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Background: Comorbid anxiety disorders and childhood maltreatment have each been linked with unfavourable outcomes in people with bipolar disorder. Because childhood maltreatment is associated with anxiety disorders in this population, their respective predictive value remains to be determined., Methods: In 174 adults with bipolar disorder, we assessed childhood maltreatment using the Childhood Trauma Questionnaire and lifetime anxiety disorders with the MINI International Neuropsychiatric Interview. We constructed an overall index of severity of bipolar disorder as a sum of six indicators (unemployment, psychotic symptoms, more than five manic episodes, more than five depressive episodes, suicide attempt, and hospital admission). We tested the relationship between childhood maltreatment, the number of anxiety disorders and the overall severity index using ordered logistic regression., Results: The number of lifetime anxiety disorders was associated with the overall severity index (OR = 1.43, 95%CI = 1.01-2.04, p = 0.047). This relationship was only slightly attenuated when controlled for childhood maltreatment (OR = 1.39, 95%CI = 0.97-2.00, p = 0.069). The relationship between childhood maltreatment and the overall severity index was not statistically significant (OR = 1.26, 95%CI = 0.92-1.74, p = 0.151). Secondary analyses revealed that childhood maltreatment was associated with suicide attempts (OR = 1.70, 95%CI = 1.15-2.51, p = 0.008) and obsessive compulsive disorder was associated with the overall severity index (OR = 9.56, 95%CI = 2.20-41.47, p = 0.003)., Limitations: This was a cross-sectional study with a moderate-sized sample recruited from a specialist program., Conclusions: While comorbid anxiety disorders are associated with the overall severity of bipolar disorder, childhood maltreatment is specifically associated with suicide attempts. Clinicians should systematically assess both factors. Interventions to improve outcomes of people with bipolar disorder with comorbid anxiety disorders and history of childhood maltreatment are needed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Antisocial individuals present behaviours that violate the social norms and the rights of others. In the present study, we examine whether biases in monitoring the self-generated cognitive material might be linked to antisocial manifestations during adolescence. We further examine the association with psychopathic traits and conduct problems (CPs)., Methods: Sixty-five incarcerated adolescents (IAs; M age = 15.85, SD = 1.30) and 88 community adolescents (CAs; M age = 15.78, SD = 1.60) participated in our study. In the IA group, 28 adolescents presented CPs (M age = 16.06, SD = 1.41) and 19 did not meet the diagnostic criteria for CPs (M age = 15.97, SD = 1.20). Source monitoring was assessed through a speech-monitoring task, using items requiring different levels of cognitive effort; recognition and source-monitoring bias scores (internalising and externalising biases) were calculated., Results: Between-group comparisons indicate greater overall biases and different patterns of biases in the source monitoring. IA participants manifest a greater externalising bias, whereas CA participants present a greater internalising bias. In addition, IA with CPs present different patterns of item recognition., Conclusions: These results indicate that the two groups of adolescents present different types of source-monitoring bias for self-generated speech. In addition, the IAs with CPs present impairments in item recognition. Future studies may examine the developmental implications of self-monitoring biases in the perseverance of antisocial behaviours from adolescence to adulthood.

Although numerous interventions are available for negative symptoms, outcomes have been unsatisfactory with pharmacological and psychological interventions producing changes of only limited clinical significance. Here, we argue that because negative symptoms occur as a complex syndrome caused and maintained by numerous factors that vary between individuals they are unlikely to be treated effectively by the present "one size fits all" approaches. Instead, a well-founded selection of those interventions relevant to each individual is needed to optimize both the efficiency and the efficacy of existing approaches. The concept of functional analysis (FA) can be used to structure existing knowledge so that it can guide individualized treatment planning. FA is based on stimulus-response learning mechanisms taking into account the characteristics of the organism that contribute to the responses, their consequences and the contingency with which consequences are tied to the response. FA can thus be flexibly applied to the level of individual patients to understand the factors causing and maintaining negative symptoms and derive suitable interventions. In this article we will briefly introduce the concept of FA and demonstrate-exemplarily-how known psychological and biological correlates of negative symptoms can be incorporated into its framework. We then outline the framework's implications for individual assessment and treatment. Following the logic of FA, we argue that a detailed assessment is needed to identify the key factors causing or maintaining negative symptoms for each individual patient. Interventions can then be selected according to their likelihood of changing these key factors and need to take interactions between different factors into account. Supplementary case vignettes exemplify the usefulness of functional analysis for individual treatment planning. Finally, we discuss and point to avenues for future research guided by this model.

Resting-state functional magnetic resonance imaging (RS-fMRI) is based on the assumption that the vascular response and the blood oxygenation level-dependent response are homogenous across the entire brain. However, this a priori hypothesis is not consistent with the well-known variability of cerebral vascular territories. To explore whether the RS networks are influenced by varied vascular speed in different vascular territories, we assessed the time-shift maps that give an estimate of the local timing of the vascular response and checked whether local differences in this timing have an impact on the estimates of RS networks. Two hundred seventeen elderly (≥60 years), healthy participants (73.74 ± 4.41 years, 143 females, 203 right handed) underwent one MRI examination, including an RS-fMRI session. After preprocessing, statistical analyses included time-shift analyses and RS-fMRI analyses using as regressor the delay maps obtained from the time-shift analyses. The functional connectivity map of default mode network (DMN) of each participant was then calculated by using the seed-to-voxel analysis in the REST toolbox. Faster cerebrovascular responses were notably present in the primary motor and somatosensory and peri-insular cortex, while slower responses were present in various regions, including notably the posterior cingulate cortex (PCC). Moreover, significant changes notably in the DMN, including medial prefrontal cortex (t = 11.95), PCC (t = 11.52), right middle temporal lobe (t = 10.72), and right angular gyrus (t = 10.88), were observed also taking into account the cerebrovascular delayed maps. As the most prominent example of the RS networks, DMN activation patterns change as a function of the cerebrovascular delay. These data suggest that a group correction for vascular maps in RS-fMRI measurements is essential to correctly depict functional differences and exclude potential confounding effects, notably in the elderly with increasing prevalence of vascular comorbidity.

Background and aims The DSM-5 includes criteria for diagnosing Internet gaming disorder (IGD) that are adapted from substance abuse and widely used in research and clinical contexts, although evidence supporting their validity remains scarce. This study compared online gamers who do or do not endorse IGD criteria regarding self-control-related abilities (impulsivity, inhibitory control, and decision-making), considered the hallmarks of addictive behaviors. Method A double approach was adopted to distinguish pathological from recreational gamers: The first is the classic DSM-5 approach (≥5 criteria required to endorse the IGD diagnosis), and the second consists in using latent class analysis (LCA) for IGD criteria to distinguish gamers' subgroups. We computed comparisons separately for each approach. Ninety-seven volunteer gamers from the community were recruited. Self-reported questionnaires were used to measure demographic- and game-related characteristics, problematic online gaming (with the Problematic Online Gaming Questionnaire), impulsivity (with the UPPS-P Impulsive Behavior Scale), and depression (with the Beck Depression Inventory-II). Experimental tasks were used to measure inhibitory control (Hybrid-Stop Task) and decision-making abilities (Game of Dice Task). Results Thirty-two participants met IGD criteria (33% of the sample), whereas LCA identified two groups of gamers [pathological (35%) and recreational]. Comparisons that used both approaches (DSM-5 and LCA) failed to identify significant differences regarding all constructs except for variables related to actual or problematic gaming behaviors. Discussion The validity of IGD criteria is questioned, mostly with respect to their relevance in distinguishing high engagement from pathological involvement in video games.

Aim: To evaluate brain atrophy in anorexic patients by automated cerebral segmentation with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) MRI sequence., Material and Methods: Twenty patients (female; mean age, 27.9 years), presenting consecutively for brain MRI between August 2014-December 2016 with clinical suspicion of anorexia nervosa and BMI<18.5 kg/m 2 were included. Controls were ten healthy females (mean age, 26.5 years). Automated brain morphometry was performed based on MP2RAGE. Means of morphometric results in the two groups were compared and correlation with BMI was analysed., Results: Significantly lower volumes of total brain, grey matter (GM), white matter (WM), cerebellum and insula were found in anorexic patients. Anorexics had higher volumes of CSF, ventricles, lateral ventricles and third ventricle. When adjusted means for weight and height were compared, the volume of WM and cerebellum were not significantly different. However, volume of WM was significantly affected by weight and positively correlated with BMI. Significant positive correlations were found between BMI and volumes of total brain, GM, cortical GM and WM. BMI was negatively correlated with volumes of CSF and third ventricle., Conclusion: Brain atrophy was demonstrated in anorexic patients with MP2RAGE-based automated segmentation, which seems to reliably estimate brain volume., Key Points: • Automated brain segmentation based on 3-D MRI seems to reliably estimate brain volume. • This technique detected brain atrophy in patients suffering from anorexia nervosa. • Brain changes in anorexia nervosa can be quantitatively and qualitatively followed-up by MRI.

Background and aims Binge-watching (i.e., seeing multiple episodes of the same TV series in a row) now constitutes a widespread phenomenon. However, little is known about the psychological factors underlying this behavior, as reflected by the paucity of available studies, most merely focusing on its potential harmfulness by applying the classic criteria used for other addictive disorders without exploring the uniqueness of binge-watching. This study thus aimed to take the opposite approach as a first step toward a genuine understanding of binge-watching behaviors through a qualitative analysis of the phenomenological characteristics of TV series watching. Methods A focus group of regular TV series viewers (N = 7) was established to explore a wide range of aspects related to TV series watching (e.g., motives, viewing practices, and related behaviors). Results A content analysis identified binge-watching features across three dimensions: TV series watching motivations, TV series watching engagement, and structural characteristics of TV shows. Most participants acknowledged that TV series watching can become addictive, but they all agreed having trouble recognizing themselves as truly being an "addict." Although obvious connections could be established with substance addiction criteria and symptoms, such parallelism appeared to be insufficient, as several distinctive facets emerged (e.g., positive view, transient overinvolvement, context dependency, and low everyday life impact). Discussion and conclusion The research should go beyond the classic biomedical and psychological models of addictive behaviors to account for binge-watching in order to explore its specificities and generate the first steps toward an adequate theoretical rationale for these emerging problematic behaviors.

Attention deficit hyperactivity disorder (ADHD) is accompanied by resting-state alterations, including abnormal activity, connectivity and asymmetry of the default-mode network (DMN). Concurrently, recent studies suggested a link between ADHD and the presence of polymorphisms within the gene BAIAP2 (i.e., brain-specific angiogenesis inhibitor 1-associated protein 2), known to be differentially expressed in brain hemispheres. The clinical and neuroimaging correlates of this polymorphism are still unknown. We investigated the association between BAIAP2 polymorphisms and DMN functional connectivity (FC) asymmetry as well as behavioral measures in ADHD adults. Resting-state fMRI was acquired from 30 ADHD and 15 healthy adults. For each subject, rs7210438 and rs8079626 within the gene BAIAP2 were genotyped. ADHD severity, impulsiveness and anger were assessed for the ADHD group. Using multivariate analysis of variance, we found that genetic features do have an impact on DMN FC asymmetry. In particular, polymorphism rs8079626 affects medial frontal gyrus and inferior parietal lobule connectivity asymmetry, lower for AA than AG/GG carriers. Further, when combining FC asymmetry and the presence of the rs8079626 variant, we successfully predicted increased externalization of anger in ADHD. In conclusion, a complex interplay between genetic vulnerability and inter-hemispherical DMN FC asymmetry plays a role in emotion regulation in adult ADHD., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Humans are sensitive to gaze direction from early life, and gaze has social and affective values. Borderline personality disorder (BPD) is a clinical condition characterized by emotional dysregulation and enhanced sensitivity to affective and social cues. In this study we wanted to investigate the temporal-spatial dynamics of spontaneous gaze processing in BPD. We used a 2-back-working-memory task, in which neutral faces with direct and averted gaze were presented. Gaze was used as an emotional modulator of event-related-potentials to faces. High density EEG data were acquired in 19 females with BPD and 19 healthy women, and analyzed with a spatio-temporal microstates analysis approach. Independently of gaze direction, BPD patients showed altered N170 and P200 topographies for neutral faces. Source localization revealed that the anterior cingulate and other prefrontal regions were abnormally activated during the N170 component related to face encoding, while middle temporal deactivations were observed during the P200 component. Post-task affective ratings showed that BPD patients had difficulty to disambiguate neutral gaze. This study provides first evidence for an early neural bias toward neutral faces in BPD independent of gaze direction and also suggests the importance of considering basic aspects of social cognition in identifying biological risk factors of BPD., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Schizophrenia is a chronic psychiatric disorder that generally begins in late adolescence or early adulthood. This early onset is often linked with a devastating lifelong impact on both the social network and work capacities of the affected subjects. Beginning in the mid-1990s, several sets of diagnostic criteria aiming to identify "high-risk" patients were developed and applied in clinical studies. Short-term rates of onset of psychosis in this subgroup of subjects ranged from 20% to 40%. However, 20 years later, the proposal to introduce "psychosis risk syndrome" as a coded diagnostic category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders remained controversial and was finally rejected. Instead, "attenuated psychosis syndrome" was included in section III of the newly published manual as a condition for further studies., Objective: The goal of this article is to review the extant literature concerning the advantages and risks of early assessment of psychotic symptoms ("prodrome" and "psychosis-risk syndrome") and concerning available therapeutic options, both psychosocial and pharmacological., Conclusions: "Attenuated psychosis syndrome" is a clinically useful concept. It identifies help-seeking individuals with mental health problems who need an intervention and who, if no treatment strategy is proposed, present a higher likelihood of developing a psychosis spectrum disorder in the years following their first contact with a mental health facility. In parallel with the clinical utility of this concept, additional research focused on this group of patients is warranted to further understand the emerging phase of psychotic disorders and to develop effective and efficient evidence-based prevention strategies.

Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Emotion dysregulation and interpersonal hardships constitute core features of borderline personality disorder (BPD). Research has established the link between these core dysregulations and fluctuations in the capacity to appreciate the mental states that underlie behavior (mentalizing, operationalized as reflective functioning (RF)). As emotion dysregulation and interpersonal hardships also characterize adults with attention deficit hyperactivity disorder (ADHD), this study sought to examine the potential RF impairments affecting this population. 101 adults with ADHD, 108 with BPD and 236 controls were assessed using the RF questionnaire (RFQ), evaluating how individuals employ information about mental states to better understand their own and others' behaviors. The RFQ comprises two dimensions, certainty (RF&#95;c) and uncertainty (RF&#95;u) about mental states. RF scores helped distinguish ADHD from controls, but also from BPD (F = 48.1 (2/441) ; p < 0.0001 for RF&#95;c and F = 92.5 (2/441) ; p < 0.0001 for RF&#95;u). The ADHD group showed intermediary RF scores compared to the controls (b = -0.70; p < 0.0001 and b = 0.89; p < 0.0001 for RF&#95;c and RF&#95;u) and BPD group (b = 0.44; p = 0.001 and b = -0.56; p = 0.001 for RF&#95;c and RF&#95;u). Lower RF scores correlated with poor anger control and high levels of impulsivity. Higher severity of ADHD (more attentional and hyperactive/impulsive symptoms) was correlated with RF impairments. In conclusion, RF may constitute an important process underlying attentional, hyperactive/impulsive as well as emotional symptoms in ADHD; it should therefore be considered in the assessment of these patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: We developed a smartphone application (App; EMOTEO: emotion-meteo [weather forecast]) to help borderline personality disorder (BPD) patients to monitor and regulate their inner tension. The App proposes targeted mindfulness-based exercises., Design and Methods: We assessed the usability and efficiency of this App for monitoring and reduction of aversive tension in 16 BPD participants over a 6-month period., Findings: We recorded a mean of 318.1 sessions (SD = 166.7) per participants, with a high level of satisfaction. There was a significant decrease in aversive tension (p < .05) and the App was mainly used around 10 a.m. and 9 p.m., Practice Implications: EMOTEO was user-friendly and efficient in reducing aversive tension in BPD patients., (© 2016 Wiley Periodicals, Inc.)

Aims: Cortical microinfarcts (CMI) are frequently observed in the ageing brain independent of cognitive decline, but their aetiology is not fully elucidated. To examine the potential role of different vessel pathologies, including cerebral amyloid angiopathy (CAA), arteriolosclerosis-hyalinosis and thromboembolism in the development of CMI, we examined 80 autopsy cases with more than one CMI on routine neuropathological examination., Methods: Pial and intracortical vessels around CMI were assessed for their integrity with haematoxylin-eosin staining and antibodies against amyloid-β protein and fibrinogen using a semiquantitative four-level rating scale (absent to severe) in the hippocampus, and the frontal, temporal and occipital cortex. Four histological categories of changes were defined: CAA, vessel pathology other than CAA, thromboembolism and absence of vessel pathology near CMI., Results: A differential distribution of microvascular pathology was observed depending on brain regions. In the occipital cortex, CAA was commonly associated with CMI. In contrast, in the hippocampus and the frontal cortex, cases without any vascular pathology in pial and intracortical vessels were significantly more frequent., Conclusions: The aetiology of CMI differs depending on brain location. CAA may play a role principally in the occipital cortex. The large number of intact vessels around the CMI (mainly in the frontal cortex and hippocampus) raises the possibility that pathologies other than structural microangiopathy, including hypoperfusion/arterial hypotension or large vessel atherosclerosis, play a role in the development of microvascular lesions. These results are relevant in the context of aetiopathogenesis of vascular changes associated with conditions like vascular dementia., (© 2016 British Neuropathological Society.)

Gaze conveys emotional information, and humans present sensitivity to its direction from the earliest days of life. Bipolar disorder is a disease characterized by fluctuating states of emotional and cognitive dysregulation. To explore the role of attentional control on face processing in bipolar patients (BP) we used gaze direction as an emotion modulation parameter in a two-back Working Memory (WM) task while high-density EEG data were acquired. Since gaze direction influences emotional attributions to faces with neutral expressions as well, we presented neutral faces with direct and averted gaze. Nineteen euthymic BP and a sample of age- and gender-matched controls were examined. In BP we observed diminished P200 and augmented P300 evoked responses, differentially modulated by non-repeated or repeated faces, as well as by gaze direction. BP showed a reduced P200 amplitude, significantly stronger for faces with direct gaze than averted gaze. Source localization of P200 indicated decreased activity in sensory-motor regions and frontal areas suggestive of abnormal affective processing of neutral faces. The present study provides neurophysiological evidence for abnormal gaze processing in BP and suggests dysfunctional processing of direct eye contact as a prominent characteristic of bipolar disorder.

Although recent research suggests that acute stress influences subsequent decision-making under ambiguity, less is known about the role of personality variables in this relationship. This study tested whether impulsivity traits and acute stress differentially influence the way in which a prior feedback is incorporated into further decisions involving ambiguity. Sixty college students (50% male; aged 18-25 years) were randomly assigned to a stress versus a non-stress condition before completing a laboratory gambling task. The results revealed that independently of the stress condition, subjects behaved as if the odds of winning increase after a single loss. Additionally, stress effects varied as a function of impulsivity traits. Individuals who lacked perseverance (i.e., had difficulty focusing on a difficult or boring task) gambled more after experiencing a loss in the stress condition than did those in the control condition. The present study supports that impulsivity traits can explain the differential effect of stress on the relationship between prior feedback and choices made under ambiguity.

This commentary responds to Aarseth et al.'s (in press) criticisms that the ICD-11 Gaming Disorder proposal would result in "moral panics around the harm of video gaming" and "the treatment of abundant false-positive cases." The ICD-11 Gaming Disorder avoids potential "overpathologizing" with its explicit reference to functional impairment caused by gaming and therefore improves upon a number of flawed previous approaches to identifying cases with suspected gaming-related harms. We contend that moral panics are more likely to occur and be exacerbated by misinformation and lack of understanding, rather than proceed from having a clear diagnostic system.

The aim of this study was to examine the relationship of maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), associated neural activity in response to mother-child relational stimuli, and child psychopathology indicators at child ages 12-42 months and one year later. The study tested the hypothesis that decreased maternal neural activity in regions that subserve emotion regulation would be associated with child symptoms associated with emotional dysregulation at both time points. Functional magnetic resonance imaging of 42 mothers with or without violence-exposure and associated IPV-PTSD were assessed. Their child's life-events and symptoms/behaviors indicative of high-risk subsequent PTSD diagnosis on a maternal-report questionnaire were measured one year later. Maternal IPV-PTSD severity was significantly associated with decreased ventromedial prefrontal cortex (vmPFC) activation in response to mother-child relational stimuli. Maternal IPV-PTSD severity and decreased vmPFC activation were then significantly associated with a child attachment disturbance at 12-42 months and symptoms/behaviors one year later, that were correlated with emotional dysregulation and risk for child PTSD. Maternal IPV-PTSD and child exposure to IPV were both predictive of child PTSD symptoms with maternal IPV-PTSD likely mediating the effects of child IPV exposure on child PTSD symptoms. These findings suggest that maternal IPV-PTSD severity and associated decreased vmPFC activity in response to mother-child relational stimuli are predictors of child psychopathology by age 12-42 months and one-year later. Significant findings in this paper may well be useful in understanding how maternal top-down cortico-limbic dysregulation promotes intergenerational transmission of IPV and related psychopathology and, thus should be targeted in treatment.

