Dataset Information

Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures.

ABSTRACT: Sex chromosome aneuploidy (SCA) increases risk for several psychiatric disorders associated with the limbic system, including mood and autism spectrum disorders. Thus, SCA offers a genetics-first model for understanding the biological basis of psychopathology. Additionally, the sex-biased prevalence of many psychiatric disorders could potentially reflect sex chromosome dosage effects on brain development. To clarify how limbic anatomy varies across sex and sex chromosome complement, we characterized amygdala and hippocampus structure in a uniquely large sample of patients carrying supernumerary sex chromosomes (n = 132) and typically developing controls (n = 166). After adjustment for sex-differences in brain size, karyotypically normal males (XY) and females (XX) did not differ in volume or shape of either structure. In contrast, all SCAs were associated with lowered amygdala volume relative to gonadally-matched controls. This effect was robust to three different methods for total brain volume adjustment, including an allometric analysis that derived normative scaling rules for these structures in a separate, typically developing population (n = 79). Hippocampal volume was insensitive to SCA after adjustment for total brain volume. However, surface-based analysis revealed that SCA, regardless of specific karyotype, was consistently associated with a spatially specific pattern of shape change in both amygdala and hippocampus. In particular, SCA was accompanied by contraction around the basomedial nucleus of the amygdala and an area crossing the hippocampal tail. These results demonstrate the power of SCA as a model to understand how copy number variation can precipitate changes in brain systems relevant to psychiatric disease.

SUBMITTER: Nadig A

PROVIDER: S-EPMC6354783 | biostudies-literature | 2018 Sep-Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures.

Nadig Ajay A Reardon Paul K PK Seidlitz Jakob J McDermott Cassidy L CL Blumenthal Jonathan D JD Clasen Liv S LS Lalonde Francois F Lerch Jason P JP Chakravarty M Mallar MM Raznahan Armin A

eNeuro 20180901 5

Sex chromosome aneuploidy (SCA) increases risk for several psychiatric disorders associated with the limbic system, including mood and autism spectrum disorders. Thus, SCA offers a genetics-first model for understanding the biological basis of psychopathology. Additionally, the sex-biased prevalence of many psychiatric disorders could potentially reflect sex chromosome dosage effects on brain development. To clarify how limbic anatomy varies across sex and sex chromosome complement, we character ...[more]

PMID: 30713992

Similar Datasets

Project description:ObjectiveThe limbic system is involved in memory and in processing of emotional stimuli. We measured volume of the hippocampus, amygdala, and thalamus, and assessed their relative contribution to episodic memory and emotion identification in POMS.MethodSixty-five POMS participants (Mage = 18.3 ± 3.9 years; 48 female (73.8%)), average disease duration = 3.8 ± 3.8 years) and 76 age- and sex-matched controls (Mage = 18.1 ± 4.6 years; 49 female (64.5%)) completed the Penn Computerized Neurocognitive Battery (PCNB); 59 of 65 POMS participants and 69 out of 76 controls underwent 3 T MRI scanning. We derived age-adjusted Z-scores on accuracy and response time (RT) measures of episodic memory and emotion identification of the PCNB. Magnetic resonance imaging (MRI) volumetrics were normalized using the scaling factor computed by SIENAx. On PCNB tests that differed between groups, we used multiple linear regression to assess relationships between regional brain volumes and either episodic memory or emotion identification outcomes controlling for age, sex, accuracy/RT, and parental education.ResultsPOMS participants were slower and less accurate than controls on the episodic memory domain but did not differ from controls on emotion outcomes. At the subtest level, POMS participants showed reduced accuracy on Word Memory (p = .002) and slower performance on Face Memory (p = .04) subtests. POMS participants had smaller total and regional brain volumes of the hippocampus, amygdala, and thalamus (p values ≤ 0.01). Collapsing across groups, both hippocampal and thalamic volume were significant predictors of Word Memory accuracy; hippocampal volume (B = 0.24, SE = 0.10, p = .02) was more strongly associated with Word Memory performance than thalamic volume (B = 0.16, SE = 0.05, p = .003), though the estimate with was less precise.ConclusionsPOMS participants showed reduced episodic memory performance compared to controls. Aspects of episodic memory performance were associated with hippocampal and thalamic volume. Emotion identification was intact, despite volume loss in the amygdala.

Dataset Information

Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures.

Publications

Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets