Dysregulation of neurosteroids in obsessive compulsive disorder

Abstract

Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-hour serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject with OCD than in the control subjects. DHEA and DHEA-S concentrations were substantially higher in the OCD subject than in the control subjects. In contrast, cortisol concentrations were similar in the OCD subject and the control subjects. Future clinical studies are needed to evaluate the significance of DHEA and DHEA-S in OCD. To the EditorAlterations in hormone concentrations have been reported in patients with obsessive compulsive disorder (OCD). Studies have reported differences in concentrations of cortisol (Catapano et al., 1992;Monteleone et al., 1994), melatonin (Catapano et al., 1992;Monteleone et al., 1994), corticotropin releasing hormone (Altemus et al., 1992), adrenocorticotropin (ACTH) (Bailly et al., 1994), arginine vasopressin (Altemus et al., 1992, and oxytocin (Leckman et al., 1994). Some patients with OCD demonstrate a lack of inhibition of cortisol secretion after a dexamethasone suppression test (Catapano et al., 1990;Cottraux et al., 1984), indicating hyperactivity of the hypothalamic-pituitary-adrenal axis. ContributorsKristin Bigos was involved with data acquisition, data analysis, and manuscript writing. Mary Folan was involved with data acquisition and data analysis, and manuscript revisions. Mark Jones was the social worker and therapist for the patients in this study and was involved with recruitment. Gretchen Haas completed all the psychiatric evaluations (SCID). Frank Kroboth completed all the medical histories and physicals. Patricia Kroboth was involved with funding, data analysis, and manuscript writing.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Two important steroids, dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA-S, have not been assessed in patients with OCD. DHEA is secreted synchronously with cortisol from the adrenal cortex in response to ACTH. DHEA and DHEA-S are also neurosteroids, which are both synthesized and active in the brain. DHEA-S, and to a lesser extent DHEA, is a potent noncompetitive antagonist of γ-aminobutyric acid type A (GABA A ) receptors (Majewska, 1992;Majewska et al., 1990), and induces anxiogen...

Circadian rhythms in obsessive–compulsive disorder

“…This finding appears to be compatible with central neurotransmitter alterations assumed in OCD, indicating an influence at hypothalamic or higher levels. In a single individual with OCD, the circadian patterns of DHEA and cortisol have been reported to be markedly different from control subjects, with DHEA and DHEA-S levels being substantially higher in the OCD subject (Bigos et al 2009). This preliminary finding requires the assessment of larger patient samples.…”

“…In a recent review, Kalsbeek et al (2012) have described the current view on the control by the suprachiasmatic nucleus of the daily rhythm in the activity of the hypothalamic-pituitaryadrenal (HPA) axis. Individuals with OCD have been reported to show alterations in hormone levels, including the concentrations of cortisol (Catapano et al 1992;Monteleone et al 1994), corticotrophin releasing hormone (CRH) (Altemus et al 1992), dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA-S (Bigos et al 2009), adrenocorticotrophic hormone (ACTH) (Bailly et al 1994), growth hormone (Kluge et al 2007a, b), vasopressin (Altemus et al 1992), oxytocin (Leckman et al 1994) and melatonin (Catapano et al 1992;Monteleone et al 1994).…”

Adrenal steroidogenesis following prenatal dexamethasone exposure in the spiny mouse

“…The androgen DHEA is particularly interesting because of its anti-glucocorticoid actions in the brain (Kimonides et al 1998, Cardounel et al 1999, Kimonides et al 1999, Kurata et al 2004, and because adrenal secretion has been shown to be altered in several disease states and psychopathologies (Goodyer et al 2001). For example, decreased plasma DHEA and/or its sulfated derivative DHEAS occurs in patients with rheumatoid arthritis, coronary artery disease, anorexia nervosa, anxiety, depression, and obsessive compulsive disorder (Barrett-Connor et al 1986, Wilder 1996, Goodyer et al 1998, Gordon et al 1999, Wolkowitz & Reus 2000, Harris et al 2001, van Niekerk et al 2001, Bigos et al 2009). HPA axis dysregulation has been described for psychosis in general, and for schizophrenia in particular (Cotter & Pariante 2002), and includes increased basal cortisol secretion (Ryan et al 2004), increased adrenocorticotropic hormone (ACTH)/cortisol responsiveness to the dexamethasone (DEX)/corticotrophic-releasing hormone challenge test (Lammers et al 1995), and increased plasma DHEA concentrations in severely psychotic male subjects and medicated patients with chronic schizophrenia (Oades & Schepker 1994, di Michele et al 2005.…”

Rats with differential self-grooming expression in the elevated plus-maze do not differ in anxiety-related behaviors

“…Previous studies showed that monoamines and hormone concentrations could be altered in patients with different psychopathologies, such as generalized anxiety disorder [49,50] and OCD [51][52][53]. Thus, in the present study we also evaluated if grooming expression in the EPM could be correlated with one of these parameters.…”