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.

Postpartum blues: a predictor of postpartum depression, from the IGEDEPP Cohort.

BACKGROUND: To identify the different factors associated with postpartum blues and its association with postpartum depression, from a large French cohort. METHODS: We conducted an analysis of the Interaction Gene Environment in Postpartum Depression cohort, which is a prospective, multicenter cohort including 3310 women. Their personal (according to the Diagnostic and Statistical Manual, fifth edition [DSM-5]) and family psychiatric history, stressful life events during childhood, pregnancy, and delivery were collected. Likewise, the French version of the Maternity Blues Scale questionnaire was administered at the maternity department. Finally, these women were assessed at 8 weeks and 1 year postpartum by a clinician for postpartum depression according to DSM-5 criteria. RESULTS: The prevalence of postpartum blues in this population was 33%, and significant factors associated with postpartum blues were found as personal (aOR = 1.2) and family psychiatric history (aOR = 1.2), childhood trauma (aOR = 1.3), obstetrical factors, or events related to the newborn, as well as an experience of stressful life events during pregnancy (aOR = 1.5). These factors had a cumulative effect, with each additional factor increasing the risk of postpartum blues by 31%. Furthermore, adjustment for sociodemographic measures and history of major depressive episode revealed a significant association between postpartum blues and postpartum depression, mainly at early onset, within 8 weeks after delivery (aOR = 2.1; 95% CI = 1.6-2.7), but also at late onset (aOR = 1.4; 95% CI = 1.1-1.9), and mainly if the postpartum blues is severe. CONCLUSION: These results justify raising awareness among women with postpartum blues, including reassurance and information about postpartum depression, its symptomatology, and the need for management in case of worsening or prolongation of postpartum blues.

De Novo Variants Found in Three Distinct Schizophrenia Populations Hit a Common Core Gene Network Related to Microtubule and Actin Cytoskeleton Gene Ontology Classes.

Schizophrenia (SZ) is a heterogeneous and debilitating psychiatric disorder with a strong genetic component. To elucidate functional networks perturbed in schizophrenia, we analysed a large dataset of whole-genome studies that identified SNVs, CNVs, and a multi-stage schizophrenia genome-wide association study. Our analysis identified three subclusters that are interrelated and with small overlaps: GO:0007017~Microtubule-Based Process, GO:00015629~Actin Cytoskeleton, and GO:0007268~SynapticTransmission. We next analysed three distinct trio cohorts of 75 SZ Algerian, 45 SZ French, and 61 SZ Japanese patients. We performed Illumina HiSeq whole-exome sequencing and identified de novo mutations using a Bayesian approach. We validated 88 de novo mutations by Sanger sequencing: 35 in French, 21 in Algerian, and 32 in Japanese SZ patients. These 88 de novo mutations exhibited an enrichment in genes encoding proteins related to GO:0051015~actin filament binding (p = 0.0011) using David, and enrichments in GO: 0003774~transport (p = 0.019) and GO:0003729~mRNA binding (p = 0.010) using Amigo. One of these de novo variant was found in CORO1C coding sequence. We studied Coro1c haploinsufficiency in a Coro1c+/- mouse and found defects in the corpus callosum. These results could motivate future studies of the mechanisms surrounding genes encoding proteins involved in transport and the cytoskeleton, with the goal of developing therapeutic intervention strategies for a subset of SZ cases.

Patients' awareness of recovery mediates the link between clinical and level of functional remission in schizophrenia to a larger extent in those treated with long-acting antipsychotics.

Background: Clinical remission is a step towards functional remission for subjects with schizophrenia. While recovery is both a subjective personal journey and a clinical outcome to be targeted, data on patient self-rated outcomes are scarce. Objectives: (i) To determine the extent to which the association between clinical and functional remission is mediated by the subjective experience of recovery as reported by patients versus their relatives or their psychiatrist and (ii) to assess differences according to treatment, specifically with oral antipsychotics only versus long-acting injectable antipsychotics (LAIs). Design: Clinical observational study. Methods: Community-dwelling participants with schizophrenia enrolled in the EGOFORS cohort (N = 198) were included. Clinical symptoms and remission were assessed using the Positive and Negative Syndrome Scale. Functional remission was assessed with the Functional Remission of General Schizophrenia Scale. Awareness of recovery was assessed with one question 'What percentage of recovery do you think you have now (from 0% - no recovery - to 100% - full recovery)?', asked of the patient, also of the patient's close relative, and the psychiatrist. We used mediation analyses, taking into account the type of pharmacological treatment. Results: Remission criteria and perceived remission measures were significantly correlated, both within and between groups (r > 0.330). The patient's awareness of recovery mediated the relationship between clinical remission and level of functional remission, while the level of recovery according to psychiatrists or close relatives did not. The direct effect of clinical remission on the level of functional remission became non-significant when taking into account the mediator (patients' awareness of recovery) in the group of patients with LAI (t = 1.5, p = 0.150) but not in the group of patients with other treatments (t = 3.1, p = 0.003). Conclusion: Patients with LAIs may be more efficient in reporting their level of functional remission. Higher patient awareness could be an interesting candidate to explain this. However, as the study was cross-sectional, such a proposal should be tested with a more specifically designed protocol, such as a long-term cohort.

