The results of the study "schizophrenia, related disorders and glutathione" conducted at the Laboratory of Psychiatric Neuroscience (LUNEP) DUPA of Lausanne, reinforce the hypothesis proposed that a deficit intracerebral glutathione is a vulnerability factor for Schizophrenia at least for a subgroup of patients. While pursuing the baseline study, it is appropriate now to try to restore a higher level of glutathione in patients to see if this increase is accompanied by an improvement in symptoms, particularly negative symptoms and disorders cognitive, particularly resistant to current therapy. N-acetyl-cystein (NAC) is a precursor of glutathione which is used clinically for various indications, well tolerated even at high doses. The investigators propose a double-blind cross-over with the aim to study if the N-acetyl-cystein (at a dose of oral 2g/day) leads on the one hand a rising glutathione brain (measured in resonance magnetic spectroscopic) and also improved patients' conditions (determined by clinical assessments, psychopathological, neuropsychological, biochemical and physiological), while recording any side effects. As a first step, this study should include at least thirty patients and last for two to three years. It is important to note that this is not a study of medication suggested by a pharmaceutical industry, but a medical search.
The results of the study "schizophrenia, related disorders and glutathione" conducted at the Laboratory of Psychiatric Neuroscience (LUNEP) DUPA of Lausanne, reinforce the hypothesis proposed that a deficit intracerebral glutathione is a vulnerability factor for Schizophrenia at least for a subgroup of patients. While pursuing the baseline study, it is appropriate now to try to restore a higher level of glutathione in patients to see if this increase is accompanied by an improvement in symptoms, particularly negative symptoms and disorders cognitive, particularly resistant to current therapy. N-acetyl-cysteine (NAC) is a precursor of glutathione which is used clinically for various indications, well tolerated even at high doses. The investigators propose a double-blind cross-over with the aim to study if the N-acetyl-cystein (at a dose of oral 2g/day) leads on the one hand a rising glutathione brain (measured in resonance magnetic spectroscopic) and also improved patients' conditions (determined by clinical assessments, psychopathological, neuropsychological, biochemical and physiological), while recording any side effects. As a first step, this study should include at least thirty patients and last for two to three years. It is important to note that this is not a study of medication suggested by a pharmaceutical industry, but a medical search.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
13
Once included, the patients will be randomly placed in two groups: one group (1) will receive 2 g/day of NAC (2caps of 0.5g twice a day) and the other group (2) a placebo, for a duration of 8 weeks. At the end of the 8 weeks, group (2) will receive NAC and (1) the placebo for another 8 weeks
Positive and Negative Syndrome Scale (PANSS)
Improvment of the negative symptoms, measured with the PANSS: positive and negative syndrome scale". (Score:1= absence of the symptom - 7= extreme symptoms)
Time frame: 8 months
frankfurt Complaint Questionnaire (FCQ)
Assessment of subjective troubles, " basic symptoms ": troubles of perceptive, cognitive or motor functions frequently observed in prodromal or remission phases.
Time frame: 8 months
Global Assessment of Functioning - (GAF)
Assessment of the psychological, social and professional state of the patient at a given moment.
Time frame: 8 months
Clinical Global Impression - (CGI)
Allows punctual evaluation of the severity of the disease, of the improvement and of the side effects
Time frame: 8 months
Neuropsychological evaluation
The neuropsychological tests aim to assess cognitive functions : working memory, attention, planning; also include a WAIS
Time frame: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
AIMS (Abnormal Involuntary Movements Scale): quantitative assessment of secondary hyperkinesia (excluding tremor) due to neuroleptics.
Time frame: 8 months
• Magnetic Resonance Spectroscopy (MRS)
A MRS method has originally been developed for the determination of brain GSH levels in vivo (Trabesinger et al., 1999), allowing us to observe a 51% GSH decrease in prefrontal cortex of schizophrenic patients (Do et al., 2000).
Time frame: 8 months
EEG/evoked potentials
Anomalies of amplitude and latency of the P300 wave evoked under the "auditory oddball" paradigm are reliable neurophysiological markers of schizophrenia, correlating with the negative symptoms
Time frame: 8 months
Blood and fibroblasts biochemistry
I. Plasma GSH and metabolites, plasma amino acids, particularly the sulfur containing ones II. activity of enzymes involved in GSH metabolism III. genetic analysis of enzymes involved in GSH metabolism IV. cell counts and tests of hepatic, renal and thyroid functions
Time frame: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
Simpson-Angus scale for extrapyramidal signs: tremor, rigidity, akinesia.
Time frame: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
Barnes scale: specific assessment of akathisia.
Time frame: 8 months
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