well and keeps improving (86.2%). A good tolerance to psychotropic medications, low depressive symptoms, the absence of comorbid eating disorders and anticonvulsant medication were associated to a better prognosis of adherence. Along the follow-up, the lower were the depressive symptoms, the better was the medication adherence (p < .001) LIMITATIONS: The use of a single measure of medication adherence although it is a validated instrument and a possible positive selection bias that might limit the generalization of our findings., Conclusions: This study demonstrates that medication adherence in BD patients is a heterogeneous and potentially variable phenomenon., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention., Methods: For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion., Results: Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment., Conclusions: The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia., (© 2020 Wiley Periodicals LLC.)

Background: There is growing concern about measuring patient experience with mental health care. There are currently numerous patient-reported experience measures (PREMs) available for mental health care, but there is little guidance for selecting the most suitable instruments. The objective of this systematic review was to provide an overview of the psychometric properties and the content of available PREMs., Methods: A comprehensive review following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines was conducted using the MEDLINE database with no date restrictions. The content of PREMs was analyzed using an inductive qualitative approach, and the methodological quality was assessed according to Pesudovs quality criteria., Results: A total of 86 articles examining 75 PREMs and totaling 1932 items were included. Only four PREMs used statistical methods from item response theory (IRT). The 1932 items covered seven key mental health care domains: interpersonal relationships (22.6%), followed by respect and dignity (19.3%), access and care coordination (14.9%), drug therapy (14.1%), information (9.6%), psychological care (6.8%) and care environment (6.1%). Additionally, a few items focused on patient satisfaction (6.7%) rather than patient experience. No instrument covered the latent trait continuum of patient experience, as defined by the inductive qualitative approach, and the psychometric properties of the instruments were heterogeneous., Conclusion: This work is a critical step in the creation of an item library to measure mental health care patient-reported experience that will be used in France to develop, validate, and standardize item banks and computerized adaptive testing (CAT) based on IRT. It will also provide internationally replicable measures that will allow direct comparisons of mental health care systems., Trial Registration: NCT02491866., Competing Interests: Bruno Aouizerate reports personal fees from Janssen-Cilag, Lilly, Sanofi, and Lundbeck, outside the submitted work. Pierre-Michel Llorca reports personal fees from lundbeck, otsuka, Sanofi, Recordatti, and Gedeon Richter, and personal fees and non-financial support from Janssen, outside the submitted work. The authors report no other possible conflicts of interest in this work., (© 2020 Fernandes et al.)

Genome-wide association studies on bipolar disorders (BD) have revealed an additive polygenic contribution of common single-nucleotide polymorphisms (SNPs). However, these SNPs explain only 25% of the overall genetic variance and suggest a role of rare variants in BD vulnerability. Here, we combined high-throughput genotyping data and whole-exome sequencing in cohorts of individuals with BD as well as in multiplex families with a high density of affected individuals in order to determine the contribution of both common and rare variants to BD genetic vulnerability. Using polygenic risk scores (PRS), we showed a strong contribution of common polymorphisms previously associated with BD and schizophrenia (SZ) and noticed that those specifically associated with SZ contributed more in familial forms of BD than in non-familial ones. The analysis of rare damaging variants shared by affected individuals in multiplex families with BD revealed a single interaction network enriched in neuronal and developmental biological pathways, as well as in the regulation of gene expression. We identified four genes with a higher mutation rate in individuals with BD than in the general population and showed that mutations in two of them were associated with specific clinical manifestations. In addition, we showed a significant negative correlation between PRS and the number of rare damaging variants specifically in unaffected individuals of multiplex families. Altogether, our results suggest that common and rare genetic variants both contribute to the familial aggregation of BD and this genetic architecture may explain the heterogeneity of clinical manifestations in multiplex families.