Background: Deep brain stimulation (DBS) has been proposed to treat patients with severe Tourette's syndrome, and open-label trials and two small double-blind trials have tested DBS of the posterior and the anterior internal globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS for severe Tourette's syndrome., Methods: In this randomised, double-blind, controlled trial, we recruited patients aged 18-60 years with severe and medically refractory Tourette's syndrome from eight hospitals specialised in movement disorders in France. Enrolled patients received surgery to implant bilateral electrodes for aGPi DBS; 3 months later they were randomly assigned (1:1 ratio with a block size of eight; computer-generated pairwise randomisation according to order of enrolment) to receive either active or sham stimulation for the subsequent 3 months in a double-blind fashion. All patients then received open-label active stimulation for the subsequent 6 months. Patients and clinicians assessing outcomes were masked to treatment allocation; an unmasked clinician was responsible for stimulation parameter programming, with intensity set below the side-effect threshold. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) score between the beginning and end of the 3 month double-blind period, as assessed with a Mann-Whitney-Wilcoxon test in all randomly allocated patients who received active or sham stimulation during the double-blind period. We assessed safety in all patients who were enrolled and received surgery for aGPi DBS. This trial is registered with ClinicalTrials.gov, number NCT00478842., Findings: Between Dec 6, 2007, and Dec 13, 2012, we enrolled 19 patients. We randomly assigned 17 (89%) patients, with 16 completing blinded assessments (seven [44%] in the active stimulation group and nine [56%] in the sham stimulation group). We noted no significant difference in YGTSS score change between the beginning and the end of the 3 month double-blind period between groups (active group median YGTSS score 68·5 [IQR 34·0 to 83·5] at the beginning and 62·5 [51·5 to 72·0] at the end, median change 1·1% [IQR -23·9 to 38·1]; sham group 73·0 [69·0 to 79·0] and 79·0 [59·0 to 81·5], median change 0·0% [-10·6 to 4·8]; p=0·39). 15 serious adverse events (three in patients who withdrew before stimulation and six each in the active and sham stimulation groups) occurred in 13 patients (three who withdrew before randomisation, four in the active group, and six in the sham group), with infections in DBS hardware in four patients (two who withdrew before randomisation, one in the sham stimulation group, and one in the active stimulation group). Other serious adverse events included one electrode misplacement (active stimulation group), one episode of depressive signs (active stimulation group), and three episodes of increased tic severity and anxiety (two in the sham stimulation group and one in the active stimulation group)., Interpretation: 3 months of aGPi DBS is insufficient to decrease tic severity for patients with Tourette's syndrome. Future research is needed to investigate the efficacy of aGPi DBS for patients over longer periods with optimal stimulation parameters and to identify potential predictors of the therapeutic response., Funding: French Ministry of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Studies focusing on the offspring of affected parents utilize the well-established familial aggregation of mood disorders as a powerful tool for the identification of risk factors, early clinical manifestations, and prodromes of mood disorders in these offspring. The major goals of the Lausanne-Geneva mood cohort study are to: (1) assess the familial aggregation of bipolar and unipolar mood disorders; (2) prospectively identify risk factors for mood disorders as well as their early signs and prodromes; (3) identify their endophenotypes including cognitive features, alterations in brain structure, HPA-axis dysregulation, and abnormalities of the circadian rhythm of activity., Methods: Probands with bipolar disorders, major depressive disorder, and controls with at least one child aged from 4 to 17.9 years at study intake, their offspring, as well as their spouses are invited to take part in follow-up assessments at predetermined ages of the offspring. Direct semi-structured diagnostic interviews have been used for all participants. Probands, spouses, and adult offspring also undergo neurocognitive testing, anthropomorphic measures and biochemical exams, structural Magnetic Resonance Imaging, as well as objective assessments of physical activity using accelerometers in combination with ecological momentary assessments., Results: Currently, our study has up to seven follow-up assessments extending over a period of 20 years. There are 214 probands and 389 offspring with one direct interview before age 18 as well as a second assessment over follow-up. Data on 236 co-parents are also available from whom 55% have been directly interviewed. First publications support the specificity of the familial aggregation of BPD and the strong influence of an early onset of the parental BPD, which amplifies the risk of developing this disorder in offspring., Conclusions: Information from clinical, biological, cognitive, and behavioral measures, based on contemporary knowledge, should further enhance our understanding of mood disorder psychopathology, its consequences, and underlying mechanisms.

Objectives: This study focused on patients with bipolar disorder (BD), several years after their participation in mindfulness-based cognitive therapy (MBCT). It aimed at documenting sustained mindfulness practice, perceived long-term benefit from the program, and changes regarded as direct consequences of the intervention., Design: This cross-sectional survey took place at least 2 years after MBCT for 70.4% of participants., Location: It was conducted in two specialized outpatient units for BDs that are part of the Geneva University Hospitals (Switzerland) and the Sainte-Anne Hospital in Paris (France)., Subjects: Eligibility criteria were a diagnosis of BD according to DSM-IV and participation in at least four MBCT sessions. Response rate was 66.4%. The final sample included 71 outpatients (71.8% bipolar I, 28.2% bipolar II)., Outcome Measures: A questionnaire retrospectively assessed patient-perceived change, benefit from MBCT, and current mindfulness practice., Results: Proportions of respondents who practiced mindfulness at least once a week were 54.9% for formal practice (body scan, sitting meditation, mindful walking, or movements) and 57.7% for informal practice (mindful daily activities). Perceived benefit for the prevention of relapse was moderate, but patients acknowledged long-lasting effects and persistent changes in their way of life. Formal mindfulness practice at least once a week tended to be associated with increased long-lasting effects (p = 0.052), whereas regular informal practice and mindful breathing were significantly associated with persistent changes in daily life (p = 0.038) and better prevention of depressive relapse (p = 0.035), respectively. The most frequently reported positive change was increased awareness of being able to improve one's health., Conclusions: Despite methodological limitations, this survey allowed documenting mindfulness practice and perceived sustained benefit from MBCT in patients with BD. Participants particularly valued increased awareness that they can influence their own health. Both informal and formal practices, when sustained in the long term, might promote long-lasting changes.

Gamma band oscillations participate in the temporal binding needed to synchronize cortical networks, involved in early sensory and short term memory processes. In earlier studies, alterations of these neurophysiological parameters have been found in psychotic disorders. To date no study has explored the temporal dynamics and signal complexity of gamma band oscillations in first episode psychosis (FEP). To address this issue, gamma band analysis was performed in 15 FEP patients and 18 healthy controls who successfully performed an adapted 2-back working memory task. Multiple linear and logistic regression models were computed to explore the relationship between the cognitive status and gamma oscillation changes over time. Based on regression model results, phase diagrams were constructed and their complexity was estimated using fractal dimension, a mathematical tool that describes shapes as numeric values. When adjusted for gamma values at time lags -3 to -4 ms and -15 to -16 ms, FEP patients displayed significantly higher time-dependent changes than controls, independently of the nature of the task. The present results are consistent with a discoordination of the activity of cortical generators engaged by the stimulus apparition in FEP patients, leading to a global binding deficit. In addition, fractal analysis showing higher complexity of gamma signal, confirmed this deficit. Our results provide evidence for recruitment of supplementary cortical generators as compensating mechanisms and yield further understanding for the pathophysiology cognitive impairments in FEP.

Background and Purpose: The presence of apolipoprotein E4 ( APOE * E4 ) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE * E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline., Materials and Methods: This prospective study included 382 community-dwelling elderly controls. At baseline, participants underwent MR imaging at 3T, extensive neuropsychological testing, and genotyping. After neuropsychological follow-up at 18 months, participants were classified into cognitively stable controls and cognitively deteriorating controls. Data analysis included whole-brain voxel-based morphometry and ROI analysis of GM., Results: APOE * E4 -related GM loss at baseline was found only in the cognitively deteriorating controls in the posterior cingulate cortex. There was no APOE * E4- related effect in the hippocampus, mesial temporal lobe, or brain areas not involved in Alzheimer disease pathology. Controls in the cognitively deteriorating group had slightly lower GM concentration in the hippocampus at baseline. Higher GM densities in the hippocampus, middle temporal lobe, and amygdala were associated with a decreased risk for cognitively deteriorating group status at follow-up., Conclusions: APOE * E4 -related GM loss in the posterior cingulate cortex (an area involved in Alzheimer disease pathology) was found only in those elderly controls who subsequently developed subtle cognitive decline but not in cognitively stable controls. This finding might explain the partially conflicting results of previous studies that typically did not include detailed neuropsychological assessment and follow-up. Most important, APOE * E4 status had no impact on GM density in areas affected early by neurofibrillary tangle formation such as the hippocampus and mesial temporal lobe., (© 2017 by American Journal of Neuroradiology.)

