TY - JOUR
T1 - Sex differences in cerebral blood flow among adolescents with bipolar disorder
AU - Mitchell, Rachel H. B.
AU - Grigorian, Anahit
AU - Robertson, Andrew
AU - Toma, Simina
AU - Luciw, Nicholas J.
AU - Karthikeyan, Sudhir
AU - Mutsaerts, Henri J. M. M.
AU - Fiksenbaum, Lisa
AU - Metcalfe, Arron W. S.
AU - MacIntosh, Bradley J.
AU - Goldstein, Benjamin I.
N1 - Funding Information: This study was funded by grants from the Ontario Mental Health Foundation and Canadian Institutes of Health Research (MOP 136947). Funding Information: Dr. Mitchell acknowledges research grant support from the American Foundation for Suicide Prevention, the TD Charitable Pooler Fund, the Alternative Funding Plan Innovation Fund at Sunnybrook Health Sciences Centre, the Sunnybrook Foundation outside of the submitted work, an honourarium from Medscape outside of the submitted work, and Academic Scholar Awards from the Department of Psychiatry at the University of Toronto and Sunnybrook Health Sciences Centre. Dr. Metcalfe is Director of Research of Canadian Health Solutions, Inc. and Canadian Imaging Research Centre. Canadian Health Solutions provides medical assessment services to institutional insurers in Canada. Canadian Imaging Research Centre provides imaging research services and diagnostics development for clients. The current research is unrelated to these roles, and Dr. Metcalfe's contribution to the current research predates these roles. Dr. Goldstein acknowledges research grant support from Brain Canada, Canadian Institutes of Health Research, Heart and Stroke Foundation, Dr. Goldstein also acknowledges his position as RBC Investments Chair in Children's Mental Health and Developmental Psychopathology at CAMH, a joint Hospital‐University Chair between the University of Toronto, CAMH, and the CAMH Foundation. Publisher Copyright: © 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.
PY - 2023
Y1 - 2023
N2 - Background: Abnormalities in cerebral blood flow (CBF) are common in bipolar disorder (BD). Despite known differences in CBF between healthy adolescent males and females, sex differences in CBF among adolescents with BD have never been studied. Objective: To examine sex differences in CBF among adolescents with BD versus healthy controls (HC). Methods: CBF images were acquired using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in 123 adolescents (72 BD: 30M, 42F; 51 HC: 22M, 29F) matched for age (13–20 years). Whole brain voxel-wise analysis was performed in a general linear model with sex and diagnosis as fixed factors, sex–diagnosis interaction effect, and age as a covariate. We tested for main effects of sex, diagnosis, and their interaction. Results were thresholded at cluster forming p = 0.0125, with posthoc Bonferroni correction (p = 0.05/4 groups). Results: A main effect of diagnosis (BD > HC) was observed in the superior longitudinal fasciculus (SLF), underlying the left precentral gyrus (F =10.24 (3), p < 0.0001). A main effect of sex (F > M) on CBF was detected in the precuneus/posterior cingulate cortex (PCC), left frontal and occipital poles, left thalamus, left SLF, and right inferior longitudinal fasciculus (ILF). No regions demonstrated a significant sex-by-diagnosis interaction. Exploratory pairwise testing in regions with a main effect of sex revealed greater CBF in females with BD versus HC in the precuneus/PCC (F = 7.1 (3), p < 0.01). Conclusion: Greater CBF in female adolescents with BD versus HC in the precuneus/PCC may reflect the role of this region in the neurobiological sex differences of adolescent-onset BD. Larger studies targeting underlying mechanisms, such as mitochondrial dysfunction or oxidative stress, are warranted.
AB - Background: Abnormalities in cerebral blood flow (CBF) are common in bipolar disorder (BD). Despite known differences in CBF between healthy adolescent males and females, sex differences in CBF among adolescents with BD have never been studied. Objective: To examine sex differences in CBF among adolescents with BD versus healthy controls (HC). Methods: CBF images were acquired using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in 123 adolescents (72 BD: 30M, 42F; 51 HC: 22M, 29F) matched for age (13–20 years). Whole brain voxel-wise analysis was performed in a general linear model with sex and diagnosis as fixed factors, sex–diagnosis interaction effect, and age as a covariate. We tested for main effects of sex, diagnosis, and their interaction. Results were thresholded at cluster forming p = 0.0125, with posthoc Bonferroni correction (p = 0.05/4 groups). Results: A main effect of diagnosis (BD > HC) was observed in the superior longitudinal fasciculus (SLF), underlying the left precentral gyrus (F =10.24 (3), p < 0.0001). A main effect of sex (F > M) on CBF was detected in the precuneus/posterior cingulate cortex (PCC), left frontal and occipital poles, left thalamus, left SLF, and right inferior longitudinal fasciculus (ILF). No regions demonstrated a significant sex-by-diagnosis interaction. Exploratory pairwise testing in regions with a main effect of sex revealed greater CBF in females with BD versus HC in the precuneus/PCC (F = 7.1 (3), p < 0.01). Conclusion: Greater CBF in female adolescents with BD versus HC in the precuneus/PCC may reflect the role of this region in the neurobiological sex differences of adolescent-onset BD. Larger studies targeting underlying mechanisms, such as mitochondrial dysfunction or oxidative stress, are warranted.
KW - adolescents
KW - bipolar disorder
KW - cerebral blood flow
KW - sex differences
UR - http://www.scopus.com/inward/record.url?scp=85159901411&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bdi.13326
DO - https://doi.org/10.1111/bdi.13326
M3 - Article
C2 - 37217255
SN - 1398-5647
JO - Bipolar disorders
JF - Bipolar disorders
ER -