Audrey Nallet

Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder

BACKGROUND Early-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). AIMS To investigate whether severity of childhood maltreatment is associated with increased methylation of the exon 1F NR3C1 promoter in bipolar disorder. METHOD A sample of people with bipolar disorder (n = 99) were assessed for childhood traumatic experiences. The percentage of NR3C1 methylation was measured for each participant. RESULTS The higher the number of trauma events, the higher was the percentage of NR3C1 methylation (β = 0.52, 95% CI 0.46-0.59, P<<0.0001). The severity of each type of maltreatment (sexual, physical and emotional) was also associated with NR3C1 methylation status. CONCLUSIONS Early-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood. This enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder.

Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

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 (κ)] 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 (κ = 0.66 and κ = 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 (ICC1 = 0.71 and ICC2 = 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.

METHYLATION OF SEROTONIN RECEPTOR 3A IN ADHD, BORDERLINE PERSONALITY, AND BIPOLAR DISORDERS: LINK WITH SEVERITY OF THE DISORDERS AND CHILDHOOD MALTREATMENT

Serotonin 3A receptor (5‐HT3AR) 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‐HT3AR and its association with clinical severity outcomes in relation with a functional genetic polymorphism.

Validation of the French version of the alcohol, smoking and substance involvement screening test (ASSIST)

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.

Validation of the French version of the alcohol, smoking and substance involvement screening test (ASSIST) in the elderly

BackgroundSubstance 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).MethodsOne 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).ResultsConcurrent 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 .ConclusionsThe findings demonstrate that ASSIST is a valid screening test for identifying substance use disorders in elderly.

Screening for bipolar disorder among outpatients with substance use disorders

BACKGROUND Comorbidity 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. METHODS The 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. RESULTS According 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%. CONCLUSIONS Caution is needed when using the MDQ and HCL-32 in patients treated for substance use disorders.

Internal consistency and measurement equivalence of the cannabis screening questions on the paper-and-pencil face-to-face ASSIST versus the online instrument

BackgroundValidated 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.MethodsTwo 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.ResultsThe 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.ConclusionsMeasurement 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.