Most previous magnetic resonance imaging (MRI) studies of patients with bipolar disorder (BD) report similar hippocampus (HC) volumes across patients and controls, but because patients studied were heterogeneous with respect to course of illness variables and medication status, the conclusions of these studies remain equivocal. Lithium (Li) is the reference-standard drug for BD and its role as an important agent in neuroprotection and neurogenesis has been documented in human and in animal studies. We compared the volume of the HC, hippocampal head (Hh), and body/tail (Hbt) in three groups with no history of medication use before entry into this study: (a) a group of patients treated with Li for 1-8 weeks and then scanned; (b) a group comprised of patients who were unmedicated at the time of scan; and (c) a group of patients treated with either valproic acid or lamotrigine. Healthy age- and sex-matched comparison subjects were also scanned. HC volumes did not differ between the unmedicated and healthy comparison groups. There was a bilateral increase in volumes of HC and Hh in the Li-treated group compared to the unmedicated group, an effect that was apparent even over a brief treatment period. Our study provides further confirmation that Li can exert structural effects on the HC, which are detectable in vivo. The study emphasizes the need to control for even brief exposure to medication in volumetric studies of the HC.

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Consistent with preclinical literature supporting the neuroprotective effects of lithium, long-term treatment is associated with preservation of recollective memory function and increased hippocampal size in vivo.

The anterior cingulate cortex (ACC) is implicated in the cognitive and affective abnormalities observed in mood disorders. Bilateral ACC volume reductions have been reported in patients with major depressive disorder (MDD) when compared to healthy controls. We compared regional brain volumes in the subgenual prefrontal cortex (SGPFC; Brodmann area (BA) 24 sg ), subcallosal gyrus (BA25), and paracingulate gyrus (BA32) in 65 patients receiving a first course of treatment for MDD and 93 healthy control subjects. Patients with more than three episodes of untreated MDD had smaller subcallosal gyrus volumes than healthy controls, while those with three or fewer past untreated episodes did not differ from controls. We also found preliminary evidence that medication-exposed patients had smaller SGPFC volumes than patients with no exposure to medication and healthy controls. There was no evidence that these effects related to mood state, duration of untreated illness, or to patient age. No differences were apparent in paracingulate gyrus volumes between patients and controls. These findings confirm the presence of ACC volume reductions in untreated patients with MDD and suggest that illness burden and short-term medication exposure mediate this change.