Dataset Information

Polygenic Risk for Schizophrenia Influences Cortical Gyrification in 2 Independent General Populations.

ABSTRACT: Schizophrenia is highly heritable, whereas the effect of each genetic variant is very weak. Since clinical heterogeneity and complexity of schizophrenia is high, considerable effort has been made to relate genetic variants to underlying neurobiological aspects of schizophrenia (endophenotypes). Given the polygenic nature of schizophrenia, our goal was to form a measure of additive genetic risk and explore its relationship to cortical morphology. Utilizing the data from a recent genome-wide association study that included nearly 37 000 cases of schizophrenia, we computed a polygenic risk score (PGRS) for each subject in 2 independent and healthy general populations. We then investigated the effect of polygenic risk for schizophrenia on cortical gyrification calculated from 3.0T structural imaging data in the discovery dataset (N = 315) and replication dataset (N = 357). We found a consistent effect of the polygenic risk for schizophrenia on cortical gyrification in the inferior parietal lobules in 2 independent general-population samples. A higher PGRS was significantly associated with a lower local gyrification index in the bilateral inferior parietal lobles, where case-control differences have been reported in previous studies on schizophrenia. Our findings strongly support the effectiveness of both PGRSs and endophenotypes in establishing the genetic architecture of psychiatry. Our findings may provide some implications regarding individual differences in the genetic risk for schizophrenia to cortical morphology and brain development.

SUBMITTER: Liu B

PROVIDER: S-EPMC5463795 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Polygenic Risk for Schizophrenia Influences Cortical Gyrification in 2 Independent General Populations.

Liu Bing B Zhang Xiaolong X Cui Yue Y Qin Wen W Tao Yan Y Li Jin J Yu Chunshui C Jiang Tianzi T

Schizophrenia bulletin 20170501 3

Schizophrenia is highly heritable, whereas the effect of each genetic variant is very weak. Since clinical heterogeneity and complexity of schizophrenia is high, considerable effort has been made to relate genetic variants to underlying neurobiological aspects of schizophrenia (endophenotypes). Given the polygenic nature of schizophrenia, our goal was to form a measure of additive genetic risk and explore its relationship to cortical morphology. Utilizing the data from a recent genome-wide assoc ...[more]

PMID: 27169464

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Project description:There has been a long argument over whether schizophrenia is a neurodegenerative disorder associated with progressive cognitive impairment. Given high heritability of schizophrenia, ascertaning if genetic susceptibility to schizophrenia is also associated with cognitive decline in healthy people would support the view that schizophrenia leads to an accelerated cognitive decline. Using the population representative sample of 6817 adults aged >50 years from the English Longitudinal Study of Ageing, we investigated associations between the biennial rate of decline in cognitive ability and the schizophrenia polygenic score (SZ-PGS) during the 10-year follow-up period. SZ-PGS was calculated based on summary statistics from the Schizophrenia Working Group of the Psychiatric Genomics Consortium. Cognition was measured sequentially across four time points using verbal memory and semantic fluency tests. The average baseline verbal memory was 10.4 (SD = 3.4) and semantic fluency was 20.7 (SD = 6.3). One standard deviation (1-SD) increase in SZ-PGS was associated with lower baseline semantic fluency (β = -0.25, 95%CI = -0.40 to -0.10, p = 0.002); this association was significant in men (β = -0.36, 95%CI = -0.59 to -0.12, p = 0.003) and in those who were aged 60-69 years old (β = -0.32, 95%CI = -0.58 to -0.05, p = 0.019). Similarly, 1-SD increase in SZ-PGS was associated with lower verbal memory score at baseline in men only (β = -0.12, 95%CI = -0.23 to -0.01, p = 0.040). However, SZ-PGS was not associated with a greater rate of decline in these cognitive domains during the 10-year follow-up. Our findings highlight that while genetic susceptibility to schizophrenia conveys developmental cognitive deficit, it is not associated with an ongoing cognitive decline, at least in later life. These results do not support the neo-Kraepelinian notion of schizophrenia as a genetically determined progressively deteriorating brain disease.

