Autistic and Schizotypal Traits and Global Functioning in Bipolar I Disorder

Objective: To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar I disorder (BD-I), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD-I. Method: Autistic and positive schizotypal traits were self-assessed in 797 individuals with BD-I recruited by the Bipolar Disorder Research Network. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. Results: 47.2% (CI=43.7-50.7%) showed clinically significant levels of autistic traits, and 23.22% (95% CI=20.29-26.14) showed clinically significant levels of positive schizotypal traits. In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning compared to the other groups. Individual differences analyses showed that high levels of co-occurring traits were associated with better global functioning in both mood states. Limitations: Autistic and schizotypal traits were assessed using self-rated questionnaires. Conclusions: Expression of autistic and schizotypal traits in adults with BD-I is prevalent, and may be important to predict illness aetiology, prognosis, and diagnostic practices in this population. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits.

Autistic and Schizotypal Traits and Global Functioning in Bipolar Disorder

Background and Aims To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar disorder (BD), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD. Methods Autistic and positive schizotypal traits were assessed in 797 individuals with BD recruited by the Bipolar Disorder Research Network (BDRN), using the Autism-Spectrum Quotient and Kings Schizotypy Questionnaire (KSQ), respectively. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. Results 47.2% (CI = 43.7–50.7%) showed clinically significant levels of autistic traits. Mean of sample on the KSQ-Positive scale was 11.98 (95% CI: 11.33–12.62). In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning than the low autistic, low positive schizotypal group (mean difference = 3.72, p = 0.004). High levels of co-occurring traits were associated with better global functioning in both mood states in individuals with a history of psychosis (GASM: p < 0.001; GASD: p = 0.055). Conclusions Expression of autistic and schizotypal traits in adults with BD is prevalent, and may be important to predict course of illness, prognosis, and in devising individualised therapies. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits.

Genome-wide Association Study Identifies SESTD1 as a Novel Risk Gene for Lithium Responsive Bipolar Disorder

Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10-8). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.