TY - JOUR
T1 - Ancestral, Pregnancy, and Negative Early-Life Risks Shape Children's Brain (Dis)similarity to Schizophrenia
AU - Kochunov, Peter
AU - Ma, Yizhou
AU - Hatch, Kathryn S.
AU - Gao, Si
AU - Acheson, Ashley
AU - Jahanshad, Neda
AU - Thompson, Paul M.
AU - Adhikari, Bhim M.
AU - Bruce, Heather
AU - Van der vaart, Andrew
AU - Chiappelli, Joshua
AU - Du, Xiaoming
AU - Sotiras, Aris
AU - Kvarta, Mark D.
AU - Ma, Tianzhou
AU - Chen, Shuo
AU - Hong, L. Elliot
N1 - Funding Information:
This work was supported by the National Institutes of Health (Grant Nos. R01MH123163 [to PK, PMT], R01MH112180 and R01MH116948 [to LEH], S10OD023696 [to PK], R01EB015611 [to PK], R01MH117601 [to NJ], R01AG095874 and R01MH116147 [to PMT], P50MH103222 [to PK, LEH], and U01MH108148 [to LEH, PK]). These funding sources provided financial support to enable design and conduct of the study or collection, management, or analysis of the data. None of the funding agencies had a role in the interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. LEH has received or plans to receive research funding or consulting fees on research projects from Mitsubishi, Your Energy Systems LLC, Neuralstem, Taisho, Heptares, Pfizer, Luye Pharma, Sound Pharma, IGC Pharma, Takeda, and Regeneron. None of these were involved in the design, analysis, or outcomes of the study. PMT and NJ received grant support from Biogen, Inc. for research unrelated to the topic of this manuscript. All other authors report no biomedical financial interests or potential conflicts of interest.
Funding Information:
This work was supported by the National Institutes of Health (Grant Nos. R01MH123163 [to PK, PMT] , R01MH112180 and R01MH116948 [to LEH] , S10OD023696 [to PK] , R01EB015611 [to PK] , R01MH117601 [to NJ] , R01AG095874 and R01MH116147 [to PMT] , P50MH103222 [to PK, LEH] , and U01MH108148 [to LEH, PK] ).
Funding Information:
LEH has received or plans to receive research funding or consulting fees on research projects from Mitsubishi, Your Energy Systems LLC, Neuralstem, Taisho, Heptares, Pfizer, Luye Pharma, Sound Pharma, IGC Pharma, Takeda, and Regeneron. None of these were involved in the design, analysis, or outcomes of the study. PMT and NJ received grant support from Biogen, Inc. for research unrelated to the topic of this manuscript. All other authors report no biomedical financial interests or potential conflicts of interest.
Publisher Copyright:
© 2023 Society of Biological Psychiatry
PY - 2023/8/15
Y1 - 2023/8/15
N2 - Background: Familial, obstetric, and early-life environmental risks for schizophrenia spectrum disorder (SSD) alter normal cerebral development, leading to the formation of characteristic brain deficit patterns prior to onset of symptoms. We hypothesized that the insidious effects of these risks may increase brain similarity to adult SSD deficit patterns in prepubescent children. Methods: We used data collected by the Adolescent Brain Cognitive Development (ABCD) Study (N = 8940, age = 9.9 ± 0.1 years, 4307/4633 female/male), including 727 (age = 9.9 ± 0.1 years, 351/376 female/male) children with family history of SSD, to evaluate unfavorable cerebral effects of ancestral SSD history, pre/perinatal environment, and negative early-life environment. We used a regional vulnerability index to measure the alignment of a child's cerebral patterns with the adult SSD pattern derived from a large meta-analysis of case-control differences. Results: In children with a family history of SSD, the regional vulnerability index captured significantly more variance in ancestral history than traditional whole-brain and regional brain measurements. In children with and without family history of SSD, the regional vulnerability index also captured more variance associated with negative pre/perinatal environment and early-life experiences than traditional brain measurements. Conclusions: In summary, in a cohort in which most children will not develop SSD, familial, pre/perinatal, and early developmental risks can alter brain patterns in the direction observed in adult patients with SSD. Individual similarity to adult SSD patterns may provide an early biomarker of the effects of genetic and developmental risks on the brain prior to psychotic or prodromal symptom onset.
AB - Background: Familial, obstetric, and early-life environmental risks for schizophrenia spectrum disorder (SSD) alter normal cerebral development, leading to the formation of characteristic brain deficit patterns prior to onset of symptoms. We hypothesized that the insidious effects of these risks may increase brain similarity to adult SSD deficit patterns in prepubescent children. Methods: We used data collected by the Adolescent Brain Cognitive Development (ABCD) Study (N = 8940, age = 9.9 ± 0.1 years, 4307/4633 female/male), including 727 (age = 9.9 ± 0.1 years, 351/376 female/male) children with family history of SSD, to evaluate unfavorable cerebral effects of ancestral SSD history, pre/perinatal environment, and negative early-life environment. We used a regional vulnerability index to measure the alignment of a child's cerebral patterns with the adult SSD pattern derived from a large meta-analysis of case-control differences. Results: In children with a family history of SSD, the regional vulnerability index captured significantly more variance in ancestral history than traditional whole-brain and regional brain measurements. In children with and without family history of SSD, the regional vulnerability index also captured more variance associated with negative pre/perinatal environment and early-life experiences than traditional brain measurements. Conclusions: In summary, in a cohort in which most children will not develop SSD, familial, pre/perinatal, and early developmental risks can alter brain patterns in the direction observed in adult patients with SSD. Individual similarity to adult SSD patterns may provide an early biomarker of the effects of genetic and developmental risks on the brain prior to psychotic or prodromal symptom onset.
KW - Adolescence
KW - Big data
KW - Brain development
KW - Imaging
KW - Individual prediction
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85158818095&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2023.03.009
DO - 10.1016/j.biopsych.2023.03.009
M3 - Article
C2 - 36948435
AN - SCOPUS:85158818095
SN - 0006-3223
VL - 94
SP - 332
EP - 340
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 4
ER -