Young Men With MS at Higher Risk for Psychiatric Illness

Pauline Anderson

June 07, 2016

COPENHAGEN — Patients with multiple sclerosis, particularly men diagnosed in early adulthood, are at higher risk for schizophrenia, psychoses, and bipolar disorder, Danish researchers have found.

The higher risk applies only after the MS diagnosis; before this, patients who go on to develop MS have the same rate of psychiatric comorbidities as other patients.

"We hypothesize that MS lesions could act as a biological substrate for psychiatric disease, or that MS acts as the final trigger in individuals susceptible to psychiatric disease," said lead study author, Anja Thormann, MD, PhD student at Rigshospitalet, Copenhagen University Hospital, Denmark.

She presented these findings at the Congress of the European Academy of Neurology (EAN) 2016.

The literature on psychiatric comorbidities in MS is "sparse," said Dr Thormann. Some case studies have reported a link between temporal lobe MS lesions and psychosis; an increased risk for schizophrenia, psychosis, and bipolar disorder has been reported among patients with MS in longitudinal studies; and a family history of MS has been linked to schizophrenia and psychosis.

In this new study, Dr Thormann and her colleagues investigated the risk for bipolar disorder, schizophrenia, and psychosis in patients with MS, both before and after the clinical onset of MS. The "new contribution" of the study is the addition of the period before the clinical onset of MS to the observation period, noted Dr Thormann.

The study did not include depression because, as Dr Thormann explained, "depression could be either a true comorbidity or a complication of MS."

Oldest Registry

For their study, researchers used the Danish MS registry, which, according to Dr Thormann, is the oldest in the world, dating back to 1948. The validity of diagnoses in the MS registry has been estimated at 94%, she said.

From this database, researchers identified all Danish-born patients wit MS who had clinical onset of MS between 1980 and 2005. For each patient with MS, they found 5 controls matched for age, sex, and municipality.

The study included 8947 patients with MS (both relapsing-remitting and primary progressive) and 44,735 controls.

Researchers also tapped into the Danish Psychiatric Central Research Registry, which has included complete coverage of severe mental diseases since 1970, according to Dr Thormann.

Here, too, the validity of diagnoses has been proven previously, and predictive value has been determined to be very high.

Dr Thormann pointed out that linkage of individual-level information from independent registries is possible in Denmark because of the unique personal identification number assigned to every inhabitant of the country.

The study was both a case-control and a cohort study. Case-patients and controls were followed from January 1970 or birth, whichever came last, to assess the occurrence of psychiatric comorbidities before the index date.

To assess the occurrence of psychiatric comorbidities after the index data, case-patients and controls were followed from the index date through December 2012 or death, whichever came first.

Before the index date, the researchers found no difference in the occurrence of psychiatric comorbidities between patients with MS and controls (odds ratio, 0.74; 95% confidence interval [CI], 0.53 - 1.04; P = .081).

After the index date, the case group as a whole had an increased risk for psychiatric comorbidity compared with controls (hazard ratio, 1.25; 95% CI, 1.04 - 1.51; P = .020).

"Stratification on sex and age at index revealed that the significance in the whole group was attributed to men with clinical onset of MS in young adulthood," said Dr Thormann.

Table. Risk for Psychiatric Comorbidity by Patient Group

Group Hazard Ratio (95% CI) P Value
Men with MS vs controls 1.44 (1.06 - 1.98) .022
Women with MS vs controls 1.16 (0.91 - 1.47) .225
Men aged 18 - 22 y vs controls 1.37 (1.06 - 1.78) .017


Excess Risk

This doesn't just reflect more schizophrenia among young men, stressed Dr Thormann. "Remember that cases and controls were matched on age and sex, so even though men in general have an increased risk of schizophrenia, our results show an excess risk of psychiatric comorbidity in male MS cases as compared with male population controls."

The results may have relevance to clinical practice, she said. For example, comorbidity of MS and psychiatric illness may play a role in patient adherence to treatment.

The findings could also affect research. "Our study generates new hypotheses about common susceptibility factors," said Dr Thormann.

A possible limitation of the study is that although the Danish MS registry distinguishes between MS onset and MS diagnosis, "we still don't know when MS starts," she said.

Another possible weakness is that the clinical onset of a given psychiatric comorbidity "is certainly not always identical with the date of diagnosis" entered into the Danish psychiatric registry, she said.

As well, the researchers could not control for adverse health behaviors that could affect diagnoses.

Session co-chair Finn Sellebjerg, MD, PhD, clinical professor of neurology, University of Copenhagen, asked about a possible bias in that patients are more closely followed after a diagnosis of MS and so may be more likely to be referred for psychiatric attention.

"Our study was limited to severe mental diseases, which were only diagnosed by psychiatric specialists in a hospital setting," said Dr Thormann.

"So the 'noise' from over-referral of MS patients should be, if not totally avoided, then at least reduced so much that I'm pretty confident that we see a difference from our results."

This study was funded by The Danish Multiple Sclerosis Society. Dr Thormann has served on scientific advisory boards for Biogen Idec and Novartis. She has received support for congress participation from Biogen Idec, Novartis, Teva, Senofi-Genzyme, and UCB.

Congress of the European Academy of Neurology (EAN) 2016. Abstract O2113. Presented May 29, 2016.


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