Background: A psychiatric diagnosis involves the physician's ability to create an empathic interaction with the patient in order to accurately extract semiology (i.e., clinical manifestations). Virtual patients (VPs) can be used to train these skills but need to be evaluated in terms of accuracy, and to be perceived positively by users., Methods: We recruited 35 medical students who interacted in a 35-min psychiatric interview with a VP simulating major depressive disorders. Semiology extraction, verbal and non-verbal empathy were measured objectively during the interaction. The students were then debriefed to collect their experience with the VP., Results: The VP was able to simulate the conduction of a psychiatric interview realistically, and was effective to discriminate students depending on their psychiatric knowledge. Results suggest that students managed to keep an emotional distance during the interview and show the added value of emotion recognition software to measure empathy in psychiatry training. Students provided positive feedback regarding pedagogic usefulness, realism and enjoyment in the interaction., Limitations: Our sample was relatively small. As a first prototype, the measures taken by the VP would need improvement (subtler empathic questions, levels of difficulty). The face-tracking technique might induce errors in detecting non-verbal empathy., Conclusion: This study is the first to simulate a realistic psychiatric interview and to measure both skills needed by future psychiatrists: semiology extraction and empathic communication. Results provide evidence that VPs are acceptable by medical students, and highlight their relevance to complement existing training and evaluation tools in the field of affective disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier B.V.)

Background/objectives: While excessive food consumption represents a key factor in the development of obesity, the underlying mechanisms are still unclear. Ghrelin, a gut-brain hormone involved in the regulation of appetite, is impaired in obesity. In addition to its role in eating behavior, this hormone was shown to affect brain regions controlling reward, including the striatum and prefrontal cortex, and there is strong evidence of impaired reward processing in obesity. The present study investigated the possibility that disrupted reward-related brain activity in obesity relates to ghrelin deficiency., Subjects/methods: Fifteen severely obese subjects (BMI > 35 kg/m 2 ) and fifteen healthy non-obese control subjects (BMI < 30 kg/m 2 ) were recruited. A guessing-task paradigm, previously shown to activate the ventral striatum, was used to assess reward-related brain neural activity by functional magnetic resonance imaging (fMRI). Fasting blood samples were collected for the measurement of circulating ghrelin., Results: Significant activations in the ventral striatum, ventromedial prefrontal cortex and extrastriate visual cortex were elicited by the fMRI task in both obese and control subjects. In addition, greater reward-related activations were present in the dorsolateral prefrontal cortex, and precuneus/posterior cingulate of obese subjects compared to controls. Obese subjects exhibited longer choice times after repeated reward and lower circulating ghrelin levels than lean controls. Reduced ghrelin levels significantly predicted slower post-reward choices and reward-related hyperactivity in dorsolateral prefrontal cortices in obese subjects., Conclusion: This study provides evidence of association between circulating ghrelin and reward-related brain activity in obesity and encourages further exploration of the role of ghrelin system in altered eating behavior in obesity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

CURRENT NOSOGRAPHIC CLASSIFICATIONS TOF ANXIETY DISORDERS. Anxiety disorders are psychiatric pathologies covering a wide range of clinical entities that are characterized by a pathological anxiety leading to severe emotional distress and marked impairment in daily functioning. They primarily differentiate from each other according to the general content of concerns, and originally included the panic disorder with or without agoraphobia, specific phobias, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. However, the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders introduced the classification of anxiety disorders into three separate subcategories in 2013, mainly comprising the anxiety disorders themselves (panic disorder with or without agoraphobia, specific phobia, social anxiety disorder and generalized anxiety disorder), obsessive- compulsive disorder and post-traumatic stress disorder on the basis of their respective clinical, psychological and pathophysiological determinants., Competing Interests: O. Doumy déclare des liens ponctuels (activités de conseil, conférences et prises en charge lors de congrès) avec les laboratoires Janssen Cilag, Lundbeck et Servier. B. Aouizerate déclare des liens ponctuels (activités de conseil, conférences et prises en charge lors de congrès) avec les laboratoires Janssen Cilag, Lundbeck et Lilly.

