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Abstract Background Quality of life is decreased in bipolar disorders (BD) and contributes to poor prognosis. However, little is known about the causal pathways that may affect it. This study aimed to explore health-related QoL (HRQoL) in BD and investigate its relationship with cognition and psychosocial functioning. Methods This multicenter cross-sectional study used a neuropsychological battery to assess five cognition domains. Functioning was evaluated using global and domain-based tools, and health-related HRQoL was assessed using the EQ-5D-3L. Structural equation modeling was used to test whether the association between cognition and HRQoL would be mediated by functioning in BD while controlling for covariates such as residual depression, anxiety, antipsychotic medication, and psychotic features. Results We included 1 190 adults with euthymic BD. The model provided a good fit for the data. In this model, the direct effect of cognition on HRQoL was not significant (β = − 0.03, z = −0.78, p = 0.433). The total effect of cognition on HRQoL was weak, albeit significant (β = 0.05, z = 3.6, p

Introduction: Previous studies set out cognitive impairments in major depression. However, only two studies were performed among patients suffering from treatment-resistant depression (TRD) and conducted on limited sample sizes. Here, we aimed to characterize cognitive impairments in TRD, and their association with the severity of depression and daily functioning. Method: We included 288 patients suffering from TRD (178 women, 52.5 ± 13.1 years old). They undertook sociodemographic, clinical, daily functioning and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16). We compared our patients’ performances to theoretical performances of the general population. Results: TRD was associated with poorer neuropsychological performances, except for similarities task. We found an effect of depression severity on processing speed and memory, and an impact on daily functioning affecting memory, selective attention and executive function. Conclusion: Patients suffering from TRD have significant cognitive impairments. Therapeutic interventions should be developed to manage such impairments.

Background: The objective of this study was to develop a conceptual framework to define a domain map describing the experience of patients with severe mental illnesses (SMIs) on the quality of mental health care. Methods: This study used an exploratory qualitative approach to examine the subjective experience of adult patients (18–65 years old) with SMIs, including schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder (MDD). Participants were selected using a purposeful sampling method. Semistructured interviews were conducted with 37 psychiatric inpatients and outpatients recruited from the largest public hospital in southeastern France. Transcripts were subjected to an inductive analysis by using two complementary approaches (thematic analysis and computerized text analysis) to identify themes and subthemes. Results: Our analysis generated a conceptual model composed of 7 main themes, ranked from most important to least important as follows: interpersonal relationships, care environment, drug therapy, access and care coordination, respect and dignity, information and psychological care. The interpersonal relationships theme was divided into 3 subthemes: patient-staff relationships, relations with other patients and involvement of family and friends. All themes were spontaneously raised by respondents. Conclusion: This work provides a conceptual framework that will inform the subsequent development of a patient-reported experience measure to monitor and improve the performance of the mental health care system in France. The findings showed that patients with SMIs place an emphasis on the interpersonal component, which is one of the important predictors of therapeutic alliance. Trial registration: NCT02491866

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.

Abstract Background Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. Method Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians’ opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. Results The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. Conclusion The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Abstract Background Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. Method The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. Results The expert guidelines combine scientific evidence and expert clinician’s opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. Conclusion These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

AimThe anticholinergic properties of medications are associated with poorer cognitive performance in schizophrenia. Numerous scales have been developed to assess anticholinergic burden and yet, there is no consensus indicating which anticholinergic burden scale is more relevant for patients with schizophrenia. We aimed to identify valid scales for estimating the risk of iatrogenic cognitive impairment in schizophrenia.MethodsWe identified 27 scales in a literature review. The responses to neuropsychological tests of 839 individuals with schizophrenia or schizoaffective disorder in the FACE-SZ database were collected between 2010 and 2021. We estimated the association between objective global cognitive performance and the 27 scales, the number of psychotropic drugs, and chlorpromazine and lorazepam equivalents in bivariable regressions in a cross-sectional design. We then adjusted the bivariable models with covariates: the predictors significantly associated with cognitive performance in multiple linear regressions were considered to have good concurrent validity to assess cognitive performance.ResultsEight scales, the number of psychotropic drugs, and drug equivalents were significantly associated with cognitive impairment. The number of psychotropic drugs, the most convenient predictor to compute, was associated with worse executive function (Standardized β = −0.12, p = .004) and reasoning (Standardized β = −0.08, p = .037).ConclusionAnticholinergic burden, the number of psychotropic drugs, and drug equivalents were weakly associated with cognition, thus suggesting that cognitive impairment in schizophrenia and schizoaffective disorder is explained by factors other than medication. The number of psychotropic drugs was the most parsimonious method to assess the risk of iatrogenic cognitive impairment.

