Mood Disorders of Years Past Contribute to Stroke Risk for Some

Genetic susceptibility to mood disorders may also play a causal role in stroke, according to a population-based prospective cohort study in Sweden.

A higher polygenic risk score (PRS) for mood disorders consistently tracked with both all strokes and ischemic strokes over more than 20 years of follow-up. Notably, there was an interaction by sex such that this observation applied only to women, not men, reported Isabel Gonçalves, MD, PhD, of Lund University in Malmö, Sweden, and colleagues.

Women had increasing stroke risk when polygenic risk for mood disorders was either analyzed by quintiles (HR 1.45 for highest vs lowest quintile, 95% CI 1.21-1.74) or as a continuous variable (HR 1.13 per 1 SD increase, 95% CI 1.07-1.19), the study authors showed in Stroke.

Furthermore, Mendelian randomization analyses provided evidence that mood disorders have a causal effect on strokes (OR 1.07, 95% CI 1.03-1.11) and ischemic strokes (OR 1.09, 95% CI 1.04-1.13) -- not the other way around.

"Our results, by showing that mood disorders were causally linked with risk of stroke, bring forth the importance of an early screening of mood disorders, facilitating not only the risk stratification, identification of possibly undiagnosed, faster and earlier treatment of individuals of mood disorders, but also ultimately preventing the substantial consequences of strokes for the subjects and society in general," Gonçalves and colleagues concluded.

They suggested PRS as "an ideal and simple approach to identify high-risk subjects at very early stages as germline DNA is measurable even before birth."

Mood disorders, also known as affective disorders, most often involve depression, bipolar disorder, and seasonal affective disorder. Affected individuals have been known to have cardiovascular disease as a frequent comorbid condition, the researchers noted.

For example, a recent report showed that self-reported depressive symptoms were associated with a significantly greater risk of acute stroke, including ischemic stroke and intracerebral hemorrhage in the subsequent 12 months. Depressive symptoms were also tied to greater likelihood of mortality during the first month after stroke.

Gonçalves and colleagues said their PRS for mood disorders was based on the latest large genome-wide association studies of mood disorders. To date, 73 loci had been associated with risk for mood disorders.

The connection between mood disorders and stroke was assessed in the Malmö Diet and Cancer cohort of 24,631 individuals with a median follow-up of 21.3 years. Participants had baseline examinations from 1991 to 1996 and subsequent stroke events captured on national registers.

The average age of the 24,366 stroke-free participants at baseline was 58 years, and approximately 40% were women.

Mendelian randomization analysis relied on summary statistics from large genome-wide association studies of the Psychiatric Genomics Consortium and the MEGASTROKE Consortium. This technique minimizes residual confounding and reverse causality by using genetic variants as instrumental variables to estimate potential causal effects.

"PRS and MR [Mendelian randomization] are less likely influenced by confounding factors over time, since the germline DNA is also relatively stable across the lifespan. Thereby, the path of reverse causations from outcomes to instruments is very unlikely," Gonçalves' group explained.

The study nevertheless lacked the level of detail necessary to analyze the link between mood disorders and the individual subtypes of stroke, the researchers noted. Moreover, the reported associations between the mood disorders and strokes may differ in other populations comprised of different ethnicities.

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