Children With Intermittent Exotropia Face Higher Risk of Mental Illness

Pauline Anderson

June 10, 2009

June 10, 2009 — Children diagnosed with intermittent exotropia (IXT), a form of strabismus where the eyes drift outward, are almost 3 times more likely to develop a psychiatric disorder later in life than youngsters without this diagnosis, according to new research.

The study, published in the June issue of Archives of Ophthalmology, showed that while a diagnosis of IXT is more common in females, males with this disorder are much more likely to develop mental illness.

The research also suggests that the relationship between IXT and mental illness is more likely due to a genetic predisposition than societal or environmental factors or a combination of these.

These findings should encourage doctors to consider getting a baseline psychiatric evaluation for a child with IXT, said study author Brian G. Mohney, MD, associate professor of ophthalmology at the Mayo Clinic in Rochester, Minnesota.

"If pediatricians and family practitioners have a child whose eyes intermittently drift out, they should consider having that child seen by a psychiatrist or psychologist to get a baseline exam, not at age 2 or 3 years but maybe within the first decade of life, and to maybe follow them a little more closely," Dr. Mohney told Medscape Psychiatry.

Retrospective Study

Using medical records of patients living in Olmsted County, Minnesota, researchers identified 183 patients diagnosed with IXT from January 3, 1975 to December 31, 1994. Each of these cases was paired with an age- and sex-matched control and followed for an average of 22 years.

Researchers determined the rate of psychotropic medication use, mental-health emergency-department visits or hospitalizations, suicide attempts, and suicide ideation for all subjects. They also gathered information on substance abuse, family history of psychiatric disease, and maternal substance abuse during pregnancy.

The group reported that a mental-health disorder was diagnosed in 97 (53.0%) of the 183 patients with a history of childhood IXT compared with 55 (30.1%) of the 183 controls (P < .001).

Statistical analysis determined that children with IXT were 2.7 times more likely than controls to develop a psychiatric disorder. The elevated risk may be somewhat difficult to interpret, as the children were followed for varying lengths of time, some for 2 years and others for more than years, said Dr. Mohney.

More Suicidal Ideation

Children with IXT were also significantly more likely than controls to use psychotropic medications, require psychiatric hospitalizations, make emergency-department visits, have suicidal ideation, and attempt suicide.

Males with IXT were at especially high risk for mental illness. Among males, 41 of the 65 diagnosed with IXT (63%) developed a psychiatric disorder compared with 22 of the 66 controls (33%). The equivalent rates in women were 56 of 110 (48%) vs 33 of 117 (28%).

The study also found that males with IXT were more likely to develop depression and adjustment disorder compared with controls, whereas females with IXT developed more attention-deficit/hyperactivity disorder, anxiety, and learning disabilities.

Females were more likely to have been born to mothers with a history of chemical abuse during pregnancy and to have a family history of psychiatric disease, compared with controls.

Self-Esteem Issues

It is not clear why males appear to be more prone to mental illness. Boys with IXT might develop self-esteem issues as a result of being made fun of, and this may evolve into more serious mental-health problems. But if this were true, girls, who are normally more image conscious, should face at least the same risk as boys, and the study did not find this to be the case, said Dr. Mohney.

He added that children with crossed eyes, who may be subjected to as much, if not more, social stigma compared with kids with IXT, do not have an elevated risk for mental illness.

"A potential etiologic factor points to something deeper, possibly genetic," he said. "It may be that a genetic error that causes the eyes of some patients to drift out may be physically close to the gene or on the same chromosome as that associated with an increased risk for mental illness."

This is not the first study to suggest a genetic link between exotropia and mental illness. One previous study found a single gene was associated with the rare constant form of exotropia, where the eyes are always turned out, and adult schizophrenia.

Although the current study did not find significantly more cases of schizophrenia among IXT patients compared with controls, Dr. Mohney pointed out that this mental illness typically strikes a slightly older age group.

Prospective Study Needed

Asked by Medscape Psychiatry to comment on the findings, Paramjit T. Joshi, MD, endowed professor and chair of the department of psychiatry and behavioral sciences at the Children's National Medical Center, in Washington, DC, said she questioned whether a genetic predisposition is involved in the relationship between IXT and mental illness. "The only way to answer that is to do gene mapping on these kids," she said.

As with similar retrospective reviews, the current study has a limitation in that it relies on chart reviews, said Dr. Joshi. "This study needs to be replicated prospectively and children identified with IXT need to be followed to see whether they develop mental illnesses," she said. "There needs to be some format of identifying these psychiatric symptoms, not just based on chart review, but interviewing these patients."

IXT occurs in about 1% and exotropia in about 3% of the US population. In Asian countries, these statistics are reversed. These disorders typically develop in the first few years of life, said Dr. Mohney.

The amount of ocular drifting with exotropia varies from child to child. "Some kids go a day or even a week where their parents never see it and a clinician has a hard time finding it in the office, while other kids will be 'out' 90% of the day," said Dr. Mohney.

Eye exercises and surgery are typical treatments for IXT, he said.

The authors report no financial disclosures.

Arch Ophthalmal. 2009;127:743-747. Abstract

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