Clinical and cognitive characteristics of subjects with schizophrenia and childhood attention-deficit/hyperactivity disorder: Results from the multicentric FACE-SZ cross-sectional dataset.

BACKGROUND: Childhood Attention-deficit/hyperactivity disorder (C-ADHD) is a neurodevelopmental disorder, associated with an increased risk of subsequent schizophrenia. The objective of the present study was to determine the prevalence of C-ADHD in schizophrenia and the clinical and cognitive characteristics associated with C-ADHD history in schizophrenia. METHODS: 569 subjects with schizophrenia (74 % men, mean age 30.8) were included in ten expert centers at a national level and tested with a comprehensive battery of clinician-rated, patient-reported scales and cognitive tests. C-ADHD was assessed with the WURS (Wender Utah Rating Scale) self-report questionnaire. Multivariate, correlation, and principal component analyses (PCA) were conducted. RESULTS: Thirty-nine subjects (N = 39, 6.9 %) were classified in the C-ADHD group. Compared to those without C-ADHD, subjects with C-ADHD were more frequently male, had lower education levels, more severe positive clinical symptoms, more subjective cognitive deficits complaints, and lower medication adherence with small to medium effect sizes. Two cognitive components emerged from the PCA, one component including perceptual reasoning and working memory, and another component including visuospatial search and graphomotor speed, cognitive inhibition/flexibility and central executive functioning. Both components were associated with lower performances in the C-ADHD group. CONCLUSIONS: C-ADHD is frequent in schizophrenia and associated with more severe positive symptoms and impaired cognitive performances compared to those without C-ADHD. This suggests that the pathophysiological mechanisms contributing to these disorders may lead to the worsening of the cognitive functioning in patients with both disorders. C-ADHD is a relevant clinical marker to discriminate subgroups of schizophrenia with different profiles for a precision-psychiatry approach.

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.

Social determinants in prenatal antidepressant use and continuation: Systematic review and meta-analysis.

INTRODUCTION: Depression is one of the most common co-morbidities during pregnancy; with severe symptoms, antidepressants are sometimes recommended. Social determinants are often linked with antidepressant use in the general population, and it is not known if this is the case for pregnant populations. Our objective was to determine if social determinants are associated with prenatal antidepressant intake via a systematic review and meta-analysis. METHODS: A systematic search of five databases was conducted to identify publications from inception to October 2022 that reported associations with prenatal antidepressant intake (use/continuation) and one or more social determinants: education, race, immigration status, relationship, income, or employment. Eligible studies were included in random effects meta-analyses. RESULTS: A total of 23 articles describing 22 studies were included. Education was significantly and positively associated with prenatal antidepressant continuation and heterogeneity was moderate. (Odds ratio = 0.83; 95% CI, 0.78 to 0.89; p < 0.00001; I2 = 53%). Meta-analyses of antidepressant use and education, race, and relationship status, and antidepressant continuation and income were not significant with high levels of heterogeneity. DISCUSSION: While most social determinants in this review were not linked with prenatal antidepressant intake, lower maternal education level does seem to be associated with lower rates of prenatal antidepressant continuation. CONCLUSIONS: Education appears to be linked with prenatal antidepressant intake. The low number of included studies precludes conclusive evidence for other social determinants.

Predictors of medication adherence in a large 1-year prospective cohort of individuals with schizophrenia: insights from the multicentric FACE-SZ dataset.

Schizophrenia is characterized by the most salient medication adherence problems among severe mental disorders, but limited prospective data are available to predict and improve adherence in this population. This investigation aims to identify predictors of medication adherence over a 1-year period in a large national cohort using clustering analysis. Outpatients were recruited from ten Schizophrenia Expert Centers and were evaluated with a day-long standardized battery including clinician and patient-rated medication adherence measures. A two-step cluster analysis and multivariate logistic regression were conducted to identify medication adherence profiles based on the Medication Adherence rating Scale (MARS) and baseline predictors. A total of 485 participants were included in the study and medication adherence was significantly improved at the 1-year follow-up. Higher depressive scores, lower insight, history of suicide attempt, younger age and alcohol use disorder were all associated with poorer adherence at 1 year. Among the 203 patients with initially poor adherence, 86 (42%) switched to good adherence at the 1-year follow-up, whereas 117 patients (58%) remained poorly adherent. Targeting younger patients with low insight, history of suicide, alcohol use disorder and depressive disorders should be prioritized through literacy and educational therapy programs. Adherence is a construct that can vary considerably from year to year in schizophrenia, and therefore may be amenable to interventions for its improvement. However, caution is also warranted as nearly one in five patients with initially good adherence experienced worsened adherence 1 year later.

Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression.

OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).

The association of stroke with mental and physical disorders in US adults: A nationally representative study.

Stroke has been linked to various physical and mental disorders, with both stroke and its comorbidities significantly impacting public health. In this population-based study, we evaluate the relationships between stroke, physical conditions, mental disorders, and their effect on quality of life. Data were gathered from a nationally representative sample of 36,309 civilian participants aged 18 years and older in the National Epidemiologic Survey on Alcohol and Related Conditions-III. We examined the prevalence of past-year stroke, its sociodemographic characteristics, and its associations with past-year mental disorders (according to the DSM-5) and physical conditions. Furthermore, we explored the connections between stroke and health-related quality of life, accounting for comorbidities. The past 12-month stroke prevalence was estimated at 0.82%. Participants with stroke exhibited a significantly higher past 12-month mental disorder prevalence than those without stroke. Specifically, individuals with stroke faced a higher risk of mood disorders, anxiety disorders, tobacco use disorder, and opioid use disorder compared to those without stroke. Stroke was also positively associated with 24 out of the 27 physical conditions assessed in this study. Participants with stroke experienced lower mental and physical quality of life compared to those without stroke. Stroke was significantly related to numerous mental and physical disorders. The association of stroke with diminished health-related quality of life was not only mediated by these comorbidities but should also be considered as inherently linked to stroke itself.

Association between family functioning and psychotic transition in ultra-high risk adolescents and young adults.

Background: Psychotic transition (PT) is a crucial stage in schizophrenia. The Comprehensive Assessment of At-Risk Mental States (CAARMS) scale can be used to identify individuals at ultra-high risk (UHR) for psychosis and to evaluate their risk of PT. Many environmental and genetic factors have been identified as contributing to the development and decompensation of schizophrenia. This study aimed to determine if the quality of family functioning is associated with PT risk in UHR individuals aged between 11 and 25 years after 1 year of follow-up. Methods: From January to November 2017, 45 patients aged 12 to 25 consulting for psychiatric reasons were included. Twenty-six were classified as UHR of PT at the CAARMS. Family functioning was assessed by the Family Assessment Device-Global Functioning (FAD-GF). Thirty-seven of these patients (30% men, mean age 16 ± 2.5) were reassessed at 8-14 months of recruitment. Survival analysis was used to examine the impact of family functioning on PT risk. Results: A total of 40% of UHR patients were classified as psychotic at reassessment. Survival analysis showed that better family functioning is a significant protective factor for PT in this population. Discussion: This result suggests that the global family functioning has an impact at 1 year on the risk of PT in the population of adolescents and young adults who consult the hospital for psychiatric reasons. A family intervention may be effective in reducing PT risk in this population and should be considered as a potential therapeutic option.

Psychotic-like experiences in general population: Psychiatric comorbidity and impact on quality of life across lifespan.

BACKGROUND AND HYPOTHESIS: In this study, we aimed to determine the prevalence of Psychotics-Like Experiences according to age group and their association with psychiatric disorders through these different age-group, as well as their impact on quality of life. STUDY DESIGN: Using data from the second wave of the NESARC, a large general population study, we considered 6 mutually exclusive groups according to the age at the interview: 20-29 years; 30-39 years; 40-49 years; 50-59 years; 60-69 years; 70+ years. We determined the frequency of PLEs defined as positive, negative, depressive, mania and disorganization symptoms with reference to the PANSS, and the association between the presence of PLEs in the previous year and the presence of lifetime psychiatric disorders and quality of life across different age groups. STUDY RESULTS: The prevalence of PLEs decreased across age from a 34.7 % in the 20-29 years age group, to 19.7 % in the 70+ years age group. Across all age groups, individuals who reported PLEs in the previous year had higher risk of having any psychiatric disorder, (i.e any mood disorder, any anxiety disorder any substance abuse and any personality disorder) compared to individuals not reporting PLEs. All dimensions of quality of life on the SF12 scale were negatively associated with the presence of a PLE regardless of age group. CONCLUSION: We found that the frequency of PLEs decreased with age and that the presence of PLE is associated with psychiatric disorders and with impaired quality of life in all age groups.

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.

Major depressive episode and postpartum depression: A network analysis comparison on the IGEDEPP cohort.

