101 To cite this article: Neuro Endocrinol Lett 2006; 27(1-2):101–000 ORIGINAL ARTICLE Neuroendocrinology Letters Volume 27 Nos. 1–2 February-April 2006 The double-blind sham-controlled study of high-frequency rTMS (20Hz) for negative symptoms in schizophrenia: A negative results Tomas Novak, Jiri Horacek, Pavel Mohr, Milan Kopecek, Mabel Rodriguez, Filip Spaniel, Colleen Dockery & Cyril Höschl Prague Psychiatric Centre, Centre of Neuropsychiatric Studies, 3 rd Medical Faculty of Charles University, Prague, Czech Republic. Correspondence to: Tomas Novak, M.D. Prague Psychiatric Centre, Centre of Neuropsychiatric Studies Ustavni 91, 181 03 Prague, CZECH REPUBLIC TEL .: +420266003386; FAX :+420266003366 EMAIL : novak@pcp.lf3.cuni.cz Submitted: January 10, 2006 Accepted: January 15, 2006 Key words: rTMS; prefrontal cortex; schizophrenia; negative symptoms; cognitive tests Neuroendocrinol Lett 2006; 27(1-2): 101–000 PMID: --------- NEL271206A09 © Neuroendocrinology Letters www.nel.edu Abstract The high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the prefrontal cortex is a promising method for the treatment of negative symptoms of schizophrenia. Using double-blind sham-controlled parallel design, we evaluated the effect of HF-rTMS over the left dorsolateral prefrontal cortex (DLPFC) on nega- tive symptoms in patients with schizophrenia. Sixteen schizophrenia patients with predominantly negative symptoms on stable antipsychotic medication were treated with 20Hz rTMS (90% of motor threshold, 2000 stimuli per session) over ten days within 2 weeks with six weeks follow-up. The effect was assessed using PANSS, CGI, MADRS and neuropsychological tests. We failed to find any significant effect of active rTMS. Sham rTMS showed a trend for improvement over time on positive and negative subscales of PANSS and MADRS. Between-group comparisons failed to reveal any significant differences on any rating scales except a positive subscale of PANSS after 8 weeks. Results from our study did not confirm that HF-rTMS over the left DLPCF affects the negative symptoms of schizophrenia and alternative rTMS approaches are discussed. Introduction Negative symptoms in schizophrenia, character- ized by blunted affect, apathy, attention deficits, poverty of thought or speech and social withdrawal, have been regarded as a core feature of chronic schizophrenia with clinical impact on prognosis [1;2]. Several studies have confirmed that negative symptoms are associated with impairment of brain metabolism or perfusion in the prefrontal and parietal cortex [3–6]. The treatment of negative symptoms of schizo- phrenia remains a major clinical challenge. While antipsychotic drugs are very effective for positive symptoms, the treatment of negative symptoms of schizophrenia is still a major clinical problem. The teraputical strategies for managing the negative symptoms are the same as for cognitive dysfunc- tion [7;8] and it also reflects the pathophysiological similarities in both domains [9]. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that induces the depolarization of neuron membranes and subse- quent functional changes in a discrete area of the