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity., (© 2017 American Association of Neuropathologists, Inc. All rights reserved.)

Objectives: Many adults with attention-deficit/hyperactivity disorder (ADHD) report sleeping difficulties. The relationship between sleep and ADHD is poorly understood, and shows discrepancies between subjective and objective measures. In order to determine the specificity of sleep-associated symptoms in ADHD, subjective sleep assessments among ADHD adult patients were compared with control subjects and with individuals suffering from borderline personality disorder (BPD)., Methods: 129 outpatients with ADHD, 70 with BPD (including 17 patients with BPD and ADHD comorbidity), and 65 control participants were assessed for sleep quality, insomnia, and sleepiness, using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS)., Results: ADHD- and BPD-sufferers achieved higher insomnia and lower sleep quality scores than control subjects. Clinical groups did not differ in terms of sleep quality, although insomnia was more severe among BPD patients. Depression scores explained most of sleep symptoms, but even when controlling for depression, ADHD sufferers showed higher sleep latency. Inattentive symptoms were associated with somnolence, while hyperactive/impulsive symptoms were associated with insomnia and lower sleep efficiency., Conclusion: Sleep-related symptoms associated with ADHD were partly explained by non-specific factors, especially depression symptoms. In a dimensional perspective, hyperactive and inattentive symptoms were associated with specific sleep symptoms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and aims Despite many positive benefits, mobile phone use can be associated with harmful and detrimental behaviors. The aim of this study was twofold: to examine (a) cross-cultural patterns of perceived dependence on mobile phones in ten European countries, first, grouped in four different regions (North: Finland and UK; South: Spain and Italy; East: Hungary and Poland; West: France, Belgium, Germany, and Switzerland), and second by country, and (b) how socio-demographics, geographic differences, mobile phone usage patterns, and associated activities predicted this perceived dependence. Methods A sample of 2,775 young adults (aged 18-29 years) were recruited in different European Universities who participated in an online survey. Measures included socio-demographic variables, patterns of mobile phone use, and the dependence subscale of a short version of the Problematic Mobile Phone Use Questionnaire (PMPUQ; Billieux, Van der Linden, & Rochat, 2008). Results The young adults from the Northern and Southern regions reported the heaviest use of mobile phones, whereas perceived dependence was less prevalent in the Eastern region. However, the proportion of highly dependent mobile phone users was more elevated in Belgium, UK, and France. Regression analysis identified several risk factors for increased scores on the PMPUQ dependence subscale, namely using mobile phones daily, being female, engaging in social networking, playing video games, shopping and viewing TV shows through the Internet, chatting and messaging, and using mobile phones for downloading-related activities. Discussion and conclusions Self-reported dependence on mobile phone use is influenced by frequency and specific application usage.

Background: Methylation of the serotonin 3A receptor gene (HTR3A) has been linked to child maltreatment and adult psychopathology. The present study examined whether HTR3A methylation might be associated with mothers' lifetime exposure to interpersonal violence (IPV), IPV-related psychopathology, child disturbance of attachment, and maternal neural activity., Methods: Number of maternal lifetime IPV exposures and measures of maternal psychopathology including posttraumatic stress disorder (PTSD), major depression and aggressive behavior (AgB), and a measure of child attachment disturbance known as "secure base distortion" (SBD) were assessed in a sample of 35 mothers and children aged 12-42 months. Brain fMRI activation was assessed in mothers using 30-s silent film excerpts depicting menacing adult male-female interactions versus prosocial and neutral interactions. Group and continuous analyses were performed to test for associations between clinical and fMRI variables with DNA methylation., Results: Maternal IPV exposure-frequency was associated with maternal PTSD; and maternal IPV-PTSD was in turn associated with child SBD. Methylation status of several CpG sites in the HTR3A gene was associated with maternal IPV and IPV-PTSD severity, AgB and child SBD, in particular, self-endangering behavior. Methylation status at a specific CpG site (CpG2&#95;III) was associated with decreased medial prefrontal cortical (mPFC) activity in response to film-stimuli of adult male-female interactions evocative of violence as compared to prosocial and neutral interactions., Conclusions: Methylation status of the HTR3A gene in mothers is linked to maternal IPV-related psychopathology, trauma-induced brain activation patterns, and child attachment disturbance in the form of SBD during a sensitive period in the development of self-regulation., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Child maltreatment (CM) worsens prognosis and quality of life in several psychiatric conditions. Meaning in life is a construct which relates to the sense of purpose that one can perceive in life, and is a key aspect of recovery in psychiatric patients. The lasting impact of CM on meaning in life and its mediating variables have not been studied in patients with chronic persistent psychiatric conditions. One hundred and sixty-six patients with bipolar disorder (N=35), psychotic disorder (N=73), anorexia nervosa (N=30) or borderline personality disorder (N=28) were assessed for meaning in life (revised version of the Life Regard Index (LRI-R)), for CM (Childhood Trauma Questionnaire (CTQ)) and for internalized/externalized psychopathology. CM was associated with a lower LRI score. Structural Equation Modeling showed that internalized psychopathology (depression, hopelessness and low self-esteem) was the main mediator of the impact of CM on meaning in life. The direct effect of CM on meaning in life was not significant. Having suffered from negligence or abuse during childhood is associated with lower meaning in life in adults with persistent and pervasive psychiatric disorders. Treating depressive symptoms and improving self-esteem may improve meaning in life in patients with severe mental disorders who were affected by CM., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for the motor and non-motor signs of Parkinson's disease (PD), however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption., Methods: Nineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS) scores from patients and carers that received the psychoeducation programme (n = 9) were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10). Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers' anxiety and burden were also analysed., Results: Seventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058). At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015). At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively). No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability., Conclusions: Our results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies.

Background: Crisis happens daily yet its understanding is often limited, even in the field of psychiatry. Indeed, a challenge is to assess the potential for change of patients so as to offer appropriate therapeutic interventions and enhance treatment program efficacy. This naturalistic study aimed to identify the socio-demographical characteristics and clinical profiles at admission of patients referred to a specialized Crisis Intervention Center (CIC) and to examine the effectiveness of the intervention., Method: The sample was composed of 352 adult outpatients recruited among the referrals to the CIC. Assessment completed at admission and at discharge examined psychiatric symptoms, defense mechanisms, recovery styles and global functioning. The crisis intervention consisted in a psychodynamically oriented multimodal approach associated with medication., Results: Regarding the clinical profiles at intake, patients were middle-aged (M = 38.56, SD = 10.91), with a higher proportion of women (62.22%). They were addressed to the CIC because they had attempted to commit suicide or had suicidal ideation or presented depressed mood related to interpersonal difficulties. No statistical differences were found between patients dropping out (n = 215) and those attending the crisis intervention (n = 137). Crisis intervention demonstrated a beneficial effect (p < 0.01) on almost all variables, with Effect Sizes (ES) ranging from small to large (0.12 < ES < 0.75; median = 0.49). However, the Reliable Change Index indicated that most of the issues fall into the undetermined category (range 41.46 to 96.35%; median = 66.20%)., Conclusions: This study establishes the profile of patients referred to the CIC and shows that more than half of the patients dropped out from the crisis intervention before completion. Our findings suggest that people presenting an emotional crisis benefit from crisis intervention. However, given methodological constraints, these results need to be considered with caution. Moreover, the clinical significance of the improvements is not confirmed. Thus, the effectiveness of crisis intervention in naturalistic context is not fully determined and should be more rigorously studied in future research.

