Spatio-temporal EEG dynamics during decision-making in online poker players with problem gambling.

Background and aims: Gambling activity evolves along a continuum from recreational to Gambling Disorder (GD) and a particular challenge is to identify whether there are some neurophysiological particularities already present in gamblers at an early stage. Our main goal was to determine whether, in the gamblers' population, neural responses generated during uncertain decisions were different depending on problematic gambling risk defined by the Canadian Problem Gambling Index (CPGI). We tested the following hypothesis, that the Problem Gambling group would show a different brain activity related to outcomes processing than people with low risk. Methods: For this purpose, we established a relatively homogeneous population of Online Poker Players divided into two groups according to the CPGI (Low Risk and Problem Gambling). By means of high-density EEG, we compared the spatio-temporal dynamics generated during the completion of the Iowa Gambling Task. Results: One specific topographic map was observed between 150-175 ms after a negative outcome for both groups, whereas it was displayed in the win condition only for the Problem Gambling group. We found that the Global Field Power of this map was negatively correlated with participants' adherence to a strategy. Source localization identified Anterior Cingulate Cortex and Temporal regions as generators of this map. Discussion and conclusions: Reward hypersensitivity EEG responses identified in the early outcome process could constitute a potential biomarker of problematic gambling.

Diet quality and associations with lactate and metabolic syndrome in bipolar disorder.

BACKGROUND: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome. METHODS: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses. RESULTS: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort. LIMITATIONS: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends. CONCLUSIONS: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD.

Does BioAge identify accelerated aging in individuals with bipolar disorder? An exploratory study in the FACE-BD cohort.

BACKGROUND: Individuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10-15 years. Several laboratory-measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge. METHODS: We calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use. RESULTS: Mean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed. CONCLUSIONS: A minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel.

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder.

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.

Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Prospective Acceptability of Digital Therapy for Major Depressive Disorder in France: Multicentric Real-Life Study.

BACKGROUND: Major depressive disorder is one of the leading causes of disability worldwide. Although most international guidelines recommend psychological and psychosocial interventions as first-line treatment for mild to moderate depression, access remains limited in France due to the limited availability of trained clinicians, high costs for patients in the context of nonreimbursement, and the fear of stigmatization. Therefore, online blended psychological treatment such as Deprexis could improve access to care for people with depression. It has several advantages, such as easy accessibility and scalability, and it is supported by evidence. OBJECTIVE: This study aims to evaluate the real-life acceptability of Deprexis for people with depression in France outside of a reimbursement pathway. METHODS: Deprexis Acceptability Study Measure in Real Life (DARE) was designed as a multicenter cross-sectional study in which Deprexis was offered to any patient meeting the inclusion criteria during the fixed inclusion period (June 2022-March 2023). Inclusion criteria were (1) depression, (2) age between 18 and 65 years, (3) sufficient French language skills, and (4) access to the internet with a device to connect to the Deprexis platform. Exclusion criteria were previous or current diagnoses of bipolar disorder, psychotic symptoms, and suicidal thoughts during the current episode. The primary objective was to measure the prospective acceptability of Deprexis, a new digital therapy. Secondary objectives were to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on Deprexis before enrollment to ensure that they all had the same level of information and understanding of the program. RESULTS: A total of 245 patients were eligible (n=159, 64.9% were women and n=138, 56.3% were single). The mean age was 40.7 (SD 14.1) years. A total of 78% (n=191) of the patients had moderate to severe depression (according to the Patient Health Questionnaire-9 [PHQ-9]). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders, and suicidal ideation). A total of 33.9% (n=83) of patients accepted the idea of using Deprexis; the main reason for refusal was financial at 83.3% (n=135). Multivariate logistic regression identified factors that might favor the acceptability of Deprexis. Among these, being a couple, being treated with an antidepressant, or having a low severity level favored the acceptance of Deprexis. CONCLUSIONS: DARE is the first French study aiming at evaluating the prospective acceptability of digital therapy in the treatment of depression. The main reason for the refusal of Deprexis was financial. DARE will allow better identification of factors influencing acceptability in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use, and severity of depression.

[The reversible share of cognitive deficits in older adults]. / La part réversible des déficits cognitifs chez les seniors.

Cognitive performance of older adults is very often inferior to that of younger adults on a variety of laboratory tests assessing basic functions such as memory, inhibition, or attention. Classic hypotheses and theories share the idea that these cognitive deficits are irreversible, due to profound cerebral changes. In this review article, we develop a more positive conception of aging, according to which cognitive deficits are not all irreversible, and can even be partially if not completely reversible. To this end, we present some of the most illustrative research on the reversibility of the effects of aging on cognition. We show how subtle contextual manipulations can change older adults' motivation and strategy, which improve their cognitive performance. We also show that guidance toward the selection of the most appropriate strategy, whether explicit as in selectivity paradigms or implicit as in dual-task procedures, can increase older adults' cognitive performance. We finally describe the hypotheses and theories that both account for low cognitive performance in old age and ways to reverse the effects of cognitive aging.

