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BACKGROUND: Serotonin 3A receptor (5-HT3A R) is associated at the genetic and epigenetic levels with a variety of psychiatric disorders and interacts with early-life stress such as childhood maltreatment. We studied the impact of childhood maltreatment on the methylation status of the 5-HT3A R and its association with clinical severity outcomes in relation with a functional genetic polymorphism. METHODS: Clinical severity indexes of 346 bipolar, borderline personality, and adult attention deficit hyperactivity disorders patients were tested for association with the DNA methylation status of eight 5-HT3A R gene CpGs. Relationship between the functional variant rs1062613 (C > T) and methylation status on severity of the disorders were also assessed. RESULTS: Childhood maltreatment was associated with higher severity of the disease (higher number of mood episodes, history of suicide attempts, hospitalization, and younger age at onset) across disorders and within each individual disorder. This effect was mediated by two 5-HT3A R CpGs. Compared to T allele carriers, CC carriers had higher methylation status at one CpG located 1 bp upstream of this variant. CONCLUSIONS: This study shows that epigenetic modification of the 5-HT3A R is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood. Language: en

BackgroundComorbidity of bipolar disorder and alcohol or substance abuse/dependence is frequent and has marked negative consequences on the course of the illness and treatment compliance. The objective of this study was to compare the validity of two short instruments aimed at screening bipolar disorders among patients treated for substance use disorders.MethodsThe Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32) were tested with reference to the mood section of the Structured Clinical Interview for DSM-IV axis I disorders (SCID) in 152 patients, recruited in two outpatient clinics providing specialized treatment for alcohol and opiate dependence.ResultsAccording to the SCID, 33 patients (21.7%) had a diagnosis within the bipolar spectrum (two bipolar I, 21 bipolar II and 10 bipolar not otherwise specified). The HCL-32 was more sensitive (90.9% vs. 66.7%) and the MDQ more specific (38.7% vs. 77.3%) for the whole sample. The MDQ displayed higher sensitivity and specificity in patients treated for alcohol than for opiate dependence, whereas the HCL-32 was highly sensitive but poorly specific in both samples. Both instruments had a positive predictive value under 50%.ConclusionsCaution is needed when using the MDQ and HCL-32 in patients treated for substance use disorders.

Mindfulness based therapies are nowadays widely spread. During the last decades, several approches and specific programs have been scientifically challenged and developped. In the field of addictions the Mindfulness Based Relapse Prevention is the main reference program. Within this frame, mindfulness increases the awarness regarding triggers and automatic behavior related to drug abuse. It also has a favorable impact when dealing with craving. Currently, the scientific research has come to promissing conclusions as far as craving and relapse prediction are concerned.

Background Validated Internet-based screening tools for cannabis use and abuse are needed. The present study aimed to establish equivalence between the previously validated Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) as a paper-and-pencil (PaP)-administered questionnaire and its online use. Methods Two groups of cannabis users took part in this study and the results were analyzed using structural equation modeling. One group consisted of 150 participants and was assessed with the ASSIST PaP questionnaire in a face-to-face interview (the PaP group). They were recruited from three settings: a primary health care outpatient clinic, a general psychiatric facility, and an ambulatory specialized addiction treatment facility. The other group (the Web group) comprised 1382 persons who answered the online version of the same questionnaire. This sample was drawn from people who naturalistically visited a website dedicated to helping people with cannabis addiction. Results The internal consistency was good for the online questionnaire (0.74) and high for the already validated PaP questionnaire (0.91). The Web group, however, had higher scores on cannabis use than did the PaP group. The results show support for configural invariance, meaning that the one-factor structure was preserved across groups, although measurement equivalence between these two survey modes was not achieved. However, when the Web group was split into two random subsamples, measurement invariance was demonstrated between them by cross-validation. Conclusions Measurement equivalence was not achieved between the two survey modes. Nonetheless, subanalyses of the Web group demonstrated that the cannabis screening questions of the ASSIST can be used for online screening. Differences in ASSIST scores between samples may be due to the sensitive nature of the information surveyed, with possible underreporting in face-to-face interviews, or to the different characteristics of the Web group because of the specialized nature of the website.

BackgroundEarly-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. This may be the consequence of a sustained alteration of the hypothalamic–pituitary–adrenal (HPA) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (NR3C1).AimsTo investigate whether severity of childhood maltreatment is associated with increased methylation of the exon? 1FNR3C1promoter in bipolar disorder.MethodA sample of people with bipolar disorder (n= 99) were assessed for childhood traumatic experiences. The percentage ofNR3C1methylation was measured for each participant.ResultsThe higher the number of trauma events, the higher was the percentage ofNR3C1methylation (β = 0.52, 95% CI 0.46–0.59,P

Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

Temperament is considered as a biological disposition reflected by relatively stable features related to mood and reactivity to external and internal stimuli, including variability in emotional reactions. The aim of the present study is to test the hypothesis that affective temperaments might differ according to co-occurring mood disorders among patients with alcohol and/or opiate dependence; to explore the relationship between temperaments and dual substance use disorders (SUDs, alcohol and other drugs). Ninety-two patients attending an alcohol addiction treatment facility and 47 patients in an opiate addiction treatment facility were assessed for SUDs, mood disorders and affective temperaments using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego 39-item auto-questionnaire. Comparison of patients with bipolar disorder, depressive unipolar disorder and no (or substance-induced) mood disorder revealed significant differences for the cyclothymic subscale, with highest scores among patients with bipolar disorder. No difference was observed for the depressive, irritable, hyperthymic and anxious subscales. After adjustment for age, gender and bipolar disorder, irritable temperament was a significant risk factor for past or present history of drug use disorders in patients treated for alcohol addiction (odds ratio [OR] 1.42, 95 % confidence interval [CI] 1.05–1.93). Anxious temperament was a significant risk factor for history of alcohol use disorders in patients treated for opiate addiction (OR 3.30, 95 % CI 1.36–7.99), whereas the hyperthymic subscale appeared as a significant protective factor (OR 0.65, 95 % CI 0.42–0.99). The results highlight the need to consider temperamental aspects in further research to improve the long-term outcome of patient with addictive disorders, who often present complex comorbidity patterns.

Background Substance use disorders seem to be an under considered health problem amongst the elderly. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), was developed by the World Health Organization to detect substance use disorders. The present study evaluates the psychometric properties of the French version of ASSIST in a sample of elderly people attending geriatric outpatient facilities (primary care or psychiatric facilities). Methods One hundred persons older than 65 years were recruited from clients attending a geriatric policlinic day care centre and from geriatric psychiatric facilities. Measures included ASSIST, Addiction Severity Index (ASI), Mini-International Neuropsychiatric Interview (MINI-Plus), Alcohol Use Disorders Identification Test (AUDIT), Revised Fagerstrom Tolerance Questionnaire-Smoking (RTQ) and MiniMental State(MMS). Results Concurrent validity was established with significant correlations between ASSIST scores, scores from ASI, AUDIT, RTQ, and significantly higher ASSIST scores for patients with a MINI-Plus diagnosis of abuse or dependence. The ASSIST questionnaire was found to have high internal consistency for the total substance involvement along with specific substance involvement as assessed by Cronbach’s α, ranging from 0.66, to 0.89 . Conclusions The findings demonstrate that ASSIST is a valid screening test for identifying substance use disorders in elderly.

Background: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was developed to detect substance use disorders. Aims: The objective of the present study was to evaluate the psychometric properties of the French version of ASSIST in various clinical groups with different levels of substance use. Methods: 150 subjects were recruited from clients attending primary health care, psychiatric and addiction treatment facilities. Measures included ASSIST, Addiction Severity Index (ASI), Mini-International Neuropsychiatric Interview (MINI-Plus), Alcohol Use Disorders Identification Test (AUDIT) and Revised Fagerstrom Tolerance Questionnaire-Smoking (RTQ). Results and Conclusion: Concurrent validity was demonstrated by significant correlations between ASSIST scores and scores from ASI, AUDIT and RTQ, as well as significantly greater ASSIST scores for patients with a MINI-Plus diagnosis of abuse or dependence. The ASSIST questionnaire was found to have high internal consistency for the total substance involvement as well as for specific substance involvement as assessed with Cronbach’s α, ranging from 0.74 to 0.93. When possibly computed, ASSIST cutoff scores have interesting sensitivity and specificity for discrimination between use and abuse and between abuse and dependence. The findings demonstrated that the French version of ASSIST is a valid screening test for identifying substance use disorders in various health care settings, including psychiatric settings.

BackgroundThe present open study investigates the feasibility of Mindfulness-based cognitive therapy (MBCT) in groups solely composed of bipolar patients of various subtypes. MBCT has been mostly evaluated with remitted unipolar depressed patients and little is known about this treatment in bipolar disorder.MethodsBipolar outpatients (type I, II and NOS) were included and evaluated for depressive and hypomanic symptoms, as well as mindfulness skills before and after MBCT. Patients’ expectations before the program, perceived benefit after completion and frequency of mindfulness practice were also recorded.ResultsOf 23 included patients, 15 attended at least four MBCT sessions. Most participants reported having durably, moderately to very much benefited from the program, although mindfulness practice decreased over time. Whereas no significant increase of mindfulness skills was detected during the trial, change of mindfulness skills was significantly associated with change of depressive symptoms between pre- and post-MBCT assessments.ConclusionsMBCT is feasible and well perceived among bipolar patients. Larger and randomized controlled studies are required to further evaluate its efficacy, in particular regarding depressive and (hypo)manic relapse prevention. The mediating role of mindfulness on clinical outcome needs further examination and efforts should be provided to enhance the persistence of meditation practice with time.