What You Need to Know
People with bipolar disorder have an increased risk and earlier onset of heart disease compared to people without the disorder. The strength of this association is beyond what can be explained by common risk factors, such as high blood pressure and smoking. In this study, researchers used retinal photography and magnetic resonance imaging (MRI) to study retinal microvessels and white matter circuits in youth with and without bipolar disorder. The results show a link between the structure of small vessels (microvessels) and the health of brain circuits. Youth with bipolar disorder had wider retinal vessels than the control group. Study participants who had poorer vessel health had lower regional white matter integrity, this was the case in both youth with bipolar disorder as well as in controls. Overall, these preliminary findings suggest that the brain may be sensitive to cardiovascular risk early in life and that early vessel-focused intervention may be particularly beneficial in youth with bipolar disorder.
What Is This Research About?
Bipolar disorder is associated with increased risk and early onset of heart disease. Microvessels play an important role in brain blood flow and oxygen exchange, and could explain why bipolar disorder is associated with excessive risk of heart disease.
Researchers have been studying microvessels to determine if they play a role in this heart-brain link. Information regarding vessel health can be gleaned from imaging of the brain, the heart, and other organ systems throughout the body. The eye’s retina is of particular interest, as it is an extension of the central nervous system and retinal microvessels have many similarities with brain blood vessels.
A benefit of studying retinal vessels is that they can be easily and inexpensively photographed using digital techniques commonly used in ophthalmology offices. Previous studies using this technology have shown differences in these microvessels in youth and adults with psychiatric diagnoses and symptoms. However, such studies have not incorporated brain imaging or studied how vascular changes might underlie changes to brain structure and function in people with psychiatric disorders.
This study aimed to clarify the connection between retinal microvessels and the brain’s white matter circuits in youth with and without bipolar disorder.
What Did the Researchers Do?
The study participants were a group of 42 youth with bipolar disorder and a control group of 42 youth without bipolar disorder or other major psychiatric diagnoses. Researchers took digital images of retinal microvessels. They also used diffusion tensor imaging, a type of MRI that detects how water travels along white matter tracts in the brain. This technique helped determine the structural integrity of white matter circuits, which are commonly disrupted in psychiatric conditions like bipolar disorder.
The researchers then compared the relationship between microvascular structure and white matter structural integrity, looking for any differences in this association between the bipolar disorder and control groups.
What Did the Researchers Find?
Retinal microvessels were wider in youth with bipolar disorder than in the control youth. Wider retinal microvessels were associated with lower structural integrity in white matter circuits in both the youth with bipolar disorder and the control youth.
The researchers also found 5 brain regions where the connection between retinal vessels and brain circuits differed between the 2 groups. In each of these instances, wider retinal microvessels was associated with better white matter circuit structural integrity in youth with bipolar disorder compared to the control group.
Limitations of the Research
This study was the first of its kind in a group of youth with a psychiatric diagnosis but there are some limitations. The sample was small, which limits the statistical power of the study to confirm if the relationship between vessel health and white matter integrity differs between youth with bipolar disorder and controls. The study was also cross-sectional, which means the researchers can’t make conclusions about whether poor vessel health causes changes in brain structure and function.
A meaningfully larger sample size will help answer important questions about the influence of biological sex, psychiatric medication use, and psychiatric symptoms on study findings. In addition, a longitudinal study with repeated measurements over time will help clarify the timing of the associations. For example, such a study would be able to answer the question, do vessel differences precede brain circuit differences, is the opposite true, or do both emerge together?
How Can You Use This Research?
The study findings are important for researchers, clinicians, and youth living with bipolar disorder. Given that this study is the first of its kind, it is intended to guide future studies on vascular-brain associations, a topic that is still neglected in psychiatry. This research may also help guide interventions that target vascular causes of psychiatric conditions. Some approaches might include using cardiovascular medications earlier in the course of illness or newer approaches that directly target microvessels.
About the Researchers
Megan Mio,1 Kody G. Kennedy,1 Anahit Grigorian,1 Yi Zou,1 Mikaela K. Dimick,1 Beth Selkirk,2 Peter J. Kertes,2,3 Walter Swardfager,4,5 Margaret K. Hahn,6,7,8 Sandra E. Black,5 Bradley J. MacIntosh,5,9 Benjamin I. Goldstein1,4,8
- Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, Canada
- John and Liz Tory Eye Centre, Department of Ophthalmology and Vision Sciences, Sunnybrook Health Sciences Centre, Canada
- University of Toronto, Ophthalmology and Vision Sciences, Toronto, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada
- Hurvitz Brain Sciences Research Program, Sunnybrook Health Sciences Centre, Toronto, Canada
- Schizophrenia Department, Centre for Addiction and Mental Health, Toronto, Canada
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada
- Department of Psychiatry, University of Toronto, Toronto, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Canada