A Pilot Study on Plasma N-Acetylaspartate Levels at Admission and Discharge in Hospitalized Psychiatric Patients: Impact of Lithium Treatment and Clinical Correlations

N-Acetylaspartate (NAA) plays a critical role in neuronal function, metabolism, and neurotransmitter release. Evidence from magnetic resonance spectroscopy indicates diminished NAA levels in individuals diagnosed with schizophrenia and bipolar disorder; however, this process is time-consuming, expensive, and not viable in individuals with acute illness exacerbation. In order to address these limitations, we developed a novel method for the quantification of plasma NAA based on tandem mass spectrometry coupled to liquid chromatography (HPLC-MS). Our study aimed to assess whether plasma NAA levels change during hospitalization and whether these changes correlate with symptomatic improvement in patients experiencing acute psychiatric exacerbations. We recruited 31 inpatients with acute symptoms of psychotic (48.39%) and/or mood (51.61%) disorders. Symptom severity was assessed using the brief psychiatric rating scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale. Plasma NAA was measured at admission and discharge. We observed a significant decrease in symptom scores and a significant increase in plasma NAA levels between admission and discharge. The initiation of therapy with lithium salts significantly influenced plasma NAA changes. Our study shows that our HPLC-MS method can detect clinically meaningful changes in plasma NAA levels. These results might lay the groundwork for future research exploring the relationship between plasma NAA levels and cerebral NAA levels measured by MRS.