The International Journal of Neuropsychopharmacology

Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene

Rickard L. Sjöberg a1c1, Kent W. Nilsson a1, Niklas Nordquist a2, John Öhrvik a1, Jerzy Leppert a1, Leif Lindström a1 and Lars Oreland a2
a1 Centre for Clinical Research, Uppsala University, Central Hospital Västerås, Västerås, Sweden
a2 Department of Neuroscience, Unit of Pharmacology, Uppsala University, Uppsala, Sweden

Article author query
sjoberg rl   [PubMed][Google Scholar] 
nilsson kw   [PubMed][Google Scholar] 
nordquist n   [PubMed][Google Scholar] 
ohrvik j   [PubMed][Google Scholar] 
leppert j   [PubMed][Google Scholar] 
lindstrom l   [PubMed][Google Scholar] 
oreland l   [PubMed][Google Scholar] 


Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16–19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls.

(Received March 1 2005)
(Revised April 9 2005)
(Revised June 9 2005)
(Accepted June 9 2005)
(Published Online September 15 2005)

Key Words: Depression; gene–environment interaction; genotype; phenotype; sex characteristics.

c1 Centre for Clinical Research, Central Hospital Västerås, S-721 89 Västerås, Sweden. Tel.: +46 21 173254 Fax: +46 21 173733 E-mail: