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Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition affecting millions of children and adolescents worldwide. And while ADHD itself presents with a constellation of symptoms, its association with other psychiatric comorbidities adds a layer of complexity to its diagnosis and treatment.

Due to this association, a recent study conducted by physicians in South Korea investigated the risk of schizophrenia diagnosis among children and adolescents with ADHD and at least one other psychiatric comorbidity.

Study Background and Methodology

Published in JAMA Network Open in November 2023, this retrospective cohort study focused on the prevalence of psychiatric comorbidities among youths with ADHD using the Health Insurance Review and Assessment claims database (HIRA), which is a government-operated agency mandated for all Korean citizens.

From January 2010 through December 2019, investigators analyzed the data of the participants, who were children and adolescents ranging from 5 to 19 years old that received an ADHD diagnosis between January 2007 and December 2018.

The participants were split into two groups: one group was comprised of patients diagnosed with ADHD with at least one comorbidity diagnosed within the same year, and the other group was made up of ADHD patients with no psychiatric comorbidities. Depression, anxiety, intellectual disability, nonorganic sleep disorders, tic disorder, bipolar disorder, autism spectrum disorder, conduct disorder, obsessive-compulsive disorder, and substance abuse disorder were recognized and defined as psychiatric comorbidities by the investigators.

To analyze the presence and types of additional conditions, researchers further grouped patients based on both the total number of comorbidities and the specific disorders they had.

All study populations were followed up from either the initial schizophrenia diagnosis or at the end of December 2019. The occurrence of psychiatric comorbidity during the follow-up period was also investigated among patients who did not have psychiatric comorbidity at the beginning of the study.

Lastly, the study used Cox proportional hazard models to assess the relationship between psychiatric comorbidities and the risk of being diagnosed with schizophrenia. These models estimated hazard ratios and 95 percent confidence intervals to examine the association and to provide a way to compare the rate of the schizophrenia diagnosis between those with and without psychiatric comorbidities, all while considering their age, sex, insurance, and prior hospitalization.

Analyzing the Data

Of the 211,705 participants, nearly 37 percent had other mental health diagnoses within a year of their ADHD diagnosis, while 63 percent did not.

Among those with comorbidities, 8.3 percent developed schizophrenia over a 5.6-year follow-up, compared to 3.3 percent of those without comorbidities who developed it after 6.6 years on average. Patients with comorbidities were older, more likely female, and used more psychiatric medications compared to those without.

These results reveal a clear association between psychiatric comorbidities and later schizophrenia in patients with ADHD as the presence of comorbidities roughly doubled the risk of schizophrenia. This remained true even after adjusting for the potential influence of various medications. Other factors also emerged as significant contributors to the risk, including sex, age, and insurance type. Interestingly, several psychotropic medications were found to elevate the risk of developing schizophrenia.

Among specific mental health disorders, autism had the strongest link to schizophrenia risk in ADHD patients, followed by intellectual disability, tic disorder, depression, and bipolar disorder. However, substance use disorder didn't show a significant association.

Even among patients with ADHD and no diagnosed mental health issues at the beginning of the study, over 70 percent developed new mental health problems before receiving a schizophrenia diagnosis. This trend held true across different age groups, with depression and anxiety disorders being the most common new conditions. This suggests that even if kids with ADHD don't have any other mental health problems at first, many develop them before getting diagnosed with schizophrenia.

And when you account for age, although schizophrenia typically manifests later in life, the fact that ADHD patients with other mental health issues develop it more often cannot be solely attributed to their being older. Statistical adjustments for age and analyses within different age groups revealed that having additional mental health conditions is an independent risk factor for schizophrenia in ADHD patients.

Limitations

These findings, while robust, have limitations that require consideration. For instance, diagnosis codes for ADHD, schizophrenia, and other conditions might be inaccurate due to underdiagnosis, overdiagnosis, or stigma-driven avoidance of specific labels.

And reliance on claims data limited the researchers’ ability to assess ADHD severity beyond using psychiatric hospitalization as a proxy. So while they controlled for several potential confounding factors, fully eliminating their influence is difficult.

Key Takeaways

Despite these limitations, the findings of the study emphasize the importance of understanding the influence of psychiatric comorbidities on the risk of developing schizophrenia, identifying the occurrence of psychiatric comorbidity over time in this patient population, decreasing subsequent risk, and allowing for early diagnosis and intervention.

After all, early detection and intervention for schizophrenia in children and adolescents with ADHD is crucial, as schizophrenia can have a significantly negative impact on quality of life, academic and social functioning, and mortality.

References:

Jeon SM, Lee DY, Cha S, Kwon J. Psychiatric Comorbidities and Schizophrenia in Youths With Attention-Deficit/Hyperactivity Disorder. JAMA Netw Open. 2023;6(11):e2345793. doi:10.1001/jamanetworkopen.2023.45793

Bender, Eve. “ADHD plus Comorbidities Linked to Higher Schizophrenia Risk.” Medscape, Medscape, 2 Jan. 2024, www.medscape.com/viewarticle/adhd-plus-comorbidities-linked-increased-schizophrenia-risk-2024a100000p.