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Gene-Temperament Interactions Might Distinguish Between Bipolar I and Bipolar II Disorders: A Cross-Sectional Survey of Han Chinese in Taiwan

J Clin Psychiatry 2012;73(3):339-345
10.4088/JCP.10m06330

Background: Whether bipolar II disorder is a distinct disorder or simply a milder form of bipolar I disorder has been debated. Family, twin, and adoption studies provide robust evidence of genetic contributions to bipolar disorder, and heritable temperaments are also believed to contribute to the susceptibility to bipolar disorders. In this study, we sought to clarify the relationship between bipolar I and bipolar II disorder.

Method: In this cross-sectional survey, 314 participants (82 bipolar I disorder patients, 121 bipolar II disorder patients, and 111 healthy controls) completed the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Tridimensional Personality Questionnaire, which assessed the personality dimensions of novelty seeking and harm avoidance. We also determined which participants carried the serine-to-glycine substitution at amino acid position 9 polymorphism of the dopamine D3 receptor gene (DRD3) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) genotypes. All patients met the DSM-IV-TR diagnosis criteria for bipolar disorder. This study was conducted from September 2005 to July 2009 at National Cheng Kung University Hospital, Tainan, Taiwan, and Tri-Service General Hospital, Taipei, Taiwan.

Results: Binary logistic regression analysis showed significant main effects for the 5-HTTLPR polymorphism (P = .045), novelty seeking (P = .022), and harm avoidance (P = .017) scores and a significant interaction effect between harm avoidance and 5-HTTLPR genotypes (P = .042) in distinguishing between bipolar I and bipolar II disorder patients. Bipolar I disorder patients with the long allele at 5-HTTLPR had lower harm avoidance scores than did bipolar II disorder patients (bipolar I disorder = 16.23, bipolar II disorder = 19.80; P = .023); however, the difference was not significant after multiple test correction. All these data suggest a distinction between bipolar I and bipolar II disorder.

Conclusions: We provide initial evidence that 5-HTTLPR genotypes might moderate the association between harm avoidance and bipolar I and bipolar II disorder. There appear to be unique differences in the gene-temperament interactions of bipolar I and bipolar II disorder patients.

J Clin Psychiatry, 2012; 73(3):333-338