Effects of low dose lithium on hippocampal neuropathology in people at ultra-high risk for psychosis

Background: Indicated intervention prior to the onset of psychosis may help to delay, attenuate or even prevent the illness. To date, successful intervention trials using atypical antipsychotics and/or cognitive behavioural therapy have been reported, but it is not clear that these treatments are targeting the underlying brain pathology. Given our previous findings of progressive grey matter loss over the transition to psychosis, agents that can prevent this, such as lithium, might be useful for preventing or delaying the onset of psychosis. Methods: In this open-label trial, 11 ultra-high-risk patients who received low- dose lithium treatment for four months were compared with 10 similar patients who received only needs-based intervention. Magnetic resonance imaging, including T2 relaxometry and proton spectroscopy was performed prior to initiation of treatment and after four months. Results: Hippocampal T2 declined significantly in the treatment group (p=0.018). No significant group x time effects were seen for brain metabolites, although N-acetyl aspartate (NAA), myo-inositol, creatine and choline all tended to increase with lithium administration and decrease or remain unchanged in the comparison group. Conclusions: Decreased T2 relaxation time and increased concentrations of NAA are indicators of increased neuronal function/viability. Low-dose lithium may help regulate synaptic pruning and reduce neuronal dysfunction associated with the onset of psychosis.