Bilateral Hippocampal Volume Increase in Patients with Bipolar Disorder and Short-term Lithium Treatment

Abstract

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.

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol

“…In conclusion, numerous studies have demonstrated lithium's neuroprotective, neurotrophic and antiapoptotic effects [17][18][19][20][21][22][23]35,37 and highlighted the importance of glucocorticoids for hippocampal structure and function. [33][34][35]38,77,78,80 The results reported here add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.…”

“…21,22 Notably, short-term lithium administration has recently been reported to increase hippocampal volume bilaterally in bipolar patients. 23 The glutamatergic system has been implicated in the pathophysiology and treatment of mood disorders. 24,25 However, to date, absolute brain glutamate concentrations in bipolar patients have not been determined quantitatively in vivo.…”

Prefrontal gray matter increases in healthy individuals after lithium treatment: A voxel-based morphometry study

“…Recently, Yucel and colleagues [19] examined the effects of lithium on hippocampal volume in a medication-naïve sample of bipolar patients, treated with 1-8 weeks of lithium, and showed that there was a bilateral increase in total hippocampus and hippocampal head volumes in patients treated with lithium, compared to unmedicated patients.…”

Lithium blocks ethanol-induced modulation of protein kinases in the developing brain

“…It has been demonstrated that lithium has neuroprotective effects against a variety of insults in cultured neurons [12][13][14][15], in animal models of neurodegenerative diseases [16], and in human studies [16,17]. Because lithium inhibits GSK-3β activity [18], it has been postulated that part of the neuroprotective effects of lithium is due to its ability to inhibit GSK-3β, a pro-apoptotic enzyme [19].…”