
While it cannot be concluded that MS is the cause of schizophrenia and bipolar disorder, or vice versa, the data argue for shared similar risk factors, such as infection, that increase the risk of schizophrenia and bipolar disorder in patients with MS.
Recent population-based studies concerning a suggested link between MS and schizophrenia and bipolar disorder have been equivocal, with analysis of national register data from Denmark indicating increased risk of schizophrenia and decreased risk of bipolar disorder in MS patients (Eaton et al. 2010), with the opposite findings apparent from an analysis of Swedish registry data (Johansson et al. 2014).
“In standard systems, the HES record is made for each admission, and successive records for the same person are not routinely brought together; the HES records are not routinely linked to the person’s death record,” explained Dr. Ramagopalan. “We performed matching -- the process of comparing personal identifiers on HES records to decide whether or not the records belong to the same person -- and linkage, which is the process of physically bringing together records that belong to the same person, so that they can be held together and analysed as ‘the person.’”
The linked data involved hospitals admission for all of England from 1999 to 2011, and included about 82,176 patients admitted for treatment of MS-related health issues and, as a control, records of 9,818,240 patients admitted for minor conditions like hernia. All data was scrutinised for subsequent admission for bipolar disorder and/or schizophrenia. The relative risk of bipolar disorder and schizophrenia was determined by adjustment for age, sex, socioeconomic status, placed of residence, and year.
Patients with MS displayed significantly elevated risks for schizophrenia (rate ratio [RR], 2.08; P < .001) and bipolar disorder (RR, 1.98; P < .001). These associations were seen in males and females.
When admissions occurring within 1 year of admission for MS were excluded, the significance remained between MS and schizophrenia (RR, 2.00; P < .001) and bipolar disorder (RR, 1.91; P < .001), suggesting that the associations did not reflect a surveillance bias.
MS has a suggested association with subsequent self-harm and suicide. These associations were reflected when data for patients admitted with MS were scrutinised (self-harm: RR, 1.59; suicide: RR, 1.86; P < .001 for both).
The co-associations evident between MS, schizophrenia, and bipolar disorder could have a genetic basis and/or a shared environmental basis. While a genetic link could not be excluded, intestinal infections, skin infection, respiratory infection, central nervous system infection, and sepsis all increased the risk of subsequent hospitalisation with MS, schizophrenia, and bipolar disorder in the HES dataset.
“We observed associations of MS with schizophrenia and bipolar disorder,” said Dr. Ramagopalan. “These associations were seen ‘both ways’ and thus it is not likely that MS causes either schizophrenia or bipolar disorder. There may be shared similar risk factors that increase the risk of schizophrenia and bipolar disorder in patients with MS; these factors may potentially involve infections.”