Acid accumulation in bipolar disorder

Acid accumulation (AA) describes the continuum of hydrogen ions concentration in the body reflected by increased acid-base buffer activity manifested by low bicarbonate (HCO3) concentration, increased anion gap (AG) or corrected AG (CAG). AA is associated with dietary acid-load, mitochondrial dysfunction, alcohol-abuse, obesity, hypertension, insulin resistance, and kidney disease. Despite these factors being highly prevalent in bipolar disorder (BD) AA has not been studied in this population. In this study we assessed AA in persons with BD and compared them primarily to controls and secondarily to individuals with BD and alcohol withdrawal syndrome (AWS). Available electronic health record data was analyzed from persons with BD (n = 733) enrolled in the Mayo Clinic Bipolar Disorder Biobank, controls (n = 548) and BD inpatients with AWS (BD + AWS, n = 399). AA analyses were adjusted for age, sex, BMI, and eGFR. Compared to controls, persons with BD had lower HCO3, higher AG, and higher CAG - thus greater acid accumulation. In analyses adjusted for age, sex, BMI, and eGFR we still observed higher AG (10.8 vs 10.1 mEq/L, p = 0.006) and CAG (11.7 vs 10.4 mEq/L, p < 0.001) in BD. In a secondary analysis considering BD + AWS and excluding persons with alcohol use disorder in the other groups, persons with BD + AWS had significantly higher AA than both persons with BD and controls (all p < 0.001). We found greater AA in persons with BD, and this was accentuated in BD + AWS. Future studies may focus on the risk factors of AA in BD to personalize prevention strategies.