Simultaneous Quantification of Psychotropic Drugs in Human Plasma and Breast Milk and Its Application in Therapeutic Drug Monitoring and Peripartum Treatment Optimization.

BACKGROUND: Therapeutic drug monitoring is recommended for several psychotropic drugs, particularly in sensitive situations such as the peripartum period. This study aimed to develop an ultra-high-performance liquid chromatography-tandem spectrometry method for the simultaneous quantification of 14 psychotropic drugs in human plasma and 4 in breast milk. METHODS: The samples were precipitated with methanol containing the stable isotope-labeled analogs. Chromatographic separation was performed using a Phenomenex Luna Omega Polar C18 column. Detection was performed using a triple-quadrupole mass spectrometer equipped with an electrospray ionization interface. The method was fully validated in plasma according to the European Guidelines on Bioanalytical Method Validation and partially validated in breast milk by determining the intraday precision and accuracy, linearity, lower limit of quantification, and matrix effect. RESULTS: The correlation coefficients of the calibration curves were greater than 0.99. Coefficients of variation ranged from 3.05% to 14.66% and 0.62%-14.90% for internal standard-normalized matrix effect, 1.4%-14.1% and 2.1%-10.4% for intraday precision, and 3.2%-13.9% and 4.1%-9.6% for interday precision, in plasma and milk, respectively. The relative error in accuracy did not exceed ±15% for any analyte. The method was successfully applied clinically to measure the concentrations of psychotropic drugs in 952 plasma samples, among which 43% of the concentrations were out of the therapeutic range, and 13 breast milk samples, with calculated relative infant doses ranging from 0.32% to 8.18%. CONCLUSIONS: To the best of the authors' knowledge, this is the first routine technique validated for the quantification of psychotropic drugs in both plasma and breast milk, allowing for treatment optimization and prevention of adherence issues, including those in breastfeeding patients.

French Society for Biological Psychiatry and Neuropsychopharmacology and French-speaking Marcé Society guidelines for the management of mood disorders in women before, during, and after pregnancy.

PURPOSE: The French Society for Biological Psychiatry and Neuropsychopharmacology and the French-speaking Marcé Society have joined forces to establish expert recommendations on the prescription of psychotropic drugs before, during, and after pregnancy in women with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: To elaborate recommendations, we used the RAND/UCLA Appropriateness Method, which combines scientific evidence and expert clinicians' opinions. A written survey was completed by 48 psychiatrists, who have expertise in the management of mood disorders and/or in perinatal psychiatry. Key recommendations are provided by the scientific committee based on data analysis and interpretation of the results of the survey. RESULTS: The recommendations address the following three areas that are deemed essential in women with mood disorders, with an emphasis on screening, treatment options, and monitoring: (i) management of mood disorders in women of childbearing age, (ii) management during pregnancy, (iii) management during the post-partum period. As first-line strategies, experts recommend treating mood symptoms during pregnancy and maintaining a pharmacological treatment, even in euthymic or stabilized patients. First-line options include only medications with no teratogenic risk, and during breastfeeding, only medications without evidence of adverse effects in nursing infants. CONCLUSION: The expert consensus guidelines will help facilitate treatment decisions for clinicians in the daily assessment and management of mood disorders in women of childbearing age, during pregnancy, and in the post-partum period.

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.

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.

Associations of potential plasma biomarkers with suicide attempt history, current suicidal ideation and subsequent suicidal events in patients with depression: A discovery study.

