This is the first report of DHEA and DHEA-S concentrations in a patient with OCD and in control subjects. The data showed that not only were the patterns of DHEA and cortisol different from the control subjects, the mean concentration of DHEA and DHEA-S were higher in the OCD patient by a magnitude of 72% and 93% respectively.
Dysregulation of DHEA and DHEA-S has been reported in other mood and anxiety disorders (Eser et al., 2006
; Le Mellédo & Baker, 2002
; Le Mellédo & Baker, 2004
). For example, plasma DHEA is higher in drug-free panic disorder patients than in control subjects (Brambilla et al., 2005
). Patients with major depression have increased diurnal plasma DHEA (Heuser et al., 1998
); notably, DHEA and DHEA-S have been reported to decrease with remission of depression in older adults (Fabian et al., 2001
). One study identified a positive correlation between morning serum DHEA-S concentration and anxiety ratings in drug-free major depressive patients, but no relationship to depression ratings (Hsiao, 2006
). Patients with anorexia or bulimia nervosa have significantly higher DHEA, DHEA-S, and cortisol concentrations than controls (Monteleone et al., 2001
). Since patients with OCD experience high levels of anxiety similar to panic disorder and anorexia, the elevated DHEA and DHEA-S concentrations observed in this patient is not surprising.
Several studies have reported the relative amounts of DHEA and/or DHEA-S are maintained between brain and blood (Bernardi et al., 2005
; Guazzo et al., 1996
). In rats, oral DHEA administration increased DHEA-S content in a dose-dependent manner in hippocampus, hypothalamus, and serum (Bernardi et al., 2005
). In humans, the proportional levels of DHEA and DHEA-S in cerebrospinal fluid (CSF) compared to blood are 5.4% and 0.15% respectively, and these blood/CSF ratios are similar in subjects taking steroids and steroid-free subjects (Guazzo et al., 1996
). There are significant correlations between blood and CSF levels for DHEA (r = 0.65) and DHEAS (r = 0.88) (Guazzo et al., 1996
), therefore it is reasonable to believe that elevated DHEA and/or DHEA-S concentrations in serum would reflect elevated DHEA and/or DHEA-S in the brain.
While the DHEA and DHEA-S data described herein are exciting and previously unreported, the data are limited by the fact that we have data from only a single subject with OCD. The data raise questions as to whether the DHEA pattern and magnitude of DHEA or DHEA-S concentrations could be used as a biomarker for or provide insight into the pathophysiology of OCD. DHEA and DHEA-S are modulators of GABAA
(Le Mellédo & Baker, 2004
; Majewska, 1992
; Majewska et al., 1990
; Reddy & Kulkarni, 1997
) and N-methyl-D-aspartate (NMDA) receptors (Compagnone & Mellon, 2000
; Rupprecht, 1997
); they also play a role in NMDA-evoked norepinephrine release (Monnet et al., 1995
). Alterations in norepinephrine have been implicated in other anxiety disorders, and therefore may also be a link between DHEA dysregulation and anxiogenesis resulting in OCD (Sullivan et al., 1999
). Due to these neuropsychopharmacological properties, future clinical studies are needed to evaluate the role of DHEA and DHEA-S in OCD, which may lead to a greater understanding of the neurocircuitry behind this illness.