The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality

Background. Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case–control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD. Method. One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets. Results. No association between 5-HTTLPR and SAD was found in the new case–control material, in the combined analysis of all samples, or when only including 316 patients with controls (N=298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2·24 (1·03–4·91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set. Conclusions. These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.

[1]  A. Korten,et al.  An association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms , 1998, Molecular Psychiatry.

[2]  R. Murray,et al.  A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. , 1996, Molecular psychiatry.

[3]  L. Nyberg,et al.  Betula: A Prospective Cohort Study on Memory, Health and Aging , 2004 .

[4]  D. Goldman,et al.  The role of genetic factors in the etiology of seasonal affective disorder and seasonality. , 1999, Journal of affective disorders.

[5]  Kurt Hornik,et al.  No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism , 2001, Biological Psychiatry.

[6]  K. Lesch,et al.  Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region , 1996, Science.

[7]  N J Cox,et al.  Evidence of linkage between the serotonin transporter and autistic disorder , 1997, Molecular Psychiatry.

[8]  D. Murphy,et al.  Seasonality associated with the serotonin transporter promoter repeat length polymorphism. , 1999, The American journal of psychiatry.

[9]  D Winkler,et al.  A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder , 2003, Molecular Psychiatry.

[10]  D. Murphy,et al.  Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder , 1999, Molecular Psychiatry.

[11]  T. Paunio,et al.  Seasonal Affective Disorder and Serotonin-Related Polymorphisms , 2001, Neurobiology of Disease.

[12]  A C Heath,et al.  Seasonal changes in mood and behavior. The role of genetic factors. , 1996, Archives of general psychiatry.

[13]  D. Goldman,et al.  Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder , 1998, Molecular Psychiatry.

[14]  W. Ewens,et al.  Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). , 1993, American journal of human genetics.

[15]  J. Terwilliger,et al.  A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. , 1992, Human heredity.

[16]  Andreas Heinz,et al.  A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity , 2000, Biological Psychiatry.

[17]  P. Vernon,et al.  Gender differences in the heritability of seasonal mood change , 1997, Psychiatry Research.

[18]  U. Lahaie,et al.  Seasonal Affective Disorder , 1986, British Journal of Psychiatry.

[19]  F. Goodwin,et al.  Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. , 1984, Archives of general psychiatry.

[20]  Jeanine J. Houwing-Duistermaat,et al.  Power of Selective Genotyping in Genetic Association Analyses of Quantitative Traits , 2000, Behavior genetics.

[21]  Alexander Neumeister,et al.  [123I]-β-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder , 2000, Biological Psychiatry.

[22]  K. Hornik,et al.  Role of family history and 5-HTTLPR polymorphism in female seasonal affective disorder patients with and without premenstrual dysphoric disorder , 2002, European Neuropsychopharmacology.