HPA axis genetic variation, cortisol and psychosis in major depression

• Published in: Molecular psychiatry Vol. 19; no. 2; pp. 220 - 227
• Main Authors: Schatzberg, A F, Keller, J, Tennakoon, L, Lembke, A, Williams, G, Kraemer, F B, Sarginson, J E, Lazzeroni, L C, Murphy, G M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2014; Nature Publishing Group
• Subjects: 631/208/726/649; 631/378/1689/1761; 631/378/340; 692/699/476/1414; Adult; Adult and adolescent clinical studies; Affective Disorders, Psychotic - diagnosis; Affective Disorders, Psychotic - genetics; Affective Disorders, Psychotic - physiopathology; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain research; Cognition; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - genetics; Depression; Depression, Mental; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - genetics; Depressive Disorder, Major - physiopathology; Female; Genes; Genetic aspects; Genetic diversity; Genetic engineering; Genetic variation; Genotypes; Glucocorticoids; Hormones; Humans; Hydrocortisone; Hydrocortisone - blood; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - physiopathology; Hypothalamus; Identification and classification; Interview, Psychological; Linkage Disequilibrium; Male; Medical sciences; Medicine; Medicine & Public Health; Mental depression; Mental disorders; Miscellaneous; Mood disorders; Neurosciences; original-article; Patients; Pharmacotherapy; Pituitary; Pituitary-Adrenal System - physiopathology; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychosis; Receptors, Corticotropin-Releasing Hormone - genetics; Receptors, Glucocorticoid - genetics; Receptors, Mineralocorticoid - genetics; Stress; Stress response; Tacrolimus Binding Proteins - genetics; Palo Alto California; United States > US; cortisol; HPA axis; glucocorticoid genes; major depression; psychosis; Mood disorder; Corticosteroid; Genetic variability; Hypothalamohypophysoadrenal axis; Steroid hormone; Antiinflammatory agent; Depression; Cortisol; Hydrocortisone; Genetic determinism; Glucocorticoid; Psychosis; Gene; Adrenal hormone; Genetics
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2013.129

Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with non-psychotic major depression (NPMD); and 29 HCs. Collection of genetic material was added one third of the way into a larger study on cortisol, cognition and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 1800 to 0900 h and for the assessment of alleles for six genes involved in HPA axis regulation. Two of the six genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression and psychosis, and medication status, only allelic variation for the glucocorticoid receptor (GR) gene accounted for a significant variance for mean cortisol levels from 1800 to 0100 h ( r 2 =0.288) and from 0100 to 0900 h ( r 2 =0.171). In addition, GR and corticotropin-releasing hormone receptor 1 (CRHR1) genotypes contributed significantly to psychosis measures and CRHR1 contributed significantly to depression severity rating.