Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 15, Issue 8, Pages 1051-1061Publisher
OXFORD UNIV PRESS
DOI: 10.1017/S1461145711001556
Keywords
CSF; neuropeptides; norquetiapine; quetiapine; schizophrenia
Funding
- AstraZeneca GmbH, Germany [D1449L00033]
- Swedish Medical Research Council [10414]
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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 DNPY-LI and DCRH-LI levels predicted 63% (p < 0.001) of the variability of the DPANSS total score, DNPY-LI 42% (p < 0.05) of the DPANSS anxiety items (G2) and DCRH-LI 40% (p = 0.05) of the DPANSS 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.
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