Cerebrospinal fluid glutamate inversely correlates with positive symptom severity in unmedicated male schizophrenic/schizoaffective patients

Background: Recent hypotheses have suggested that diminished brain glutamat e may be of importance in the neurochemical basis of schizophrenia. Methods: We assayed cerebrospinal fluid for glutamate and obtained clinical symptom ratings in 19 medication-free (except p.r.n. chloral hydrate) schi zophrenic or schizoaffective (typically with significant schizophrenic qual ities) male inpatients. Results: Ratings of positive symptoms were significantly inversely correlat ed (r(s) = -.457, p <.05, one-railed test) with glutamate concentrations. H allucinatory behavior was strongly correlated (r(s) = -.621, p <.01, one-ra iled test) with glutamate. A subset of 11 patients consented to a second lu mbar puncture (LP) after treatment with haloperidol (typically 15 or 20 mg/ day)for 2-4 week. Haloperidol treatment did not alter glutamate concentrati ons, No correlations were noted between glutamate and symptoms in the medic ated subsample. Though approximately half the patients received chloral hyd rate during the 72 hours prior to the unmedicated LP, the correlations betw een positive symptoms and glutamate in the patients who received no chloral hydrate prior to the LP were quire similar to those found in the overall s ample. Conclusions: The results provide further support for the potential importan ce of glutamate in the neurochemical basis of schizophrenia. Biol Psychiatr y 1999;45: 68-75 (C) 1999 Society of Biological Psychiatry.