Objectives: A sizable fraction of people with bipolar I disorder (BDI) experience a deteriorating clinical course with increasingly frequent mood episodes and chronic disability. This is believed to result from neurobiological illness progression, or neuroprogression. Excessive weight gain predicts neuroprogression across multiple brain illnesses, but no prospective studies have investigated this in BDI. The objective of this study was to determine whether BDI patients who experienced clinically significant weight gain (CSWG; gaining ≥7% of baseline weight) over 12 months had greater 12-month brain volume loss in frontal and temporal regions important to BDI. Methods: In 55 early-stage BDI patients we measured (i) rates of CSWG, (ii) the number of days with mood symptoms, using NIMH LifeCharts, and (iii) baseline and 12-month brain volumes, using 3T MRI. We quantified brain volumes using the longitudinal processing stream in FreeSurfer v6.0. We used general linear models for repeated measures to investigate whether CSWG predicted volume loss, adjusting for potentially confounding clinical and treatment variables. Results: After correction for multiple comparisons, CSWG in patients predicted greater volume loss in the left orbitofrontal cortex (effect size [ES; Cohen's d] = −1.01, P = 0.002), left cingulate gyrus (ES = −1.31, P < 0.001), and left middle temporal gyrus (ES = −0.96, P = 0.004). Middle temporal volume loss predicted more days with depression (β = −0.406, P = 0.010). Conclusions: These are the first prospective data on weight gain and neuroprogression in BDI. CSWG predicted neuroprogression, and neuroprogression predicted a worse clinical illness course. Trials of weight loss interventions are needed to confirm the causal direction of the weight gain-neuroprogression relationship, and to determine whether weight loss is a disease-modifying treatment.
Bibliographical noteFunding Information:
The data for this manuscript were generated from the Systematic Treatment Optimization Program for Early Mania (STOP‐EM), which was supported by an unrestricted grant to LNY from AstraZeneca Canada. The sponsor had no input into the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or ap‐ proval of the manuscript. Dr. Bond has received speaking/consult‐ ing fees or research grants from the Canadian Institutes of Health Research (CIHR), the Canadian Network for Mood and Anxiety Treatments (CANMAT), and Myriad Genetics. Mr. Su, Ms. Dhanoa, Ms. Batres‐y‐Carr, and Dr. Lee declare no conflicts of interest. Dr. Honer has been on advisory boards for In Silico, Otsuka/Lundbeck, Roche, and Eli Lily. He was additionally supported by the UBC Jack Bell Chair in Schizophrenia. Dr. Torres has received speaking/ consulting fees or research grants from CIHR, Lundbeck Canada, and Sumitomo Dainippon. Dr. Lam has been on speaker/advisory boards for, or has received research grants from Asia‐Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol Myers Squibb, Canadian Depression Research and Intervention Network, CANMAT, CIHR, CPA, Janssen, Lundbeck, Lundbeck Institute, Medscape, Movember Foundation, Otsuka, Pfizer, St. Jude Medical, and Takeda. Dr. Yatham has been on speaker/advisory
boards for, or has received research grants from AstraZeneca, Bristol Myers Squibb, CANMAT, CIHR, Eli Lilly, GlaxoSmithKline, Janssen, the Michael Smith Foundation for Health Research, Pfizer, Servier, Sunovion, and the Stanley Foundation.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Copyright 2019 Elsevier B.V., All rights reserved.
- bipolar disorder
- body mass index
- weight gain