Introduction A 10-15 years decrease in life expectancy has been observed in individuals with bipolar disorder (BD) and has been associated with premature cellular aging, but mechanisms involved remain unclear. Our team recently identified a subgroup of young individuals with prematurely shortened telomere length (TL). Objectives The aims of the present study were to replicate this observation in a larger sample and to analyze the expression levels of genes associated with age or TL in a subsample of these individuals. Methods TL was measured by qPCR using peripheral blood DNA from 542 individuals with BD. Clustering analyzes were performed with age and TL as classification variables to identify similar groups. Gene expression of 29 genes, including 20 associated with age and 9 with TL, was analyzed by RT-qPCR using peripheral blood RNA in a subgroup of 129 individuals. Gene expressions were compared between groups obtained from the previous clustering analyzes by Kruskal-Wallis and Mann-Whitney tests. Results Clustering analyzes identified 3 subgroups and replicated the clustering previously described: a subgroup of aged individuals with a low TL (mean age : 51.73 years ; mean TL : 2), a subgroup of young individuals with a high TL (mean age : 29.02 years ; mean TL : 4.36) and a subgroup of young individuals but with a low TL (mean age : 29.64 years ; mean TL : 1.96). None of the tested clinical variables were significantly associated with this subgroup. Furthermore, gene expression level analyzes showed that only POT1 expression was different between the two subgroups of young individuals, with a downregulation of POT1 expression in the subgroup with a lower TL level. POT1 is a protein involved in the maintenance of TL. POT1 binds to another protein TPP1 allowing the recruitment of telomerase, the enzyme which extends TL. Our hypothesis is that in the subgroup presenting a lower POT1 expression, the POT1-TPP1 complex cannot form and thus prevents telomerase recruitment and TL elongation. Conclusions This study confirms, on a larger sample, the existence of a subgroup of young individuals with BD presenting accelerated cellular aging. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening. Disclosure of Interest None Declared

Introduction The synaptic pruning process is based on the joint action of the complement system and microglia. In schizophrenia, accumulating evidence support that abnormal synaptic pruning during adolescence may be due to an altered Complement system activity. While this hypothesis is supported by C4 overexpression in various brain regions of individuals with schizophrenia, such alterations should be replicated and extended to other brain regions. Moreover, transcriptional studies of genes encoding regulators of the complement system activity (complement control proteins, CCP) and microglia-specific genes are lacking. Furthermore, it remains unknown whether brain and peripheral expression of such genes are related. Objectives To explore expression of C4 as well as 4 CCP encoding genes and 10 microglia-specific genes at the brain and peripheral levels in individuals with schizophrenia as compared to healthy controls. Methods We analyzed candidate gene expression from 9 Gene Expression Omnibus datasets obtained from 333 individuals with schizophrenia and 306 healthy controls (HC). We first compared expression of the candidate genes between individuals with schizophrenia and HC in postmortem brain samples from 7 different brain regions. Then, the same comparison was made in 4 different peripheral tissues. Results Regarding the complement system, we observed C4 overexpression in the DLPFC, parietal, temporal cortex and associative striatum of individuals with schizophrenia. We report distinct altered expression patterns of CCP genes in the DLPFC, hippocampus and cerebellum of individuals with schizophrenia. Only CD46 expression was altered in the blood of individuals with schizophrenia. Regarding microglia, we report an underexpression of several microglia-specific genes in the cerebellum, associative striatum, hippocampus and parietal cortex of individuals with schizophrenia vs. HC. At the peripheral level, we observed a mixed altered expression pattern in the whole blood of individuals with schizophrenia. Conclusions Firstly, our results suggest that the CCP-mediated regulatory mechanisms of the Complement system are impaired in the brain of individuals with schizophrenia, potentially contributing to an excessive Complement system activity (CSA). Secondly, our results support the hypothesis of a widespread underexpression of microglia-specific genes in brain tissues of individuals with schizophrenia. Functionally, the observed transcriptional alterations may be related to the synaptic pruning impairment. Alternatively, they may translate a compensatory mechanism for neuroinflammation. In the whole blood, the altered transcriptional pattern may represent a potential peripheral signature of SZ. Disclosure of Interest None Declared

