Structural imaging findings in psychiatric disorders, including the mood disorders, have been inconsistent, with rare replications and frequent contradictory findings. The argument that is presented here is that it is ultimately the clinical variables which will allow us to clarify the seemingly confusing neuroimaging findings. This can be demonstrated in the example of hippocampal volumes in bipolar disorders (BPD). Whereas cumulatively, bipolar patients show preserved hippocampal volumes, when studies are subdivided, based on exposure to lithium (Li), BPD subjects not exposed to Li show smaller hippocampal volumes than controls, who have smaller hippocampal volumes than Li-treated participants. In addition, hippocampal volumes in BPD seem to be negatively associated with the illness burden (duration of illness, numbers of episodes) but only among participants with limited exposure to Li. This neuroprogressive nature of illness translates into increased risk of neurodegenerative disorders in patients with BPD, a risk that may be alleviated by Li treatment.
Keywords: bipolar, neuroprotection, neurodegenerative, hippocampus