Polymorphisms in BDNF (Va166Met) and 5-HTTLPR, morning cortisol and subsequent depression in at-risk adolescents


Goodyer, IM; Croudace, T; Dudbridge, F; Ban, M; Herbert, J; (2010) Polymorphisms in BDNF (Va166Met) and 5-HTTLPR, morning cortisol and subsequent depression in at-risk adolescents. The British journal of psychiatry, 197 (5). pp. 365-371. ISSN 0007-1250 DOI: https://doi.org/10.1192/bjp.bp.110.077750

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Abstract

Background There is increasing evidence for genetic effects on the hypothalamic-pituitary axis system. More than one gene is likely to moderate corticoid-mediated activity. Aims To investigate whether the brain-derived neurotrophic factor (BONE) polymorphism (rs6265, Va166Met) is associated with morning waking salivary cortisol and moderates the corticoid-mediated risk for subsequent depressive episode onset independently of the known effects of 5-HTTLPR (the serotonin transporter gene promoter). Method High-risk adolescents (n = 401) were genotyped for Va166Met BONE and 5-HTTLPR. Salivary samples were obtained on four consecutive school days within 1 h of waking. There were 365 (91%) remaining participants reassessed at 12 months for episodes of psychiatric disorder in the follow-up period. Of these, 357 (89%) had complete data for multivariate modelling. Results There were 41 (11.2%) individuals who reported a new episode of clinical depression over the follow-up period. Increased risk for subsequent depression was found in carriers of the Val66Val genotype in BONE with higher morning waking cortisol. This remained present when the known interaction between carriers of a short allele of 5-HTTLPR with higher morning salivary cortisol was taken into account. Conclusions Both BONE and 5-HTTLPR genes show evidence of modifying the risk of a subsequent new depressive episode associated with elevated morning salivary cortisol. In adolescents morning salivary cortisol levels may constitute a biomarker for some forms of unipolar depression.

Item Type: Article
Keywords: SEROTONIN TRANSPORTER GENE, NEUROTROPHIC FACTOR, FEELINGS, QUESTIONNAIRE, MAJOR DEPRESSION, ONSET DEPRESSION, CHILDHOOD-ONSET, DENTATE GYRUS, LIFE EVENTS, ADULT-RAT, STRESS
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 21037213
Web of Science ID: 284294700007
URI: http://researchonline.lshtm.ac.uk/id/eprint/1895

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