Background: Androgen deprivation (AD) therapy combined to radiotherapy (RT) is a curative therapeutic option for patients with non-metastatic locally advanced or aggressive intermediate prostate cancer (PC), though with a range of nutritional, physical, and psychological side effects. A multidisciplinary care program was created to help frail patients to prevent and manage those side effects., Material and Methods: We conducted a longitudinal interventional study in frail patients, presenting either cardiovascular/pulmonary comorbidities, old age (≥75 years), vulnerability ratings, or balance impairment. Patients were treated by AD and RT and, benefited from nutritional coaching, supervised biweekly 45 minute physical training, and psychological counseling for two years. Treatment outcomes included PC-related quality of life (QoL), body mass index, fat mass index, and fat-free mass index derived from bioelectrical impedance analysis, Six-Minute Walk Test, Timed Up&Go, handgrip strength, Hospital Anxiety and Depression scale, Mini Mental State Examination. Measures were repeated after zero, three, six, nine, 12, 18, 24 months, and 12-months post-study follow-up. A prospective mixed-model design was used to assess longitudinal outcome., Results: Regression analyses revealed no significant change over the two years, including post-study follow-up. Means of QoL, nutritional, physical, as well as psychological variables remained stable over more than two years in the 35 men aged 74 (range 68-76) years., Conclusion: The expected side effects of AD and RT were not observed in frail PC patients who followed this multidisciplinary care program.

Although the DSM-5 has suggested the two new categories of Persistent Depressive Disorders (PDD) and Other Specified Depressive Disorders (OSDD), no study so far has applied the DSM-5 criteria throughout the range of depressive disorders. The aims of the present study were to 1) establish the lifetime prevalence of specific depressive disorders according to the new DSM-5 definitions in a community sample, and 2) determine their clinical relevance in terms of socio-demographic characteristics, comorbidity, course and treatment patterns. The semi-structured Diagnostic Interview for Genetic Studies was administered by masters-level psychologists to a random sample of an urban area (n=3720). The lifetime prevalence was 15.2% for PDD with persistent major depressive episode (MDE), 3.3% for PDD with pure dysthymia, 28.2% for Major Depressive Disorder (MDD) and 9.1% for OSDD. Subjects with PDD with persistent MDE were the most severely affected, followed by those with recurrent MDD, single episode MDD, PDD with pure dysthymia and OSDD and finally those without depressive disorders. Our data provide further evidence for the clinical significance of mild depressive disorders (OSDD), but cast doubt on the pertinence of lumping together PDD with persistent MDE and the former DSM-IV dysthymic disorder within the new PDD category., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Molecular imaging of the D 2/3 receptor is widely used in neuropsychiatric research. Non-displaceable binding potential (BP ND ) is a very popular quantitative index, defined as the product of the receptor concentration (B avail ) and the radiotracer affinity for the receptor (1/appK d ). As the appK d is influenced by parameters such as the endogenous neurotransmitter dynamics, it often constitutes a confounding factor in research studies. A simplified method for absolute quantification of both these parameters would be of great interest in this context. Here, we describe the use of a partial saturation protocol that permits to produce an in vivo Scatchard plot and thus estimate B avail and appK d separately , through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [ 123 I]IBZM using a 3-tissue compartment, 7-parameter model (3T-7k). Finally, more "classic" BP ND estimation methods are also validated against the results of the 3T-7k., Methods: Twenty-nine male rats were used. Binding parameters were estimated using the 3T-7k in a multi-injection protocol. A partial saturation protocol was applied at the region- and voxel-level and results were compared to those obtained with the 3T-7k model. The partial saturation protocol was applied after an adenovirus-mediated D 2 receptor striatal overexpression and in an amphetamine-induced dopamine release paradigm. The Simplified Reference Tissue Model (SRTM), the Logan's non-invasive graphical analysis (LNIGA) and a simple standardized uptake ratio (SUR) method were equally applied., Results: The partial saturation experiments gave similar values as the 3T-7k both at the regional and voxel-level. After adenoviral-mediated D 2 -receptor overexpression, an increase in B avail by approximately 18% was observed in the striatum. After amphetamine administration, a 16.93% decrease in B avail (p<0.05) and a 39.12% increase (p<0.01) in appK d was observed. BP ND derived from SRTM, LNIGA and SUR correlated well with the B avail values from the 3T-7k (r=0.84, r=0.84 and r=0.83, respectively, p<0.0001 for all correlations)., Conclusion: A partial saturation protocol permits the non-invasive and time-efficient estimation of B avail and appK d separately. Given the different biological phenomena that underlie these parameters, this method may be applied for the in-depth study of the dopaminergic system in translational molecular imaging studies. It can detect the biological variations in these parameters, dissociating the variations in receptor density (B avail ) from affinity (1/appK d ), which reflects the interactions of the receptor with its endogenous ligand., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Previous research suggests that antisocial individuals present impairment in social cognitive processing, more specifically in emotion recognition (ER) and perspective taking (PT). The first aim of the present study was to investigate the recognition of a wide range of emotional expressions and visual PT capacities in a group of incarcerated male adolescents in comparison to a matched group of community adolescents. Secondly, we sought to explore the relationship between these two mechanisms in relation to psychopathic traits., Methods: Forty-five male adolescents (22 incarcerated adolescents (Mage = 16.52, SD = 0.96) and 23 community adolescents (Mage = 16.43, SD = 1.41)) participated in the study. ER abilities were measured using a dynamic and multimodal task that requires the participants to watch short videos in which trained actors express 14 emotions. PT capacities were examined using a task recognized and proven to be sensitive to adolescent development, where participants had to follow the directions of another person whilst taking into consideration his perspective., Results: We found a main effect of group on emotion recognition scores. In comparison to the community adolescents, the incarcerated adolescents presented lower recognition of three emotions: interest, anxiety and amusement. Analyses also revealed significant impairments in PT capacities in incarcerated adolescents. In addition, incarcerated adolescents' PT scores were uniquely correlated to their scores on recognition of interest., Conclusions: The results corroborate previously reported impairments in ER and PT capacities, in the incarcerated adolescents. The study also indicates an association between impairments in the recognition of interest and impairments in PT., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline., Materials and Methods: Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coefficients., Results: Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22-0.92; P = .028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep location of cerebral microbleeds., Conclusions: Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age., (© 2017 by American Journal of Neuroradiology.)

