Genetic risk for bipolar disorder and schizophrenia predicts structure and function of the ventromedial prefrontal cortex

被引：16

作者：

Abe, Christoph ^{[1
]}

Petrovic, Predrag ^{[1
]}

Ossler, William ^{[1
]}

Thompson, William H. ^{[1
,2
]}

Liberg, Benny ^{[1
]}

Song, Jie ^{[3
]}

Bergen, Sarah E. ^{[3
]}

Sellgren, Carl M. ^{[4
]}

Fransson, Peter ^{[1
]}

Ingvar, Martin ^{[1
,5
]}

Landen, Mikael ^{[1
,6
]}

机构：

[1] Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden

[2] Stanford Univ, Dept Psychol, Stanford, CA USA

[3] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[4] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden

[5] Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden

[6] Gothenburg Univ, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden

来源：

JOURNAL OF PSYCHIATRY & NEUROSCIENCE | 2021年 / 46卷 / 04期

基金：

瑞典研究理事会; 英国医学研究理事会;

关键词：

HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; CORTICAL THICKNESS; ASSOCIATION; NETWORK; SELF; MRI; SEGMENTATION; VARIANTS; AREA;

D O I：

10.1503/jpn.200165

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Bipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders. Methods: We tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics. Results: Higher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network. Limitations: Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined. Conclusion: Our multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging-genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.

引用

页码：E441 / E450

页数：10

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