Serum carboxylated osteocalcin in youth with bipolar disorder; association with manic symptom severity

BACKGROUND: Preclinical studies suggest that osteocalcin can modulate parasympathetic tone and affective responses to stress. Depression and anxiety have been associated with lower circulating osteocalcin concentrations, and the carboxylated form (cOC) has been associated with perceived stress in adults with depression. This study compares serum cOC concentrations between youth with and without bipolar disorder (BD) and investigates relationships with manic and depressive symptom severity. METHODS: Among youth aged 13-21 years, psychiatric diagnoses were determined using the Kiddie Schedule for Affective Disorders-Present and Lifetime version. cOC was quantified from fasting serum by enzyme-linked immunosorbent assay. Depressive and manic symptom severity were assessed as Depression Rating Scale (DRS) and Mania Rating Scale (MRS) scores, respectively. Stratified analyses were performed based on the presence of hypomanic or depressive episodes. RESULTS: The study included 78 participants with BD (mean age 17.7 ± 1.7 years, 65.4% female) and 74 healthy controls (HC; mean age 17.3 ± 2.0 years, 54.1% female). Concentrations of cOC were lower in BD than in HC (β=-0.13, p = 0.04), but this was attenuated when adjusting for psychiatric comorbidities. Among participants with BD (β=0.29, p = 0.046), and particularly among those experiencing a hypomanic episode (n = 27; β=0.89, p = 0.003), cOC was associated with manic symptom severity. cOC was not associated with depressive symptoms. CONCLUSION: In youth, serum cOC concentrations may be a neuroendocrine marker of psychopathology, and of hypomania symptom severity in those with bipolar disorder.