TREATMENT OF SHIZOPHRENIC PATIENTS AND rTMS

Introduction: Schizophrenia (SCH) is a heterogeneous syndrome characterized by positive and negative symptoms. Despite appropriate medication, about 1/4 of patients suffer for refractory positive and/or negative symptoms, which are associated with functional handicap, increase of duration and of the number of hospitalizations. Numerous studies have suggested that the pathophysiology of auditory hallucinations (AH) is related to a hyper activity of the left temporoparietal cortex (TPC). On the other hand, negative symptoms are associated with a prefrontal hypoactivity and the efficiency of pharmacological treatments is frequently partial. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool with excellent tolerability and safety. Given its hypothesized mechanisms of action and the clinical beneficial effects obtained in several types of pathology (Aleman et al. 2007), the efficacy of rTMS has been investigated for drug-resistant SCH symptoms. Objective: Our objective is to expose the knowledge concerning the rTMS use in the treatment of these symptoms and to purpose a critical analysis of these data. Method: a systematic review of the literature has been conducted using NIH Pubmed. The following search terms were used: TMS - rTMS - Schizophrenia - negative symptoms - hallucinations. Results: Concerning the treatment of AH, 16 publications and 4 meta analyses were selected. For the negative symptoms, we retained 16 studies and 3 meta analyses. The most extensively investigated application for rTMS in SCH is the use of low-frequency stimulation to the left TPC with the aim to improve AH symptomatology. When compared to sham, this type of acute course of rTMS has been proven to induce a substantial and significant reduction in AH. But this effect does not seem long-lasting and maintenance protocols must be developed. Concerning negative symptoms, the results are less solid but we find some works which demonstrate an improvement of these symptoms while various stimulation parameters were used. Recently, new parameters of stimulation in particular the theta burst stimulation have permitted us to obtain larger effects with longer duration. The interest of these new parameters will be discussed here. Conclusion: Overall, rTMS studies have demonstrated some promise in the treatment of SCH. However, more research is required to enhance rTMS efficacy and increase its beneficial effect duration and to test new therapeutic strategies in this topic

TREATMENT OF SHIZOPHRENIC PATIENTS AND rTMS

Introduction: Schizophrenia (SCH) is a heterogeneous syndrome characterized by positive and negative symptoms. Despite appropriate medication, about 1/4 of patients suffer for refractory positive and/or negative symptoms, which are associated with functional handicap, increase of duration and of the number of hospitalizations. Numerous studies have suggested that the pathophysiology of auditory hallucinations (AH) is related to a hyper activity of the left temporoparietal cortex (TPC). On the other hand, negative symptoms are associated with a prefrontal hypoactivity and the efficiency of pharmacological treatments is frequently partial. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool with excellent tolerability and safety. Given its hypothesized mechanisms of action and the clinical beneficial effects obtained in several types of pathology (Aleman et al. 2007), the efficacy of rTMS has been investigated for drug-resistant SCH symptoms. Objective: Our objective is to expose the knowledge concerning the rTMS use in the treatment of these symptoms and to purpose a critical analysis of these data. Method: a systematic review of the literature has been conducted using NIH Pubmed. The following search terms were used: TMS - rTMS - Schizophrenia - negative symptoms - hallucinations. Results: Concerning the treatment of AH, 16 publications and 4 meta analyses were selected. For the negative symptoms, we retained 16 studies and 3 meta analyses. The most extensively investigated application for rTMS in SCH is the use of low-frequency stimulation to the left TPC with the aim to improve AH symptomatology. When compared to sham, this type of acute course of rTMS has been proven to induce a substantial and significant reduction in AH. But this effect does not seem long-lasting and maintenance protocols must be developed. Concerning negative symptoms, the results are less solid but we find some works which demonstrate an improvement of these symptoms while various stimulation parameters were used. Recently, new parameters of stimulation in particular the theta burst stimulation have permitted us to obtain larger effects with longer duration. The interest of these new parameters will be discussed here. Conclusion: Overall, rTMS studies have demonstrated some promise in the treatment of SCH. However, more research is required to enhance rTMS efficacy and increase its beneficial effect duration and to test new therapeutic strategies in this topic

Dopaminergic transmission in STOP null mice.

International audienceNeuroleptics are thought to exert their anti-psychotic effects by counteracting a hyper-dopaminergic transmission. Here, we have examined the dopaminergic status of STOP (stable tubule only polypeptide) null mice, which lack a microtubule-stabilizing protein and which display neuroleptic-sensitive behavioural disorders. Dopamine transmission was investigated using both behavioural analysis and measurements of dopamine efflux in different conditions. Compared to wild-type mice in basal conditions or following mild stress, STOP null mice showed a hyper-locomotor activity, which was erased by neuroleptic treatment, and an increased locomotor reactivity to amphetamine. Such a behavioural profile is indicative of an increased dopaminergic transmission. In STOP null mice, the basal dopamine concentrations, measured by quantitative microdialysis, were normal in both the nucleus accumbens and the striatum. When measured by electrochemical techniques, the dopamine efflux evoked by electrical stimulations mimicking physiological stimuli was dramatically increased in the nucleus accumbens of STOP null mice, apparently due to an increased dopamine release, whereas dopaminergic uptake and auto-inhibition mechanisms were normal. In contrast, dopamine effluxes were slightly diminished in the striatum. Together with previous results, the present study indicates the association in STOP null mice of hippocampal hypo-glutamatergy and of limbic hyper-dopaminergy. Such neurotransmission defects are thought to be central to mental diseases such as schizophrenia

Optimizing the Temporal Resolution of Fast-Scan Cyclic Voltammetry

[Image: see text] Electrochemical detection with carbon-fiber microelectrodes has become an established method to monitor directly the release of dopamine from neurons and its uptake by the dopamine transporter. With constant potential amperometry (CPA), the measured current provides a real time view of the rapid concentration changes, but the method lacks chemical identification of the monitored species and markedly increases the difficulty of signal calibration. Monitoring with fast-scan cyclic voltammetry (FSCV) allows species identification and concentration measurements but often exhibits a delayed response time due to the time-dependent adsorption/desorption of electroactive species at the electrode. We sought to improve the temporal resolution of FSCV to make it more comparable to CPA by increasing the waveform repetition rate from 10 to 60 Hz with uncoated carbon-fiber electrodes. The faster acquisition led to diminished time delays of the recordings that tracked more closely with CPA measurements. The measurements reveal that FSCV at 10 Hz underestimates the normal rate of dopamine uptake by about 18%. However, FSCV collection at 10 and 60 Hz provide identical results when a dopamine transporter (DAT) blocker such as cocaine is bath applied. To verify further the utility of this method, we used transgenic mice that overexpress DAT. After accounting for the slight adsorption delay time, FSCV at 60 Hz adequately monitored the increased uptake rate that arose from overexpression of DAT and, again, was similar to CPA results. Furthermore, the utility of collecting data at 60 Hz was verified in an anesthetized rat by using a higher scan rate (2400 V/s) to increase sensitivity and the overall signal