Efficacy of the my health too online cognitive behavioral therapy program for healthcare workers during the COVID-19 pandemic: A randomized controlled trial.

Background: Healthcare workers' mental health has been impacted by the COVID-19 pandemic, emphasizing the need for mental health interventions in this population. Online cognitive behavioral therapy (CBT) is efficient to reduce stress and may reach numerous professionals. We developed "MyHealthToo", an online CBT program to help reduce stress among healthcare workers during the COVID-19 pandemic. Objective: The aim of our study is to investigate the efficacy of an online CBT program on stress and mental health conditions among healthcare workers during a health crisis. Methods: We performed a multicentric randomized controlled trial among 155 participants allocated either to the experimental or active control group (bibliotherapy). The primary outcome was the decrease of perceived stress scores (PSS-10) post-treatment. Secondary outcomes included depression, insomnia and PTSD symptoms along with self-reported resilience and ruminations. Assessments were scheduled pretreatment, mid-treatment (4 weeks), post-treatment (8 weeks), and at 1-month and 4-months follow-up. Results: For both interventions, mean changes on the PSS-10 were significant post-therapy (W8), as at 1-month (W12) and 4-months (W24) follow-ups. The between-group comparison showed no difference at any time point (ps > 0.88). Work-related ruminations significantly decreased in the experimental group with a significant between-group difference at W8 (Δ = -1.83 [-3.57; -0.09], p = 0.04). Posttraumatic stress symptoms significantly decreased in the experimental group with a significant between-group difference at W12 (Δ = -1.41 [-2.68; -0.14], p = 0.03). The decrease in work-related ruminations at W8 mediated the decrease in posttraumatic stress symptoms at W12 (p = 0.048). Conclusion: The "MyHealthToo" online CBT intervention may help reduce ruminations about work and posttraumatic stress symptoms among healthcare workers during a major health crisis. Work-related ruminations may represent a relevant target of online interventions to improve mental health among healthcare workers.

Dietary linoleic acid supplementation protects against obesity-induced microglial reactivity in mice.

We investigated whether linoleic acid (LA) supplementation could modulate emotional behavior and microglia-related neuroinflammation. For that, male mice of C57BL/6J genetic background fed either a high-fat diet (HFD) or a standard diet (STD) for 12 weeks, were treated with a vehicle or LA solution for 5 weeks before being evaluated for emotional behavior using a battery of behavioral tests. The animals were subsequently sacrificed and their brains collected and processed for immunofluorescence staining, targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was assessed in multiple hypothalamic, cortical and subcortical brain regions. We show an anxio-depressive-like effect of sustained HFD feeding that was neither alleviated nor worsened with LA supplementation. However, increased IBA-1 expression and microgliosis in the HFD group were largely attenuated by LA supplementation. These observations demonstrate that the anti-neuroinflammatory properties of LA are not restricted to hypothalamic areas but are also evident at the cortical and subcortical levels. This study discloses that neuroinflammation plays a role in the genesis of neuropsychiatric disorders in the context of obesity, and that LA supplementation is a useful dietary strategy to alleviate the impact of obesity-related neuroinflammation.

Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1.

Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.

The gated cascade diffusion model: An integrated theory of decision making, motor preparation, and motor execution.

This article introduces an integrated and biologically inspired theory of decision making, motor preparation, and motor execution. The theory is formalized as an extension of the diffusion model, in which diffusive accumulated evidence from the decision-making process is continuously conveyed to motor areas of the brain that prepare the response, where it is smoothed by a mechanism that approximates a Kalman-Bucy filter. The resulting motor preparation variable is gated prior to reaching agonist muscles until it exceeds a particular level of activation. We tested this gated cascade diffusion model by continuously probing the electrical activity of the response agonists through electromyography in four choice tasks that span a variety of domains in cognitive sciences, namely motion perception, numerical cognition, recognition memory, and lexical knowledge. The model provided a good quantitative account of behavioral and electromyographic data and systematically outperformed previous models. This work represents an advance in the integration of processes involved in simple decisions and sheds new light on the interplay between decision and motor systems. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Impact of online poker gambling on behavioural and neurophysiological responses to a virtual gambling task.

Online poker gambling (OPG) involves various executive control processes and emotion regulation. In this context, we hypothesized that online poker players, accustomed to handling virtual cards, would show high performance on computerized decision-making tasks such as the Iowa Gambling Task (IGT). Using press advertisements, we recruited a non-gambler group (NG; n = 20) and an OPG group (n = 22). All participants performed the IGT while their cerebral activity was recorded by electroencephalography. Compared with the OPG group, the NG group showed significantly better progression in the IGT in the last trials. Recording of brain activity revealed the appearance of a temporal map between 150 and 175 ms specific to the gain condition in both groups. A second map was observed at 215-295 ms specifically in the NG group, and the generators were identified in the occipital regions. This activity is indicative of a high level of visual awareness; thus, it reflects additional processing of visual information, which can be assumed to be induced by the lower exposure of the NGs to online card games. We hypothesize that the absence of this activity in the OPG group might be due to their online habituation to virtual environments.

Acute effect of transcranial direct current stimulation (tDCS) on postural control of trained athletes: A randomized controlled trial.

Transcranial direct current stimulation (tDCS) is used to modulate brain function, and can modulate motor and postural control. While the acute effect of tDCS is well documented on patients, little is still known whether tDCS can alter the motor control of healthy trained participants. This study aimed to assess the acute effect of tDCS on postural control of parkour practitioners, known for their good balance abilities and their neuromuscular specificities that make them good candidates for tDCS intervention. Eighteen parkour practitioners were tested on three occasions in the laboratory for each stimulation condition (2 mA; 20 minutes)-primary motor cortex (M1), dorsolateral prefrontal cortex (dlPFC) and sham (placebo). Postural control was evaluated PRE and POST each stimulation by measuring Center of Pressure (CoP) displacements on a force platform during static conditions (bipedal and unipedal stance). Following M1 stimulation, significant decreases were observed in CoP area in unipedal (from 607.1 ± 297.9 mm2 to 451.1 ± 173.9 mm2, P = 0.003) and bipedal (from 157.5 ± 74.1 mm2 to 117.6 ± 59.8 mm2 P<0.001) stances. As well, the CoP total length was significantly reduced in bipedal (from 3416.8 ± 295.4 mm to 3280.6 ± 306.2 mm, P = 0.005) as well as in unipedal stance (from 4259.6 ± 398.4 mm to 3846.5 ± 468.9 mm, P<0.001), only after M1 stimulation. Relative pre-post changes observed after M1 stimulation were negatively correlated to experience in parkour only after unipedal stance (r = 0.715, P<0.001), meaning that the more participants were trained the less tDCS was effective. No significant changes were noticed after sham and dlPFC stimulation. These results suggested that the modulation of gait performance in athletes following an acute intervention of tDCS is specific to the targeted brain region, and that postures with reduced base of support (such as unipedal stance) were more sensitive to tDCS.

Indirect effect of impulsivity on suicide risk through self-esteem and depressive symptoms in a population with treatment-resistant depression: A FACE-DR study.

INTRODUCTION: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship. METHOD: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire. RESULTS: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable. CONCLUSION: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety.

Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.

BACKGROUND: Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. METHODS: This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. RESULTS: Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35-0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24-0.79; p = 0.008). CONCLUSIONS: This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

Understanding the potential of digital therapies in implementing the standard of care for depression in Europe.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

Evolution of Cognitive Impairments in Treatment-Resistant Depression: Results from the Longitudinal French Centers of Expertise for Treatment-Resistant Depression (FACE-DR) Cohort.

Previous studies set out profound cognitive impairments in subjects with treatment-resistant depression (TRD). However, little is known about the course of such alterations depending on levels of improvement in those patients followed longitudinally. The main objective of this study was to describe the course of cognitive impairments in responder versus non-responder TRD patients at one-year follow-up. The second aim was to evaluate the predictive aspect of cognitive impairments to treatment resistance in patients suffering from TRD. We included 131 patients from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centers. They undertook comprehensive sociodemographic, clinical, global functioning, and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16) at baseline (V0) and one-year follow-up (V1). Most patients (n = 83; 63.36%) did not respond (47 women, 49.47 ± 12.64 years old), while one-third of patients responded (n = 48, 30 women, 54.06 ± 12.03 years old). We compared the cognitive performances of participants to average theoretical performances in the general population. In addition, we compared the cognitive performances of patients between V1 and V0 and responder versus non-responder patients at V1. We observed cognitive impairments during the episode and after a therapeutic response. Overall, each of them tended to show an increase in their cognitive scores. Improvement was more prominent in responders at V1 compared to their non-responder counterparts. They experienced a more marked improvement in code, digit span, arithmetic, similarities, and D2 tasks. Patients suffering from TRD have significant cognitive impairments that persist but alleviate after therapeutic response. Cognitive remediation should be proposed after therapeutic response to improve efficiency and increase the daily functioning.

Crossed clinical features between eating disorders and types of bipolar disorder: Results from the FondaMental Advanced Centers of Expertise - Bipolar Disorder cohort.

