Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via
non-genomic mechanisms. Especially 3 alpha-reduced pregnane
steroids are potent positive allosteric modulators of the
gamma-aminobutyric acid type A (GABA(A)) receptor. During major
depression, there is a disequilibrium of 3 alpha-reduced
neuroactive steroids, which is corrected by clinically effective
pharmacological treatment. To investigate whether these alterations
are a general principle of successful antidepressant treatment, we
studied the impact of nonpharmacological treatment options on
neuroactive steroid concentrations during major depression. Neither
partial sleep deprivation, transcranial magnetic stimulation, nor
electroconvulsive therapy affected neuroactive steroid levels
irrespectively of the response to these treatments. These studies
suggest that the changes in neuroactive steroid concentrations
observed after antidepressant pharmacotherapy more likely reflect
distinct pharmacological properties of antidepressants rather than
the clinical response. In patients with panic disorder, changes in
neuroactive steroid composition have been observed opposite to
those seen in depression. However, during experimentally induced
panic induction either with cholecystokinine-tetrapeptide or sodium
lactate, there was a pronounced decline in the concentrations of 3
alpha-reduced neuroactive steroids in patients with panic disorder,
which might result in a decreased GABAergic tone. In contrast, no
changes in neuroactive steroid concentrations could be observed in
healthy controls with the exception of 3 alpha,5
alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A)
receptors by neuroactive steroids might contribute to the
pathophysiology of depression and anxiety disorders and might offer
new targets for the development of novel anxiolytic compounds.
Copyright (c) 2006 S. Karger AG, Basel.