François Ferrero

Diagnostic interview for genetic studies (DIGS): inter-rater and test-retest reliability of the French version

Abstract The National Institute of Mental Health developed the semi-structured Diagnostic Interview for Genetic Studies (DIGS) for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS was translated into French in a collaborative effort of investigators from sites in France and Switzerland. Inter-rater and test-retest reliability of the French version have been established in a clinical sample in Lausanne. Excellent inter-rater reliability was found for schizophrenia, bipolar disorder, major depression, and unipolar schizoaffective disorder while fair inter-rater reliability was demonstrated for bipolar schizoaffective disorder. Using a six-week test-retest interval, reliability for all diagnoses was found to be fair to good with the exception of bipolar schizoaffective disorder. The lower test-retest reliability was the result of a relatively long test-retest interval that favored incomplete symptom recall. In order to increase reliability for lifetime diagnoses in persons not currently affected, best-estimate procedures using additional sources of diagnostic information such as medical records and reports from relatives should supplement DIGS information in family-genetic studies. Within such a procedure, the DIGS appears to be a useful part of data collection for genetic studies on major mood disorders and schizophrenia in French-speaking populations.

Prevalence estimates of pathological gambling in Switzerland

Objective: The purpose of this study was to evaluate the prevalence of pathological gambling in the Swiss adult population before the introduction of new forms of gambling, and the link between pathological gambling and alcohol abuse.

Prevalence of pathological gambling in Switzerland after the opening of casinos and the introduction of new preventive legislation

Objective: This survey aimed to evaluate the prevalence of pathological gambling (PG) in the Swiss population in 2005 and the link between PG and alcohol abuse. This replication study made it possible to compare the prevalence rates of PG measured before and after the introduction of casinos and new preventive legislation.

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non-parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (AAO of 21 years or below). Non-parametric multipoint analysis suggested eight regions of linkage with P-values<0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide P-value estimated over 10 000 simulated replicates of 0.015 [0.01–0.02]). After genome-wide search analysis, we performed additional linkage analyses with increased marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non-parametric linkage score increased from 3.51 to 3.83. This study is the first to use early-onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families.

Diagnostic interview for genetic studies (DIGS): inter-rater and test-retest reliability of alcohol and drug diagnoses.

The semi-structured diagnostic interview for genetic studies (DIGS) was developed to assess major mood and psychotic disorders and their spectrum manifestations in genetic studies. Our research group developed a French version of the DIGS and tested its inter-rater and test-retest reliability in psychiatric patients. In this article, we present estimates of the reliability of substance use and antisocial personality disorders. High kappa coefficients for inter-rater reliability were found for drug and alcohol as well as antisocial personality diagnoses and slightly lower kappas for test-retest reliability. Combined with evidence of the reliability of major mood and psychotic disorders, these findings support the suitability of the DIGS for studies of familial aggregation and comorbidity of psychiatric disorders including substance use and antisocial personality disorders.

Parent-child agreement and prevalence estimates of diagnoses in childhood: direct interview versus family history method.

Diagnostic information on children is typically elicited from both children and their parents. The aims of the present paper were to: (1) compare prevalence estimates according to maternal reports, paternal reports and direct interviews of children [major depressive disorder (MDD), anxiety and attention‐deficit and disruptive behavioural disorders]; (2) assess mother–child, father–child and inter‐parental agreement for these disorders; (3) determine the association between several child, parent and familial characteristics and the degree of diagnostic agreement or the likelihood of parental reporting; (4) determine the predictive validity of diagnostic information provided by parents and children. Analyses were based on 235 mother–offspring, 189 father–offspring and 128 mother–father pairs. Diagnostic assessment included the Kiddie‐schedule for Affective Disorders and Schizophrenia (K‐SADS) (offspring) and the Diagnostic Interview for Genetic Studies (DIGS) (parents and offspring at follow‐up) interviews. Parental reports were collected using the Family History – Research Diagnostic Criteria (FH‐RDC). Analyses revealed: (1) prevalence estimates for internalizing disorders were generally lower according to parental information than according to the K‐SADS; (2) mother–child and father–child agreement was poor and within similar ranges; (3) parents with a history of MDD or attention deficit hyperactivity disorder (ADHD) reported these disorders in their children more frequently; (4) in a sub‐sample followed‐up into adulthood, diagnoses of MDD, separation anxiety and conduct disorder at baseline concurred with the corresponding lifetime diagnosis at age 19 according to the child rather than according to the parents. In conclusion, our findings support large discrepancies of diagnostic information provided by parents and children with generally lower reporting of internalizing disorders by parents, and differential reporting of depression and ADHD by parental disease status. Follow‐up data also supports the validity of information provided by adolescent offspring. Copyright

Ultra-rapid opiate detoxification using deep sedation with oral midazolam: short and long-term results

The present study describes an ultra-rapid opiate detoxification method using direct transition from heroin or methadone to oral naltrexone after deep sedation with oral midazolam in conjunction with ondansetron and clonidine treatment. Twenty patients were detoxified with the method. No serious events occurred, but two out of three patients vomited during the acute phase of deep sedation, which involves some risks. Withdrawal symptoms were still present 24 h after detoxification and 80% of the patients relapsed during a 6-month follow-up.

Mental disorders in offspring of parents with bipolar and major depressive disorders

Vandeleur C, Rothen S, Gholam‐Rezaee M, Castelao E, Vidal S, Favre S, Ferrero F, Halfon O, Fumeaux P, Merikangas KR, Aubry J‐M, Burstein M, Preisig M. Mental disorders in offspring of parents with bipolar and major depressive disorders. Bipolar Disord 2012: 14: 641–653.

Levels and Determinants of Inflammatory Biomarkers in a Swiss Population-Based Sample (CoLaus Study)

Objective to assess the levels and determinants of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) in a healthy Caucasian population. Methods population sample of 2884 men and 3201 women aged 35 to 75. IL-1β, IL-6 and TNF-α were assessed by a multiplexed particle-based flow cytometric assay and CRP by an immunometric assay. Results Spearman rank correlations between duplicate cytokine measurements (N = 80) ranged between 0.89 and 0.96; intra-class correlation coefficients ranged between 0.94 and 0.97, indicating good reproducibility. Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. Median (interquartile range) for participants with detectable values were 1.17 (0.48–3.90) pg/ml for IL-1β; 1.47 (0.71–3.53) pg/ml for IL-6; 2.89 (1.82–4.53) pg/ml for TNF-α and 1.3 (0.6–2.7) ng/ml for CRP. On multivariate analysis, greater age was the only factor inversely associated with IL-1β levels. Male sex, increased BMI and smoking were associated with greater IL-6 levels, while no relationship was found for age and leisure-time PA. Male sex, greater age, increased BMI and current smoking were associated with greater TNF-α levels, while no relationship was found with leisure-time PA. CRP levels were positively related to age, BMI and smoking, and inversely to male sex and physical activity. Conclusion Population-based levels of several cytokines were established. Increased age and BMI, and to a lesser degree sex and smoking, significantly and differentially impact cytokine levels, while leisure-time physical activity has little effect.

Monoamine Oxidase A and Tryptophan Hydroxylase Gene Polymorphisms

Most of the candidate gene studies in bipolar disorder have focused on the major neurotransmitter systems that are influenced by drugs used in the treatment of this disorder. The monoamine oxidase A (MAOA) and the tryptophan hydroxylase (TPH1, TPH2) genes are two of the candidates that have been tested in a series of association studies using unrelated or family-based controls. This review summarizes the existing association studies regarding these genes. Most of these studies were based on the unrelated case-control design with samples of 50 to 600 subjects. Regarding MAOA, three meta-analyses with partially overlapping samples supported a modest effect of this gene in bipolar disorder in female Caucasians. However, as several studies could not replicate these findings, more work is necessary to demonstrate unequivocally the involvement of MAOA in bipolar disorder and establish the biological mechanism underlying the genetic association. With respect to TPH1 and TPH2, the majority of studies did not provide evidence for an association between these genes and bipolar disorder. The genes are more likely to be related to suicidal behavior than to bipolar disorder.