Dataset Information

Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

ABSTRACT: Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (mean gestational age 29.7 weeks), we combined Magnetic Resonance Imaging with a polygenic risk score (PRS) for five psychiatric pathologies to test the prediction that: deep grey matter abnormalities frequently seen in preterm infants are associated with increased polygenic risk for psychiatric illness. The variance explained by the PRS in the relative volumes of four deep grey matter structures (caudate nucleus, thalamus, subthalamic nucleus and lentiform nucleus) was estimated using linear regression both for the full, mixed ancestral, cohort and a subsample of European infants. Psychiatric PRS was negatively associated with lentiform volume in the full cohort (??=?-0.24, p?=?8?×?10^-4) and a European subsample (??=?-0.24, p?=?8?×?10^-3). Genetic variants associated with neuropsychiatric disease increase vulnerability to abnormal lentiform development after perinatal stress and are associated with neuroanatomic changes in the perinatal period.

SUBMITTER: Cullen H

PROVIDER: S-EPMC6374514 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

Cullen Harriet H Krishnan Michelle L ML Selzam Saskia S Ball Gareth G Visconti Alessia A Saxena Alka A Counsell Serena J SJ Hajnal Jo J Breen Gerome G Plomin Robert R Edwards A David AD

Scientific reports 20190213 1

Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (m ...[more]

PMID: 30760829

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Project description:In Parkinson's disease (PD), pathological microstructural changes occur and such changes might be detected using diffusion magnetic resonance imaging (dMRI). However, it is unclear whether dMRI improves PD diagnosis or helps differentiating between phenotypes, such as postural instability gait difficulty (PIGD) and tremor dominant (TD) PD. We included 105 patients with PD and 44 healthy controls (HC), all of whom underwent dMRI as part of the prospective Swedish BioFINDER study. Diffusion kurtosis imaging (DKI) and neurite density imaging (NDI) analyses were performed using regions of interest in the basal ganglia, the thalamus, the pons and the midbrain as well as tractography of selected white matter tracts. In the putamen, the PD group showed increased mean diffusivity (MD) (p = .003), decreased fractional anisotropy (FA) (p = .001) and decreased mean kurtosis (MK), compared to HC (p = .024). High MD and a low MK in the putamen were associated with more severe motor and cognitive symptomatology (p < .05). Also, patients with PIGD exhibited increased MD in the putamen compared to the TD patients (p = .009). In the thalamus, MD was increased (p = .001) and FA was decreased (p = .032) in PD compared to HC. Increased MD and decreased FA correlated negatively with motor speed and balance (p < .05). In the superior longitudinal fasciculus (SLF), MD (p = .019) and fiso were increased in PD compared to HC (p = .03). These changes correlated negatively with motor speed (p < .002) and balance (p < .037). However, most of the observed changes in PD were also present in cases with either multiple system atrophy (n = 11) or progressive supranuclear palsy (n = 10). In conclusion, PD patients exhibit microstructural changes in the putamen, the thalamus, and the SLF, which are associated with worse disease severity. However, the dMRI changes are not sufficiently specific to improve the diagnostic work-up of PD. Longitudinal studies should evaluate whether dMRI measures can be used to track disease progression.

Dataset Information

Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

Publications

Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

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