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Objectives Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD. Methods A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype. Results Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups. Limitations All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias. Conclusions Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention.

International audience; Optimal classification of the response to lithium (Li) is crucial in genetic and biomarker research. This proof of concept study aims at exploring whether different approaches to phenotyping the response to Li may influence the likelihood of detecting associations between the response and genetic markers. We operationalized Li response phenotypes using the Retrospective Assessment of Response to Lithium Scale (i.e., the Alda scale) in a sample of 164 cases with bipolar disorder (BD). Three phenotypes were defined using the established approaches, whilst two phenotypes were generated by machine learning algorithms. We examined whether these five different Li response phenotypes showed different levels of statistically significant associations with polymorphisms of three candidate circadian genes (RORA, TIMELESS and PPARGC1A), which were selected for this study because they were plausibly linked with the response to Li. The three original and two revised Alda ratings showed low levels of discordance (misclassification rates: 8–12%). However, the significance of associations with circadian genes differed when examining previously recommended categorical and continuous phenotypes versus machine-learning derived phenotypes. Findings using machine learning approaches identified more putative signals of the Li response. Established approaches to Li response phenotyping are easy to use but may lead to a significant loss of data (excluding partial responders) due to recent attempts to improve the reliability of the original rating system. While machine learning approaches require additional modeling to generate Li response phenotypes, they may offer a more nuanced approach, which, in turn, would enhance the probability of identifying significant signals in genetic studies.

International audience; Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD. Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first). Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p

Background Suicide attempts (SA) are more frequent in bipolar disorder (BD) than in most other mental disorders. Prevention strategies would benefit from identifying the risk factors of SA recurrence in BD. Substance use disorders (SUD) (including tobacco-related) are strongly associated with both BD and SA, however, their specific role for the recurrence of SA in BD remains inadequately investigated. Thus, we tested if tobacco smoking - with or without other SUDs – was independently associated with recurrent SA in BD. Methods 916 patients from France and Norway with ascertained diagnoses of BD and reliable data about SA and SUD were classified as having no, single, or recurrent (≥2) SA. Five SUD groups were built according to the presence/absence/combination of tobacco, alcohol (AUD) and cannabis use disorders. Multinomial logistic regression was used to identify the correlates of SA recurrence. Results 338 (37%) individuals reported at least one SA, half of whom (173, 51%) reported recurrence. SUD comorbidity was: tobacco smoking only, 397 (43%), tobacco smoking with at least another SUD, 179 (20%). Regression analysis showed that tobacco smoking, both alone and comorbid with AUD, depressive polarity of BD onset and female gender were independently associated with recurrent SA. Limitations Lack of data regarding the relative courses of SA and SUD and cross-national differences in main variables. Conclusion Tobacco smoking with- or without additional SUD can be important risk factors of SA recurrence in BD, which is likely to inform both research and prevention strategies.

BACKGROUND: Tobacco smoking increases the global burden of bipolar disorder (BD). We examined markers of physical and mental health that are associated with tobacco smoking, controlling for confounders that have not always been considered in previous studies of BD. METHODS: Over 600 individuals with BD I or II referred to the French Network for bipolar disorder (FACE-BD) who completed standardized assessments, and could be reliably classified as current (CS) or former smokers (FS), were compared with those who were never smokers (NS) on: BD symptom load and psychiatric comorbidities; prevalence of alcohol and substance use disorders (ASUD); medication usage; functioning and physical health parameters. The bivariate and multivariate analyses took into account age and gender. RESULTS: 300 cases (49%) were CS, 78 (13%) FS and 238 (39%) had never smoked. Rates were similar across genders regardless of BD subtype. Compared with NS, CS were more likely to have an ASUD (Odds Ratio (OR) 5.18), BD I (OR 2.09), and lower abdominal obesity (OR 0.97), and FS were more likely to have an ASUD (OR 6.32) and higher abdominal obesity (OR 1.03). LIMITATIONS: The sample comprised of white Europeans; the FS subgroup was relatively small and we did not apply any statistical correction for the bivariate analyses. CONCLUSIONS: The increased risk of physical and mental health burden in CS and FS compared to NS represents avoidable morbidity in BD. This study offers support to the argument that individuals with BD should be routinely offered support to prevent or stop tobacco smoking.