Competing Interests: B. Aouizerate déclare des liens ponctuels (activités de conseil, conférences et prises en charge lors de congrès) avec les laboratoires Janssen Cilag, Lundbeck et Lilly. A. Bouvard et T. Bienvenu n’ont pas de lien d’intérêts à déclarer. O. Doumy déclaredes liens ponctuels (activités de conseil, onférences et prises en charge lors de congrès) avec les aboratoires Janssen Cilag,Lundbeck et Servier. A. Bouvard et T. Bienvenu n’ont pas de lien d’intérêts à déclarer.

The Questionnaire of Cognitive and Affective Empathy (QCAE) is a tool for self-assessing the cognitive and emotional components of empathy. A study showed that a two-factor model fits the data of patients with schizophrenia, whereas other reports on healthy subjects have suggested a five-factor decomposition. We aimed to replicate the model of Horan et al. in a French population with schizophrenia spectrum disorders (i.e., schizophrenia and schizoaffective disorders) participating in the EVACO Study (NCT02901015). In total, 133 patients were assessed with the QCAE, the Positive and Negative Symptom Scale (PANSS), the Personal and Social Performance Scale (PSP), and the Self rating Quality of Life Scale (S-QoL). The two-factor model demonstrated an adequate fit with the data, comparable to that reported by Horan et al . Males scored higher on the Affective subscore than females. After correction for multiple tests, psychopathology (PANSS) and functioning (PSP) did not correlate significantly with the QCAE subscores. However, quality of life (S-QoL) correlated positively with the Emotional Contagion subscore. Thus, the variability of empathetic disposition in schizophrenia may be considered through the cognitive versus affective dichotomy and properly investigated with the QCAE. The results support further investigation of the relationship between QCAE scores and subjective outcome measurements, such as quality of life, and emphasize the importance of cross-cultural comparisons., (Copyright © 2019 Brunet-Gouet, Myszkowski, Ehrminger, Urbach, Aouizerate, Brunel, Capdevielle, Chereau, Dubertret, Dubreucq, Fond, Lançon, Leignier, Mallet, Misdrahi, Pires, Schneider, Schurhoff, Yazbek, Zinetti-Bertschy, Bazin, Passerieux, Zenasni and Roux.)

Background: Extrapyramidal side effects (EPS) have been identified as a complication of antipsychotic treatment. Previous meta-analyses have investigated EPS prevalence and risk factors in randomized clinical trials with highly selected patients, but studies in real-world schizophrenia are missing., Objective: To examine the prevalence and clinical correlates associated with EPS in a nonselected national multicenter sample of stabilized patients with schizophrenia., Methods: Between 2010 and 2016, patients suffering from schizophrenia (DSM-IV-TR criteria) were recruited through the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) network and data were collected during a comprehensive 1-day-long standardized evaluation. The Simpson-Angus Scale and the Abnormal Involuntary Movement Scale were used to assess drug-induced parkinsonism (DIP) and tardive dyskinesia, respectively., Results: The overall prevalence of DIP and tardive dyskinesia was 13.2% and 8.3%, respectively, in this community-dwelling sample of 674 patients. DIP was associated with negative symptoms (Positive and Negative Syndrome Scale [PANSS] subscore) (adjusted odds ratio [aOR] = 1.102, P < .001), first-generation antipsychotic prescription (aOR = 2.038, P = .047), and anticholinergic drug administration (aOR = 2.103, P = .017) independently of sex, age, disorganization (PANSS disorganized factor), and antipsychotic polytherapy. Tardive dyskinesia was associated with PANSS disorganized factor (aOR = 1.103, P = .049) independently of sex, age, negative symptoms, excitation, first-generation antipsychotic prescription, and benzodiazepine and anticholinergic drug administration., Conclusions: Our results indicate the high prevalence of EPS in a nonselected community-dwelling clinically stable sample of outpatients with schizophrenia. In the monitoring of antipsychotic treatment, EPS should be systematically evaluated, especially when negative symptoms and disorganization or cognitive alteration are present. Monotherapy with a second-generation antipsychotic should be preferentially initiated for patients with these side effects., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