A growing body of evidences suggests that suicidal ideation (SI) and suicidal behaviors have biological bases. However, no biological marker is currently available to evaluate the suicide risk in individuals with SI or suicide attempt (SA). Moreover, the current risk assessment techniques poorly predict future suicidal events. The aim of this study was to examine the association of 39 new and already described peripheral cells and proteins (implicated in the immune system, oxidative stress and plasticity) with lifetime SA, past month SA, current SI, and future suicidal events (visit to the Emergency Department for SI or SA) in 266 treatment-seeking individuals with mood disorders. Equal parts of patients with and without past history of SA were recruited. All individuals at inclusion gave blood, were evaluated for SA recency, current SI, and were followed for two years afterwards. The 39 peripheral blood cellular and protein markers were entered separately for each outcome in Elastic Net models with 10-fold cross-validation, followed by single-analyte covariate-adjusted regression analyses for pre-selected analytes. Past month SA was associated with increased plasma levels of thrombospondin-2 and C-reactive protein, whereas current SI was associated with lower plasma serotonin levels. These associations were robust to adjustments for key covariates and corrections for multiple testing. The Cox proportional hazards regression showed that higher levels of thrombospondin-1 and of platelet-derived growth factor-AB predicted a future suicidal event. These two associations remained after adjustment for sex, age, and SA history, and outperformed the predictive value of past SA. Thrombospondins and platelet-derived growth factors have never been investigated in the context of suicide. Altogether, our results highlight the involvement in the suicidal process of platelet biological response and plasticity modifiers and also of inflammatory factors. They also suggest that SI and SA may have different biological correlates and that biomarkers associated with past SA or current SI do not automatically also predict future events.

Associations of white blood cell and platelet counts with specific depressive symptom dimensions in patients with bipolar disorder: Analysis of data from the FACE-BD cohort.

Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation.

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.

Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative.

OBJECTIVES: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. METHODS: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors. RESULTS: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. CONCLUSIONS: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.

Association between childhood maltreatment and the clinical course of bipolar disorders: A survival analysis of mood recurrences.

OBJECTIVES: Childhood maltreatment, also referred as childhood trauma, increases the severity of bipolar disorders (BD). Childhood maltreatment has been associated with more frequent mood recurrences, however, mostly in retrospective studies. Since scarce, further prospective studies are required to identify whether childhood maltreatment may be associated with the time to recurrence in BD. METHODS: Individuals with BD (N = 2008) were assessed clinically and for childhood maltreatment at baseline, and followed up for two years. The cumulative probability of mood recurrence over time was estimated with the Turnbull's extension of the Kaplan-Meier analysis for interval-censored data, including childhood maltreatment as a whole, and then maltreatment subtypes as predictors. Analyses were adjusted for potential confounding factors. RESULTS: The median duration of follow-up was 22.3 months (IQR:12.0-24.8). Univariable analyses showed associations between childhood maltreatment, in particular all types of abuses (emotional, physical, and sexual) or emotional neglect, and a shorter time to recurrence (all p < 0.001). When including potential confounders into the multivariable models, the time to mood recurrence was associated with multiple/severe childhood maltreatment (i.e., total score above the 75th percentile) (HR = 1.32 95%CI (1.11-1.57), p = 0.002), and more specifically with moderate/severe physical abuse (HR = 1.44 95%CI(1.21-1.73), p < 0.0001). Living alone, lifetime anxiety disorders, lifetime number of mood episodes, baseline depressive and (hypo)manic symptoms, and baseline use of atypical antipsychotics were also associated with the time to recurrence. CONCLUSIONS: In addition to typical predictors of mood recurrences, an exposure to multiple/severe forms of childhood maltreatment, and more specifically to moderate to severe physical abuse, may increase the risk for a mood recurrence in BD. This leads to the recommendations of more scrutiny and denser follow-up of the individuals having been exposed to such early-life stressors.

Handedness in bipolar disorders is associated with specific neurodevelopmental features: results of the BD-FACE cohort.

