Association of 11 beta-hydroxysteroid dehydrogenase type1 (HSD11b1) gene polymorphisms with outcome of antidepressant therapy and suicide attempts

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Figaro-Drumond, Fernanda Viana ^[1] ; Pereira, Sherliane Carla ^[2] ; Menezes, Itiana Castro ^[3] ; Baes, Cristiane von Werne ^[3] ; Coeli-Lacchini, Fernanda Borchers ^[4] ; Oliveira-Paula, Gustavo Henrique ^[2] ; Cleare, Anthony J. ^[5] ; Young, Allan H. ^[5] ; Tanus-Santos, Jose Eduardo ^[2] ; Juruena, Mario F. ^[5] ; Lacchini, Riccardo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Coll Nursing, Dept Psychiat Nursing & Human Sci, Av Bandeirantes 3900, BR-14040902 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Sao Paulo - Brazil

^[5] Kings Coll London & South London & Maudsley NHS F, Bethlem Royal Hosp, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, Monks Orchard Rd, Beckenham BR3 3BX, Kent - England

• Tipo de documento: Artigo Científico
• Fonte: Behavioural Brain Research; v. 381, MAR 2 2020.
• Citações Web of Science: 0

Resumo

The hypothalamic-pituitary-adrenal axis has been implicated in the pathophysiology of depressive disorders. HSD11B1 encodes 11 beta-hydroxysteroid dehydrogenase type1 enzyme, responsible for converting cortisone to cortisol. Genetic polymorphisms in HSD11B1 may impact in depression outcome and risk of suicide. This study aimed to assess whether HSD11B1 genotypes and haplotypes are associated with depression risk, severity of symptoms and suicidal attempts, considering early-life stress as an environmental factor. Here, 142 depressive patients and 103 healthy controls were included. Patients were enrolled from the Affective Disorders ambulatory and day hospital units, both within the University General Hospital of Ribeirao Preto. All subjects were clinically assessed applying the Mini-PLUS International Neuropsychiatric Interview, followed by the 21-item GRID-Hamilton Depression Scale, Childhood Trauma Questionnaire and Beck Scale for Suicidal Ideation (BSI). All subjects underwent antecubital vein puncture to obtain blood for DNA extraction. Genotyping of rs11119328 and rs11811440 were performed using allele-specific oligonucleotide polymerase chain reaction. We found a significant association of rs11119328 variant genotypes with increased risk for at least one suicide attempt (OR: 7.10, p = 0.049) and an association of variant genotypes of rs11811440 with euthymic mood under optimized pharmacological treatment (OR: 0.05, P = 0.014). These tests included correction for confounding factors. The association of genetic markers with depression risk, GRID-HAM-D21 and BSI scores and the number of suicidal attempts were nonsignificant. Haplotypes combining both markers were not associated with the studied phenotypes. We conclude that HSD11B1 polymorphisms may be relevant biomarkers for detecting subjects genetically vulnerable to poorer antidepressant response and higher risk of suicide attempts. (AU)

• Processo FAPESP: 16/04449-0 - Bases genéticas da disfunção erétil: dimetil arginina assimétrica e genes relacionados afetando a resposta ao sildenafil
• Beneficiário: Riccardo Lacchini
• Modalidade de apoio: Auxílio à Pesquisa - Regular