Mental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden

Abstract

Previous studies have yielded conflicting results as to the putative role of the functional polymorphism of the promoter region of the serotonin transporter gene (SLC6A4) in the etiology of anxiety-related traits and depressive disorders. Recently, a significant geneenvironment interaction was found between life stressors, the short allele of the SLC6A4 polymorphism and depression. The aim of the present study was to investigate if such a geneenvironment interaction could be replicated within a different population with a different risk structure. A total of 1005 subjects from a general population sample (Study of Health in Pomerania) were genotyped. Mental and physical distress were assessed on 38 items of the modified complaint scale (BL-38). The interaction between the SLC6A4 genotype, social stressors and chronic diseases with regard to the BL-38 score was evaluated by ANOVA. There was no independent association of genotype with mental and physical distress. However, significant interactions between genotype, unemployment and chronic diseases (F ¼ 6.6; df ¼ 3, 671; Po0.001) were found in females but not in males. The genotype explained 2% of the total variance of the BL-38 score and 9.1% of the explained variance. The results partly confirm previous findings of a significant gene-environment interaction of the short allele, indicating a higher mental vulnerability to social stressors and chronic diseases. The relevance of this finding is sustained by the fact that the sample characteristics and the risk structure were highly different from previous studies. Molecular Psychiatry (2005) 10, 220-224.

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

“…Even in a study where positive results were reported separately for both genders, the G Â E was stronger in females. 15 Of the four studies with predominantly middle-aged to elderly samples, two showed no evidence of interaction with the non-significant interaction signs pointing in the opposite direction; 44,45 one identified an interaction in the expected direction for female participants only, 41 and one in the whole sample after correcting for gender. 32 The observed pattern of variation by age and gender is likely to reflect several interacting factors.…”

“…48 Six studies were cross-sectional surveys. 30,31,34,37,39,41,45 One study used a combined cohort/case-control design, selecting participants with extreme scores on either environmental adversity or depression for genotyping. 40 One study examined individuals exposed to a major stressor (myocardial infarction).…”

“…However, no such direct association was reported in the older samples. 32,41,44,45 Therefore, the alternative explanation should be considered that the 5-HTTLPR genotype-mediated vulnerability operates in a developmental period comprising young adulthood.…”

“…32 Some authors assumed a dominant s based on an early 5-HTT expression study and did not report results separately for heterozygotes. 41 On the other hand, Kendler and colleagues 15 found that a model with recessive s (that is with ll and ls combined) provided best fit to their data and at least one other study showed results consistent with recessive s. 34 Results from child and adolescent samples place heterozygotes intermediate but close to ll homozygotes, suggesting a predominantly recessive s effect for early-onset depression. 30,40,42 When multiple outcomes were considered within one sample, a co-dominant effect was shown for the more common outcome of alcohol abuse, but a recessive s effect was apparent for the less common illicit drug use.…”

“…Taken at face value, there were eleven replications, 15,[29][30][31][32][33][34][35][36][37][38][39] three partial replications in females only, [40][41][42] and three non-replications. [43][44][45] Importantly, two studies with very large samples were negative.…”