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Brain mapping takes next step toward precision psychiatry

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Can biomarkers define brain disease?

A growing body of evidence suggests that “conventional psychiatric diagnoses of serious mental illness (SMI), when tested, do not show a common biology,” wrote Carol A. Tamminga, MD, and Elena I. Ivleva, MD, PhD, in an accompanying editorial. The editorialists noted the work of the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium to identify subtype disease clusters.

However, they wrote: “We question whether these biotype structures represent disease groups as opposed to mere brain biomarker clusters. Dr. Tamminga and Dr. Ivleva also expressed concern about whether biologically based subgroups would be clinically useful and questioned what evidence would be needed to accept such subtypes as disease subgroups.

Their ideas for further exploration included identifying a characteristic genetic fingerprint to help determine a common pathophysiology. In addition, “a disorder clustered by biological features might also show a distinctive pharmacological profile,” they wrote.

Next steps include making severe mental illness into a condition diagnosable based on biomarkers that also can serve as a foundation for treatment, which would be “a revolution in our ability to understand and treat complex brain disorders,” they noted (JAMA Psychiatry. 2018 Oct. doi: 10.1001/jamapsychiatry.2018.2451).

Dr. Tamminga and Dr. Ivleva are affiliated with the University of Texas, Dallas. Both of them serve as researchers with the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium and reported funding from the National Institute for Mental Health.



Brain mapping patterns varied with clinical mental health diagnoses in a study of 218 patients with schizophrenia spectrum disorders.

Illustration of the brain copyright Thinkstock

“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,” wrote Thomas Wolfers of Radboud University, Nijmegen, the Netherlands, and his colleagues. They also said schizophrenia and bipolar disorder “are excellent examples of highly heterogeneous mental disorders.”

To explore brain structure homogeneity, the researchers used brain scans and mapping models to compare results in 218 adults aged 18-65 years with schizophrenia disorders (163 with schizophrenia and 190 with bipolar disorder) and 256 healthy controls. Demographics were similar between the groups.

The MRI data showed that the same abnormalities in more than 2% of patients with the same disorder occurred in very few loci. Schizophrenia patients showed significantly reduced gray matter in the frontal, cerebellar, and temporal regions; most bipolar patients showed changes in the cerebellar region.

The researchers identified extreme deviations across patients and controls in gray and white matter.

In gray matter, schizophrenia patients had a significantly higher percentage of extreme negative deviations across voxels (0.9% of voxels), compared with both bipolar patients and healthy controls (0.24% and 0.23%, respectively).

Extreme positive deviations were significantly higher among healthy controls (1.08% of voxels), compared with bipolar patients and schizophrenia patients (0.79% and 0.78%, respectively).

In white matter, a similar pattern emerged; schizophrenia patients had a significantly higher percentage of extreme negative deviations (0.62%), compared with healthy controls and bipolar patients (0.25% and 0.41%, respectively). In addition, extreme positive deviations were significantly higher among the controls (1.14% of voxels), compared with schizophrenia and bipolar patients (0.83% for both).

The findings support data from previous studies suggesting reduced cortical volume in schizophrenia patients, compared with healthy controls and bipolar disorder patients, the researchers noted.

“In this study, patients with schizophrenia and bipolar disorder differed extremely on an individual level; the lack of substantial overlap among patients in terms of extreme deviations from the normative model is evidence of the high degree of biological heterogeneity in both disorders,” wrote Mr. Wolfers and his colleagues.

The main limitations of the study were the inability to control for confounding variables and to make conclusions about causality, the researchers said. However, the absence of overlap in patients with the same disorder supports the use of brain mapping to study individual pathophysiologic signatures in schizophrenia and bipolar disorder patients, they concluded.

Mr. Wolfers had no financial conflicts to disclose. The study was supported by grants from multiple organizations, including the Netherlands Organisation for Scientific Research and the Wellcome Trust U.K. Strategic Award.

SOURCE: Wolfers T et al. JAMA Psychiatry. 2018. doi: 10.1001/jamapsychiatry.2018.2467.

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