Risk of a second mental disorder increased sharply in the year following an individual’s initial diagnosis, and this risk continued beyond a decade, a Danish study of nearly 6 million people found.
In patients with mood disorders, for example, the risk of a subsequent neurotic disorder diagnosis was highest in the first 6 months from initial diagnosis (HR 77.8, 95% CI 76.5-79.2), and was still increased at 15 years (HR 4.3, 95% CI 4.1-4.4), reported John McGrath, MD, PhD, of Aarhus University in Denmark, and colleagues.
Overall, each mental disorder examined — schizophrenia, substance use, intellectual disabilities, as well as organic, mood, neurotic, eating, personality, developmental, and behavioral disorders — was associated with an increased risk for all others, with the level of increased risk differing across pairs, they wrote in JAMA Psychiatry.
HRs ranged from 2.0 for the risk of eating disorders in individuals initially diagnosed with intellectual disabilities (95% CI 1.7-2.4) to 48.6 for the risk of intellectual disabilities in those with prior developmental disorders (95% CI 46.6-50.7) after adjusting for age, calendar time, and sex. Further adjustments for previous disorders demonstrated a similar pattern, but with weaker associations, McGrath’s group noted.
With certain disorders, the absolute risk of developing a comorbid condition was “substantial,” they said. For example, women and men who had been diagnosed with mood disorders before age 20 were 38.4% and 30.6%, respectively, more likely to develop neurotic disorders within 5 years.
The associations between disorders were also bidirectional, meaning linked disorders remained related regardless of which was diagnosed first.
“The data suggest that some disorders share common (upstream) risk factors,” McGrath told MedPage Today in an email. “These could be genetic or environmental factors.”
Steven Hyman, MD, of the Broad Institute of MIT and Harvard, who penned an accompanying editorial, told MedPage Today that the study findings speak to the complicated nature of diagnosing mental disorders and provides evidence that the risk of developing one of these disorders is “highly polygenic.”
“The DSM has divided up the landscape into many discrete categorical disorders so that you have ‘disorder x’ or you don’t — sort of like you have smallpox or your don’t, or you have Ebola or you don’t,” Hyman said.
“The trouble in psychology is that then people get a second discreet diagnosis and a third discreet diagnosis,” he said. “Looking at this analysis and genetics, this may not be a very good way of thinking about it.”
Hyman said that previous research certainly suggests psychiatric disorders are related, particularly those often clustered together, such as depression and anxiety. He said that what is striking about this study, however, is that the observed increases in risk were seen across clusters of disorders that are thought to have very different risk factors.
“It’s premature to say what this sharing consists of, or that it’s only one factor — and a factor here might mean a cluster of shared risk genes,” he said. “But it’s a really interesting and important problem that is very different from neurologic disorders, which do not share [risk] with each other.”
For the current study, McGrath and colleagues collected sociodemographic data from the Danish Civil Registration System for patients born from 1900 to 2015 and matched data regarding mental disease from the Danish Psychiatric Central Research Register. They used ICD-8 (1969 to 1993) and ICD-10 (1994 onward) codes to classify diagnoses.
In total, 5,940,778 individuals were included (evenly split between men and women) and followed for 83.9 million person-years. Patients were a mean age 32.1 years at initial diagnosis. Across the study period, 882,730 died and 85,356 emigrated from Denmark and were lost to follow-up.
Patients were more likely to present with subsequent disorders if they received the index diagnosis at a younger age, according to McGrath.
Also, absolute risk was time-dependent, the researchers found. For example, about 11% of men and 10% of women diagnosed with a mood disorder were diagnosed with neurotic disorders within a month. At 5 years, 22.9% of men and 24.1% of women had been diagnosed with a neurotic disorder. By 10 years, these rates were 27.2% and 28.9%, respectively.
In future studies, the authors said they would concentrate on more complex forms of comorbidity, such as individuals with at least three types of disorders and would also look to estimate risks for specific types of disorders rather than clusters of disorders.
Several limitations to the study were cited by the authors, including the fact that patients with less severe disorders who were treated by general practitioners might have been excluded from the data set. Lastly, as the study was strictly a Danish population, the findings may not be generalizable across other countries, they noted.
The study was supported by the Danish National Research Foundation and the authors received grant support from various foundations.
McGrath is supported by the John Cade Fellowship and the National Health and Medical Research Council. Co-authors reported relationships with Sanofi, Johnson & Johnson, Sage, Shire, Takeda, and Lundbeck.
Hyman disclosed fees from Janssen, BlackThorn Therapeutics, F-Prime Capital Partners, Voyager Therapeutics, and Q-State Biosciences.