In February, 2015, French television screened a report on Internet addiction (IA) in which an individual, identifying himself as cyberdependent, was offered treatment with repetitive Transcranial Magnetic Stimulation (rTMS), a Non-Invasive Brain Stimulation (NIBS) technique. Two issues deserve to be emphasized. Firstly, the concept of IA is not unanimously recognized by scientists and has raised a number of questions. Secondly, although the first results suggest that brain stimulation techniques could be a potential therapy for Substance Use Disorders (SUDs), no data are available on the therapeutic effects of rTMS on IA or even excessive Internet use. Currently, we cannot promote the use of rTMS for Internet detoxification because there is no evidence to prove its efficacy. Nevertheless, the similarities between SUDs and IA, and the results of NIBS on SUDs suggest that research can be done to examine the efficacy of NIBS techniques to treat Internet gaming disorder and other forms of IA., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Cerebral microbleeds (CMB), also known as cerebral microhemorrhages, are small areas of susceptibility on brain magnetic resonance imaging (MRI), that are increasingly detected due to the higher availability of high-field MRI systems and dedicated pulse sequences. The prevalence of CMBs increases in cases with cognitive decline. The current investigation assessed the poorly investigated radiologic-histopathologic correlation of CMBs on MRI., Methods: The local ethical committee approved the current investigation. We retrospectively assessed a consecutive series of 1303 autopsy cases hospitalized in Geneva University Hospitals between 2000-2014. Of 112 cases with pre-mortem T2* sequences, we included 25 cases (mean age 77.3 ± 9.6, 9 females) with at least one CMB. We compared pre-mortem CMBs with targeted histopathology and post-mortem MRI., Results: 25 cases had 31 CMB lesions detected by pre-mortem MRI. 25 additional CMB were detected on histopathology. 4 CMBs on pre-mortem MRI were false positives, resulting in a total of 52 CMBs. 27 CMBs on pre-mortem MRI were confirmed on histopathology, corresponding to a sensitivity or true positive rate of 51.9% (95% CI 37.6-66.0%). The false negative rate of pre-mortem MRI was 48.1% (95% CI 34.0-62.4%). Post-mortem MRI showed only 3 cases with additional CMBs. Overall, pre-mortem MRI significantly underestimated CMBs (p = 0.0001)., Conclusions: Routine clinical brain MRI underestimates the prevalence of CMBs by approximately 50%, and 12% of radiologic pre-mortem MRI CMBs were false positives. Post-mortem MRI confirmed that this discordance is not explained by microbleeds occurring after the pre-mortem MRI., Competing Interests: The authors have declared that no competing interests exist.

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule-associated protein tau gene correlates with the expression changes in Alzheimer's disease and Parkinson's disease brains. However, few studies examine the sequences beyond the constitutive promoter., Objectives: Because activating different microtubule-associated protein tau gene control regions via methylation might regulate the differential tau expression constituting the specific signatures of individual tauopathies, we compared methylation of a candidate promoter, intron 0., Methods: We assessed DNA methylation in the brains of patients with different tauopathies (35 Alzheimer's disease, 10 corticobasal degeneration, and 18 PSP) and 19 controls by intron 0 pyrosequencing. We also evaluated methylation in an independent cohort of 11 PSP cases and 12 controls. Frontal (affected by tau pathology) and occipital (unaffected) cortices were analyzed., Results: In the initial samples, one CpG island site in intron 0 (CpG1) showed significant hypomethylation in PSP-affected frontal cortices when compared with controls (P = .022). Such hypomethylation was observed in replicate samples, but not in occipital cortices or other tauopathies. PSP and control samples (combining the initial and replicate samples) remained significantly different after adjustment for potential confounding factors (age, H1/H1 diplotype; P = .0005). PSP-affected tissues exhibited microtubule-associated protein tau RNA hyperexpression when compared with controls (P = .004), although no correlation with CpG1 methylation was observed., Conclusions: This exploratory study suggests that regions other than the constitutive promoter may be involved in microtubule-associated protein tau gene regulation in tauopathies and that intron 0 hypomethylation may be a specific epigenetic signature of PSP. These preliminary findings require confirmation. © 2016 International Parkinson and Movement Disorder Society., (© 2016 International Parkinson and Movement Disorder Society.)

In the psychiatric institution, the sex act is a matter of controversy, all the more so when elderly patients with dementia are concerned. Yet, a question imposes itself: thinking beyond the biomedical model, the current governing paradigm for explaining senile dementia, what effects does the repression of the sex act have on the symptoms of the demented patient? The psychoanalytic exploration of the institutional situation described here suggests that the sexual demands of the patient suffering from dementia would not be meaningless, but would constitute a defensive modality against the return of a former threat of castration. Their repression, by means of practices that impede the libido in its search of an object, would reinforce the process of dementia by encouraging a regression toward earlier stages of development. More generally, the authors argue that unconscious dynamic processes might play a major role in the development of senile dementia. They show that psychoanalysis constitutes an essential method for the understanding of dementia and challenges the predominance of the biomedical model and its therapeutic arsenal in this context., (Copyright © 2016 Institute of Psychoanalysis.)

Post-movement beta synchronization (PMBS) modulations have been related to sensory reafferences after movement initiation and inhibitory processes after movement interruption. Although these processes have been separately studied in young and old adults, little is known about the age-related changes in PMBS during selective inhibitory control (i.e. stop a part of an action). The present study examines the age-related modulations of PMBS associated with sensory reafferences and inhibitory processes in selective inhibitory control. Young (n = 17) and old (n = 13) participants performed a switching task first engaging bimanual finger tapping then requiring to stop the left while maintaining the right unimanual tapping (i.e. selective inhibition) at an imperative stimulus. Age groups were compared on behavioral (mean, variability and percentage of errors of inter-tap interval during and after the switching) and electrophysiological (time-frequency and source estimations in the 14-30 Hz beta frequency range) data time-locked on the imperative stimulus. Behaviorally, old adults showed larger variability and percentage of errors during the switching but performed as well as young adults after the switching. Electrophysiologically, PMBS significantly increased after the switching in the old compared to the young group within bilateral frontal and parietal areas. Our results show that the effort to maintain selective inhibition involves increased brain activation in old compared to young adults. The larger PMBS within frontal and parietal regions in old adults may reflect an age-related brain compensation enabling to efficiently maintain post-switching inhibition.

Spirituality and religiousness are associated with a lower risk of suicide. A detailed assessment of spirituality among 88 suicide attempters hospitalized after a suicide attempt was performed. Factors associated with the recurrence of suicide attempts over 18 months were looked into. Spirituality was low among most suicide attempters in comparison with the general population. Two groups were identified: those with a high score of depression who featured "low" in spirituality and those with a more heterogeneous profile, for example, involving personality disorders, characterized by a "high" spirituality. At the follow-up, the "meaning in life" score appeared to correlate with recurrence of suicide. Clinical implications are discussed herein.

Background: We aimed to assess the opinion of primary care workers, social workers, translators and mental health caregivers who work with asylum seekers about the latter's unmet needs and barriers to access to mental healthcare., Methods: We used a Likert scale to assess the opinion of 135 primary care workers (general practitioners, nurses, social workers and translators) and mental health caregivers about the proportion of asylum seekers with psychiatric disorders, their priority needs and their main barriers to mental health services., Results: Insufficient access to adequate financial resources, poor housing and security conditions, access to employment, professional training and legal aid were considered as priority needs, as were access to dental and mental healthcare. The main barriers to access to mental healthcare for asylum seekers included a negative representation of psychiatry, fear of being stigmatized by their own community and poor information about existing psychiatric services., Conclusions: We found a good correlation between the needs reported by healthcare providers and those expressed by the asylum-seeking population in different studies. We discuss the need for greater mobility and accessibility to psychiatric services among this population.

