Can the neurotrophic effects of mood stabilizers be demonstrated in the human brain?
While the body of preclinical data demonstrating neurotrophic and neuroprotective effects of lithium is striking, considerable caution must clearly be exercised in extrapolating to the clinical situation with humans. In view of lithium and VPA’s robust effects on the levels of the cytoprotective protein bcl-2 in the frontal cortex, Drevets and associates have re-analyzed their data demonstrating ~40% reductions in subgenual PFC volumes in familial mood disorder subjects. Consistent with neurotrophic/neuroprotective effects of lithium and VPA, they found that the patients treated with chronic lithium or VPA exhibited subgenual PFC volumes which were significantly higher than the volumes in non lithium- or VPA-treated patients, and not significantly different from controls (personal communication from W Drevets to HK Manji, July 1999). A longitudinal clinical study was recently undertaken to determine if lithium also exerts neurotrophic/ neuroprotective effects in the human brain in vivo