Objective: Predicting relapse is a major challenge in schizophrenia from a clinical and medico-economic point of view. During recent decades, major psychiatric disorders have been found to be extensively associated with metabolic disorders, even before the illness onset, with a prevalence estimated to be 35% in this population. However, no study to date has, to our knowledge, explored the potential impact of metabolic syndrome (MetS) on relapse., Methods: From 2010 to 2016, 185 patients (mean age = 32 years) with a DSM-IV-TR diagnosis of schizophrenia were included in the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) cohort and followed up for 1 year. Multivariable logistic regression was performed to estimate the adjusted odds ratio for relapse., Results: Thirty-seven percent of stabilized outpatients with schizophrenia (mean illness duration = 11 years) experienced a relapse at least once during the 1 year of follow-up. MetS strongly predicted relapse at 1 year, independently of illness severity, insight into illness, and treatment characteristics (including medication compliance). Patients with MetS at baseline had a 3 times higher risk (95% CI, 1.1-8.4) of experiencing a new episode of psychosis during the 12 months of follow-up., Conclusions: Further studies should determine if reducing or preventing MetS could help to protect subjects with schizophrenia from relapse., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Introduction: Little is known about perception of physical pain in schizophrenia (SZ). Some studies have suggested that patients with SZ may have an increased pain threshold, while others have suggested that patients with SZ may suffer from undetected and untreated high physical pain levels. The objectives of this study were (i) to investigate the prevalence of self-reported physical pain in stabilized SZ subjects, and (ii) to determine whether physical pain was associated with psychiatric characteristics and somatic comorbidities (iii) to determine whether antidepressants and benzodiazepine administration were associated with lower self-reported pain., Method: 468 community-dwelling stable SZ subjects (73% men, mean aged 32 years) were recruited in the Schizophrenia Expert Center national network. Patients with moderate to extreme pain, assessed with the EQ5D-5L questionnaire, were classified as belonging to the "pain group"., Results: 104 (22.2%) reported moderate to extreme pain levels. In multivariate analysis, pain has been associated with headache (OR = 2.63 [1.04-6.63], p = 0.04), higher anxiety (OR = 1.61 [1.18-2.21], p = 0.003), higher current depressive symptoms (OR = 1.09 [1.01-1.17], p = 0.03), history of childhood trauma (1.03 [1.01-1.06], p = 0.01) and older age (OR = 1.04 [1.01-1.07], p = 0.03), independently of current psychotic severity, sociodemographic variables, antipsychotic, antidepressant and benzodiazepine treatments. No association with addictive behaviors or illness characteristics has been found., Conclusion: The present findings suggest that community-dwelling SZ outpatients report a high rate of self-reported physical pain, associated with headache, depression and anxiety and history of childhood trauma. Physical pain should be systematically assessed and specifically treated, when needed, in patients with SZ., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Recent reports suggest that the risk of depressive symptoms in obesity is potentiated in subjects presenting a metabolically unhealthy phenotype. Inflammation is often considered a defining criteria of metabolic health. However, this factor may drive the association of metabolic health with depressive symptoms given its well-known role in the pathophysiology of depression. This study aimed at determining the relative contribution of inflammation and metabolic abnormalities to depressive symptoms in obesity., Methods: One-hundred severely obese adults (BMI ≥ 35-40 kg/m 2 ) and 25 non-obese control individuals (BMI < 30 kg/m 2 ) were recruited. Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and Mini-International Neuropsychiatric Interview (MINI). Serum high-sensitive C-reactive protein (hs-CRP) was measured as a marker of systemic inflammation. Metabolically unhealthy obesity was defined as obesity associated with two or more metabolic alterations, including low high-density lipoprotein cholesterol, hypertriglyceridemia, high fasting glucose and hypertension., Results: Total MADRS scores were significantly higher in obese subjects with significant inflammation (hs-CRP ≥ 5 mg/L) compared to those with low inflammation (hs-CRP < 5 mg/L) and non-obese controls. Interestingly, hs-CRP levels significantly predicted MADRS scores in the whole population under study and in the group of obese subjects. Overall, no association was found between MADRS scores and individual metabolic alterations or the composite measure of metabolically unhealthy obesity. Similarly, the association of hs-CRP with MADRS scores in obese patients was not modulated by metabolic health factors., Conclusions: These results indicate that systemic inflammation represents a stronger contributor of obesity-related depressive symptoms than metabolic health per se. This supports the notion that inclusion of inflammation in the definition of metabolically unhealthy obesity drives the association found between poor metabolic health and depressive symptoms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The relationship between greater insight and increased risk of suicide in patients with schizophrenia is debated. The purpose of this study was to assess whether quality of life (QoL) and depression mediated the association between insight and suicidality., Methods: Between March 2010 and December 2015, 527 community-dwelling adults with stable schizophrenia according to DSM-IV criteria were included in a multicenter cross-sectional study, the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study. Structural equation modeling was used for mediation analyses among insight, QoL, depression, and suicidality, controlling for the global level of schizophrenic symptoms., Results: The model provided a good fit for the data (χ²₃ = 1.4, P = .708, Tucker-Lewis index = 1, comparative fit index = 1, root mean square error of approximation = 0, standardized root mean square residual = 0.008) and explained 27% of the variance in suicidality. Poorer QoL and greater severity of depression mediated 68.4% of the positive association between insight and suicidality (full mediation). Poorer QoL mediated 48% of the positive effect of insight on depression (partial mediation). The severity of depression mediated 91.2% of the negative relationship between QoL and suicidality (full mediation)., Conclusions: Insight appears to be an indirect risk factor for suicide in patients with schizophrenia, with the link being mediated by poorer QoL and worse underlying depression, mainly by a sequential pathway but also by a less important parallel pathway., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Background The relationship between residual depressive symptoms, cognition and functioning in patients with euthymic bipolar disorder is a subject of debate. Aims To assess whether cognition mediates the association between residual depressive symptoms and functioning in patients with bipolar disorder who were euthymic. Method We included 241 adults with euthymic bipolar disorder in a multicentre cross-sectional study. We used a battery of tests to assess six cognition domains. A path analysis was then used to perform a mediation analysis of the relationship between residual depressive symptoms, cognitive components and functioning. Results Only verbal and working memory were significantly associated with better functioning. Residual depressive symptoms were associated with poorer functioning. No significant relationship was found between residual depressive symptoms and any cognitive component. Conclusions Cognition and residual depressive symptoms appear to be two independent sources of variation in the functioning of people with euthymic bipolar disorder., Competing Interests: Declaration of interestNone., (© The Royal College of Psychiatrists 2017.)

