Gender moderates the relationship between mania spectrum and serotonin transporter polymorphisms in depression

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 150B; no. 7; pp. 907 - 913
• Main Authors: Rucci, P., Nimgaonkar, V.L., Mansour, H., Miniati, M., Masala, I., Fagiolini, A., Cassano, G.B., Frank, E.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05.10.2009; Wiley-Liss
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aged; Biological and medical sciences; Bipolar Disorder - complications; Bipolar Disorder - genetics; Demography; Depression; Depression - complications; Depression - genetics; Female; gender; Gene Frequency; Genotype; Humans; hypomania; Linkage Disequilibrium - genetics; Male; Mania; Medical genetics; Medical sciences; Middle Aged; Miscellaneous; Mood disorders; mood spectrum; Polymorphism, Single Nucleotide - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Serotonin Plasma Membrane Transport Proteins - genetics; serotonin transporter polymorphisms; Sex Characteristics; Young Adult; Mood disorder; Affect affectivity; Serotonin; gender; Biological transport; mood spectrum; Sex; Depression; Spectrum; Neurotransmitter; Mania; serotonin transporter polymorphisms; Hypomania; Polymorphism
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30917

The short (s) variant of the serotonin transporter gene linked functional polymorphic region (5‐HTTLPR) is associated with depression. Stressful life events, gender, and race have been shown to moderate this association. Because features of mania/hypomania seem to constitute an indicator of higher severity of depression, we examined the relationship between 5‐HTTLPR genotype and symptoms of mania‐hypomania spectrum occurring over the lifetime in patients with major depression. The possible moderating role of gender in this relationship was taken into account. Two hundred twenty‐two patients with unipolar major depression were genotyped for 5‐HTTLPR and nine other representative polymorphisms, and were administered the Mood Spectrum Questionnaire, Lifetime Version (MOODS‐SR). The manic‐hypomanic (MH) component score was used for analysis. Using a linear model of the MH score as a function of genotypes and gender, controlling for age, severity of depression, and site, we found significant effects of gender (F = 8.003, df = 1, P = 0.005), of the interaction gender × genotype (F = 4.505, df = 2, P = 0.012), and of the baseline Hamilton score (F = 5.404, df = 1, P = 0.021), non‐significant effects of genotype (F = 1.298, df = 2, P = 0.275), age (F = 0.310, df = 1, P = 0.578) site (F = 0.504, df = 1, P = 0.479). Significant associations were also detected at three other SNPs. The association between the manic/hypomanic component of the MOODS‐SR and the polymorphisms of the 5‐HTTLPR is moderated by gender. This finding is intriguing from a clinical point of view because women with unipolar disorder and the “ss” genotype seem to constitute a sub‐group with higher severity of depression. These results should be considered tentative pending replication in other samples. © 2009 Wiley‐Liss, Inc.