Abstract Background Response to lithium (Li) is highly variable in bipolar disorders (BD). Despite decades of research, no clinical predictor(s) of response to Li prophylaxis have been consistently identified. Recently, we developed epigenetic Methylation Specific High-Resolution Melting (MS-HRM) assays able to discriminate good responders (GR) from non-responders (NR) to Li in individuals with BD type 1 (BD-I). This study examined whether a combination of clinical and epigenetic markers can distinguish NR from other types of Li responders. Methods We recorded clinical variables that are potentially associated with Li response in 64 individuals with BD-I. MS-HRM assays were performed on DNA isolated from peripheral blood. We used backward stepwise logistic regression analyses, followed by receiver operating characteristic (ROC) curve analysis to estimate the performance of the clinical variables, alone then in combination with the epigenetic biomarkers, to identify GR and partial responders (PaR) vs NR. Results Polarity at onset, psychotic symptoms at onset and family history of BD classified correctly 70% of individuals according to their Li response (PaR + GR = 86%; NR = 35%). When combined with the epigenetic biomarkers, these three clinical variables plus alcohol misuse (and one DMR: Differentially Methylated Region) correctly classified 86% of individuals, improving the prediction of PaR + GR (93%) and of NR (70%). The ROC analysis demonstrated an improvement in the area under the curve from 0.75 (clinical variables alone) to 0.87 (combination of clinical and epigenetic markers). Conclusions Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone.

Introduction: History of Childhood Maltreatment (CM) has repeatedly been associated with an increased risk of developing bipolar disorders (BD) or schizophrenia (SZ). The impact of severe stress induced by CM is thought to be mediated by increased inflammation reflected by deregulated levels of circulating pro- and anti-inflammatory cytokines. However, little is known about the potential impact of exposition to CM on lymphocyte subpopulations or the role of pre-existing infections on the impact of CM. We thus explored the role of CM and the impact of past exposure to infections on lymphocyte subpopulation.as these could be important avenues to better understand the impact of severe stress in major mood and psychotic disorders. Patients and Methods: 118 adult patients with SZ and 152 with BD were included in the analysis. History of CM was assessed using the Childhood Trauma Questionnaire (CTQ), current and past psychiatric symptomatology were evaluated. Circulating lymphocytes subsets were analyzed using flow cytometry-based analysis. Past exposure to common infectious stigma including toxoplasma, Cytomegalovirus (CMV) and Ebstein-Barr Virus (EBV) were measured by solid phase-enzyme microplate and ELISA immunoassays. Relationship between CM, biological phenotypes and clinical phenotypes were analyzed using univariate and multivariate analyses. Results: We found that patients with BD and CM, as compared to those without, had higher levels of CD3+CD8+ cytotoxic T cells and CMV antibodies along decreased levels of CD45RA+CCR7+CD8+ naïve CD8 T cells, and a more severe clinical profile. We also observed that levels of CMV antibodies were inversely associated with the CD3+CD8+ lymphocyte subset level.Patients with SZ and CM have decreased levels of CD14+ monocytes. Accumulation of types of maltreatment is associated with increased Body Mass Index and CMV autoantibodies as well as decreased levels of CD14+ monocytes. Conclusion: We observed that adult patients with BD or SZ having been exposed to CM exhibit specific immune cell subset profiles, clinical features and stigma of past infections. Altogether, our findings, especially in the context of BD, allows us to suggest a possible interplay between CM and CMV infectious events possibly inducing premature aging and cellular senescence, two events already known to be associated with psychiatric conditions. Longitudinal studies of patients exposed to maltreatment are warranted to replicate, predict and anticipate the specific needs of these patients.

