Relatives of Patients with Psychotic Disorders Have Distinct Brain Abnormalities

By mapping the brain of schizophrenia and bipolar disorder patients and family members, investigators have learned different patterns in the brain that could help lead to better diagnosis practices.

An investigative team, led by Sonja M.C. de Zwarte, of the Department of Psychiatry, University Medical Center Utrecht Brain Center, recently conducted a meta-analysis of global and subcortical brain measures of 6008 participants, 1228 of which are first-degree relatives of patients with schizophrenia (FDR-SZ), 852 of which are first-degree relatives of patients with bipolar disorder (FDRs-BD), 2246 control subjects, 1016 patients with schizophrenia and 666 patients with bipolar disorder from 34 schizophrenia and/or bipolar disorder family cohorts using standardized methods.

The investigators repeated the analysis with a correction for intracranial volume (ICV), as well as for the presence of any psychopathology in both the relatives and the control subjects.

The team found that the first-degree relatives of bipolar patients had significantly larger intracranial volume (d = +.16, q < .05 corrected), while the first-degree relatives of schizophrenia patients had smaller thalamic volumes than the control subjects (d = −0.12, q < .05 corrected).

Intracranial volume also explained the brain enlargement measurements in first-degree relatives of bipolar patients.

In first-degree relatives of schizophrenic patients, after a correction for intracranial volume, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller, while the cortex was thinner (d < −.09, q < .05 corrected). The third ventricle was also larger (d = +.15, q < .05 corrected).

de Zwarte explained that the study could help diagnose either disease for people with a family history.

"The size of intracranial volume is considered a marker for early brain development,” de Zwarte said in a statement. “Thus, our findings suggest that the familial risk for these disorders is influencing brain development already early in life, and in a different manner.”

The findings were not explained by psychopathology in either the relatives or control subjects, while the study emphasized the usefulness of studying family members of people with psychiatric disorders to better understand how the risk of illness impacts the brain.

“Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV,” the authors wrote. “This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.”

Schizophrenia and bipolar disorder are similar in genetic liability with some structural brain abnormalities commonly found in both conditions. Genetically, first-degree relatives of schizophrenia patients show similar brain abnormalities to patients, with smaller effect sizes.

Imaging findings in first-degree relatives for bipolar patients have also been inconsistent in the past. However, research in recent years show regionally greater volumes compared with control subjects.

The study, “The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder,” was published online in Biological Psychiatry: A Journal of Psychiatric Neuroscience and Therapeutics.