Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-23T11:01:36.255Z Has data issue: false hasContentIssue false

Association analyses of depression and genes in the hypothalamus–pituitary–adrenal axis

Published online by Cambridge University Press:  06 June 2016

Henrietta Nørmølle Buttenschøn*
Affiliation:
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
Jesper Krogh
Affiliation:
Mental Health Center Copenhagen, Mental Health Services in Capital Region, University of Copenhagen, Copenhagen, Denmark
Marit Nyholm Nielsen
Affiliation:
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
Linda Kaerlev
Affiliation:
Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
Merete Nordentoft
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Mental Health Center Copenhagen, Mental Health Services in Capital Region, University of Copenhagen, Copenhagen, Denmark
Ole Mors
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
*
Henriette Nørmølle Buttenschøn, Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark. Tel: +45 78471163; Fax: +45 78471108; E-mail: [email protected]

Abstract

Objective

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme (ACE).

Methods

In total, 78 single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were genotyped. The study included 408 individuals with depression and 289 controls. In a subset of cases, the interaction between genetic variants and stressful life events (SLEs) was investigated.

Results

After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated with depression. One nominally significant interaction, most likely due to chance, was identified.

Conclusion

The results indicate that ACE could be a potential candidate gene for depression.

Type
Short Communication
Copyright
© Scandinavian College of Neuropsychopharmacology 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Sullivan, PF, Neale, MC, Kendler, KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000;157:15521562.Google Scholar
2. Lopizzo, N, Bocchio, CL, Cattane, N et al. Gene-environment interaction in major depression: focus on experience-dependent biological systems. Front Psychiatry 2015;6:68.Google Scholar
3. Pariante, CM, Lightman, SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci 2008;31:464468.Google Scholar
4. Aguilera, G, Kiss, A, Luo, X, Akbasak, BS. The renin angiotensin system and the stress response. Ann N Y Acad Sci 1995;771:173186.Google Scholar
5. Armando, I, Volpi, S, Aguilera, G, Saavedra, JM. Angiotensin II AT1 receptor blockade prevents the hypothalamic corticotropin-releasing factor response to isolation stress. Brain Res 2007;1142:9299.Google Scholar
6. Wright, JW, Harding, JW. Brain renin-angiotensin – a new look at an old system. Prog Neurobiol 2011;95:4967.Google Scholar
7. World Health Organization. Diagnosis and clinical measurement in psychiatry. In: Wing JK, Sartorius N and Üstün TB, editors. A reference manual for SCAN. World Health Organization: Cambridge University Press, 1998.Google Scholar
8. Montgomery, SA, Asberg, M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382389.Google Scholar
9. Brugha, T, Bebbington, P, Tennant, C, Hurry, J. The List of Threatening Experiences: a subset of 12 life event categories with considerable long-term contextual threat. Psychol Med 1985;15:189194.Google Scholar
10. Brugha, TS, Cragg, D. The list of threatening experiences: the reliability and validity of a brief life events questionnaire. Acta Psychiatr Scand 1990;82:7781.Google Scholar
11. Barrett, JC, Fry, B, Maller, J, Daly, MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263265.Google Scholar
12. Purcell, S, Neale, B, Todd-Brown, K et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559575.Google Scholar
13. Li, Y, Abecasis, GR. Rapid haplotype reconstruction and missing genotype inference. Am J Hum Genet 2006;S79:2290.Google Scholar
14. Curtis, D, Vine, AE, Knight, J. A simple method for assesing the strength of evidence for assocation at the level of whole gene. Adv Appl Bioinform Chem 2008;1:115120.Google Scholar
15. Wu, Y, Wang, X, Shen, X, Tan, Z, Yuan, Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord 2012;136:971978.Google Scholar
16. Bondy, B, Baghai, TC, Zill, P et al. Genetic variants in the angiotensin I-converting-enzyme (ACE) and angiotensin II receptor (AT1) gene and clinical outcome in depression. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:10941099.Google Scholar
17. Hui, L, Wu, JQ, Ye, MJ et al. Association of angiotensin-converting enzyme gene polymorphism with schizophrenia and depressive symptom severity in a Chinese population. Hum Psychopharmacol 2015;30:100107.CrossRefGoogle ScholarPubMed
18. Baghai, TC, Binder, EB, Schule, C et al. Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism. Mol Psychiatry 2006;11:10031015.Google Scholar
19. Ancelin, ML, Carriere, I, Scali, J, Ritchie, K, Chaudieu, I, Ryan, J. Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression. Transl Psychiatry 2013;3:e322.Google Scholar
20. Uher, R. Gene-environment interactions in severe mental illness. Front Psychiatry 2014;5:48.CrossRefGoogle ScholarPubMed
21. Kaerlev, L, Kolstad, HA, Hansen, AM et al. Are risk estimates biased in follow-up studies of psychosocial factors with low base-line participation? BMC Public Health 2011;11:539.Google Scholar
22. Kolstad, HA, Hansen, AM, Kaergaard, A et al. Job strain and the risk of depression: is reporting biased? Am J Epidemiol 2011;173:94102.Google Scholar
23. Uher, R, Maier, W, Hauser, J et al. Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. Br J Psychiatry 2009;194:252259.Google Scholar
24. Farmer, A, Breen, G, Brewster, S et al. The Depression Network (DeNT) study: methodology and sociodemographic characteristics of the first 470 affected sibling pairs from a large multi-site linkage genetic study. BMC Psychiatry 2004;4:42.Google Scholar
25. Krogh, J, Petersen, L, Timmermann, M, Saltin, B, Nordentoft, M. Design paper: the DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of aerobic versus non-aerobic versus relaxation training for patients with light to moderate depression. Contemp Clin Trials 2007;28:7989.Google Scholar
Supplementary material: File

Buttenschøn supplementary material

Supplementary Table

Download Buttenschøn supplementary material(File)
File 10.6 KB