Introduction Migraine and bipolar disorder (BD) are two chronic and recurrent disorders with a major impact on patient’s quality of life. It is now well known that affective disorders and migraine are often comorbid (Leo et al. Scand J Pain. 2016; 11:136-145). Starting from these observations, we can hypothesis that BD patients with comorbid migraine might have specifical clinical and biological features. Objectives The aim of this study was to estimate the prevalence of migraine in a cohort of French BD patients; determine sociodemographic, clinical, and biological features associated BD-migraine comorbidity. Methods 4348 BD patients from the FACE-BD cohort were included from 2009 to 2022. Sociodemographic and clinical characteristics, lifestyle information, and data on antipsychotic treatment and comorbidities were collected, and a blood sample was drawn. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis of BD. Migraine diagnosis was established according to a clinician-assessed questionnaire. Results 20.1% of individuals with BD had comorbid migraine. Half of these patients received treatment for migraine. Multivariate logistic regression model showed that risk of migraine in women was nearly twice that in men (OR = 1.758; 95% CI, 1.345-2.298). Anxiety disorder, sleep disturbances and childhood trauma were also associated with an increased risk of migraine comorbidity. Patients receiving antipsychotic treatment had less risk of developing migraine than those not receiving those treatment (OR 0.716, 95% CI, 0.554-0.925), independent of other potential confounders. Conclusions The prevalence of migraine in our cohort was lower than those previously reported in other studies. This result might suggest an overestimation of migraine diagnosis in BD patients population studies. However, BD-migraine comorbidity could constitute a subphenotype of bipolar disorder requiring specific treatments. Disclosure of Interest None Declared

Introduction Bipolar Disorder (BD) is a common psychiatric disease. It has been demonstrated a long time ago that bipolar patients are more painful than the healthy subjects. Substance use disorder is a frequent comorbidity in BD, but also in painful patients. The aim of our study was to analyze if bipolar patients with a painful expression have more substance use disorder than bipolar patients without pain. Objectives The aim of our study was to analyze if bipolar patients with a painful expression have more substance use disorder than bipolar patients without pain Methods We included all bipolar patients from the FACE-BD cohort which is a prospective cohort of French outpatients with BD enrolled at the 12 advanced Centers of Expertise in Bipolar Disorder (CEBD). Pain has been evaluated by the “pain item” of the EQ-5D scale and we divided subjects in four categories: “no pain”, “slight pain”, “moderate pain”, “severe or extreme pain”. A multivariate analysis was performed to identify differences between each pain’s groups according to the kind of substance use disorder, psychiatric comorbidities and clinicals data. Results The cohort enrolled 1897 bipolar patients, 970 had no pain (51.1%), 507 had slight pain (26.7%), 298 had moderate pain (15.7%) and 122 had severe or extreme pain (6.4%). We found significant differences according to age, comorbidities and clinicals data with older, more anxious, and more severe patients more represented in the more painful groups. Painful bipolar patients had also more frequently lifetime substance use disorders (alcohol, opioid, sedative, marijuana) and we were able to characterize different profiles in bipolar patients. Conclusions Bipolar patients with a painful expression had more risks to have a lifetime substance use disorder, an anxiety disorder, and a higher score on MADRS. Interestingly, subjects seemed to prefer substances with anxiolytic or antalgic effects during the acute intoxication as alcohol, marijuana, opioid and sedatives. Disclosure of Interest None Declared

Introduction In schizophrenia, abnormal synaptic pruning during adolescence may be due to an altered Complement system activity. While this hypothesis is supported by C4 overexpression in various brain regions of individuals with schizophrenia, such alterations should be replicated and extended to other brain regions relevant to schizophrenia. Moreover, transcriptional studies of genes coding for proteins regulating the Complement system activity are lacking. Furthermore, it remains unknown whether cerebral and peripheral expression of C4 and Complement control proteins (CCP) are related. Objectives To identify altered expression of C4 and CCP (CSMD1, CSMD2, CD46) coding genes at the cerebral and peripheral levels in schizophrenic individuals. Methods We explored C4 and CCP coding genes expression at the cerebral and peripheral levels. Using shinyGEO application we analyzed gene expression from eight Gene Expression Omnibus datasets obtained from 196 schizophrenic individuals and 182 control subjects. First, we compared gene expression between schizophrenic patients and controls in postmortem cerebral samples from 7 different brain regions. Then, we compared gene expression between schizophrenic patients and controls in 4 peripheral tissues. Results We observed C4 overexpression in the DLPFC, parietal, temporal cortex and associative striatum of schizophrenic individuals. We report altered transcriptional patterns of CCP genes in the DLPFC, hippocampus and cerebellum of schizophrenic individuals. CD46 expression was altered in opposite directions between brain and blood of schizophrenic individuals. No significant alteration of C4 expression was observed in peripheral tissues. Conclusions Our results support the hypothesis of an altered Complement system activity in various brain regions of schizophrenic individuals which may disrupt the synaptic pruning process during adolescence. Disclosure No significant relationships.