Background: Major depression is characterized by (i) a high lifetime prevalence of 16-17% in the general population; (ii) a high frequency of treatment resistance in around 20-30% of cases; (iii) a recurrent or chronic course; (iv) a negative impact on the general functioning and quality of life; and (v) a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD), as performed under the leadership of the Fondation FondaMental., Methods: The principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies., Discussion: This approach is expected to improve the overall clinical assessments and to provide evidence-based information to those clinicians most closely involved in the management of TRD thereby facilitating treatment decisions and choice in everyday clinical practice. This could contribute to significantly improve the poor prognosis, the relapsing course, daily functioning and heavy burden of TRD. Moreover, the newly created French network of expert centers for TRD will be particularly helpful for a better characterization of sociodemographic, clinical, neuropsychological, and biological markers of treatment resistance required for the further development of personalized therapeutic strategies in TRD.

Competing Interests: L. Capuron déclare n’avoir aucun lien d’intérêts. B. Aouizerate déclare des liens ponctuels interventions,congrès avec Lundbeck et Janssen.

In a perspective of personalized care for smoking cessation, a better clinical characterization of smokers with schizophrenia (SZ) is needed. The objective of this study was to determine the clinical characteristics of SZ smokers with severe nicotine (NIC) dependence. 240 stabilized community-dwelling SZ smokers (mean age = 31.9 years, 80.4% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. Severe NIC dependence was defined by a Fagerstrom questionnaire score ≥ 7. Depression was defined by a Calgary score ≥ 6. Childhood trauma was self-reported by the Childhood Trauma Questionnaire score (CTQ). Ongoing psychotropic treatment was recorded. Severe NIC dependence was identified in 83 subjects (34.6%), depression in 60 (26.3%). 44 (22.3%) subjects were treated by antidepressants. In a multivariate model, severe NIC dependence remained associated with depression (OR = 3.2, p = 0.006), male gender (OR = 4.5, p = 0.009) and more slightly with childhood trauma (OR = 1.03, p = 0.044), independently of socio-demographic characteristics, psychotic symptoms severity, psychotropic treatments and alcohol disorder. NIC dependence was independently and strongly associated with, respectively, depression and male gender in schizophrenia, and only slightly with history of childhood trauma. Based on these results, the care of both nicotine dependence and depression should be evaluated for an effective smoking cessation intervention in schizophrenia.

The association between advanced paternal age (APA) and increased risk of schizophrenia (SZ) is well established. The objectives of the present study were to further determine if SZ participants with APA (APA+), versus those without (APA-), had: (i) different illness characteristics; (ii) different responses to antipsychotic medication; and (iii) different cognitive characteristics. Participants were a non-selected representative multicentric sample of stabilized community-dwelling people diagnosed with SZ included in the FACE-SZ cohort. 389 participants (73% males, mean aged 32.7 years, mean illness duration 10.8 years) formed the study sample, with each comprehensively evaluated, clinically and neuropsychologically, over 2 days. 118 participants (30.3%) were defined as APA+ according to their father's age at birth (≥35 years). APA+ was associated with a wide range of cognitive dysfunctions in univariate analyses. In multivariate analyses, the only significant difference was the age at onset, with a mean 1.6 year earlier in APA+, compared to APA- (20.7 vs. 22.3 years; p=0.02). This difference is independent of sociodemographic characteristics and I.Q. No association with clinical symptomatology and treatment response was found. The present study supports the neomutation hypothesis and confirms APA as a relevant clinical variable to discriminate potential schizophrenia subtypes. Potential underlying pathophysiological mechanisms are discussed., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD., Methods: We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster. Subsequently, subjects from each cluster were compared on demographic, clinical functioning, and pharmacological variables., Results: A four-cluster solution was identified. The global cognitive performance was above normal in one cluster and below normal in another. The other two clusters had a near-normal cognitive performance, with above and below average verbal memory, respectively. Among the four clusters, significant differences were observed in estimated intelligence quotient and social functioning, which were lower for the low cognitive performers compared to the high cognitive performers., Conclusions: These results confirm the existence of several distinct cognitive profiles in BD. Identification of these profiles may help to develop profile-specific cognitive remediation programs, which might improve functioning in BD., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The most largely used definition of the treatment-resistant depression relies on the failure of two successive trials of antidepressant treatment at an adequate dose and duration. The absence of response to previous antidepressant treatments should be assessed using specific and appropriate clinical instruments enabling a correct staging of the therapeutic resistance. A wide range of socio-demographic and clinical factors (i.e. psychiatric/somatic comorbidities) are classically associated with the therapeutic resistance. The aim of the treatment of major depression is to achieve a complete clinical remission. The presence of residual symptoms increases the risk for the subsequent occurrence of relapses and recurrences, hence facilitating the development of therapeutic resistance. The treatment-resistant depression has a deleterious impact on the social, familial or professional functioning, thereby leading to an impaired quality of life with serious socioeconomic consequences and costs., (Copyright © 2016. Published by Elsevier Masson SAS.)

Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects., (Copyright © 2016. Published by Elsevier Masson SAS.)

