CSF of neuroleptic-naive first-episode schizophrenic patients: Levels of biogenic amines, substance P, and peptides derived from chromogranin A (GE-25) and secretogranin II (secretoneurin)

Lumbar cerebrospinal fluid (CSF) was collected from controls and neuroleptic-naive patients with their first acute schizophrenic episode. The CSF was analyzed for several biogenic amines and their metabolites [dopamine, dihydroxyphenylacetic acid (DOPAC), noradrenaline, 5-hydroxytryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA)]. For these transmitters, which are stored and secreted from synaptic vesicles, there was no significant difference between controls and schizophrenic patients. As constituents of large dense-core vesicles substance P (SP) and GE-25 (derived from chromogranin A)—and secretoneurin (derived from secretogranin II)—immunoreactivities were determined. SP-like immunoreactivity levels did not differ between controls and patients; however, GE-25 was elevated and especially the GE-25/secretoneurin ratio was significantly (p < .001) higher in patients. Characterization of the immunoreactivities by high-performance liquid chromatography did not reveal any difference between patients (n = 3) and controls in the processing of the two proproteins chromogranin A and secretogranin II. These data indicate that proteolytic processing of the two widespread constituents of large dense-core vesicles, i.e., chromogranin A and secretogranin II, is not altered in schizophrenic patients. The increase in the chromogranin A/secretoneurin ratio in schizophrenic patients deserves further investigation in order to elucidate its possible pathogenetic significance.