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Poststroke depression and 5-HTTLPR
  1. Filippo Queirazza,
  2. Jonathan Cavanagh
  1. IHW, University of Glasgow, Southern General Hospital, Glasgow, UK
  1. Correspondence to Dr Jonathan Cavanagh, IHW, University of Glasgow, Southern General Hospital, Glasgow G51 4TF, UK; jonathan.cavanagh{at}

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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 …

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  • Contributors Both authors have contributed equally.

  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.

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