Tuesday, May 1, 2012

Bipolar Disorder, Lithium and Hippocampal Volume

Brain neuroimaging studies continue to outline the structural and functional abnormalities in disorders of mood.  A relatively consistent finding has been a reduced volume of the brain hippocampus in major depressive disorder.  Studies of hippocampal volume in the less common bipolar disorder have been inconsistent--some studies have found reduced hippocampal volumes while others have not.

The hippocampus is an important brain region to understand in the mood disorders.  The hippocampus has a key role in memory.  Patients with mood disorders commonly display impairments in mood including deficitis in autobiographical memory.  Unipolar depression appears to increase risk for later development of Alzheimer's disease.  Hippocampal volume reduction is a common finding in Alzheimer's disease.

In an attempt to explain the discrepant findings of hippocampal volume in bipolar disorder, Hajek and colleagues completed a meta-analysis of 16 previous studies.  They hypothesized that lithium pharmacotherapy status may be a confounder in studies of hippocampal volume in this disorder.

Lithium is noted to have significant neuroprotective effects.  The authors of this study note the neuroprotective effects of lithium have been demonstrated in tissue culture and animal models involving neurons.  It is possible that bipolar patients treated with lithium may experience less hippocampal atrophy than those not treated with lithium.

The key elements of the design of this study were:
Study inclusion: MEDLINE and other online journal studies of hippocampal volumes in bipolar disorder were included if subjects current lithium treatment status was noted
Statistical analysis: Comprehensive Meta-Analysis software was used to calculate a Cohens d (a standardized measure of effect size) of right and left hippocampal volume in three groups:  bipolar disorder on lithium (n=101), bipolar disorder not on lithium (n=245) and controls (n=456) without bipolar disorder

The key results from the study were:
Bipolar subjects not on lithium: smaller hippocampal volumes were noted compared to controls for both the left hippocampus (effect size= -0.36) and the right hippocampus (effect size= -0.38)
Bipolar subjects on lithium: larger hippocampal volumes were noted compared to bipolar subjects not on lithium for the left hippocampus (effect size=0.93) and the right hippocampus (effect size=1.07).  Additionally, the bipolar subjects on lithium had larger hippocampal volumes than controls for the left hippocampus (effect size =0.51) and right hippocampus (effect size=0.53).

The authors note their study had significant limitations.  Current lithium status is a dichotomous variable and does not reflect historical duration and dose exposure to lithium in the subjects.  The study does not example include any neuropsychological data that might inform whether volume preservation with lithium results in memory preservation in the disorder.

However, this study does provide an important contribution to the research in brain structure in bipolar disorder.  Future studies in bipolar subjects will need to examine historical and current exposure to lithium and other psychotropics in structural and functional imaging results.

Photo of macaw from Palm Beach zoo from the author's files.

Hajek T, Kopecek M, Höschl C, & Alda M (2012). Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis. Journal of psychiatry & neuroscience : JPN, 37 (3) PMID: 22498078

No comments:

Post a Comment