OBJECTIVES: High rates of non-right-handedness (NRH) and mixed-handedness exist in neurodevelopmental disorders. Dysfunctional neurodevelopmental pathways may be implicated in the underlying pathophysiology of bipolar disorders (BD), at least in some subgroups. Yet little is known about correlates of NRH and mixed-handedness in BD. The objectives of this national study are to determine (i) the prevalence of NRH and mixed-handedness in a well-stabilized sample of BD individuals; (ii) if NRH/mixed-handedness in BD is associated with a different clinical, biological and neurocognitive profile. METHODS: We included 2174 stabilized individuals. Participants were tested with a comprehensive battery of neuropsychological tests. Handedness was assessed using a single oral question. Learning and/or language disorders and obstetrical complications were recorded using childhood records. Common environmental, clinical and biological parameters were assessed. RESULTS: The prevalence of NRH and mixed-handedness were, respectively, 11.6 and 2.4%. Learning/language disorders were found in 9.7% out of the total sample and were associated with atypical handedness (only dyslexia for mixed-handedness (p < 0.01), and dyslexia and dysphasia for NRH (p = 0.01 and p = 0.04, respectively). In multivariate analyses, NRH was associated with a younger age of BD onset (aOR 0.98 (95% CI 0.96-0.99) and lifetime substance use disorder (aOR 1.40 (95% CI 1.03-1.82) but not with any of the cognitive subtasks. Mixed-handedness was associated in univariate analyses with lifetime substance use disorder, lifetime cannabis use disorder (all p < 0.01) and less mood stabilizer prescription (p = 0.028). No association was found between NRH or mixed-handedness and the following parameters: trauma history, obstetrical complications, prior psychotic symptoms, bipolar subtype, attention deficit/hyperactivity disorder, peripheral inflammation or body mass index. CONCLUSIONS: Handedness may be associated with specific features in BD, possibly reflecting a specific subgroup with a neurodevelopmental load.

Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.

Antidepressants (ADs) are, for now, the best everyday treatment we have for moderate to severe major depressive episodes (MDEs). ADs are among the most prescribed drugs in the Western Hemisphere; however, the trial-and-error prescription strategy and side-effects leave a lot to be desired. More than 60% of patients suffering from major depression fail to respond to the first AD they are prescribed. For those who respond, full response is only observed after several weeks of treatment. In addition, there are no biomarkers that could help with therapeutic decisions; meanwhile, this is already true in cancer and other fields of medicine. For years, many investigators have been working to decipher the underlying mechanisms of AD response. Here, we provide the first systematic review of animal models. We thoroughly searched all the studies involving rodents, profiling transcriptomic alterations consecutive to AD treatment in naïve animals or in animals subjected to stress-induced models of depression. We have been confronted by an important heterogeneity regarding the drugs and the experimental settings. Thus, we perform a meta-analysis of the AD signature of fluoxetine (FLX) in the hippocampus, the most studied target. Among genes and pathways consistently modulated across species, we identify both old players of AD action and novel transcriptional biomarker candidates that warrant further investigation. We discuss the most prominent transcripts (immediate early genes and activity-dependent synaptic plasticity pathways). We also stress the need for systematic studies of AD action in animal models that span across sex, peripheral and central tissues, and pharmacological classes.

Non-alcoholic fatty liver disease in a sample of individuals with bipolar disorders: results from the FACE-BD cohort.

OBJECTIVE: Non-Alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease in Western populations. While obesity and metabolic abnormalities are highly frequent in bipolar disorders (BD), no studies have been performed to estimate the prevalence of NALFD in individuals with BD. The aim of our study is to estimate the prevalence of NAFLD and to identify the potential associated risk factors in a large sample of BD individuals. METHODS: Between 2009 and 2019, 1969 BD individuals from the FACE-BD cohort were included. Individuals with liver diseases, Hepatitis B or C, and current alcohol use disorders were excluded from the analyses. A blood sample was drawn from participants. Screening of NAFLD was determined using fatty liver index (FLI). Individuals with FLI> 60 were considered as having NAFLD. RESULTS: The prevalence of NAFDL in this sample was estimated at 28.4%. NAFLD was observed in 40% of men and 21% of women. NAFLD was independently associated with older age, male gender, sleep disturbances, and current use of atypical antipsychotics or anxiolytics. As expected, the prevalence of NALFD was also higher in individuals with overweight and in those with metabolic syndrome. CONCLUSIONS: This study reinforces the view that individuals with BD are highly vulnerable to metabolic and cardiovascular diseases. The prevalence of NAFLD in individuals with BD was two times higher than the prevalence reported in the general population. The regular screening of the MetS in individuals with BD should be therefore complemented by the additional screening of NAFLD among these vulnerable individuals.

Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study.

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

Characterization of depressed bipolar patients with current suicidal ideation.

