Stéphane Rothen

Major Depressive Disorder With Subthreshold Bipolarity in the National Comorbidity Survey Replication

OBJECTIVE There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R). METHOD The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organizations Composite International Diagnostic Interview. RESULTS Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypo-mania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical severity than those with bipolar II disorder. CONCLUSIONS These findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice.

Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts.

Major depressive disorder (MDD) is a highly prevalent disorder with substantial heritability. Heritability has been shown to be substantial and higher in the variant of MDD characterized by recurrent episodes of depression. Genetic studies have thus far failed to identify clear and consistent evidence of genetic risk factors for MDD. We conducted a genome-wide association study (GWAS) in two independent datasets. The first GWAS was performed on 1022 recurrent MDD patients and 1000 controls genotyped on the Illumina 550 platform. The second was conducted on 492 recurrent MDD patients and 1052 controls selected from a population-based collection, genotyped on the Affymetrix 5.0 platform. Neither GWAS identified any SNP that achieved GWAS significance. We obtained imputed genotypes at the Illumina loci for the individuals genotyped on the Affymetrix platform, and performed a meta-analysis of the two GWASs for this common set of approximately half a million SNPs. The meta-analysis did not yield genome-wide significant results either. The results from our study suggest that SNPs with substantial odds ratio are unlikely to exist for MDD, at least in our datasets and among the relatively common SNPs genotyped or tagged by the half-million-loci arrays. Meta-analysis of larger datasets is warranted to identify SNPs with smaller effects or with rarer allele frequencies that contribute to the risk of MDD.

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors

BackgroundThe Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as sociodemographic and somatic characteristics of the sample.MethodsAll 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was collected on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree relatives, whereas the collection of DNA and plasma samples was already part of the original CoLaus survey.ResultsA total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam.ConclusionDespite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders.

Cognitive behavioural therapy for weight gain associated with antipsychotic drugs

BACKGROUND Overweight and obesity are common concerns in individuals with severe mental disorders. In particular, antipsychotic drugs (AP) frequently induce weight gain. This phenomenon lacks current management and no previous controlled studies seem to use cognitive therapy to modify eating and weight-related cognitions. Moreover, none of these studies considered binge eating or eating and weight-related cognitions as possible outcomes. AIM The main aim of this study is to assess the effectivity of cognitive and behavioural treatment (CBT) on eating and weight-related cognitions, binge eating symptomatology and weight loss in patients who reported weight gain during AP treatment. METHOD A randomized controlled study (12-week CBT vs. Brief Nutritional Education) was carried out on 61 patients treated with an antipsychotic drug who reported weight gain following treatment. Binge eating symptomatology, eating and weight-related cognitions, as well as weight and body mass index were assessed before treatment, at 12 weeks and at 24 weeks. RESULTS The CBT group showed some improvement with respect to binge eating symptomatology and weight-related cognitions, whereas the control group did not. Weight loss occurred more progressively and was greater in the CBT group at 24 weeks. CONCLUSION The proposed CBT treatment is particularly interesting for patients suffering from weight gain associated with antipsychotic treatment.

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

Does Self-Selection Affect Samples’ Representativeness in Online Surveys? An Investigation in Online Video Game Research

Background The number of medical studies performed through online surveys has increased dramatically in recent years. Despite their numerous advantages (eg, sample size, facilitated access to individuals presenting stigmatizing issues), selection bias may exist in online surveys. However, evidence on the representativeness of self-selected samples in online studies is patchy. Objective Our objective was to explore the representativeness of a self-selected sample of online gamers using online players’ virtual characters (avatars). Methods All avatars belonged to individuals playing World of Warcraft (WoW), currently the most widely used online game. Avatars’ characteristics were defined using various games’ scores, reported on the WoW’s official website, and two self-selected samples from previous studies were compared with a randomly selected sample of avatars. Results We used scores linked to 1240 avatars (762 from the self-selected samples and 478 from the random sample). The two self-selected samples of avatars had higher scores on most of the assessed variables (except for guild membership and exploration). Furthermore, some guilds were overrepresented in the self-selected samples. Conclusions Our results suggest that more proficient players or players more involved in the game may be more likely to participate in online surveys. Caution is needed in the interpretation of studies based on online surveys that used a self-selection recruitment procedure. Epidemiological evidence on the reduced representativeness of sample of online surveys is warranted.

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.

Atypical depression and alcohol misuse are related to the cardiovascular risk in the general population

The aims of the present study were to assess the associations between mood, anxiety and substance use disorders, including their subtypes, and the prevalence of cardiovascular risk factors (CVRFs).

Inter-informant agreement on diagnoses and prevalence estimates of anxiety disorders: direct interview versus family history method.

The aims of the present study were to: (1) assess agreement for diagnoses of specific anxiety disorders between direct interviews and the family history method; (2) compare prevalence estimates according to direct interviews and family history information; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) test covariates of inter-informant agreement; and (5) test the likelihood of reporting disorders by informants. Analyses were based on family study data which included 1625 distinct informant (first-degree relatives and spouses)-index subject pairs. Our main findings were: (1) inter-informant agreement was satisfactory for panic disorder, agoraphobia, social phobia and obsessive-compulsive disorder; (2) the family history method provided lower prevalence estimates for all anxiety disorders (except for generalized anxiety disorder and obsessive-compulsive disorder) than direct interviews; (3) the lowering of diagnostic thresholds and the combination of multiple family history reports increased the accuracy of prevalence estimates according to the family history method; (4) female gender of index subjects was associated with poor agreement; and (5) informants, who themselves had a history of an anxiety disorder, were more likely to detect this disorder in their relatives which entails the risk of overestimation of the size of familial aggregation.

Personality traits in children of parents with unipolar and bipolar mood disorders

BACKGROUND Using family study data, the following questions regarding the mechanisms of association between personality traits and mood disorders were addressed: 1) Is there an association between unipolar and bipolar mood disorders and personality traits in probands? 2) Are personality traits associated with depression in their 9 to 17 year-old children? 3) Is there an association between parental mood disorders and personality traits in offspring? 4) Are parental personality traits associated with the risk of depression in offspring? METHODS The study included 50 probands with bipolar and 37 with unipolar mood disorder, 34 healthy controls as well as 178 of their children between 9 and 17 years. Diagnoses were made according to a best-estimate procedure based on a semi-structured interview (DIGS), medical records and family history information. Personality traits were assessed using the Eysenck Personality Questionnaire in adults and the Eysenck Personality Questionnaire Junior in offspring. RESULTS Personality traits, and in particular Neuroticism, were found to be associated with mood disorders in currently affected as well as remitted probands and offspring. However, there was no association between mood disorders in parents and personality traits in their children, and conversely, parental personality traits were not associated with the risk of depression in offspring. LIMITATIONS 1) Relatively small proportion of offspring who were still unaffected but likely to subsequently develop mood disorders; 2) cross-sectional design. CONCLUSIONS The findings were best compatible with the complication or scar hypothesis, which assumes the occurrence of abnormal personality traits as a consequence of previous depressive episodes.