Short sleep as an environmental exposure: a preliminary study associating 5-HTTLPR genotype to self-reported sleep duration and depressed mood in first-year university students

Objectives: This study examined whether the 5-HTTLPR polymorphism in the SLC6A4 gene is associated with self-reported symptoms of depressed mood in first-year university students with a persistent pattern of short sleep.

Design: Students provided DNA samples and completed on-line sleep diaries and a mood scale during the first semester. A priori phenotypes for nocturnal sleep and mood scores were compared for the distribution of genotypes.

Setting: Brown University, Providence, Rhode Island.

Participants: A sample of 135 first-year students, 54 male, 71 Caucasian, mean age 18.1 (± 0.5) yr.

Interventions: None.

Measurements: Students completed on-line sleep diaries daily across the first term (21-64 days; mean = 51 days ± 11) and Center for Epidemiologic Studies-Depression (CES-D) mood scale after 8 wk. DNA was genotyped for the triallelic 5-HTTLPR polymorphism. Low-expressing S and L(G)polymorphisms were designated S', and high-expressing L(A) was designated L'. Phenotype groups were identified from a combination of CES-D (median split: high > 12; low < 13) and mean nocturnal total sleep time (TST) from diaries: (shorter ≤ 7 hr; longer ≥ 7.5 hr). Three genotypes were identified (S'S', S'L', L'L'); the S'S' genotype was present in a higher proportion of Asian than non-Asian students.

Results: FOUR PHENOTYPE GROUPS WERE COMPARED: 40 students with shorter TST/high CES-D; 34 with shorter TST/low CES-D; 29 with longer TST/high CES-D; 32 with longer TST/low CES-D. Female:male distribution did not vary across phenotype groups (chi-square = 1.39; df = 3; P = 0.71). S'S' participants (n = 23) were overrepresented in the shorter TST/high CES-D group (chi- square = 15.04; df = 6; P < 0.02). This association was sustained after removing participants with preexisting evidence of depressed mood (chi-square = 12.90; df = 6; P = 0.045).

Conclusion: These data indicate that young adults who reported shorter nocturnal sleep and higher depressed mood are more likely than others to carry a variant of the SLC6A4 gene associated with low expression of the serotonin transporter.