Molecular epidemiology of major depressive disorder

Abstract

Major depressive disorder causes significant morbidity, affecting people's ability to work, function in relationships, and engage in social activities. Moreover, major depressive disorder increases the risk of suicidal ideation, attempted suicide and death by completed suicide. There is evidence that chronic stress can cause major depressive disorder. As for genetic factors, only minor susceptibility genes have been reliably identified. The serotonin system provides a logical source of susceptibility genes for depression, because this system is the target of selective serotonin reuptake-inhibitor drugs that are effective in treating depression. The 5-hydroxytryptamine (serotonin) transporter (5-HTT) has received particular attention because it is involved in the reuptake of serotonin at brain synapses. One common polymorphic variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which affects the promoter of the 5-HTT gene, causes reduced uptake of the neurotransmitter serotonin into the presynaptic cells in the brain. The authors discussed the relationship between genetic polymorphisms and major depressive disorder, with special emphasis on the 5-HTTTLPR polymorphism. As the 5-HTTLPR polymorphism was significantly associated with an increased risk of major depressive disorder, the 5-HTT gene may be a candidate for a major depressive disorder susceptibility gene. As major depressive disorder is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for major depressive disorder. Hopefully, in the future we will be able to screen for major depressive disorder susceptibility by using specific biomarkers.

Fig. 1

The S allele frequency of 21 Caucasian populations and three Asian populations among controls. The center of a box and the horizontal line (logarithm) indicate the prevalence and the 95% confidence interval (CI) in each study, with the areas of the boxes representing the weight of each study. The summary ORs of Caucasians and Asians based on the random effects model are 42.5% (95% CI = 40.8–44.2) and 76.8% (95% CI = 73.9–79.7), respectively. The summary OR is shown by the dotted vertical line. Statistical heterogeneity between studies among Caucasians and Asians were assessed as Q = 43.7, p = 0.002 and Q = 2.60, p = 0.27), respectively, by Cochran’s Q test

Fig. 2

Meta-analysis of the 5-HTTLPR and major depressive disorder according to DSM IV among 17 Caucasian populations. The center of a box and the horizontal line (logarithm) indicate the odds ratio (OR) and the 95% confidence interval (CI) in each study, with the areas of the boxes representing the weight of each study. The summary OR based on the random effects model is represented by the middle of a diamond whose width indicates the 95% CI. The summary OR is shown by the dotted vertical line. Statistical heterogeneity between studies was assessed with Cochran’s Q test (Q = 12.1, p = 0.74). Summary OR = 1.31 (95% CI = 1.14–1.52). SS + LS versus LL