Patients With Psychosis May Face Multisystem Disorder

People with psychotic disorders must often deal with more than just disordered thoughts and behaviors; for instance, they tend to die younger than people without psychosis, predominantly due to cardiovascular disease. Historically, it was thought that poor physical health in people with psychosis arose from external factors, such as side effects of medications or the high rate of smoking among this patient population. But growing evidence suggests that the onset of psychosis is associated with abnormalities in several organ systems.

A review in Molecular Psychiatry now suggests that the changes outside the brain may be just as pronounced and varied as changes within the brain.

Toby Pillinger, M.D., and colleagues at King’s College London compiled data from 165 existing studies (and over 13,000 participants) that compared the levels of specific biomarkers between psychosis patients and healthy controls.

To reduce the chance that observed differences were due to chronic effects of psychosis, such as long-term exposure to antipsychotics, Pillinger and his team focused on studies that looked at individuals with first-episode psychosis. They also limited their analysis to six key biological systems: three in the brain (brain structure, brain physiology, and brain chemistry) and three outside the brain (immune system, cardiometabolic activity, and stress response).

The researchers found that of the six parameters, biomarkers in the immune system differed the most between people with psychosis and controls, followed by neurophysiology and the stress response.

When the researchers divided the six parameters into two groups (brain and non-brain areas), they found that alterations in brain and non-brain areas were similar. This suggests that psychosis is associated with roughly equal changes to neurological and non-neurological biomarkers.

“Abnormalities in multiple organ systems in addition to the CNS [central nervous system] are seen at onset of psychotic disorders with similar magnitudes to those seen in the CNS,” the authors wrote. “While the causal relationship between non-CNS and CNS alterations remains to be determined, this evidence indicates that psychosis involves multiple systems from illness onset. …”

While William Eaton, Ph.D., a professor of mental health at the Johns Hopkins Bloomberg School of Public Health, commended the review of the evidence by Pillinger and colleagues, he said he believes it is premature to think about reclassifying psychotic disorders as multisystem disorders. For one, psychosis itself is not a diagnosed disorder. “I understood the logic in looking at first-episode psychosis, but their analysis captured not only people who went on to develop schizophrenia, but some who developed bipolar disorder and others without any further illness,” Eaton said. “And we don’t know how all these changes influence the progression of psychosis.”

The analysis also overlooked the role of other body systems, notably the gastrointestinal (GI) tract, he added. There is emerging evidence that gliadin proteins, a component of gluten, may be involved in some cases of schizophrenia. Since the GI tract also interacts with the brain and immune system, Eaton thinks it’s important to assess how GI alterations fit in with other changes.

Pillinger and his coauthors agreed that the question of whether psychosis is a multisystem disorder is far from answered: “[W]hat is currently lacking is robust evidence that the changes in non-CNS systems have commensurate clinical impacts … on functioning, prognosis, or mortality,” they wrote.

Still, Pillinger thinks these results do have clinical implications for clinicians.

“Regardless of the mechanism, there is evidence at the onset of psychotic illness of alterations that increase an individual’s risk of cardiovascular disease, which is widely recognized as a cause for schizophrenia’s shockingly high excess mortality,” he told Psychiatric News.

“Thus, from illness onset, we need to be considering the body as well as the mind,” he continued. “Make sure you check patients’ blood pressure, their blood sugars, their cholesterol. Encourage smokers to engage in smoking-cessation programs. Take into consideration the metabolic profile of psychiatric medications when deciding on treatment.”

This study was funded by the Medical Research Council. ■

“Is Psychosis a Multisystem Disorder? A Meta-Review of Central Nervous System, Immune, Cardiometabolic, and Endocrine Alterations in First-Episode Psychosis and Perspective on Potential Models” can be accessed here.