Objectives We investigated the feasibility and acceptability of an integrated group therapy (called HABIT) for comorbid bipolar disorder (BD) and alcohol and substance use disorders (ASUD) (BD-ASUD), a disabling clinical presentation for which no specific treatment has been validated. The 14-session HABIT programme employs psychoeducation-oriented cognitive-behaviour therapy (CBT) followed by mindfulness-based relapse prevention (MBRP) therapy. Method Potential group participants were recruited from adult clients with a DSM-IV diagnosis of BD and an ASUD who were referred by their treating clinician. Observer-rated changes in mood symptoms and ASUD, attendance rates and subjective feedback are reported. Results Eight of 12 clients referred to the programme initially agreed to join the group, six attended the first group session and five clients completed the programme. Group mean scores for mood symptoms improved over time, with slightly greater reductions in depression during the first module. About 50% of individuals showed clinically significant improvement (≥30% reduction) in alcohol and substance use. Attendance rates showed some variability between individuals and across sessions, but the average attendance rate of the group was marginally higher for the first module (86%) as compared with the second module (77%). Most clients reported high levels of general satisfaction with a group specifically targeted at individuals with BD-ASUD. Conclusion This small pilot study suggests our intensive group therapy is acceptable and feasible. If findings are replicated, we may have identified a therapy that, for the first time, leads to improvement in both mood and substance use outcomes in clients with difficult-to-treat comorbid BD-ASUD. Copyright © 2016 John Wiley & Sons, Ltd. Key Practitioner Message Comorbidity between bipolar and alcohol and substance use disorders (BD-ASUD) is frequent and highly disabling; Therapeutic research on approaches that can simultaneously help BD and ASUD is lacking; Previous research highlights the need for integrated treatment of both conditions but showed improvements limited to either element of the comorbid disorder; This pilot study supports the feasibility and acceptability of an intensive, 14-session group therapy programme that integrates CBT and mindfulness approaches.

Major Depressive Disorder (MDD) is the 3rd source for burden worldwide according to the World Health Organization (WHO). This comes partly from unsatisfactory response rates after usual treatment, highlighting the need for early indicators such as early improvement of depressive symptoms to adapt treatment strategies, especially for severe inpatients. Thus our objective was to assess the predictive value of baseline partial resistance in early antidepressant response (EAR), hypothesizing that previous treatment failures would decrease the probability of early response.We included 122 consecutive inpatients with current unipolar MDE. The Mini-Neuropsychiatric Interview was used to ascertain DSM-IV diagnoses of MDD as well as psychiatric comorbidities, and to exclude patients with a history of bipolar disorder. A specifically designed questionnaire was used to collect data on previous treatment trials for the current episode so as to generate scores on the five existing methods for quantifying treatment resistance. We prospectively assessed EAR, defined as a 50% decrease in MADRS after 14 days of steady regimen of antidepressant.In the per protocol sample (N=76), multivariate analyses showed that psychotic features at baseline remained an independent predictor of absence of EAR (p.01), unlike baseline partial resistance, which may rather be associated with a lack of any improvement.Lack of data about further response and non-randomized treatment allocation.Available methods for quantifying treatment resistance are heterogeneous and do not predict short-term response among severely depressed inpatients, despite potential usefulness in predicting a lack of early improvement.

