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Little overlap exists in individuals with same schizophrenia spectrum disorder

After mapping interindividual differences in brain structure, researchers found only a few brain loci had the same abnormalities in more than 2% of patients with the same schizophrenia spectrum disorder.

The study, published in JAMA Psychiatry, showed that patients with schizophrenia and with bipolar disorder differed greatly on an individual level.

“Psychiatry is now the last area of medicine in which diseases are diagnosed solely on the basis of symptoms, and biomarkers to assist treatment remain to be developed,” Thomas Wolfers, MSc, from Radboud University, the Netherlands, and colleagues wrote. “To bring precision medicine to psychiatry, large-scale international initiatives work toward stratifying mental disorders into biologically more homogeneous subtypes based on the integration of many levels of information across multiple dimensions of functioning.”

Researchers examined the degree to which case-control analyses disguise interindividual differences in brain structure in patients with schizophrenia and bipolar disorder and mapped the brain variations associated with these disorders at the individual level using cross-sectional, MRI data. The investigators measured interindividual differences in brain structure among patients with schizophrenia and bipolar disorder recruited from inpatient and outpatient clinics in the Oslo area of Norway as well as healthy controls, then computed voxel-based morphometry maps to chart the range of differences.

Overall, 218 patients with schizophrenia spectrum disorders (163 with schizophrenia and 190 with bipolar disorder) and 256 healthy individuals were included in the study. When analyzed at the individual level, Wolfers and colleagues observed frequent deviations from the normative model as well as a high degree of biological heterogeneity of both disorders.

On average, participants with schizophrenia had reduced cortical volume in the frontal regions, the cerebellum and the temporal cortex, whereas there were mainly mean deviations in cerebellar regions among those with bipolar disorder, according to the report. Moreover, these mean variances masked extreme interindividual differences, with only a few brain loci (mostly in frontal, temporal and cerebellar regions) demonstrating overlap of more than 2% among patients.

“Although the shift from group-level psychiatry toward precision medicine has only just started, on the basis of these results, it appears that appropriate ways to incorporate interindividual differences may determine the success of the transition,” Wolfers and colleagues wrote. “Our results suggest that a full understanding of the biological features underlying schizophrenia and bipolar disorder may not be achieved by studying the average patient but by mapping patients’ individual pathophysiologic signatures.”

Using brain-based phenotyping to advance neurobiology and understanding of serious mental illnesses is important to the future of psychiatry, Carol A. Tamminga, MD, and Elena I. Ivleva, MD, PhD, from the department of psychiatry at University of Texas Southwestern Medical School, wrote in an editorial.

“The task that psychiatry researchers have today is to make [serious mental illness] and other disorders into diagnoses with known biological bases that can be characterized by broad array of biomarkers and for which treatments can be determined by biomarker characteristics,” they wrote. “It will be a revolution in our ability to understand and treat complex brain disorders. This is not an idle exercise, but one which will establish molecular disease targets and rational treatments for intractable psychiatric disorders. It will give us diagnoses that we can rationally treat.” – by Savannah Demko

Disclosure s : Wolfers reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Tamminga and Ivleva report funding from the NIMH.