LAUSR

Cerebral white matter lesions (WML) are major risk factors for bipolar disorder (BD). However, studies on the association between cerebral WML volume and BD risk are limited. This study aimed to investigate the relationship between cerebral WML volume and BD incidence. This is a secondary retrospective analysis of patients (N = 146, 72 males, 74 females, mean age = 41.77 years) who have previously undergone magnetic resonance imaging examinations. Information was obtained from the Dryad database. Univariate analysis, piecewise linear regression model, and multivariable logistic regression model were used for statistical analysis. A non-linear relationship was recognized between the cerebral WML volume and BD incidence, in which the inflection point of the WML volume was 6,200 mm3. The effect sizes and confidence intervals on the left and right sides of the emphasis point were 1.0009 (1.0003, 1.0015) and 0.9988 (0.9974, 1.0003), respectively. Subgroup analysis (WML volume < 6,200 mm3) showed that the cerebral WML volume (for 0.1 mm3 increase) was positively related to the BD incidence (OR = 1.11, 95% confidence interval [CI] (1.03, 1.21)). Here we show that the cerebral WML volume is positively and non-linearly correlated to the BD risk. Volumetric analysis of WML provide a better understanding of the association between WML and the BD risk, and thereby the pathophysiological mechanisms of BD. Graphical abstract A non-linear relationship between the volume of cerebral white matter lesions (WML) and bipolar disorder (BD) incidence is shown. The cerebral WML volume is positively and non-linearly correlated to the BD risk. The correlation is stronger when the cerebral WML volume was <6,200 mm3. Graphical Abstract A non-linear relationship between the volume of cerebral white matter lesions and bipolar disorder incidence is shown after adjusting for age; sex; lithium, atypical antipsychotic, antiepileptic, and antidepressant drug use; BMI; migraine; smoking; hypertension; diabetes mellitus; substance and alcohol dependency; and anxiety disorder.