Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

• Published in: Frontiers in neuroendocrinology Vol. 30; no. 1; pp. 65 - 91
• Main Authors: Maninger, Nicole, Wolkowitz, Owen M., Reus, Victor I., Epel, Elissa S., Mellon, Synthia H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2009
• Subjects: Adult; Aged; Aging; Animals; Antioxidants - pharmacology; Apoptosis; Brain - drug effects; Brain - metabolism; Cortisol; Dehydroepiandrosterone; Dehydroepiandrosterone - pharmacology; Dehydroepiandrosterone - physiology; Dehydroepiandrosterone - therapeutic use; Dehydroepiandrosterone Sulfate - pharmacology; Dementia; Dementia - drug therapy; Depression; Depression - drug therapy; DHEA; DHEAS; Endocrinology & Metabolism; Female; Humans; Hypoxia-Ischemia, Brain - drug therapy; Male; Middle Aged; Neurogenesis; Neuroprotection; Neuroprotective Agents - pharmacology; Schizophrenia; Schizophrenia - drug therapy; Stress Disorders, Post-Traumatic - drug therapy; DHEA; 5HT; eNOS; TNFα; AMPA; DMSO; ACh; ACTH; EPS; PVN; Cortisol; MPP; FGF2; Aβ; NF-κB; SF-1; STS; STZ; σ 1; 11β-HSD1; SULT2A1; NE-100; GABA A; EEG; 3βHSD; HST; PKC; s.c; i.p; BD1063; NGF; PPARα; PBMC; bFGF; IL-6; H 2O 2; i.v; Dehydroepiandrosterone; NOS; NE; ROS; HPA; DU-14; SAPK3; MK801; MAP; Dementia; C/EBP; NO; Neuroprotection; MRI; Schizophrenia; CNS; Neurogenesis; LPS; SPECT; DHEA(S); CREB; DHEAS; SNP; MMSE; CSF; NMDA; GSH; AP1; BDNF; EGF; LIF; Depression; d-AP5; GR; OGD; PTSD; HIV; 5-HIAA; SCI; DA; HNE; BACE; EPI; Apoptosis; norepinephrine; glucocorticoid receptor; activator protein-1; N-methyl- d-aspartate; hydroxysteroid sulfotransferase; interleukin-6; subcutaneous; serotonin; 1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine; brain-derived neurotrophic factor; nitric oxide synthase; cAMP response element binding protein; hypothalamic-pituitary-adrenal axis; nitric oxide; central nervous system; β-site amyloid β precursor protein-cleaving enzyme; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; human immunodeficiency virus; 11β-hydroxysteroid dehydrogenase type 1; epidermal growth factor; lipopolysaccharide; post-traumatic stress disorder; nuclear factor kappa B; oxygen-glucose deprivation; 3β-hydroxysteroid dehydrogenase; nerve growth factor; peripheral blood mononuclear cells; intraperitoneal; hydroxysteroid sulfotransferase or DHEA sulfotransferase TH, tyrosine hydroxylase; 1-methyl-4-phenylpyridinum; d-2-amino-5-phosphonopentanoic acid; microtubule-associated protein; dopamine; basic fibroblast growth factor; adrenocorticotropic hormone; fibroblast growth factor; sodium nitroprusside; endothelial nitric oxide synthase; N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)-ethylamine monohydrochloride; hydrogen peroxide; single photon emission computed tomography; p- O-(sulfamoyl)- N-tetradecanoyl tyramine; epinephrine; dehydroepiandrosterone; steroidogenic factor 1; electroencephalogram; streptozotocin; cerebrospinal fluid; paraventricular nucleus; magnetic resonance imaging; tumor necrosis factor α; Mini-Mental Status Examination; glutathione; sigma subtype 1 receptor; CCAAT/enhancer-binding protein; dehydroepiandrosterone and dehydroepiandrosterone-sulfate; γ-aminobutyric acid type A receptor; dimethyl sulfoxide; intravenous; reactive oxygen species; protein kinase C; spinal cord injury; dehydroepiandrosterone-Sulfate; (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate; 5-hydroxyindole-3-acetic acid; amyloid β protein; 4-hydroxynonenal; steroid sulfatase; stress-activated protein kinase 3; acetylcholine; leukemia inhibitory factor; extrapyramidal symptoms; peroxisome proliferator-activated receptor α
• ISSN: 0091-3022; 1095-6808; 1095-6808
• DOI: 10.1016/j.yfrne.2008.11.002

DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.