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The British Journal of Psychiatry The British Journal of Psychiatry

Article contents

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

Published online by Cambridge University Press:  02 January 2018

Ian M. Goodyer ,
Tim Croudace ,
Frank Dudbridge ,
Maria Ban  and
Joe Herbert
Ian M. Goodyer*
Affiliation:
Developmental and Lifespan Research Group, Department of Psychiatry, University of Cambridge, Cambridge
Tim Croudace
Affiliation:
Developmental and Lifespan Research Group, Department of Psychiatry, University of Cambridge, Cambridge
Frank Dudbridge
Affiliation:
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
Maria Ban
Affiliation:
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge
Joe Herbert
Affiliation:
Department of Physiology, Development and Neurosciences and the Cambridge Centre for Brain Repair, Cambridge, UK
*
Ian M. Goodyer, Developmental Psychiatry Section, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge CB2 8AH, UK. Email: ig104@cam.ac.uk
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Abstract

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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.

Type
Papers
Information
The British Journal of Psychiatry , Volume 197 , Issue 5 , November 2010 , pp. 365 - 371
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NC
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial licence (http://creativecommons.org/licenses/by-nc/4.0/), which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
Copyright © Royal College of Psychiatrists, 2010

Footnotes

†

See pp. 341–342, this issue.

This work was funded by a Wellcome Trust programme grant (no. 053642) awarded to I.M.G. and J.H. T.J.C. is supported by a Career Scientist Award from the Department of Health. The work was carried out within the NIHR Collaborating Centre for Applied Health Research and Care hosted by the Cambridge and Peterborough Foundation Trust and the University of Cambridge.

Declaration of interest

None.

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