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Impact of gene-gender effects of adrenergic polymorphisms on hypothalamic-pituitary-adrenal axis activity in depressed patients.
Neuropsychobiology. 2008; 58(3-4):154-62.N

Abstract

OBJECTIVE

There is overwhelming evidence that activation of the hypothalamic-pituitary-adrenal (HPA) system plays a major role in depression and cardiovascular disease in genetically susceptible individuals. We hypothesized that due to the multiple interactions between the sympathetic and the HPA systems via adrenoceptors, polymorphisms in these genes could have an impact on HPA axis activity in major depression.

METHODS

Using the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test, we investigated the association of alpha(2)-adrenoceptor (ADRA2A -1291C-->G) and the beta(2)-adrenoceptor gene (ADRB2 Arg16Gly) in 189 patients with major depression during the acute state of the disease and after remission.

RESULTS

Male ADRA2A -1291G allele homozygotes showed significant pretreatment HPA axis hyperactivity, with increased adrenocorticotropin (ACTH; F = 4.9, d.f. = 2, p = 0.009) and cortisol responses (F = 6.4, d.f. = 2, p = 0.003). In contrast, female ADRB2 Arg/Arg homozygotes had increased pretreatment ACTH (F = 7.17, d.f. = 2, p = 0.001) and cortisol (F = 8.95, d.f. = 2, p = 0.000) levels. Interestingly, in the respective genotypes, the stress hormones remained elevated in the second DEX/CRH test, despite a reduction in depressive symptoms.

CONCLUSIONS

This study provides evidence that, depending on gender and polymorphisms, there is continuous HPA axis overdrive in a proportion of patients irrespective of the status of depression. Considering the importance of stress hormones for cardiovascular disorders, our data might suggest that these patients are at high risk of comorbidity between depression and cardiovascular disorders.

Authors+Show Affiliations

Department of Psychiatry and Psychotherapy, Ludwig Maximilian University of Munich, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19088492

Citation

Haefner, S, et al. "Impact of Gene-gender Effects of Adrenergic Polymorphisms On Hypothalamic-pituitary-adrenal Axis Activity in Depressed Patients." Neuropsychobiology, vol. 58, no. 3-4, 2008, pp. 154-62.
Haefner S, Baghai TC, Schule C, et al. Impact of gene-gender effects of adrenergic polymorphisms on hypothalamic-pituitary-adrenal axis activity in depressed patients. Neuropsychobiology. 2008;58(3-4):154-62.
Haefner, S., Baghai, T. C., Schule, C., Eser, D., Spraul, M., Zill, P., Rupprecht, R., & Bondy, B. (2008). Impact of gene-gender effects of adrenergic polymorphisms on hypothalamic-pituitary-adrenal axis activity in depressed patients. Neuropsychobiology, 58(3-4), 154-62. https://doi.org/10.1159/000182891
Haefner S, et al. Impact of Gene-gender Effects of Adrenergic Polymorphisms On Hypothalamic-pituitary-adrenal Axis Activity in Depressed Patients. Neuropsychobiology. 2008;58(3-4):154-62. PubMed PMID: 19088492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of gene-gender effects of adrenergic polymorphisms on hypothalamic-pituitary-adrenal axis activity in depressed patients. AU - Haefner,S, AU - Baghai,T C, AU - Schule,C, AU - Eser,D, AU - Spraul,M, AU - Zill,P, AU - Rupprecht,R, AU - Bondy,B, Y1 - 2008/12/16/ PY - 2008/03/18/received PY - 2008/10/05/accepted PY - 2008/12/18/entrez PY - 2008/12/18/pubmed PY - 2009/4/17/medline SP - 154 EP - 62 JF - Neuropsychobiology JO - Neuropsychobiology VL - 58 IS - 3-4 N2 - OBJECTIVE: There is overwhelming evidence that activation of the hypothalamic-pituitary-adrenal (HPA) system plays a major role in depression and cardiovascular disease in genetically susceptible individuals. We hypothesized that due to the multiple interactions between the sympathetic and the HPA systems via adrenoceptors, polymorphisms in these genes could have an impact on HPA axis activity in major depression. METHODS: Using the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test, we investigated the association of alpha(2)-adrenoceptor (ADRA2A -1291C-->G) and the beta(2)-adrenoceptor gene (ADRB2 Arg16Gly) in 189 patients with major depression during the acute state of the disease and after remission. RESULTS: Male ADRA2A -1291G allele homozygotes showed significant pretreatment HPA axis hyperactivity, with increased adrenocorticotropin (ACTH; F = 4.9, d.f. = 2, p = 0.009) and cortisol responses (F = 6.4, d.f. = 2, p = 0.003). In contrast, female ADRB2 Arg/Arg homozygotes had increased pretreatment ACTH (F = 7.17, d.f. = 2, p = 0.001) and cortisol (F = 8.95, d.f. = 2, p = 0.000) levels. Interestingly, in the respective genotypes, the stress hormones remained elevated in the second DEX/CRH test, despite a reduction in depressive symptoms. CONCLUSIONS: This study provides evidence that, depending on gender and polymorphisms, there is continuous HPA axis overdrive in a proportion of patients irrespective of the status of depression. Considering the importance of stress hormones for cardiovascular disorders, our data might suggest that these patients are at high risk of comorbidity between depression and cardiovascular disorders. SN - 1423-0224 UR - https://www.unboundmedicine.com/medline/citation/19088492/Impact_of_gene_gender_effects_of_adrenergic_polymorphisms_on_hypothalamic_pituitary_adrenal_axis_activity_in_depressed_patients_ L2 - https://www.karger.com?DOI=10.1159/000182891 DB - PRIME DP - Unbound Medicine ER -