Manpreet Sehmbi, PhD*; Christopher D. Rowley, PhD*; Luciano Minuzzi, MD, PhD; Flavio Kapczinski, MD, PhD; Jacek M. Kwiecien, DVM, MSc, PhD; Nicholas A. Bock, PhD; Benicio N. Frey, MD, MSc, PhD
Background: Previous studies have implicated white-matter-related changes in the pathophysiology of bipolar disorder. However, most of what is known is derived from in vivo subcortical white-matter imaging or postmortem studies. In this study, we investigated whole-brain intracortical myelin (ICM) content in people with bipolar disorder type I and controls.
Methods: Between Sept. 1, 2014, and Jan. 31, 2017, we used a 3 T General Electric scanner to collect T1-weighted images in 45 people with bipolar disorder type I and 60 controls aged 17 to 45 years using an optimized sequence that was sensitive to ICM content. We analyzed images using a surface-based approach. We used general linear models with quadratic age terms to examine the signal trajectory of ICM across the age range.
Results: In healthy controls, the T1-weighted signal followed an inverted-U trajectory over age; in people with bipolar disorder type I, the association between ICM and age followed a flat trajectory (p < 0.05, Bonferroni corrected). Exploratory analyses showed that ICM signal intensity was associated with duration of illness, age of onset, and anticonvulsant and antipsychotic use in people with bipolar disorder type I (p < 0.05, uncorrected). Limitations: Because of the cross-sectional nature of the study, we were unable to comment on whether the effects were due to dysmyelination or demyelination in bipolar disorder.
Conclusion: This foundational study is, to our knowledge, the first to show global age-related deficits in ICM maturation throughout the cortex in bipolar disorder. Considering the impact of myelination on the maintenance of neural synchrony and the integrity of neural connections, this work may help us better understand the cognitive and behavioural deficits seen in bipolar disorder.
*These authors contributed equally to this work.
Submitted Nov. 1, 2017; Revised Apr. 16, 2018; Accepted Jun. 3, 2018; Published online Dec. 10, 2018
Acknowledgements: This project was supported by an Independent Investigator Award, Brain and Behavior Research Foundation (Frey; grant number 22200) and the AFP Innovations Award, Department of Psychiatry and Behavioural Neurosciences, McMaster University (Minuzzi).
Affiliations: From the Graduate Student, MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON (Sehmbi, Rowley); the Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON (Minuzzi, Kapczinski, Frey); the Women’s Health Concerns Clinic, St. Joseph’s Healthcare, Hamilton, ON (Minuzzi, Frey); the Department of Pathology and Molecular Medicine, M. deGroote School of Medicine, McMaster University, Hamilton, ON (Kwiecien); the Department of Psychology, Neuroscience, and Behaviour, McMaster University, Hamilton, ON (Bock); and the Department of Clinical Pathomorphology, Medical University of Lublin, Poland (Kwiecien).
Competing interests: L. Minuzzi has received grants/research support from the Alternative Funding Plan Innovations Award, the Brain and Behavior Research Foundation, the Canadian Institutes of Health Research, the Hamilton Health Sciences Foundation, the Ontario Brain Institute and the Ontario Mental Health Foundation; and has received speaker fees/honoraria from Bristol-Myers Squibb, Lundbeck, Sunovion, the Canadian Psychiatric Association, CANMAT and Allergan. F. Kapczinski reports personal fees from Daiichi Sankyo and Janssen-Cilag, as well as grants from Stanley Medical Research Institute, INCT–CNPq and the Canada Foundation for Innovation, outside the submitted work. B. Frey has received grants/research support from the Brain and Behavior Research Foundation, the Canadian Institutes of Health Research, the J. P. Bickell Foundation, the Ontario Brain Institute, the Ontario Mental Health Foundation, the Ontario Ministry of Research and Innovation, the Society for Women’s Health Research and Pfizer; and has received consultant and/or speaker fees from Lundbeck, Pfizer and Sunovion. The other authors declare no competing financial interests.
Contributors: L. Minuzzi, N. Bock and B. Frey designed the study. M. Sehmbi acquired and analyzed the data, which C. Rowley, F. Kapczinski, J. Kwiecien, N. Bock and B. Frey also analyzed. M. Sehmbi wrote the article, which all authors 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.N. Frey, 100 West 5th St, Suite C124, Hamilton ON L8N 3K7; email@example.com