Non-selective and irreversible MAOI have become as third or fourth-line strategy for the management of treatment-resistant depression. Non-selective and irreversible MAOI requires careful monitoring of drug interactions and dietary restrictions. Nutritional supplements such as omega-3 have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. The glutamate antagonist ketamine has been found to produce beneficial effects in the management of treatment-resistant depression while administered alone. Dopamine and/or norepinephrine agonists, such as methylphenidate, modafinil or pramipexole, have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment., (Copyright © 2016. Published by Elsevier Masson SAS.)

Introduction: Behavioral adaptation generally follows the contextual changes arising from the consequences (rewards and punishments) of an action. According to the reciprocal determinism model, there is a mutual influence between external context, cognitive processes and behavior. The maladaptive behaviors observed in obsessive-compulsive disorder (OCD) have been hypothesized to result from the disruption of the interactions between these three entities. For this, we assessed the influence of error signals and checking behavior on prefrontal cortical functions during decision-making in 14 OCD patients and 14 matched healthy participants., Methods: We used a behavioral task designed to elicit intolerance of uncertainty (IU) followed by the free expression of checking behaviors, which was coupled with functional magnetic resonance imaging., Results: At the behavioral level, IU intensity was correlated to the number of checking behaviors in both checking OCD patients and healthy controls during decision-making. However, external error signals did not influence checking behaviors in OCD patients, whereas they appeared to trigger checking behaviors in healthy subjects. At the neural level, IU intensity was positively correlated with activation in the orbitofrontal cortex (OFC) in both the OCD and control groups. At the region of interest (ROI) level, error signals increased IU-related OFC activations; in contrast, checking behaviors contributed to decreasing these neural activations in the healthy subjects, but no such modulation was observed in the OCD patients., Conclusions: Our results show that IU-related OFC dysfunctions are not under the influence of the context and the behavioral response in OCD, suggesting that alterations of the dynamic features for this neural network may contribute to the expression of OCD symptoms., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

High-frequency deep brain stimulation (DBS) represents a major stake for treatment for treatment-resistant depression (TRD). We describe a preliminary trial of DBS of two potential brain targets in chronic TRD: the nucleus accumbens (Acb) and, in the event of failure, the caudate nucleus. Patients were followed for 6 months before surgery (M0). From M1 to M5, they underwent stimulation of the Acb target. PET scans allowed us to track metabolic modifications resulting from this stimulation. The caudate target of nonresponders was stimulated between M5 and M9. Patients then entered an extension phase, in which it was possible to adapt stimulation parameters and treatments. Six patients were included and four were operated on. At M5, none of the patients were either responders or remitters, but we did observe a decrease in Hamilton Depression Rating Scale (HDRS) scores. Three patients were switched to caudate stimulation, but no improvement was observed. During the extension phase, the Acb target was stimulated for all patients, three of whom exhibited a significant response. A decrease in glucose metabolism was observed after Acb stimulation, in the posterior cingulate gyrus, left frontal lobe, superior and medial gyrus, and bilateral cerebellum. An increase in metabolism was observed in the bilateral frontal lobe (superior gyrus), left frontal lobe (medial gyrus), and right limbic lobe (anterior cingulate gyrus). The results of this trial suggest that Acb is a more promising target than the caudate. NCT01569711., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

