Summary: The brains’ of first degree relatives of those with schizophrenia and bipolar disorder differ from those with no family history of the disorders. Relatives of those with bipolar disorder tend to have larger intracranial volume, while those who had a relative with schizophrenia had smaller brain volume.
Brain abnormalities in people at familial risk of schizophrenia and bipolar disorder emerge in unique patterns, despite the symptom and genetic overlap of the disorders, according to a study in Biological Psychiatry. Similarities between schizophrenia and bipolar disorder have led to the diagnoses being increasingly combined in studies of psychosis, but the findings highlight that risk for the disorders has distinct effects on the brain.
Schizophrenia and bipolar disorder tend to run in families, as relatives share genetic risk factors and exposure to life events that can increase risk of the disease, referred to as environmental risk factors. “We were interested in the relationship between this increased risk for schizophrenia or bipolar disorder and brain development,” said first author Sonja M.C. de Zwarte, MSc, University Medical Center Utrecht, The Netherlands.
Relatives of bipolar disorder patients had larger intracranial volumes–a measure that includes total brain tissue and cerebrospinal fluid–and relatives of schizophrenia patients had smaller brain volumes when compared with people without family history of these disorders.
“The size of intracranial volume is considered a marker for early brain development. Thus, our findings suggest that the familial risk for these disorders is influencing brain development already early in life, and in a different manner,” said Ms. de Zwarte.
The differences in brain development between the disorders will be an important consideration for future brain imaging studies of psychiatric disorders. “Recent focus on dimensional cross-diagnostic features of psychiatric disorders has deemphasized important complementary categorical distinctions. This imaging genomics study reminds us of the potential importance of these categorical distinctions,” said John Krystal, MD, Editor of Biological Psychiatry.
The researchers also found differences in brain anomalies when the participants were separated by their relationship with the patients, though no clear pattern developed based on relative type. First-degree relatives share about 50 percent of their genes, so the variation between the types of first-degree relatives suggests that environmental risk factors also contribute to the brain anomalies in family members.
The international collaborative study by researchers of the ENIGMA consortium was the largest examination of first-degree relatives of patients with schizophrenia or bipolar disorder, including over 6,000 brain imaging datasets in a meta-analysis. The study emphasizes the usefulness of studying family members of people with psychiatric disorders to better understand how risk of the illnesses affects the brain, an approach that avoids the disease or medication effects that complicate studies of patients.
About this neuroscience research article
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The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder
Background Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.
Methods We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. Results FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = −0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < −0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.
Conclusions Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.