OBJECTIVE: Bipolar disorder is one of the most frequent psychiatric disorders among suicidal patients. A large part of patients with bipolar disorder (30-50%) will attempt suicide. Suicidal ideation being a major risk factor of suicidal act, it is crucial to better characterize patients with suicidal bipolar depression (i.e. depression with current suicidal ideation). The aim of this study was to characterize suicidal bipolar depressed patients in comparison with non-suicidal depressed patients in terms of clinical characteristics, evolution of depression and suicidal ideation course over time, and risk of suicide attempt during follow-up. METHODS: Among patients with bipolar disorder recruited from the network of FondaMental expert centres for bipolar disorder between 2009 and 2017, we selected patients with at least mild depression (Montgomery-Åsberg Depression Rating Scale total score >11) and without current manic symptomatology (Young Mania Rating Scale total score <7) at baseline (N = 938). Suicidal depression was defined by a baseline score ⩾2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report (N = 271, 28.9%). Non-suicidal depression was defined by a baseline item 12 of the Quick Inventory of Depressive Symptomatology-Self Report score <2 (N = 667, 71.1%). A subsample of about 300 patients (with or without suicidal ideation at baseline) was followed up for 2 years. RESULTS: Baseline clinical features (e.g. depression severity, childhood trauma, global functioning) were more severe in patients with than without suicidal depression. Suicidal patients tended to remain more suicidal throughout the follow-up than patients without suicidal ideation at baseline (3.4-fold higher risk of persistent suicidal ideation at the 2-year visit despite an improvement in depressive symptomatology). CONCLUSIONS: Depressed bipolar disorder patients reporting suicidal ideation had more severe clinical features at baseline and were more prone to report persistent suicidal ideation during the follow-up, independently of thymic state. Clinicians should closely monitor this subgroup of patients.

The Impact of Bipolar Disorder on Couple Functioning: Implications for Care and Treatment. A Systematic Review.

If there is an abundant literature on the impact of bipolar illness on the family and/or caregivers of patients, few studies have addressed its impact on marital relationship and couple functioning. Uncovering information relating specifically to this topic may be particularly relevant due to the unusually high divorce rate among individuals with bipolar disorder. We therefore conducted a systematic literature search to evaluate the existing data on bipolar disorder and marital issues, with a special focus on the help and support that can be provided by mental health professionals in this regard. We identified quantitative studies with pre-defined outcomes as well as qualitative investigations trying to understand the experiences of partners. A total of 27 articles were included in the review. The literature was found to capture the impact of bipolar disorder on partners as well as on the marital relationship itself or the children. Bipolar illness has a negative impact on the lives of partners including self-sacrifice, caregiver burden, emotional impact, and health problems. This negative impact can be aggravated by a lack of care and a lack of information from health personnel. The negative impact on the relationship includes volatility in the relationship, stigmatization, dissatisfaction with sexual life, and lower rates of childbearing. Negative impacts are likely to favor disease relapses for the patient. Children may also be negatively impacted. However, the illness may sometimes have positive impacts such as personal evolution, strengthening relationship, or new hope and perspectives. Based on these findings, the interventions of mental health professionals should be aimed at minimizing the negative impacts while favoring the positive ones.

Suicide and suicide behaviors: A review of transcriptomics and multiomics studies in psychiatric disorders.

Aberrant gene expression can contribute to brain and nervous system dysfunction that causes many psychiatric illnesses. Here, we review how transcriptomic approaches have deepened our understanding of the neurobiological underpinnings of psychiatric disorders and how they have to the identification of biomarkers for these disorders, with a focus on their relevance to suicide and suicide behaviors. We begin by providing an overview of the genetic, transcriptomic, and epigenetic factors (including non-coding RNAs) implicated in suicide and their roles in the regulation of gene expression. Then, we highlight the unique benefits and limitations of using either postmortem brain or peripheral tissues in transcriptomic analyses. We examine the current shift from candidate gene to genome-wide approaches in psychiatric research, which are concurrently emerging with the increased consideration of the Research Domain Criteria (RDoC) framework for classifying mental illnesses. Furthermore, we discuss the use of transcription networks and how they can be integrated into multiomic analyses. Finally, we end by highlighting recent findings of peripheral markers of suicide risk identified through the use of transcriptomic tools. Technological advancements and increased accessibility of these technologies are drastically shaping the current research landscape. We present an overview of the significant changes currently taking place to usher in a new era of psychiatric research.

