Association Between the Serum Carnitine Level and Ammonia and Valproic Acid Levels in Patients with Bipolar Disorder

Abstract

Purpose: Valproic acid (VPA) is not only an antiepileptic drug but also a mood stabilizer for patients with bipolar disorder. Long-term VPA therapy can cause carnitine deficiency, which may result in an increase in the blood ammonia level, in patients with epilepsy. However, information about this effect in patients with bipolar disorder is limited. The aim of this study was to investigate the associations between the serum VPA level and the carnitine and ammonia levels in psychiatric adult patients with epilepsy. Methods: The subjects were 182 consecutive Japanese adult patients (mean age 54.3 ± 19.5 years) diagnosed with bipolar disorder and treated with VPA. The serum VPA level, carnitine fraction, and plasma ammonia level were measured. Furthermore, the free carnitine and acylcarnitine fractions were measured using an enzyme cycling method. Results: Sixty-nine patients (38%) had a low free carnitine level. There were significant differences in sex, height, VPA dose, serum VPA level, total carnitine level, acylcarnitine level, and acylcarnitine/free carnitine ratio between patients with a low free carnitine level and those with a normal range of free carnitine. The simple and multiple regression analyses revealed that the VPA dose and the serum VPA level were inversely and significantly correlated with the free carnitine level. The plasma ammonia level was correlated with the VPA dose, serum VPA level, and acylcarnitine level but not with the free carnitine level. Conclusions: These findings suggest that carnitine deficiency is associated with the VPA dose and the serum VPA level in patients with bipolar disorder. However, it is unlikely that carnitine deficiency is associated with hyperammonemia in patients with bipolar disorder.

Alterations of Plasma Lipids in Adult Women With Major Depressive Disorder and Bipolar Depression

“…Herein, we found that the levels of MGDG, phSM, AcCa and PS were decreased while GM2 and PIP were increased both in MDD and BPD when compared with HC. Supporting this finding, previous studies found that plasma SM was negatively correlated with depressive symptoms ( 49 ) and lower concentrations of AcCa were observed in the plasma or serum in MDD and BD patients when compared with healthy control previously ( 50 – 52 ). Moreover, alterations in AcCa were also involved in the action of citalopram/escitalopram in major depression ( 53 ).…”

Alterations in the Plasma Lipidome of Adult Women With Bipolar Disorder: A Mass Spectrometry-Based Lipidomics Research

“…Herein we found that the levels of SM, AcCa, PE, PS, and Co decreased in BD and were negatively correlated with the severity of psychotic, affective, or mania symptoms. Previous studies also found that plasma SM was negatively correlated with depressive symptoms ( 42 ), and lower concentrations of AcCa and PE were also observed in the plasma of BD patients than that of HCs ( 43 – 45 ). Considering that PS biosynthesis via the serine base exchange reaction using PE and PS can be converted to PE by PS decarboxylase in the mitochondria ( 46 ), the decrease in PS levels may be related to the reduction of PE.…”

Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells

“…VPA is a widely prescribed antiepileptic drug, and a longitudinal observational study showed that VPA efficacy for focal or generalized seizures is superior to that of mixed-type seizures [26]. VPA has been used in treating bipolar disorder since the 1990s [27], and has shown positive results in spinal muscular atrophy in cohort studies [28]. The successful trial of HDACis, which are currently available for clinical use in the treatment of cancers, hints at the existence of the cures for various human diseases such as epilepsy through epigenetic regulation.…”