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Cited by 67Stress Responses and CortisolNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

Polymorphisms in BDNF (Val66Met) and 5-HTTLPR, morning cortisol and subsequent depression in at-risk adolescents

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Goodyer, Ian M., Croudace, Tim, Dudbridge, Frank, Ban, Maria, Herbert, Joe·2010·British Journal of Psychiatry
DOI 10.1192/bjp.bp.110.077750PMC PMC2966502
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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 (BDNF) polymorphism (rs6265, Val66Met) 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 Val66Met BDNF 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 BDNF 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 BDNF 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.

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  • Several prospective studies have shown that morning cortisol levels, around the peak of the diurnal rhythm, prospectively predict depressive episodes or symptoms.

    “Several prospective studies of HPA functioning and depression have shown that cortisol levels during the morning (rather than average or total cortisol levels throughout the day), around the peak of cortisol’s diurnal rhythm, prospectively predict depressive episodes or symptoms (Harris et al. 2000; Halligan et al. 2007; Goodyer et al. 2010).”

    From The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history (2013) · cites this paper as Goodyer et al. 2010

    The Results section (‘Predicting subsequent depressive episode onset’) reports that adolescents with higher morning salivary cortisol at entry were more likely to experience a depressive episode during follow-up. The Cortisol assay section describes morning sampling only; this paper does not compare morning cortisol with average or total cortisol levels across the day, so it does not support that contrast. (LLM, conf=0.86)

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References 37 · Cited by 67

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Authors
Goodyer, I. M., Croudace, T., Dudbridge, F., Ban, M., & Herbert, J.
Affiliations
  • University of Cambridge (GB)
  • London School of Hygiene & Tropical Medicine (GB)
Corresponding author
Goodyer, Ian M.
ORCID
Venue
British Journal of Psychiatry
Publisher
Royal College of Psychiatrists
Published
2010-11
Volume
197
Issue
5
Pages
365-371
ISSN
  • 0007-1250 (ISSN-L)
  • 1472-1465
DOI
10.1192/bjp.bp.110.077750
PMC
PMC2966502
OpenAlex
W2107212341
Cited by
67
References
37
Citations by year
2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 14 · 2014: 10 · 2013: 6 · 2012: 10
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
Locations
  • The British Journal of Psychiatry (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion)
Funders
  • Wellcome Trust
  • National Institute for Health and Care Research (PHCS/C4/4/002)
  • University of Cambridge
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
BDNF Val66Met polymorphism, 5-HTTLPR, serotonin transporter gene, depression onset, adolescents, genetic risk, hypothalamic-pituitary-adrenal axis, gene-environment interaction, major depressive disorder, biomarkers
MeSH terms
Adolescent, Psychology, Adolescent, Adult, Circadian Rhythm, Depressive Disorder, Female, Genotype, Humans, Hydrocortisone, Life Change Events, Male, Polymorphism, Genetic, Predictive Value of Tests, Risk Factors, Saliva, Multivariate Analysis, Logistic Models, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease, Serotonin Plasma Membrane Transport Proteins, Young Adult

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