Bipolar Disorder Progression Associated With Increase in Ventricular Size, Authors Say

Stuart McKinlay, BHSc, McMaster University, Sonya Grewal, BSc, St. Michael's Hospital, Unity Health Toronto, and Bianca Wollenhaupt de Aguiar, BSc, MSc, Ph.D., McMaster University, discuss the basics of their study that primarily found an increase in ventricular size and a reduction in grey matter volume as bipolar disorder progressed in patients.

"Biomarkers of neuroprogression and late staging in bipolar disorder: A systematic review" was recently published in the Australian & New Zealand Journal of Psychiatry.

In Part 1 of this Q&A, the authors discuss the inspiration for the study, the most significant findings, and which outcomes were surprising.

Read part 2 here: Identifying the Biological Pathways Involved in Bipolar Disorder Progression, Part 2

Editor's Note: Answers have been lightly edited for clarity. 

Evi Arthur, Associate Digital Editor, Psych Congress Network: What led you and your colleagues to investigate neuroprogression in bipolar disorder?

McKinlay, Grewal, and Wollenhaupt de Aguiar: Recent literature has significantly improved our knowledge of the biological underpinnings associated with bipolar disorder. It has now been suggested that bipolar disorder may be best understood through the use of clinical staging models—an effort to characterize the progressive course of illness often reported in a subset of patients. As a team, we were motivated to contribute to the developing field that explores biomarkers in bipolar disorder and illness progression. We felt that a systematic review was promptly needed to synthesize the available literature, as well as to provide a narrative analysis that would highlight prominent themes and research gaps that may require further investigation. We hope that this review will help to inform future research efforts and contribute to clinical advancements in the diagnosis, prognosis, and treatment of bipolar disorder.

Arthur, PCN: Please briefly describe the study method and included articles.

McKinlay, Grewal, and Wollenhaupt de Aguiar: In our systematic review, we included 2 types of studies to investigate the biomarkers associated with illness progression in bipolar disorder: (1) studies that used staging models to assess biomarkers in patients with bipolar disorder and (2) studies that used relevant clinical parameters to correlate biomarkers with illness progression. Relevant clinical parameters included, but were not limited to, number of episodes, illness duration, and patient symptom severity. Ultimately, participants between the ages of 15 and 65 with a diagnosis of bipolar disorder met the inclusion criteria for our study. Title and abstract screening, in addition to full-text screening, was performed blindly and independently by members of the research team, and a total of 35 studies were included in our systematic review. Relevant data from the eligible studies was extracted and reported.

Arthur, PCN: Please briefly describe the most significant finding(s).

McKinlay, Grewal, and Wollenhaupt de Aguiar: According to our systematic review, the 2 most prominent findings associated with illness progression in bipolar disorder were an increase in ventricular size and a reduction in grey matter volume. Furthermore, grey matter alterations were found to correlate with several relevant clinical parameters, including the number of episodes and illness duration. Notably, the inflammatory markers were among the most assessed biomarkers. Across the included studies, however, we found conflicting results. While several studies suggested that inflammation may be a trait marker of bipolar disorder, other studies indicated that chronic inflammation in patients with bipolar disorder may be associated with brain changes and immune system impairment. These results are congruent with the principles of neuroprogression.

Arthur, PCN: Which outcomes were different than you expected?

McKinlay, Grewal, and Wollenhaupt de Aguiar: Markers of inflammation were an area of considerable intrigue in our systematic review. Across several studies, activation of certain inflammatory markers and immune system dysregulation were consistently more prominent in later stages of illness. However, there were conflicting findings regarding the pro-inflammatory cytokine interleukin-6 in our included studies. Several of the studies also did not report significant differences in anti-inflammatory cytokine interleukin-10 across stages of illness. While there is sufficient overall evidence to suggest that an association between bipolar disorder and progressive inflammatory processes exists in a subset of patients, the high heterogeneity hindered further comparisons. Inflammatory markers are a considerable area of research interest, and we believe that future research should continue to explore the complex role of inflammation in the pathophysiology of bipolar disorder.

Stay tuned for part 2.

Stuart McKinlay, BHSc, completed his bachelor of health sciences (Honours) at McMaster University in 2021. He is a current student of the MD program at the University of Toronto (Class of 2026). His research interests include exploring the etiology and pathophysiological mechanisms associated with bipolar disorder. He is also interested in health services research, with a focus on integrated care delivery and long-term patient health outcomes. 

Sonya Grewal, BSc, is a research coordinator in the genomics health services and policy research program at St. Michael's Hospital, Unity Health Toronto. She completed her BSc at McMaster University in the Integrated Science program, where her undergraduate honours thesis focused on understanding biological pathways involved in bipolar disorder. Sonya is an incoming MSc student in Health Services Research at the University of Toronto, and her current research interests lie in clinical genomics and identifying best practices to enhance EDI in health services.

Bianca Wollenhaupt de Aguiar, BSc, MSc, Ph.D., is the research laboratory manager at the centre for clinical neurosciences in the department of psychiatry and behavioural neurosciences at McMaster University (Canada), where she focuses on translational projects aiming to understand the pathophysiology of bipolar disorder. Dr Wollenhaupt de Aguiar graduated in biomedical sciences with a Master's in medical sciences and a Ph.D. in biochemistry at the Federal University of Rio Grande do Sul (UFRGS), Brazil. She completed a Postdoctoral fellowship at the Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA) in 2016, and a Postdoctoral fellowship at the Department of Psychiatry and Behavioral Neurosciences at McMaster University, Canada, in 2021. Dr. Wollenhaupt de Aguiar’s research has been focused on the study of the molecular and neurobiological basis of psychiatric disorders, with an emphasis on bipolar disorder, since 2007.