Project description:The aberration in cortical gyrification seen in schizophrenia likely originates in the earliest phase of life, as gyrification begins in utero and reaches its peak in infancy. However, emerging observations have indicated a later reduction in gyrification, especially in early adulthood, may also occur in schizophrenia. At present, it is unclear whether the baseline and later gyrification reduction has any prognostic importance in schizophrenia. We address this question in a longitudinal design in patients minimally medicated at inception. About 108 minimally medicated (duration of medication = <14 days of antipsychotics) patients and 106 healthy controls underwent structural magnetic resonance imaging, with 34 patients being selectively re-scanned when clinically stable following antipsychotic treatment. The cortical surface from each structural image was reconstructed, and the local gyrification index and cortical thickness were computed for each vertex on the surface. We found minimally medicated schizophrenia patients during the first episode had a relatively higher gyrification in bilateral supramarginal, left superior temporal, and right posterior cingulate and paracentral regions. However, poor prognostic features were more likely in patients with lower baseline gyrification. Longitudinal reductions in left superior parietal and right precentral gyrification were associated with lower improvements in both positive and negative symptoms over time. The spatial pattern of longitudinal changes in gyrification was distinct from the changes in cortical thickness. These results indicated that schizophrenia is characterized by a relative hypergyrification in parieto-temporal and medial cortical areas at a group level at first presentation, but poor outcomes relate to lower-gyrification elsewhere both at the onset and during the early course. The early post-onset reduction of gyrification is rather limited in space and magnitude, but occurs unrelated to the progressive thinning, representing a distinct, prognostically important structural trajectory.

Project description:Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder, particularly among military personnel and veterans. Cortical gyrification, as a specific metric derived from structural MRI, is an index of the convoluted folding and patterning of the gyri and sulci, and is thought to facilitate the efficiency of local neuronal wiring. It has the potential to act as a neurobiological risk factor for emergent psychiatric disorders - to date, it has been understudied in PTSD. Here, using a local measure of the degree of gyrification (local Gyrification Index, lGI) we investigate cortical gyrification morphology in 48 adult male soldiers with (n = 23) and without (n = 25) a PTSD diagnosis. We also examine the relation between lGI and PTSD severity within the PTSD group. General linear models yielded significant between-group differences with greater lGI found in PTSD in a cluster located in the medial occipito-parietal lobe on the left hemisphere and reduced lGI in a cluster located on the lateral surface of the parietal lobe on the right hemisphere. Brain-behaviour analyses within the PTSD group yielded significant positive associations between lGI and PTSD severity in a cluster located in the frontal cortex of the left hemisphere and scattered clusters located within all lobes of the right hemisphere. After accounting for the effects of comorbid psychiatric symptoms common in PTSD, the associations in the right hemisphere reduced to clusters only located in the frontal lobe, while the cluster in the left hemisphere remained significant. Our results suggest that atypical cortical gyrification in parietal and occipital regions may be implicated in the psychopathology of PTSD diagnosis, and properties of prefrontal gyrification associated with the emergent severity of PTSD after trauma. The importance of these regions in PTSD may be attributed to a pre-existing neurobiological risk factor, or neuromorphological changes after trauma precipitating emergent psychiatric illness. Our brain-behaviour relations provide support for the existing literature by highlighting the importance of the frontal lobe in the pathogenesis of PTSD. Future large-scale longitudinal studies including female participants may infer causal implications of atypical gyrification in PTSD and shed light on the potential effect of sex on this brain metric.

Dataset Information

Polygenic Risk for Schizophrenia Influences Cortical Gyrification in 2 Independent General Populations.

Publications

Polygenic Risk for Schizophrenia Influences Cortical Gyrification in 2 Independent General Populations.

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