INTRODUCTION: Major depression episode (MDE) and postpartum depression (PPD) have the same diagnosis criteria, but dissimilarities may be present regarding the frequency and structure of depressive symptoms. METHODS: We used data from the IGEDEPP Cohort (France) to examine DSM-5 depressive symptoms in two groups of women: 486 with PPD and 871 with a history of non-perinatal MDE. We compare (i) the frequency of each depressive symptom adjusted for the severity of depression, (ii) the global structure of depressive symptom networks, and (iii) the centrality of each symptom in the two networks. RESULTS: Women with PPD were significantly more likely to have appetite disturbance, psychomotor symptoms, and fatigue than those with MDE, while sadness, anhedonia, sleep disturbance, and suicidal ideation were significantly less common. There were no significant differences in the global structure of depressive symptoms of MDE and PPD. However, the most central criterion of the MDE network was "Sadness" while it was "Suicidal ideations" for the PPD network. "Sleep" and "Suicidal ideations" criteria were more central for PPD network, whereas "Culpability" was more important for MDE network than for PPD network. CONCLUSION: We found differences in depressive symptoms expression between PPD and MDE, which justify continuing to clinically distinguish PPD from MDE.

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. MATERIAL AND METHODS: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. RESULTS: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was -0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. CONCLUSIONS: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS.

Clinical and pharmacological correlates of caffeine consumption in subjects with schizophrenia - Data from the FACE-SZ cohort.

Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = -0.12) but significant.

Physical and mental health status of former smokers and non-smokers patients with bipolar disorder.

OBJECTIVES: Up to 70% individuals with bipolar disorder (BD) are lifetime tobacco smokers, a major modifiable risk factor for morbidity. However, quitting smoking is rarely proposed to individuals with BD, mainly because of fear of unfavorable metabolic or psychiatric changes. Evaluating the physical and mental impact of tobacco cessation is primordial. The aim of this study was to characterize the psychiatric and nonpsychiatric correlates of tobacco smoking status (never- vs. current vs. former smokers) in individuals with BD. METHODS: 3860 individuals with ascertained BD recruited in the network of Fondamental expert centers for BD between 2009 and 2020 were categorized into current, former, and never tobacco smokers. We compared the sociodemographic and clinical characteristics assessed by standard instruments (e.g., BD type, current symptoms load, and non-psychiatric morbidity-including anthropometric and biological data) of the three groups using multinomial regression logistic models. Corrections for multiple testing were applied. RESULTS: Current smokers had higher depression, anxiety, and impulsivity levels than former and never-smokers, and also higher risk of comorbid substance use disorders with a gradient from never to former to current smokers-suggesting shared liability. Current smokers were at higher risk to have a metabolic syndrome than never-smokers, although this was only evidenced in cases, who were not using antipsychotics. CONCLUSIONS: Tobacco smoking was associated with high morbidity level. Strikingly, as in the general population, quitting smoking seemed associated with their return to the never-smokers' levels. Our findings strongly highlight the need to spread strategies to treat tobacco addiction in the BD population.

Definition of early age at onset in bipolar disorder according to distinctive neurodevelopmental pathways: insights from the FACE-BD study.

BACKGROUND: Converging evidence suggests that a subgroup of bipolar disorder (BD) with an early age at onset (AAO) may develop from aberrant neurodevelopment. However, the definition of early AAO remains unprecise. We thus tested which age cut-off for early AAO best corresponds to distinguishable neurodevelopmental pathways. METHODS: We analyzed data from the FondaMental Advanced Center of Expertise-Bipolar Disorder cohort, a naturalistic sample of 4421 patients. First, a supervised learning framework was applied in binary classification experiments using neurodevelopmental history to predict early AAO, defined either with Gaussian mixture models (GMM) clustering or with each of the different cut-offs in the range 14 to 25 years. Second, an unsupervised learning approach was used to find clusters based on neurodevelopmental factors and to examine the overlap between such data-driven groups and definitions of early AAO used for supervised learning. RESULTS: A young cut-off, i.e. 14 up to 16 years, induced higher separability [mean nested cross-validation test AUROC = 0.7327 (± 0.0169) for ⩽16 years]. Predictive performance deteriorated increasing the cut-off or setting early AAO with GMM. Similarly, defining early AAO below 17 years was associated with a higher degree of overlap with data-driven clusters (Normalized Mutual Information = 0.41 for ⩽17 years) relatively to other definitions. CONCLUSIONS: Early AAO best captures distinctive neurodevelopmental patterns when defined as ⩽17 years. GMM-based definition of early AAO falls short of mapping to highly distinguishable neurodevelopmental pathways. These results should be used to improve patients' stratification in future studies of BD pathophysiology and biomarkers.