Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder.
Declarative memory impairments are common in patients with bipolar illness, suggesting underlying hippocampal pathology. However, hippocampal volume deficits are rarely observed in bipolar disorder. Here we used surface-based anatomic mapping to examine hippocampal anatomy in bipolar patients treated with lithium relative to matched control subjects and unmedicated patients with bipolar disorder. High-resolution brain magnetic resonance images were acquired from 33 patients with bipolar disorder (21 treated with lithium and 12 unmedicated), and 62 demographically matched healthy control subjects. Three-dimensional parametric mesh models were created from manual tracings of the hippocampal formation. Total hippocampal volume was significantly larger in lithium-treated bipolar patients compared with healthy controls (by 10.3%; p=0.001) and unmedicated bipolar patients (by 13.9%; p=0.003). Statistical mapping results, confirmed by permutation testing, revealed localized deficits in the right hippocampus, in regions corresponding primarily to cornu ammonis 1 subfields, in unmedicated bipolar patients, as compared to both normal controls (p=0.01), and in lithium-treated bipolar patients (p=0.03). These findings demonstrate the sensitivity of these anatomic mapping methods for detecting subtle alterations in hippocampal structure in bipolar disorder. The observed reduction in subregions of the hippocampus in unmedicated bipolar patients suggests a possible neural correlate for memory deficits frequently reported in this illness. Moreover, increased hippocampal volume in lithium-treated bipolar patients may reflect postulated neurotrophic effects of this agent, a possibility warranting further study in longitudinal investigations.
Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, USA. cbearden@mednet.ucla.edu
Carrie E
CE
Bearden
Paul M
PM
Thompson
Rebecca A
RA
Dutton
Benício N
BN
Frey
Marco A M
MA
Peluso
Mark
M
Nicoletti
Nicole
N
Dierschke
Kiralee M
KM
Hayashi
Andrea D
AD
Klunder
David C
DC
Glahn
Paolo
P
Brambilla
Roberto B
RB
Sassi
Alan G
AG
Mallinger
Jair C
JC
Soares
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D018020:Lithium Compounds / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged
D000928:Antidepressive Agents; D018020:Lithium Compounds