Subcellular target recognition in the CNS is the culmination of a multiple-step program including axon guidance, target recognition, and synaptogenesis. In cerebellum, basket cells (BCs) innervate the soma and axon initial segment (AIS) of Purkinje cells (PCs) to form the pinceau synapse, but the underlying mechanisms remain incompletely understood. Here, we demonstrate that neuropilin-1 (NRP1), a Semaphorin receptor expressed in BCs, controls both axonal guidance and subcellular target recognition. We show that loss of Semaphorin 3A function or specific deletion of NRP1 in BCs alters the stereotyped organization of BC axon and impairs pinceau synapse formation. Further, we identified NRP1 as a trans-synaptic binding partner of the cell adhesion molecule neurofascin-186 (NF186) expressed in the PC AIS during pinceau synapse formation. These findings identify a dual function of NRP1 in both axon guidance and subcellular target recognition in the construction of GABAergic circuitry., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Attention deficit hyperactivity disorder (ADHD) is associated with marked impairments in familial, social, and professional functioning. Although stimulant treatments can be effective in adult ADHD, some patients will respond poorly or not at all to medication. Previous studies demonstrated that cognitive behavioural therapy- (CBT) and dialectical behavior therapy- (DBT) oriented interventions are effective in reducing the burden of the disease, which is mainly marked by depression, interpersonal difficulties, low self-esteem, and low quality of life. In order to determine the effectiveness of this intervention, we assessed the benefits of a CBT/DBT programme to reduce residual symptoms and help patients improve their quality of life., Subjects and Methods: 49 ADHD-patients, poor responders to medication, were enrolled in a one-year programme where they received individual therapy, associated with weekly sessions of group therapy with different modules: Mindfulness, Emotion Regulation, Interpersonal Effectiveness and Distress Tolerance, Impulsivity/Hyperactivity and Attention. Each subject was assessed at baseline, at months 3 and 6, and at the end of the treatment for ADHD severity (ASRS v1.1), depression severity (BDI-II), hopelessness (BHS), mindfulness skills (KIMS), anger expression and control (STAXI), impulsivity (BIS-11), quality of life (WHOQOL-BREF), and social functioning (QFS). The 49 ADHD patients were compared with 13 ADHD subjects on a waiting list. Linear mixed models were used to measure response to treatment., Results: Overall, the psychotherapeutic treatment was associated with significant improvements in almost all dimensions. The most significant changes were observed for BDI-II (b=-0.30; p<0.0001), ASRS total score (b=-0.16; p<0.0001), and KIMS AwA (b=0.21; p<0.0001), with moderate to large effect sizes. Compared with the waiting list controls, ADHD patients showed a better, albeit non-significant, pattern of response., Conclusions: Individual and structured psycho-educational DBT/CBT groups support existing data suggesting that a structured psychotherapeutic approach is useful for patients who respond partially or not at all to drug therapy.

Humans are able to categorize face properties with impressively short latencies. Nevertheless, the latency at which gaze recognition occurs is still a matter of debate. Through spatio-temporal analysis of high-density event-related potentials (ERP), we investigated the brain activity underlying the ability to spontaneously and quickly process gaze. We presented neutral faces with direct and averted gaze in a matching picture paradigm, where subjects had to detect repetition of identical faces and gaze was implicitly manipulated. The results indicate that faces with averted gaze were better discriminated than faces with direct gaze, and evoked stronger P100 amplitudes localized to the right fusiform gyrus. In contrast, direct gaze induced stronger activation in the orbital frontal gyrus at this latency. Later in time, at the beginning of the N170 component, direct gaze induced changes in scalp topography with a stronger activation in the right medial temporal gyrus. The location of these differential activations of direct vs. averted gaze further support the view that faces with averted gaze are perceived as less rewarding than faces with direct gaze. We additionally found differential ERP responses between repeated and novel faces as early as 50ms, thereby replicating earlier studies of very fast detection of mnestic aspects of stimuli. Together, these results suggest an early dissociation between implicit gaze detection and explicit identity processing., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Sleep problems in children and adolescents are a significant public health concern and may be linked to a variety of psychoemotional difficulties. This study aimed to evaluate sleep quality and associated factors in conflict-affected Georgian adolescents after 9 months of forced displacement. Thirty-three internally displaced adolescents (mean age 11.4 years) and 33 adolescents (mean age 10.8 years) from the general population completed the Epworth Sleepiness Scale and the Children's Depression Inventory (CDI). Parents completed the Children's Sleep-Wake Scale and provided information on their socioeconomic status (SES) and the adolescents' sleep behavior, academic performance, and peer social relationships. The groups differed significantly in sleep quality, peer relationships, SES, and CDI scores. In the internally displaced group, the only significant predictor of sleep quality was SES, which increased the predictive capacity of the model (demographic and psychosocial variables) by 20% in the hierarchical analyses. The most significant predictor in the non-internally displaced group was CDI. This research indicates that displacement may affect sleep quality and psychosocial functioning. The importance of family SES as a contributing factor to displaced adolescents' poor sleep quality is highlighted. An integrated approach designed to improve the psychosocial environment of internally displaced adolescents is needed for their protection., (© The Author(s) 2015.)

Depression is a highly prevalent condition worldwide, yet multiple barriers to treatments means that the development of low intensive and easily accessible psychological interventions is crucially needed. The current study sought to investigate the efficacy of a brief, self-administered imagery cognitive bias modification (imagery CBM) procedure delivered online to a sample of 101 individuals with depressive symptoms. Compared to a closely matched control condition or a waitlist condition, imagery CBM led to greater improvements in depressive symptoms (d = 0.86, 95% CI = [0.33, 1.3] and d = 1.17, 95% CI = [0.62, 1.65]) interpretation bias and anhedonia. Despite the limitation to a two week follow-up, the study findings highlight the potential of imagery CBM as a brief, easily accessible intervention for depression that can be delivered remotely in peoples' home., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease., Discussion: Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue., Conclusion: Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P =  5.87 × 10  -   9 ; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P =  4.53 × 10  -   9 ; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS., (Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.)

Background: Emotional dysregulation in subjects with attention deficit and hyperactivity disorder (ADHD) is a topic of growing interest among clinicians and researchers. The present study aims at investigating components of emotional dysregulation in adults ADHD compared to subjects suffering from bipolar disorder (BD)., Methods: A total of 150 adults ADHD, 335 adults BD subjects and 48 controls were assessed using the Affective Lability Scale (ALS) and the Affect Intensity Measure (AIM), measuring respectively emotion lability and emotion responsiveness., Results: ADHD and BD subjects scored significantly higher on the ALS compared to controls (p=0.0001). BD subjects scored above ADHD ones (3.07 (SD=0.66) vs. 2.30 (SD=0.68); p<0.0001). The average total scores achieved on the AIM were significantly different for the three groups (p=0.0001) with significantly higher scores for ADHD subjects compared to BD ones (3.74 (SD=0.59) vs. 3.56 (SD=0.69); p<0.0001)., Limitations: Suspected cases of ADHD in the BD and control groups were derived from the Wender Utah Rating Scale (WURS). This study is a retrospective one., Conclusion: Our study thus highlights the importance of emotional dysregulation in adults suffering from ADHD, showing that they display higher emotional intensity than bipolar disorder subjects and controls. Although the current diagnostic criteria of ADHD do not contain an emotional dimension, a better recognition of the significance of emotional responsiveness in ADHD patients can improve the care afforded to these patients, beyond the inattentive and hyperactive/impulsive components., (Copyright © 2016 Elsevier B.V. All rights reserved.)