We investigated the feasibility and acceptability of an integrated group therapy (called HABIT) for comorbid bipolar disorder (BD) and alcohol and substance use disorders (ASUD) (BD-ASUD), a disabling clinical presentation for which no specific treatment has been validated. The 14-session HABIT programme employs psychoeducation-oriented cognitive-behaviour therapy (CBT) followed by mindfulness-based relapse prevention (MBRP) therapy.Potential group participants were recruited from adult clients with a DSM-IV diagnosis of BD and an ASUD who were referred by their treating clinician. Observer-rated changes in mood symptoms and ASUD, attendance rates and subjective feedback are reported.Eight of 12 clients referred to the programme initially agreed to join the group, six attended the first group session and five clients completed the programme. Group mean scores for mood symptoms improved over time, with slightly greater reductions in depression during the first module. About 50% of individuals showed clinically significant improvement (≥30% reduction) in alcohol and substance use. Attendance rates showed some variability between individuals and across sessions, but the average attendance rate of the group was marginally higher for the first module (86%) as compared with the second module (77%). Most clients reported high levels of general satisfaction with a group specifically targeted at individuals with BD-ASUD.This small pilot study suggests our intensive group therapy is acceptable and feasible. If findings are replicated, we may have identified a therapy that, for the first time, leads to improvement in both mood and substance use outcomes in clients with difficult-to-treat comorbid BD-ASUD. Copyright © 2016 John WileySons, Ltd. Key Practitioner Message Comorbidity between bipolar and alcohol and substance use disorders (BD-ASUD) is frequent and highly disabling; Therapeutic research on approaches that can simultaneously help BD and ASUD is lacking; Previous research highlights the need for integrated treatment of both conditions but showed improvements limited to either element of the comorbid disorder; This pilot study supports the feasibility and acceptability of an intensive, 14-session group therapy programme that integrates CBT and mindfulness approaches.

Bipolar disorder is a chronic, disabling, frequent and highly comorbid illness. It is often associated with addictive disorders (ADDs), another chronic and relapsing condition, with a lifetime prevalence three to five times higher than in the general population. However, knowledge is scarce about the possible mechanisms and the optimal treatment of this co-occurrence. Moreover, previous research has focused on separate ADDs, and few incidence data were available at the time. Our objective was, therefore, to evaluate the relevance of regrouping ADDs as classified in the preliminary version of the DSM-V in understanding the comorbidity of bipolar and ADDs.

Objective Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients. Methods A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses. Results In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=−5.60 95% CI=−7.65 to −3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant. Limitations Despite the multivariate approach, differences between the two samples may lead to spurious findings related to hidden confounders. Substance use and mood episode information was collected retrospectively, and potential birth cohort effects could not be controlled for. Conclusion Studies have found associations between tobacco smoking and poorer outcomes in BD. In this study on tobacco smoking BD patients we report an association between CUD and illness severity, suggesting that CUD exacerbates the disease evolution independently of tobacco smoking. Specific treatment and prevention programs addressing CUD in BD patients are warranted.

Introduction Bipolar disorder (BIPD) is a chronic and disabling illness with frequent comorbid addictive disorders (ADD). Little is known about the prevalence and correlates of cannabis use disorders (CUD) in that population. Objectives We sought to characterize clinical, sociodemographic, childhood trauma and psychological correlates associated with CUD in bipolar patients. Aims Our main hypothesis was that BIPD + CUD patients would be more impulsive and affectively unstable than those without. Methods Patients enrolled in a French national network underwent a thorough assessment including lifetime diagnoses using the SCID-IV questionnaire and measures of current symptomatology (Altman and MADRS), impulsivity (BIS-10), emotional instability (AIM and ALS), hostility (BDHI) and history of childhood trauma (CTQ). Univariate and multivariate analyses were used to identify specific associations between several correlates and CUD status. Results Among the 718 patients included, 414 (57.7%) were women, with a mean age of 43 years, and 546 (76.4%) were diagnosed with type I bipolar disorder and 190 (26.9%) had at least one lifetime substance use disorder. CUD were associated with lifetime history of suicidal behavior, psychotic symptoms during an affective episode, rapid cycling and CTQ sub-scores, clinical and psychological dimensions. Parts of these associations remained after controlling for comorbid alcohol use disorders. Conclusions These results suggest a high prevalence of CUD in BIPD, which was associated with a higher severity and worse outcomes of illness. Although the retrospective nature of this study prevents causal interpretations, our results suggest that at-risk traits among CUD+BIPD patients may induce these clinical features.