Introduction Bipolar disorder has been repeatedly associated with abnormalities of white matter. However, DTI is intrinsically limited and the precise cellular mechanisms that underlie these alterations remains unknown. Objectives Our aim was to investigate microscopical characteristics of white matter using MRI in patients with bipolar and healthy controls. Methods 77 patients and 71 controls from 3 sites had a T1 structural MRI, a multi-shell HARDI MRI and at one site with a T1-weighted VFA-SPGR acquisition, and a T2 MSME acquisition. The volume fraction and the orientation dispersion was extracted using NODDI from DW images in each site. Myelin Water Fraction was extracted in 33 patients and 36 controls to probe myelin characteristics. White matter bundles were reconstructed using deterministic tractography. Statistical analyses were performed after harmonization by the ComBat algorithm and controlled for age, gender and handedness. Results We found significant lower axonal density in patients along the short fibers of the left cingulum, the left anterior arcuate and the left inferior fronto-occipital fasciculus. We found lower mean MWF in patients along the short fibers of the right cingulum, the left inferior fronto-occipital fasciculus, the left anterior arcuate and the splenium of the corpus callosum. We found higher mean orientation dispersion in patients only along the left uncinate fasciculus. Conclusions We report alterations of limbic and inter-hemispheric white matter tracts in patients with bipolar disorder reflecting axonal loss, demyelination and architecture alterations. These results contribute to better capture the plurality of the mechanisms involved in bipolar disorder that cannot be deciphered with classical diffusion MRI. Disclosure No significant relationships.

Introduction Schizophrenia and bipolar disorder are severe mental illnesses that are known to have a considerable overlap in underlying pathophysiological mechanisms. More specifically, disturbances in the kynurenine pathway have been hypothesized as processes bridging altered immune responses and clinical manifestations of these illnesses. Objectives The aim of this study was to investigate the abnormalities in serum kynurenine metabolites in schizophrenic and bipolar patients and the impact of clinical factors. Methods Four patient groups were included in the current study: 1) Acute bipolar inpatients (n=205); 2) stable bipolar outpatients (n=116); 3) acute schizophrenia inpatients (n=111) and 4) stable schizophrenia outpatients (n=75); and one healthy control group (n=185). Clinical symptoms were established using symptom severity scales. The quantitative determination of serum kynurenine metabolites was performed using LC-MS/MS. General linear model and multivariate linear regression analyses were used to perform the statistical analysis with JMP Pro 15. Results In line with previous research, the results indicate that serum kynurenine metabolites are disturbed in schizophrenic and bipolar patients compared to healthy controls. Whereas no differences were observed between schizophrenia and bipolar disorder, illness state and duration of illness clearly impacted kynurenine metabolite levels. Acutely ill patients had significantly lower levels compared to stable patients, which seemed to be driven by psychotic symptoms. Conclusions To conclude, the results confirm the involvement of the kynurenine pathway in the pathophysiology of schizophrenia and bipolar disorder by lowered peripheral kynurenine metabolite level. In addition, an important role of acute psychotic symptoms and longer illness duration on these metabolite aberrances is demonstrated. Disclosure No significant relationships.

AbstractBackgroundPsychiatric comorbidities and suicide attempts are highly prevalent in Bipolar Disorders (BD). We examined the associations between childhood maltreatment, psychiatric comorbidities, and suicide attempts, in terms of lifetime prevalence, sequence of onset, and current symptoms.MethodsWe assessed 3,047 individuals with BD for suicide attempts, anxiety disorders, substance use disorders, and eating disorders. Participants completed a self-report for the assessment of childhood maltreatment. Associations between childhood maltreatment and characteristics of comorbidities (lifetime prevalence, current symptoms, and age at onset) were examined using logistic regressions and network analyses.ResultsPsychiatric comorbidities were frequent with a mean number per individual of 1.23 (SD = 1.4). Most comorbidities occurred prior to the onset of BD. Participants who reported higher levels of childhood maltreatment had more frequent and multiple comorbidities, which were also more currently active at inclusion. Childhood maltreatment did not decrease the age of onset of comorbidities, but was associated with a faster accumulation of comorbidities prior to the onset of BD. Logistic regression and network analyses showed that emotional abuse and sexual abuse might play a prominent role in the lifetime prevalence of psychiatric comorbidities and suicide attempts.ConclusionsChildhood maltreatment was associated with suicide attempts, and with frequent, multiple, and persistent psychiatric comorbidities that accumulated more rapidly prior to the onset of BD. Hence, childhood maltreatment should be systematically assessed in individuals with BD, in particular when the course of the disorder is characterized by a high comorbid profile or by a high suicidality.