Post-mortem brain analysis reveals altered monoaminergic system in the dorsolateral prefrontal cortex and hippocampus in chronic schizophrenia

Schizophrenia is a multifactorial psychiatric disorder in which monoaminergic neurotransmission, particularly dopamine (DA), serotonin (5-HT), and norepinephrine (NE), is implicated in both pathophysiology and response to treatments. However, the regional composition and functional interaction among these neurotransmitters and their catabolites remain unclear. In this study, using high-performance liquid chromatography (HPLC), we quantified DA, 5-HT, NE and their metabolites, HVA, DOPAC, and 5-HIAA, along with protein levels of key monoamine-metabolizing enzymes (MAO-A, MAO-B, and COMT isoforms) in post-mortem dorsolateral prefrontal cortex (DLPFC) and hippocampus from chronic schizophrenia patients and matched healthy controls. Although absolute monoamine and enzyme levels did not differ between cases and controls, partial correlation analyses revealed remarkable schizophrenia-specific interactions. In particular, patients exhibited distinct 5-HT-DOPAC correlations in both regions, suggesting an abnormal coupling between serotonergic and dopaminergic metabolism. In the DLPFC, the DA-NE correlation was markedly attenuated in schizophrenia, potentially reflecting disrupted catecholaminergic integration relevant to cognitive function and salience processing. Furthermore, an increased 5-HIAA-5-HT correlation emerged in the hippocampus of schizophrenia patients, indicative of abnormal serotonin turnover. In conclusion, our observations indicate that while the cerebral concentrations of monoamines and their catabolites remain relatively stable in patients with schizophrenia, their interactions are significantly dysregulated compared to those reported in healthy controls. These postmortem findings provide new insights into the monoaminergic neurotransmission crosstalk in the schizophrenia brain.