CONTEXT: 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. DESIGN: 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. SETTING: Subjects were recruited from the population, the Netherlands Twin Register, and the twin pair cohort at the University Medical Center Utrecht, Utrecht, The Netherlands. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN: 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. SETTING: Subjects were recruited from the population, the Netherlands Twin Register, and the twin pair cohort at the University Medical Center Utrecht, Utrecht, The Netherlands. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
Authors: Jens Foell; Isabella M Palumbo; James R Yancey; Nathalie Vizueta; Traute Demirakca; Christopher J Patrick Journal: Neuroimage Date: 2018-10-28 Impact factor: 6.556
Authors: Hidayet E Arat; Virginie-Anne Chouinard; Bruce M Cohen; Kathryn E Lewandowski; Dost Öngür Journal: Schizophr Res Date: 2014-12-24 Impact factor: 4.939
Authors: Jenny van Dongen; P Eline Slagboom; Harmen H M Draisma; Nicholas G Martin; Dorret I Boomsma Journal: Nat Rev Genet Date: 2012-07-31 Impact factor: 53.242
Authors: Annabel Vreeker; Lucija Abramovic; Marco P M Boks; Sanne Verkooijen; Annet H van Bergen; Roel A Ophoff; René S Kahn; Neeltje E M van Haren Journal: J Affect Disord Date: 2017-07-06 Impact factor: 4.839
Authors: Anderson M Winkler; Peter Kochunov; John Blangero; Laura Almasy; Karl Zilles; Peter T Fox; Ravindranath Duggirala; David C Glahn Journal: Neuroimage Date: 2009-12-16 Impact factor: 6.556
Authors: P Cédric M P Koolschijn; Neeltje E M van Haren; Gerty J L M Lensvelt-Mulders; Hilleke E Hulshoff Pol; René S Kahn Journal: Hum Brain Mapp Date: 2009-11 Impact factor: 5.038
Authors: Esther Verstraete; Martijn P van den Heuvel; Jan H Veldink; Niels Blanken; René C Mandl; Hilleke E Hulshoff Pol; Leonard H van den Berg Journal: PLoS One Date: 2010-10-27 Impact factor: 3.240