Prevalence and determinants of cognitive impairment in the euthymic phase of bipolar disorders: results from the FACE-BD cohort.

BACKGROUND: Cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, but risk factors associated with cognitive deficits in euthymic BD are still poorly understood. We aimed to validate classification criteria for the identification of clinically significant cognitive impairment, based on psychometric properties, to estimate the prevalence of neuropsychological deficits in euthymic BD, and identify risk factors for cognitive deficits using a multivariate approach. METHODS: We investigated neuropsychological performance in 476 euthymic patients with BD recruited via the French network of BD expert centres. We used a battery of tests, assessing five domains of cognition. Five criteria for the identification of neuropsychological impairment were tested based on their convergent and concurrent validity. Uni- and multivariate logistic regressions between cognitive impairment and several clinical and demographic variables were performed to identify risk factors for neuropsychological impairment in BD. RESULTS: One cut-off had satisfactory psychometric properties and yielded a prevalence of 12.4% for cognitive deficits in euthymic BD. Antipsychotics use were associated with the presence of a cognitive deficit. CONCLUSIONS: This is the first study to validate a criterion for clinically significant cognitive impairment in BD. We report a lower prevalence of cognitive impairment than previous studies, which may have overestimated its prevalence. Patients with euthymic BD and cognitive impairment may benefit from cognitive remediation.

Association between binge eating disorder and psychiatric comorbidity profiles in patients with obesity seeking bariatric surgery.

BACKGROUND: Eating disorders could be an important factor in the development of obesity, but psychiatric comorbidities are very heterogeneous in patients with obesity. Moreover, relationship between binge eating disorder and other psychiatric comorbidities is not clear. Our objective was to identify psychiatric comorbidity profiles of bariatric surgery candidates and to analyze the association between these profiles and binge-eating disorder. METHODS: Our sample consisted of bariatric surgery candidates (n = 92) with mean Body Mass Index at 41.3 ±â€¯0.6 kg/m2. To construct profiles, we classified patients according to their psychiatric comorbidities using cluster analysis techniques. We used logistic regression modelling to analyze associations between the presence of binge-eating disorder and the psychiatric comorbidity profiles. RESULTS: We identified four profiles of psychiatric phenotypes. One of these profiles was not associated with any psychiatric disorder. Binge eating disorder was significantly associated with two profiles (p < 0.05): a profile with bipolar and obsessive-compulsive disorder (OR = 7.7 [1.7; 35.1]), and a profile with bipolar and panic disorder (OR = 20.7 [3.1; 137.5]). CONCLUSIONS: Our multidimensional approach identified certain profiles specifically associated with binge-eating disorder in patients with obesity seeking bariatric surgery. These results may lead to a better understanding of the relationship between obesity and psychiatric disorders.

Associations between residual depressive symptoms, cognition, and functioning in patients with euthymic bipolar disorder: results from the FACE-BD cohort.

BackgroundThe relationship between residual depressive symptoms, cognition and functioning in patients with euthymic bipolar disorder is a subject of debate.AimsTo assess whether cognition mediates the association between residual depressive symptoms and functioning in patients with bipolar disorder who were euthymic.MethodWe included 241 adults with euthymic bipolar disorder in a multicentre cross-sectional study. We used a battery of tests to assess six cognition domains. A path analysis was then used to perform a mediation analysis of the relationship between residual depressive symptoms, cognitive components and functioning.ResultsOnly verbal and working memory were significantly associated with better functioning. Residual depressive symptoms were associated with poorer functioning. No significant relationship was found between residual depressive symptoms and any cognitive component.ConclusionsCognition and residual depressive symptoms appear to be two independent sources of variation in the functioning of people with euthymic bipolar disorder.