Greater Cortical Gray Matter Density in Lithium-Treated Patients with Bipolar Disorder

Abstract

Background-The neurobiological underpinnings of bipolar disorder are not well understood. Previous neuroimaging findings have been inconsistent; however, new methods for threedimensional (3-D) computational image analysis may better characterize neuroanatomic changes than standard volumetric measures.

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

“…Left ACC gray matter volume is reduced in adult [10] and juvenile [11] bipolar patients. Research employing a statistical parametric mapping approach also revealed reduced gray matter density in the fronto-limbic cortex, particularly in the cingulate [12,13], and in Bearden and colleagues' study [5] greatest differences in gray matter density were found in the bilateral cingulate and paralimbic cortices in lithium-treated bipolar patients (n=20) compared to those not taking lithium (n=8) and healthy controls (n=28). The DLPFC is an understudied region in bipolar disorder, with one study [14] showing significantly smaller gray matter volumes in the left middle and superior, and the right middle and inferior prefrontal regions in 17 bipolar patients hospitalized for a manic episode and receiving various psychotropic medications, and another study demonstrating decreased gray matter volume in the left DLPFC in pediatric bipolar patients [15].…”

“…Another study, although crosssectional, showed that bipolar patients treated with lithium had greater total gray matter volumes than untreated bipolar patients and healthy controls, while there were no significant differences in total white matter volumes across three groups [4]. Also in Bearden and colleagues' study [5], no white matter changes were detected. It is hard to explain why we found total white matter changes in healthy subjects who took lithium for four weeks, as most other studies failed to identify any effects in white matter.…”

“…The DLPFC is an understudied region in bipolar disorder, with one study [14] showing significantly smaller gray matter volumes in the left middle and superior, and the right middle and inferior prefrontal regions in 17 bipolar patients hospitalized for a manic episode and receiving various psychotropic medications, and another study demonstrating decreased gray matter volume in the left DLPFC in pediatric bipolar patients [15]. Bearden and colleagues [5] also noted greater gray matter density in the left DLPFC in lithium-treated bipolar patients compared to healthy controls. Taken together, the detected gray matter increases in these regions may be associated with the therapeutic effects of lithium, although we should note that our subjects were all healthy controls.…”

“…It affects multiple cellular signaling pathways in the brain [1] and has neurotrophic and neuroprotective effects [2]. Studies utilizing anatomical region-of-interest [3,4] and cortical pattern matching [5] methods, as well as neurochemical imaging [6], demonstrated detectable brain changes related to lithium treatment in bipolar patients. Specifically, both cross-sectional [4,5] and longitudinal prospective [3] studies demonstrated increased total gray matter volumes in bipolar patients treated with lithium compared to both untreated patients and age-and sexmatched healthy comparisons.…”

“…Studies utilizing anatomical region-of-interest [3,4] and cortical pattern matching [5] methods, as well as neurochemical imaging [6], demonstrated detectable brain changes related to lithium treatment in bipolar patients. Specifically, both cross-sectional [4,5] and longitudinal prospective [3] studies demonstrated increased total gray matter volumes in bipolar patients treated with lithium compared to both untreated patients and age-and sexmatched healthy comparisons. Furthermore, proton magnetic resonance spectroscopy studies demonstrated increased levels of total brain N-acetyl-aspartate, a putative marker of neuronal viability, myelin formation and maintenance, after 4 weeks of lithium in bipolar patients and healthy volunteers [6].…”