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Poststroke depression and 5-HTTLPR
Subsequent to the seminal paper in 2003 by Caspi et al,1 who reported that a 44 base pair insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTT) gene (SLC6A4) moderated the relationship between stressful life events (SLEs) and depression, over 50 studies have sought to replicate this specific gene-environment interaction. In Caspi et al's original work, carriers of the short (s), transcriptionally less active, allele of a common genetic variant often referred to as the 5-HTT-linked polymorphic region (5-HTTLPR) exhibited more depressive symptoms and suicidality in response to environmental adversity and childhood maltreatment.
Poststroke depression (PSD) has been estimated to affect at least 30% of stroke survivors at any time during follow-up.2 PSD has been linked to clinically adverse outcomes such as increased mortality3 and poorer long-term functional recovery.4 The pathogenesis of PSD still remains undetermined. Various lines of evidence suggested that 5-HTTLPR polymorphism may be implicated in PSD. The association of PSD with abnormalities in central serotonergic responsiveness5 and the fundamental role of 5-HTT gene expression in regulating serotonergic signalling6 led to the hypothesis that the moderating effect of 5-HTT functional polymorphism on a major life event like stroke may be critical to the development of PSD. Subsequent findings confirmed this early hypothesis.7 and even indicated an association with other 5-HTT polymorphisms such as the variable number of tandem repeats in the second intron 2.8
In a recent issue of this journal, a meta-analysis of four studies reported a positive and significant association between the 5-HTTLPR short variant genotype and PSD. No effect was observed for other 5-HTTLPR polymorphisms such as the single-nucleotide polymorphism rs 25531 and variable number of tandem repeats in the second intron 2.9 Unfortunately the lack of consistent measures of environmental adversity …
Contributors Both authors have contributed equally.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.