Influence of genes and environment on brain volumes in twin pairs concordant and discordant for bipolar disorder.
BACKGROUND
Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown.


OBJECTIVE
To investigate the contribution of genetic and environmental factors on brain volume in bipolar disorder.


METHODS
Magnetic resonance imaging (1.5 T) brain scans of monozygotic (MZ) or dizygotic (DZ) twins concordant and discordant for bipolar disorder were compared with healthy twin pairs.


METHODS
Subjects were recruited from the population, the Netherlands Twin Register, and the twin pair cohort at the University Medical Center Utrecht, Utrecht, The Netherlands.


METHODS
A total of 234 subjects including 50 affected twin pairs (9 MZ concordant; 15 MZ discordant; 4 DZ concordant; 22 DZ discordant) and 67 healthy twin pairs (39 MZ and 28 DZ) were included.


METHODS
Volumes of the intracranium, cerebrum, cerebellum, lateral and third ventricle, and gray and white matter from the cerebrum and frontal, parietal, temporal, and occipital lobes, both with and without correction for lithium use. To estimate the influence of additive genetic, common, and unique environmental factors, structural equation modeling was applied.


RESULTS
Bipolar disorder was associated with a decrease in total cortical volume. Decreases in white matter were related to the genetic risk of developing bipolar disorder (bivariate heritability, 77%; 95% confidence interval, 38% to 100%). Significant environmental correlations were found for cortical gray matter. These relationships all became more pronounced when data were corrected for lithium use.


CONCLUSIONS
Focusing on genes controlling white matter integrity may be a fruitful strategy in the quest to discover genes implicated in bipolar disorder. Elucidating the mechanism by which lithium attenuates brain matter loss may lead to the development of neuroprotective drugs.
van der Schot
Astrid C
AC
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Vonk
Ronald
R
Brans
Rachel G H
RG
van Haren
Neeltje E M
NE
Koolschijn
P Cédric M P
PC
Nuboer
Valerie
V
Schnack
Hugo G
HG
van Baal
G Caroline M
GC
Boomsma
Dorret I
DI
Nolen
Willem A
WA
Hulshoff Pol
Hilleke E
HE
Kahn
René S
RS
D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D015331:Cohort Studies; D004200:Diseases in Twins / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D016651:Lithium Carbonate / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009929:Organ Size; D010641:Phenotype; D012931:Social Environment; D014429:Twins, Dizygotic / Q000235:genetics / Q000523:psychology; D014430:Twins, Monozygotic / Q000235:genetics / Q000523:psychology; D055815:Young Adult
D018692:Antimanic Agents; D016651:Lithium Carbonate