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 neuro leptic-naive patients with their first acute schizophrenic episode. Th e CSF was analyzed for several biogenic amines and their metabolites [ dopamine, dihydroxyphenylacetic acid (DOPAC), noradrenaline, 5-hydroxy tryptamine (5-HT) 5-hydroxyindolacetic acid (5-HIAA)]. For these trans mitters, which are stored and secreted from synaptic vesicles, there w as no significant difference between controls and schizophrenic patien ts. As constituents of large dense-core vesicles substance P (SP) and GE-25 (derived from chromogranin A)-and secretoneurin (derived from se cretogranin II)-immunoreactivities were determined SP-like immunoreact ivity levels did not differ between controls and patients; however, GE -25 was elevated and especially the GE-25/secretoneurin ratio was sign ificantly (p < .001) higher in patients. Characterization of the immun oreactivities by high-performance liquid chromatography did not reveal any difference between patients (n = 3) and controls in the processin g of the two proproteins chromogranin A and secretogranin II. These da ta indicate that proteolytic processing of the two widespread constitu ents of large dense-core vesicles, i.e., chromogranin A and secretogra nin II, is not altered in schizophrenic patients. The increase in the chromogranin A / secretoneurin ratio in schizophrenic patients deserve s further investigation in order to elucidate its possible pathogeneti c significance.