BACKGROUND: Eating disorders (EDs) are liable to alter the disease course of bipolar disorder (BD). We explored the crossed clinical features between EDs and BD, particularly as a function of BD type (BD1 vs. BD2). METHODS: 2929 outpatients attending FondaMental Advanced Centers of Expertise were assessed for BD and lifetime EDs with a semi-structured interview, and their sociodemographic, dimensional and clinical data were collected according to a standardized procedure. For each ED type, bivariate analyses were used to investigate associations between these variables and the type of BD type followed by multinomial regressions with the variables associated with EDs and BDs after Bonferroni correction. RESULTS: Comorbid EDs were diagnosed in 478 (16.4 %) cases, and were more prevalent in patients with BD2 than in those with BD1 (20.6 % vs. 12.4 %, p < 0.001). Regression models showed no difference according to the subtype of bipolar disorder on the characteristics of patients with anorexia nervosa (AN), bulimia nervosa (BN) or binge eating disorder (BED). After multiple adjustments, the factors differentiating BD patients with versus without ED were primarily age, gender, body mass index, more affective lability and comorbidity with anxiety disorders. BD patients with BED also scored higher regarding childhood trauma. BD patients with AN also showed higher risk of past suicide attempts than those with BED. CONCLUSIONS: In a large sample of patients with BD, we found a high prevalence of lifetime EDs, especially for the BD2 type. EDs were associated with several severity indicators, but not with BD type-specific characteristics. This should prompt clinicians to carefully screen patients with BD for EDs, regardless of BD and ED types.

Childhood maltreatment contributes to the medical morbidity of individuals with bipolar disorders.

BACKGROUND: Individuals with bipolar disorders (BD) are at risk of premature death, mainly due to medical comorbidities. Childhood maltreatment might contribute to this medical morbidity, which remains underexplored in the literature. METHODS: We assessed 2891 outpatients with BD (according to DSM-IV criteria). Childhood maltreatment was assessed using the Childhood Trauma Questionnaire. Lifetime diagnoses for medical disorders were retrospectively assessed using a systematic interview and checked against medical notes. Medical morbidity was defined by the sum of medical disorders. We investigated associations between childhood maltreatment (neglect and abuse) and medical morbidity while adjusting for potential confounders. RESULTS: One quarter of individuals had no medical comorbidities, while almost half of them had at least two. Multivariable regression showed that childhood maltreatment (mainly abuse, but also sexual abuse) was associated with a higher medical morbidity. Medical morbidity was also associated with sex, age, body mass index, sleep disturbances, lifetime anxiety disorders and lifetime density of mood episodes. Childhood maltreatment was associated with an increased prevalence of four (i.e. migraine/headache, drug eruption, duodenal ulcer, and thyroid diseases) of the fifteen most frequent medical disorders, however with no difference in terms of age at onset. CONCLUSIONS: This large cross-sectional study confirmed a high medical morbidity in BD and its association with childhood maltreatment. The assessment of childhood maltreatment in individuals with BD should be systematically included in routine care and the potential impact on physical health of psycho-social interventions targeting childhood maltreatment and its consequences should be evaluated.

Repeated Anodal Transcranial Direct Current Stimulation (RA-tDCS) over the Left Frontal Lobe Increases Bilateral Hippocampal Cell Proliferation in Young Adult but Not Middle-Aged Female Mice.

Repeated anodal transcranial direct current stimulation (RA-tDCS) is a neuromodulatory technique consisting of stimulating the cerebral cortex with a weak electric anodal current in a non-invasive manner. RA-tDCS over the dorsolateral prefrontal cortex has antidepressant-like properties and improves memory both in humans and laboratory animals. However, the mechanisms of action of RA-tDCS remain poorly understood. Since adult hippocampal neurogenesis is thought to be involved in the pathophysiology of depression and memory functioning, the purpose of this work was to evaluate the impact of RA-tDCS on hippocampal neurogenesis levels in mice. RA-tDCS was applied for 20 min per day for five consecutive days over the left frontal cortex of young adult (2-month-old, high basal level of neurogenesis) and middle-aged (10-month-old, low basal level of neurogenesis) female mice. Mice received three intraperitoneal injections of bromodeoxyuridine (BrdU) on the final day of RA-tDCS. The brains were collected either 1 day or 3 weeks after the BrdU injections to quantify cell proliferation and cell survival, respectively. RA-tDCS increased hippocampal cell proliferation in young adult female mice, preferentially (but not exclusively) in the dorsal part of the dentate gyrus. However, the number of cells that survived after 3 weeks was the same in both the Sham and the tDCS groups. This was due to a lower survival rate in the tDCS group, which suppressed the beneficial effects of tDCS on cell proliferation. No modulation of cell proliferation or survival was observed in middle-aged animals. Our RA-tDCS protocol may, therefore, influence the behavior of naïve female mice, as we previously described, but its effect on the hippocampus is only transient in young adult animals. Future studies using animal models for depression in male and female mice should provide further insights into RA-tDCS detailed age- and sex-dependent effects on hippocampal neurogenesis.