Am J Psychiatry 154:7, July 1997 BRIEF REPORTS BRIEF REPORTS CSF N eurotensin Concentrations and Antipsychotic Treatment in Schizophrenia and Schizoaffective Disorder Rajiv P. Sharma, M.D., Philip G. Janicak, M.D., Garth Bissette, Ph.D., and Charles B. Nemeroff, M.D., Ph.D. O bjective: The relationship between CSF neurotensin concentrations and measures of psy- chopathology in patients with schizophrenia or schizoaffective disorder was examined before and after treatment with antipsychotic drugs. Method: CSF neurotensin concentrations were measured in 42 drug-free patients with schizophrenia or schizoaffective disorder. For 18 of these patients, CSF neurotensin was measured again after 4 weeks of antipsychotic treatment. Results: Significantly higher levels of pretreatment psychopathology were observed in the pa- tients with the lowest CSF neurotensin concentrations. Furthermore, improvements in overall psychopathology and, particularly, negative symptoms were correlated with increases in CSF neurotensin concentrations during treatment. Conclusions: These findings provide further evi- dence for a role of neurotensin in the pathophysiology of psychosis and in the mechanism of action of antipsychotic drugs. (Am J Psychiatry 1997; 154:1019–1021) N eurotensin is an endogenous tridecapeptide neurotransmitter that is heterogeneously dis- tributed in the mammalian CNS and has close neuro- anatomical and functional associations with the dopa- mine neurotransmitter system (1). Considerable data indicate that exogenously administered neurotensin produces pharmacological actions similar to those of antipsychotic drugs, particularly atypical antipsy- chotics (2). In rodents, neurotensin induces catalepsy, inhibits discrete trial-conditioned avoidance respond- ing, and reduces spontaneous and psychostimulant- induced locomotor activity (1). In addition, neuroten- sin alters the firing rate and the metabolic activity of dopamine neurons, especially in the mesolimbic system. A series of studies indicate that antipsychotic drugs in- crease both neurotensin mRNA expression and neuro- tensin concentrations in specific dopamine terminal areas (3). The hypothesis that neurotensin functions as an en- dogenous antipsychotic is based on the aforementioned preclinical studies and on clinical investigations (4–8) in which low CSF neurotensin concentrations were found in drug-free schizophrenic patients. In the current study we sought to confirm and extend these observations by determining whether low concentrations of CSF neuro- tensin are associated with greater severity of psychosis and whether antipsychotic-induced improvement in specific clinical symptoms is associated with meaning- ful changes in CSF neurotensin concentrations. METHOD Forty-two patients (29 with schizophrenia and 13 with schizoaf- fective disorder) were admitted to the inpatient research unit of the University of Illinois at Chicago for an acute episode of psychiatric symptoms. The study group included 15 women and 27 men, and their mean age was 28.7 years (SD=6.4). Upon providing written informed consent after full explanation of the study procedures, all patients were maintained drug free for an average of 15.4 days (SD=6.3, range=5–35), during which a compre- hensive diagnostic workup with the Research Diagnostic Criteria was completed. Behavioral symptoms were quantified by using the Brief Psychiatric Rating Scale (BPRS), with items scored 1 through 7. The diagnostic and behavioral assessments were conducted by two-mem- ber standardized rating teams. CSF samples were obtained at the end of the drug-free period by lumbar puncture, performed with patients in the lateral decubitus po- sition, in the morning after a 10-hour bed rest and an overnight fast. The samples were immediately stored at –80°C. Eighteen of these patients (14 with schizophrenia and four with schizoaffective disorder) consented to a second lumbar puncture after receiving antipsychotic treatment. This subgroup included eight women and 10 men, and their mean age was 29.6 years (SD=7.0). Antipsychotic treatment was initiated immediately after the first lumbar puncture by means of a flexible dosing schedule based on clinical symptoms and response. An effort was made to maintain a constant antipsychotic drug dose during the week be- fore the second lumbar puncture. Ten patients received trifluoper- Received July 31, 1996; revision received Jan. 8, 1997; accepted Jan. 13, 1997. From the Department of Psychiatry, University of Illi- nois College of Medicine at Chicago; the Department of Psychiatry, University of Mississippi School of Medicine, Jackson; and the De- partment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta. Address reprint requests to Dr. Sharma, The Psychiatric Institute, University of Illinois at Chicago, 1601 West Taylor St., Chicago, IL 60612. Supported in part by NIMH grant MH-48888 to Dr. Sharma and grant MH-39415 to Dr. Nemeroff. BRIEF REPORTS Am J Psychiatry 154:7, July 1997 1019