by Kevan Cliifford

Graphic design by Geneviève Groulx

Bipolar disorder is one of the most complex and severe psychiatric illnesses, and remains all too often misunderstood by society. Bipolar disorder in youth and adolescent populations is even less understood and comes with heightened stigmatization. Clinical advances in this field require a keen eye for identifying gaps, and the ability to reimagine previous ideas for new applications. By embodying these attributes, Dr. Benjamin Goldstein deepens our understanding of bipolar disorder from new perspectives, resulting in novel, non-traditional treatment approaches. 

Dr. Goldstein is a Child and Adolescent Psychiatrist at the Centre for Addiction and Mental Health (CAMH), and Full Professor of Psychiatry and Pharmacology at the University of Toronto Temerty Faculty of Medicine. During his undergraduate studies at the University of Pennsylvania, Dr. Goldstein conducted research on attributional styles in depression. Upon arriving at the University of Toronto for graduate school, he further examined attributional styles in relation to gender differences in depression and alcohol use. Dr. Goldstein later completed residency training at the University of Toronto. While attending his first American Psychiatric Association conference, a piece on pediatric bipolar disorder serendipitously caught his eye. At the time, bipolar disorder in youth was not well characterized. Furthermore, the considerable stigma associated with individuals and families with bipolar disorder was amplified in the pediatric population. The notion of children struggling with such a debilitating illness was both unexpected and saddening. Dr. Goldstein’s interest in youth bipolar disorder quickly blossomed, and he soon found himself immersed in the field.

To get to the heart of Dr. Goldstein’s research, one must consider the connection between vascular health and bipolar disorder.¹ An initial goal of his research program was to prove to the broad medical community, and society, that pediatric bipolar disorder was a valid illness. The idea was to demonstrate that cardiovascular risk factors are elevated and associated with increased severity of bipolar disorder in youth, as is the case in adults, to support the conclusion that youth bipolar disorder is similar to adult bipolar disorder. Using population-based data, Dr. Goldstein then demonstrated that adults with bipolar disorder have excessive rates of heart disease, which onsets over a decade prematurely. This was a largely untreated population sample, and analyses controlled for numerous potential confounds (e.g., sedentary lifestyle, smoking, blood pressure, and obesity). As such, the study demonstrated that risk of cardiovascular disease in bipolar disorder is above and beyond what can be explained by other factors. Dr. Goldstein’s team further explored this connection by focusing on microvessels, which exist throughout the body. Early studies focused on neuroimaging measures of cerebral blood flow, and on peripheral measures of vascular reactivity. Their current project includes these measures and further incorporates novel approaches, such as retina photography looking at blood vessels in the eye, and notably, cardiovascular magnetic resonance imaging (MRI) examining overall structure and function of the heart. Ultimately, the study’s goal is to identify a phenotype in microvascular function unique to bipolar disorder. 

New approaches to understanding a disorder often yield new treatment ideas. The vascular connection to bipolar disorder presented an intuitive treatment option–cardiorespiratory (i.e., aerobic) exercise! However, disparities between treating physical illnesses and mental illnesses exist. It is unlikely someone with mental illness will be referred to an exercise or nutrition expert; instead, they likely receive pharmacological, and maybe psychotherapy treatment. Dr. Goldstein asserts that exercise and healthy lifestyle interventions should be front and center in bipolar disorder treatment, not an add-on or accessory item. This need is apparent in individuals with bipolar disorder, where high levels of sedentary behaviour are common.² In addition to improving aerobic fitness, Dr. Goldstein suggests potential repurposing of specific medications that benefit vascular health. Furthermore, in addition to treatment, novel cardiovascular screening approaches could aid in diagnosis and prognosis of individuals presenting with bipolar disorder symptoms. 

The vascular connection has led to the development of other exciting novel treatments. Most recently is nitrous oxide, a widely used anaesthetic. Nitrous oxide regulates vascular tone and blood flow, and may be effective for treating bipolar depression. Broadly, it works as an NMDA receptor antagonist, similar to ketamine—a leading rapid acting treatment for depression. Dr. Goldstein’s group conducted a pilot study where individuals received nitrous oxide in an MRI scanner, measuring physiological changes in cerebral blood flow. The next proposed study will have two sessions per week, for two weeks, and examine patient outcomes at one month. The potential of nitrous oxide as a fast-acting, inexpensive, and effective treatment for bipolar depression is therefore generating excitement.

Moving beyond clinical and research matters, Dr. Goldstein reflected on the role of mentorship in his career. As a mentee, support from influential mentors was key in his development. Reflecting on the time, effort, and resources mentors invested in him, Dr. Goldstein offered the saying, “To whom much is given, much is expected”, explaining it inspires him to honour their generosity by working hard and advancing his research career. As a mentor himself, Dr. Goldstein deeply values seeing mentees learn, progress, and eventually go on to support others. His advice to other mentors is to encourage mentees to aim high to bring out their best, and to lead by example, in both formal research skills and reciprocal interpersonal working relationships. 

Dr. Goldstein also shared insight into the unique path of Clinician-Scientists. It is no small feat to straddle the demanding worlds of being both a practicing clinician and researcher. Dr. Goldstein emphasizes that despite the very real challenges of navigating both fields, he feels it is an absolute privilege to be able to study the illness in the lab that he treats on a day-to-day basis in the clinic, and that this applies to whatever disease you choose to specialize in. 

Dr. Goldstein encourages us to consider that the connection between cardiovascular health and brain health does not suddenly start in adulthood. Rather, it is relevant and targetable in adolescence. It is crucial we optimize cardiovascular health in this age range to improve mental health in pediatric bipolar disorder, and other major psychiatric disorders. It is Dr. Goldstein’s hope that his program’s innovative work in understanding and treating bipolar disorder will help demonstrate that it is first and foremost, like any other illness, a physical illness, and should not be met with stigma or shame.

References

1. Goldstein BI, Carnethon MR, Matthews KA, McIntyre RS, Miller GE, Raghuveer G, Stoney CM, Wasiak H, McCrindle BW. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2015 Sep 8;132(10):965-86.
2. Kennedy KG, Ghugre NR, Roifman I, Qi X, Saul K, McCrindle BW, Macgowan CK, MacIntosh BJ, Goldstein BI. Impaired coronary microvascular reactivity in youth with bipolar disorder. Psychological Medicine. 2023 Oct 31:1-1.