Evidence suggests that
neuroactive steroids may be candidate modulators of
schizophrenia pathophysiology and
therapeutics. We therefore investigated
neuroactive steroid levels in post-mortem brain tissue from subjects with
schizophrenia,
bipolar disorder, nonpsychotic depression, and control subjects to determine if
neuroactive steroids are altered in these disorders. Posterior cingulate and parietal cortex tissue from the Stanley Foundation Neuropathology Consortium collection was analyzed for
neuroactive steroids by negative ion chemical ionization gas chromatography/mass spectrometry preceded by high-performance liquid chromatography. Subjects with
schizophrenia,
bipolar disorder, nonpsychotic depression, and control subjects were group matched for age, sex, ethnicity, brain pH, and post-mortem interval (n = 14-15 per group, 59-60 subjects total). Statistical analyses were performed by ANOVA with post-hoc Dunnett tests on log transformed
neuroactive steroid levels.
Pregnenolone and
allopregnanolone were present in human post-mortem brain tissue at considerably higher concentrations than typically observed in serum or plasma.
Pregnenolone and
dehydroepiandrosterone levels were higher in subjects with
schizophrenia and
bipolar disorder compared to control subjects in both posterior cingulate and parietal cortex.
Allopregnanolone levels tended to be decreased in parietal cortex in subjects with
schizophrenia compared to control subjects.
Neuroactive steroids are present in human post-mortem brain tissue at physiologically relevant concentrations and altered in subjects with
schizophrenia and
bipolar disorder. A number of
neuroactive steroids act at inhibitory
GABA(A) and excitatory
NMDA receptors and demonstrate neuroprotective and neurotrophic effects.
Neuroactive steroids may therefore be candidate modulators of the pathophysiology of
schizophrenia and
bipolar disorder, and relevant to the treatment of these disorders.