Research Article

Quetiapine affects neuropeptide Y and corticotropin-releasing hormone in cerebrospinal fluid from schizophrenia patients: relationship to depression and anxiety symptoms and to treatment response

Georg Nikisch^a1, Pierre Baumann^a2, Tianmin Liu^a3 and Aleksander A. Mathé^a3 c1

^a1 Department of Psychiatry and Psychotherapy, Klinikum Fulda gAG, Fulda, Germany

^a2 Department of Psychiatry, CHUV, Hospital of Cery, Prilly-Lausanne, Switzerland

^a3 Karolinska Institutet, Clinical Neuroscience, Psychiatry M56, Karolinska University Hospital Huddinge, Stockholm, Sweden

Abstract

Cumulative evidence indicates that neuropeptides play a role in the pathophysiology of schizophrenia. Early data showed increased neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from schizophrenia patients and data from rodents show that antipsychotic drugs modulate NPY levels in and release from selected rat brain regions. In view of these findings we investigated whether the atypical antipsychotic quetiapine, originally used as an antipsychotic but subsequently shown to be efficient also in major depressive disorder and in both poles of bipolar disorder, would affect NPY-like immunoreactivity (-LI), and corticotropin-releasing hormone (CRH)-LI levels in CSF of schizophrenia patients. NPY-LI and CRH-LI in CSF were determined in 22 patients with schizophrenia. Lumbar puncture was performed at baseline and again after 4 wk of quetiapine treatment (600 mg/d). Patients were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at weekly intervals. Quetiapine treatment was associated with a significant increase in NPY-LI (p<0.001) and decrease in CRH-LI (p<0.01). Stepwise multiple regression analysis revealed that ΔNPY-LI and ΔCRH-LI levels predicted 63% (p<0.001) of the variability of the ΔPANSS total score, ΔNPY-LI 42% (p<0.05) of the ΔPANSS anxiety items (G2) and ΔCRH-LI 40% (p=0.05) of the ΔPANSS depression items (G6). These results suggest that while quetiapine's effects on monoamines are probably related to its antipsychotic properties, the modulation of NPY and CRH accounts for its antidepressant and anxiolytic effects and can be markers of response.

(Received July 18 2011)

(Reviewed August 23 2011)

(Revised August 25 2011)

(Accepted September 15 2011)

Key Words:

• CSF;
• neuropeptides;
• norquetiapine;
• quetiapine;
• schizophrenia

Correspondence:

^c1 Address for correspondence: A. A. Mathé, M. D., Ph.D., Karolinska Institutet, Clinical Neuroscience, Psychiatry M56, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. Tel.: +46-70-4840743 Fax: +46-8-300972 Email: aleksander.mathe@ki.se