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August 1993

m-Chlorophenylpiperazine Effects in Neuroleptic-Free Schizophrenic PatientsEvidence Implicating Serotonergic Systems in the Positive Symptoms of Schizophrenia

Author Affiliations

From the Schizophrenia Biological Research Center, Department of Psychiatry, Yale University School of Medicine, West Haven (Conn) Veterans Affairs Medical Center, (Drs Krystal, Seibyl, and Charney), and the Clinical Neuroscience Research Unit, Abraham Ribicoff Research Facilities, Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven (Drs Krystal, Seibyl, Price, Woods, Heninger, Aghajanian, and Charney).

Arch Gen Psychiatry. 1993;50(8):624-635. doi:10.1001/archpsyc.1993.01820200034004

Objective:  This study evaluated whether alterations in serotonin function in schizophrenic patients could be demonstrated by comparing the reactivity to a serotonin partial agonist, m-chlorophenylpiperazine (MCPP) in patients and healthy subjects. This study also assessed whether stimulation of serotonin receptors influenced the symptoms of schizophrenia.

Design:  Double-blind randomized comparison of MCPP (0.1 mg/kg, intravenously, administered over 20 minutes) and placebo effects in patients and healthy subjects.

Setting:  Department of Veterans Affairs Medical Center, West Haven, Conn.

Patients and Healthy Subjects:  Fifteen healthy subjects recruited by public advertisement and 12 schizophrenic inpatients who had been neuroleptic free for at least 2 weeks prior to entry into the study.

Main Outcome Measures:  The principal outcome variable was the positive symptoms of schizophrenia operationally defined as the sum of scores on the four key items for schizophrenia on the Brief Psychiatric Rating Scale and the Brief Psychiatric Rating Scale thought disorder factor. Anxiety was assessed with a clinician-rated visual analog scale and plasma hormone levels were measured.

Results:  m-Chlorophenylpiperazine significantly increased the positive symptoms of schizophrenia in patients but not healthy subjects. Patients and healthy subjects exhibited anxiety increases of comparable magnitude following MCPP. However, patients had higher baseline levels of anxiety and exhibited more prolonged anxiogenic responses to MCPP. Anxiety elevations did not correlate with increases in the four key symptoms in patients. Patients exhibited lower baseline prolactin levels compared with healthy subjects, but the two groups did not differ in their prolactin, growth hormone, and cortisol responses to MCPP.

Conclusions:  Schizophrenics, the only psychotic patient group studied to date, are the first patient group to exhibit propsychotic responses to MCPP. These data provide further evidence that sertonin systems modulate positive symptoms in some schizophrenic patients.