Open AccessBrain‐wide versus genome‐wide vulnerability biomarkers for severe mental illnesses
Author(s) -
Kochunov Peter,
Ma Yizhou,
Hatch Kathryn S.,
Gao Si,
Jahanshad Neda,
Thompson Paul M.,
Adhikari Bhim M.,
Bruce Heather,
Van der vaart Andrew,
Goldwaser Eric L.,
Sotiras Aris,
Kvarta Mark D.,
Ma Tianzhou,
Chen Shuo,
Nichols Thomas E.,
Hong L. Elliot
Publication year - 2022
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.26056
Subject(s) - major depressive disorder , schizophrenia (object oriented programming) , bipolar disorder , biobank , psychology , vulnerability (computing) , medicine , polygenic risk score , psychiatry , clinical psychology , oncology , cognition , bioinformatics , genetics , gene , biology , genotype , single nucleotide polymorphism , computer security , computer science
Abstract Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual's brain‐wide similarity to the expected SMI patterns derived from meta‐analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual's similarity to genome‐wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 ± 7.4 years) and an independent sample of SSD patients and controls ( N = 115/111 M/F, age = 35.2 ± 13.4) were used to test this hypothesis. UKBB participants with MDD had significantly higher RVI‐MDD (Cohen's d = 0.20, p = 1 × 10 −23 ) and PRS‐MDD ( d = 0.17, p = 1 × 10 −15 ) than nonpsychiatric controls. UKBB participants with BD and SSD showed significant elevation in the respective RVIs ( d = 0.65 and 0.60; p = 3 × 10 −5 and .009, respectively) and PRS ( d = 0.57 and 1.34; p = .002 and .002, respectively). Elevated RVI‐SSD were replicated in an independent sample ( d = 0.53, p = 5 × 10 −5 ). RVI‐MDD and RVI‐SSD but not RVI‐BD were associated with childhood adversity ( p < .01). In nonpsychiatric controls, elevation in RVI and PRS were associated with lower cognitive performance ( p < 10 −5 ) in six out of seven domains and showed specificity with disorder‐associated deficits. In summary, the RVI is a novel brain index for SMI and shows similar or better specificity for SMI than PRS, and together they may complement each other in the efforts to characterize the genomic to brain level risks for SMI.