The so-called obsessive-compulsive spectrum disorder (OCD spectrum) is represented by a large variety of clinical entities. There are in general obsessive-compulsive disorder, trichotillomania or Gilles de la Tourette disease among the impulse control disorders, body dysmorphic disorder and hypochondriasis among the somatoform disorders. Updated overview of the OCD spectrum through a bipolar configuration with the impulsion-compulsion (I-C) spectrum, characterized by a failure to resist and control intrusive thoughts associated with repetitive behaviors that seem to be uncontrollable or require considerable efforts to suppress their execution. There are several disrupted processes in the I-C spectrum, including cognitive control, flexibility and behavioural inhibition. All these psychiatric affections demonstrated to share apparent similarities regarding clinical symptomatology, demographic considerations, comorbidity and course pattern, and responses to the serotonine reuptake inhibitors and cognitive behavioural therapy. The concept of I-C spectrum pleads for less categorical and more dimensional approach that seems to be consistently adapted to clinical, genetic, pathophysiology and therapeutic realities., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the effect of cosmetic surgery in patients with a minimal defect in appearance, with and without body dysmorphic disorder (BDD), 5 years after their request for plastic surgery., Methods: Thirty patients requesting cosmetic surgery with a minimal defect in appearance, 12 diagnosed with BDD and 18 not, were contacted 5 years later for a telephone interview about their cosmetic surgery, their satisfaction with it, BDD diagnosis, handicap, and psychiatric comorbidity., Results: Of the 30 patients, we were able to re-evaluate 24 subjects (80%), 10 with BDD and 14 without. Seven BDD subjects had undergone cosmetic surgery compared with 8 without BDD. Patient satisfaction with the intervention was high in both groups. Nevertheless at follow-up, 6 of the 7 BDD patients who had surgery still had a BDD diagnosis and showed higher levels of handicap and psychiatric comorbidity than their non-BDD counterparts. Moreover, 3 non-BDD patients had developed BDD at follow-up., Discussion: The high level of satisfaction with their surgery expressed by BDD patients was surprising and in contrast to the literature. It may explain, together with the patients' strong insistence, why plastic surgeons do not fully agree with psychiatrists on the contraindication of plastic surgery for BDD patients. Nevertheless in our study, most of the BDD patients were still diagnosed with BDD 5 years after surgery, with a significant handicap. The BDD diagnosis at follow-up in patients initially without BDD might be related to the presence of sub-threshold symptoms at the initial evaluation., Conclusion: This prospective study confirms that cosmetic surgery is not effective against BDD despite patients' reported satisfaction. Cosmetic surgery had no significant effects on BDD diagnosis, handicap or psychiatric comorbidity in BDD patients 5 years after surgery. Furthermore, BDD appeared at follow-up in some subjects not initially diagnosed. Patients' reported satisfaction with surgery may help explain why some plastic surgeons do not consider BDD a complete contraindication to cosmetic surgery.

Obsessive-compulsive disorder (OCD), relatively common anxiety disorder (2-3% of the general population), is characterized by persistent, intrusive and unpleasant thoughts, impulses or images and recurrent, time-consuming behaviours that are performed in a ritualistic fashion according to rigid rules and aimed at reducing anxiety and distress caused by obsessions. Significant progress in neuroscience over the last two decades has contributed to improve our knowledge about structure-function relations. Experimental neurophysiology in laboratory animals in parallel with advances in functional neuroimagery in humans, have provided precious information on the pathophysiological bases of OCD. From phenomenological considerations, several processes have been thought as disrupted in OCD, including monitoring of error detection, and emotional and motivational functions. Therefore, it has been postulated that the frontal-subcortical circuits originating in the orbito-frontal and the anterior cingulate cortices respectively, play a major role in the production of obsessive-compulsive symptoms because of their participation in the mediation of all these processes cited above. Such a pathophysiological approach of OCD is of special importance in the development of new strategies for treating OCD such as deep brain stimulation for instance, an innovative non-lesion neurosurgical procedure, which has recently been introduced in the management of severe, chronic forms of OCD resistant to conventional treatments.

Using a Stroop-like visuo-motor task in monkeys, we studied the unitary neuronal activity of the anterior cingulate cortex (ACC, CMAr : 24c) during error detection and conflict monitoring. A high percentage of cingular neurons modified their firing frequency during both attentional and evaluation periods. During the latter period, however, changes in discharge rates were always much more pronounced for erroneous responses than for successful movements that induced reward delivery. Moreover, some neurons responded more markedly to the warning stimulus when a previous trial failed In this case, the probability of a subsequent correct response increased. Such a neuronal apparatus could represent an error compensation system that serves to adapt a subject's behavioral response following an unfavorable and unexpected outcome. Abnormal activity of these neurons, which appear to take advantage of past errors, could contribute to the genesis of obsessive-compulsive disorders (OCD).