Volume of Gray Matter May Be an Indicator of Bipolar Disorder

brain xray
brain xray
Gray matter volumes within the limbic-striatal, cerebellum, and occipital networks may be critical neural markers.

Reduced volume of bilateral cerebellar gray matter is an endophenotype of bipolar disorder, according to a study published in the Journal of Affective Disorders. Additionally, normalized gray matter in high-risk individuals may indicate resilience, but increased gray matter in the right occipital lobe may confer compensatory activity in combined-high-risk individuals.

This study included 42 young individuals with non-comorbid bipolar disorder and 42 healthy controls. Additionally, 72 undiagnosed individuals who were both medication-naive and at high genetic risk were subdivided into 2 groups: 34 in an asymptomatic high-risk group, and 38 in a combined-high-risk group who presented with symptoms of bipolar disorder. 

Reduced volumes of gray matter in cerebellar and bilateral temporal limbic-striatal areas were associated with illness and enhanced the specificity of clinical categorization by 20% between healthy participants and those with bipolar disorder. Both gray matter reduction in bilateral cerebellar regions and parieto-occipital gray matter variations appeared to be an endophenotype, enhancing clinical categorization specificity of combined-high-risk subjects (10%) and high-risk and healthy individuals (27%). Normalized volumes of gray matter among high-risk subjects is suspected to indicate resilience.

Gray matter markers were identified using support vector machine and logistic regression analyses, which allowed predictive and classifying values to be assessed. Limitations to this study include a lack of independent cross-validation, as well as baseline age and sex distributions in the bipolar group that were statistically unaccounted for. 

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The study researchers conclude that “[we] provide broad support for the reduced bilateral cerebellar [gray matter] volume as a [bipolar disorder] endophenotype, the preservation of which in the [high-risk] group may confer resilience. The increased right occipital [gray matter] volume in the [combined high-risk] group may indicate compensatory processes. Our framework for delineating markers for different [bipolar disorder]-related processes can be applied in future in other measurement domains to generate more complete profiles for patients and various high-risk groups, ultimately towards improving illness diagnosis, enabling earlier identification of liable individuals and forming strategies for promoting resilience.”


Lin K, Shao R, Geng X, et al. Illness, at-risk and resilience neural markers of early-stage bipolar disorder. J Affect Disord. 2018; 21;238:16-23.