J Psychiatry Neurosci 2018;43(2):120-130
Alvi H. Islam, MSc; Arron W.S. Metcalfe, PhD; Bradley J. MacIntosh, PhD; Daphne J. Korczak, MD, MSc; Benjamin I. Goldstein, MD, PhD
Background: Higher body mass index (BMI) and obesity is common among youth with bipolar disorder (BD) and is associated with greater psychiatric illness severity, including suicidality. Obesity has been associated with frontal, temporal and subcortical volumetric reductions in adults with BD. We examined the neurostructural correlates of BMI in adolescents early in their course of BD.
Methods: We processed T1-weighted images of adolescents with BD and psychiatrically healthy controls using FreeSurfer to derive a priori region of interest (ROI) volumes/cortical thickness for the frontal lobe (FL), prefrontal cortex (PFC) and orbitofrontal cortex (OFC) as well as volumes for the amygdala and hippocampus. General linear models assessed the association between BMI and the ROIs, controlling for age, sex and intracranial volume. We also conducted exploratory within-BD group and whole brain vertex-wise analyses.
Results: We included 40 adolescents with BD and 48 controls in our analyses. In addition to a main effect of BMI on the ROIs, there were significant diagnosis × BMI interaction effects on FL volumes. In the BD group only, BMI was negatively associated with FL, OFC and PFC cortical thickness. Whole brain analysis of BMI–volume correlations revealed 2 significant interaction clusters: 1 in the medial OFC and 1 in the caudal anterior cingulate cortex, with BD showing a stronger negative correlation.
Limitations: Reliance on BMI rather than a more nuanced measure of obesity may have influenced the findings.
Conclusion: Our results suggest that elevated BMI among adolescents with BD is associated with frontal neurostructural differences that are not observed in controls. Prospective studies examining the direction of the observed associations and the effect of BMI optimization on brain structure in adolescents with BD are warranted.
Submitted Feb. 15, 2017; Revised July 5, 2017; Revised Aug. 20, 2017; Accepted Sept. 5, 2017; Online first Oct. 31, 2017
Acknowledgements: This study was funded by the Ontario Mental Health Foundation and the Canadian Institutes of Health Research [CIHR MOP 136947]. The authors thank MRI technologists Ruby Endre and Garry Detzler for their unwavering support with scanning participants and data collection.
Affiliations: From the Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Ont., Canada (Islam, Metcalfe, Goldstein); the Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Korczak, Goldstein); the Hurvitz Brain Sciences, Sunnybrook Research Institute, Toronto, Ont., Canada (Metcalfe, MacIntosh); the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ont., Canada (Metcalfe, MacIntosh, Goldstein); the Hospital for Sick Children, Toronto, Ont., Canada (Korczak); the Department of Medical Biophysics, University of Toronto, Toronto, Ont., Canada (MacIntosh); the Department of Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, Ont., Canada (MacIntosh); and the Department of Pharmacology, University of Toronto, Toronto, Ont., Canada (Goldstein).
Competing interests: A. Metcalfe declares having started a position at the Canadian Imaging Research Centre, a private diagnostic imaging company, after submission of the final version of the present work. No other competing interests declared.
Contributors: A. Islam, B. MacIntosh and B. Goldstein designed the study. A. Islam acquired and analyzed the data, which A. Metcalfe, B. MacIntosh and D. Korczak also analyzed. A. Islam wrote the article, which all authors critically reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: B.I. Goldstein, Sunnybrook Health Sciences Centre, FG-53, 2075 Bayview Ave., Toronto ON M4N 3M5; email@example.com