Greater cortical gray matter density in lithium-treated patients with bipolar disorder.
BACKGROUND
The neurobiological underpinnings of bipolar disorder are not well understood. Previous neuroimaging findings have been inconsistent; however, new methods for three-dimensional (3-D) computational image analysis may better characterize neuroanatomic changes than standard volumetric measures.


METHODS
We used high-resolution magnetic resonance imaging and cortical pattern matching methods to map gray matter differences in 28 adults with bipolar disorder, 70% of whom were lithium-treated (mean age = 36.1 +/- 10.5; 13 female subject), and 28 healthy control subjects (mean age = 35.9 +/- 8.5; 11 female subjects). Detailed spatial analyses of gray matter density (GMD) were conducted by measuring local proportions of gray matter at thousands of homologous cortical locations.


RESULTS
Gray matter density was significantly greater in bipolar patients relative to control subjects in diffuse cortical regions. Greatest differences were found in bilateral cingulate and paralimbic cortices, brain regions critical for attentional, motivational, and emotional modulation. Secondary region of interest (ROI) analyses indicated significantly greater GMD in the right anterior cingulate among lithium-treated bipolar patients (n = 20) relative to those not taking lithium (n = 8).


CONCLUSIONS
These brain maps are consistent with previous voxel-based morphometry reports of greater GMD in portions of the anterior limbic network in bipolar patients and suggest neurotrophic effects of lithium as a possible etiology of these neuroanatomic differences.
Bearden
Carrie E
CE
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California 90095, USA. cbearden@mednet.ucla.edu
Thompson
Paul M
PM
Dalwani
Manish
M
Hayashi
Kiralee M
KM
Lee
Agatha D
AD
Nicoletti
Mark
M
Trakhtenbroit
Michael
M
Glahn
David C
DC
Brambilla
Paolo
P
Sassi
Roberto B
RB
Mallinger
Alan G
AG
Frank
Ellen
E
Kupfer
David J
DJ
Soares
Jair C
JC
D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000188:drug therapy*; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008032:Limbic System / Q000187:drug effects / Q000473:pathology; D018020:Lithium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use
D019208:Brain-Derived Neurotrophic Factor; D018020:Lithium Compounds; D018696:Neuroprotective Agents