Adults with nonparalytic forms of strabismus face increased risk of mental illness

April 12, 2016

A case-controlled, retrospective study indicates that adults with some forms of strabismus — divergence insufficiency (DI) and small‑angle hypertropia (HT) — may be at increased risk of mental illness and its comorbidities.

"In studies published in 2008 in Pediatrics and 2012 in Ophthalmology, children diagnosed with some forms of strabismus, such as intermittent exotropia, convergence insufficiency (CI) and congenital esotropia, were found to have a threefold increased incidence of developing mental illness by early adulthood, compared with controls," says Brian G. Mohney, M.D., Ophthalmology, at Mayo Clinic's campus in Rochester, Minnesota. "There was no research that indicated whether adults with nonparalytic forms of strabismus were similarly at risk."

Using data from the Rochester Epidemiology Project, Dr. Mohney and a research team reviewed medical records of the 118 adults (19 years or older) diagnosed with CI, 80 adults diagnosed with DI and 99 adults diagnosed with small-angle HT in Olmsted County, Minnesota, between Jan. 1, 1985, and Dec. 31, 2008. Mental health disorders were diagnosed in:

65 (55 percent) adults with CI compared with 54 (46 percent) controls
51 (64 percent) adults with DI compared with 42 (53 percent) controls
63 (64 percent) adults with small-angle HT compared with 57 (58 percent) controls

The research team identified the timing of the initial mental health diagnosis among the adults — before or after their strabismus diagnosis. The majority of adults with CI (63 percent) and DI (59 percent) were diagnosed with a mental health disorder before they were diagnosed with strabismus, while the majority of adults with small-angle HT (57 percent) were diagnosed with a mental health disorder after their strabismus diagnosis.

Each case was then compared with a sex- and birth date-matched nonstrabismic control. The medical records of the adults with strabismus and the matched controls were reviewed for a diagnosis of mental illness using codes from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision, use of psychotropic medication, mental health emergency department visits or hospitalizations, suicide attempts, and suicidal or homicidal ideation.

Study results, published in Strabismus in 2015, indicate:

Adults with DI were significantly more likely to have psychiatric-related hospitalizations and psychotropic medication use than controls.
Adults with small-angle HT had a mild increase in specific mental health disorders compared with controls.
Adults with CI did not have an increased risk of mental health illness when compared with controls.

Adults with DI were found to have a higher number of psychiatric-related hospitalizations and psychotropic medication use (both number and length of time), and were also diagnosed with unspecified anxiety disorder more than their controls in this population-based study. Adults with small-angle HT had a higher rate of generalized anxiety disorder, while adults with CI had no increased risk of mental health illnesses compared to controls.

Hypothesis-generating research

"Although degenerative changes associated with aging are potential causes for the development of DI and small-angle HT, they may also be due to microvascular disease or other causes currently unknown. Mental illness and these two types of strabismus could both be a result of these vascular insults to the brain over time," says Dr. Mohney. "Alternatively, CI is thought to be linked with the decline in the ability to accommodate with aging. The degenerative etiology for adult-onset CI could explain why those who have the condition are not at an increased risk of developing mental illness.

"Additionally, a link between constant exotropia and schizophrenia was found to be associated with polymorphisms in a gene encoding a transcription factor. Although the genetic and molecular basis of adult-onset nonparalytic strabismus is not yet known, it is possible that mutations could be responsible for the development and progression of both mental illness and strabismus.

"This study should be viewed as hypothesis-generating research. It is possible that some of the significant associations need to be confirmed by reproducing this study in a different population."