Affective dysregulation is a core feature of bipolar disorder (BD), and inter-episodic affect lability is associated with more severe outcomes including comorbidity. Rates of daily tobacco smoking and substance use disorders in BD are high. Knowledge regarding relationships between affective lability and abuse of the most commonly used substances such as tobacco, alcohol and cannabis in BD is limited.
We investigated whether dimensions of inter-episodic affective lability as measured with the Affective Lability Scale - short form (ALS-SF) were associated with lifetime daily tobacco use or alcohol (AUD) or cannabis use disorders (CUD) in a sample of 372 French and Norwegian patients with BD I and II.
ALS-SF total score and all sub-dimensions (anxiety-depression, depression-elation and anger) were significantly associated with AUD, while only the depression-elation sub-dimension was associated with CUD, after controlling for possible confounders such as gender, age at interview, age at illness onset, BD subtype, duration of illness and other substance use disorders. Daily tobacco smoking was not significantly associated with affective lability.
Data for recent substance use or psychiatric comorbidities such as personality or hyperkinetic disorders were not available, and could have mediated the relationships.
AUD is associated with several dimensions of inter-episodic affective lability in BD, while CUD is associated with increased oscillations between depression and elation only. Increased affective lability may partly explain the increased illness severity of patients with BD and AUD or CUD. Affective lability should be treated in order to prevent these comorbidities.
Beyond genetic risk variants, the pathophysiology of bipolar disorders is likely to be partly determined by environmental susceptibility factors. Our study is one of the first to investigate, in a large sample of well-characterized bipolar patients, associations between clinical presentations and childhood trauma subtypes, including neglect and abuse items.
587 patients with DSM-IV-defined bipolar disorder were recruited from France and Norway between 1996-2008 and 2007-2012, respectively. History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Clinical variables were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (Norwegian sample) or the Diagnostic Interview for Genetic Studies (French sample).
Earlier age at onset of bipolar illness, suicide attempts, rapid cycling, and an increased number of depressive episodes each had significant associations (P = .001) with at least 1 subtype of childhood trauma (emotional abuse, sexual abuse, and emotional neglect). Multivariate analyses investigating trauma variables together showed that both emotional and sexual abuse were independent predictors of lower age at onset (P = .002 for each) and history of suicide attempts (OR = 1.60 [95% CI, 1.07 to 2.39], P = .023; OR = 1.80 [95% CI, 1.14 to 2.86], P = .012, respectively), while sexual abuse was the strongest predictor of rapid cycling (OR = 2.04 [95% CI, 1.21 to 3.42], P = .007). Females reported overall higher childhood trauma frequency and greater associations to clinical expressions than males (P values
Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive-compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically-matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders.
Though genetic risk factors are important for the development of autism, no specific risk alleles have yet been identified. DOPA decarboxylase (DDC) is involved in both the catecholaminergic and serotonergic pathways and may be considered a functional candidate gene for autism. The present study is the first to test if two new variants of possible functional significance in the DDC gene increase the susceptibility to autism. A total of 90 parent-offspring trios recruited in Denmark and France were investigated using the transmission disequilibrium test (TDT). We found no evidence of linkage disequilibrium between autism and either of the two polymorphisms. Nor did we find linkage disequilibrium between autism and haplotypes of the two variants using a multiallelic TDT. These findings suggest that the DDC gene is unlikely to play a major role in the development of autism in our data set.
ECEVE, UMRS 1123, Université Paris Diderot, Sorbonne Paris Cité, INSERM, Paris, France; AP-HP, URC-Eco, DHU Pepsy, F-75004 Paris, France; Foundation FondaMental, French National Science Foundation, Créteil, France. Electronic address: firstname.lastname@example.org.
As part of the Roamer project, we aimed at revealing the share of health research budgets dedicated to mental health, as well as on the amounts allocated to such research for four European countries. Finland, France, Spain and the United Kingdom national public and non-profit funding allocated to mental health research in 2011 were investigated using, when possible, bottom-up approaches. Specifics of the data collection varied from country to country. The total amount of public and private not for profit mental health research funding for Finland, France, Spain and the UK was €10·2, €84·8, €16·8, and €127·6 million, respectively. Charities accounted for a quarter of the funding in the UK and less than six per cent elsewhere. The share of health research dedicated to mental health ranged from 4·0% in the UK to 9·7% in Finland. When compared to the DALY attributable to mental disorders, Spain, France, Finland, and the UK invested respectively €12·5, €31·2, €39·5, and €48·7 per DALY. Among these European countries, there is an important gap between the level of mental health research funding and the economic and epidemiologic burden of mental disorders.
BACKGROUND: It was recently reported that a rare functional variant, R441H, in the human tryptophan hydroxylase-2 gene (hTPH2) could represent an important risk factor for unipolar major depression (UP) since it was originally found in 10% of UP patients (vs. 1.4% in control subjects). METHODS: We explored the occurrence of this variation in patients with affective disorders (n = 646), autism spectrum disorders (n = 224), and obsessive-compulsive disorder (OCD) (n = 201); in healthy volunteers with no psychiatric disorders (n = 246); and in an ethnic panel of control individuals from North Africa, Sub-Saharan Africa, India, China, and Sweden (n = 277). RESULTS: Surprisingly, we did not observe the R441H variant in any of the individuals screened (3188 independent chromosomes). CONCLUSIONS: Our results do not confirm the role of the R441H mutation of the hTPH2 gene in the susceptibility to UP. The absence of the variant from a large cohort of psychiatric patients and control subjects suggests that the findings reported in the original study could be due to a genotyping error or to stratification of the initial population reported. Additional data by other groups should contribute to the clarification of the discrepancy between our results and those previous published.
The aim of this study was to investigate the psychometric properties of the original 54 item version (ALS-54) and the short 18 item version (ALS-18) of the Affective Lability Scale (ALS) in patients with bipolar disorders, their first-degree relatives and healthy controls. Internal Consistency and Confirmatory Factor Analysis were performed, comparing clinical and non-clinical group comparisons on ALS scores.
A total of 993 participants (patients with bipolar disorders [n=422], first-degree relatives [n=201] and controls [n=370]) were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I), or the Diagnostic Interview for Genetic Studies (DIGS). Affective lability was measured using the ALS-54 and ALS-18.
Both ALS-54 and ALS-18 showed high internal consistency, but the subdimensions of both versions were highly inter-correlated. From confirmatory factor analysis both versions revealed acceptable to good model fit. Patients had significantly higher ALS scores compared to controls, with affected first-degree relatives presenting intermediate scores.
Both the original ALS-54 version and the short ALS-18 version showed good psychometric properties. They also discriminated between patients with a bipolar disorder (high ALS), first degree relatives (intermediate ALS), and healthy controls (low ALS). A high correlation between ALS items for both versions was observed. Our study supports reducing the scale from 54 to 18 items.
Recent studies have highlighted the involvement of rare (15,000 controls (p = 0.009). The discovery of apparent reduced penetrance of ASD in females bearing inherited autosomal SHANK1 deletions provides a possible contributory model for the male gender bias in autism. The data are also informative for clinical-genetics interpretations of both inherited and sporadic forms of ASD involving SHANK1.