Transcranial magnetic stimulation in depression--lessons from the multicentre trials

Looking at novelties and advances in medicine in particular in the treatment of major depressive disorder no principally new antidepressant treatment strategy has been established in clinical routine in the last fifty years. However, regarding the considerable issue of treatment resistance in depression, new therapeutic strategies are urgently required. In this context, repetitive transcranial magnetic stimulation above the dorsolateral prefrontal cortex has been proposed as a potential new treatment option for depression; furthermore, in October 2008 a first rTMS-device (NeuroStar TMS Therapy System™) was approved by the FDA for the treatment of treatment resistant major refractory depression in adults. Yet, despite now nearly two decades of research in this field, no final answer concerning its validity for antidepressant treatment in the clinical practice is given. Numerous studies with small sample sizes and heterogeneous designs have been performed in this field yielding to different results. These were subjected to meta-analyses, assessing the antidepressant effect of rTMS, which are briefly summarized in this article. Further, multicentre-trials with larger numbers of patients were performed, which are presented and critically discussed here in more detail. This short review shall thus provide an overview of the current status of knowledge concerning rTMS in depression and it also provides some recommendations for future research in this field

Clinical, Epidemiologic, Histopathologic and Molecular Features of an Unexplained Dermopathy

BACKGROUND: Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. METHODS: A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. RESULTS: We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. CONCLUSIONS: This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation

Biochim. Biophys. Acta-Biomembr.

Recently discovered macrocyclic carbon suboxide (MCS) factors with the general formula (C3O2)(n) were found to strongly inhibit rabbit and rat Na,K-ATPase as well as SR Ca-ATPase. Highly active MCS factors were obtained by a base/acid treatment of their lipophilic precursor isolated from plants. In the ESI-MS spectra, the dominant molar mass ion of 431 Da corresponds to a 1:1 complex of the carbon suboxide hexamer (n = 6; M-r = 408 Da) with a Na+ ion. Additional mass ions identified in positive and negative ion mode were assigned as complexes of the MCS hexamer (n = 6) and octamer (n = 8) with Na+ or with TFA(-) in various ratios. The dominant mass ion values of these active MCS factors from plants are also found in mass spectra of previously described endogenous digitalis- like factors (EDLF) from animals. This would suggest that ubiquitously distributed MCS factors may function as putative endogenous regulatory substances of Na,K-ATPase and possibly of other ATPases. With the symmetric display of several equivalent carbonyl or hydroxy groups, the structure of MCS factors is particularly suited for interactions with proteins and other bio-molecules. This could explain the high biological activity and the unusual properties of the MCS factors. (C) 2002 Elsevier Science B.V. All rights reserved

Biochim. Biophys. Acta-Biomembr.

Recently discovered macrocyclic carbon suboxide (MCS) factors with the general formula (C3O2)(n) were found to strongly inhibit rabbit and rat Na,K-ATPase as well as SR Ca-ATPase. Highly active MCS factors were obtained by a base/acid treatment of their lipophilic precursor isolated from plants. In the ESI-MS spectra, the dominant molar mass ion of 431 Da corresponds to a 1:1 complex of the carbon suboxide hexamer (n = 6; M-r = 408 Da) with a Na+ ion. Additional mass ions identified in positive and negative ion mode were assigned as complexes of the MCS hexamer (n = 6) and octamer (n = 8) with Na+ or with TFA(-) in various ratios. The dominant mass ion values of these active MCS factors from plants are also found in mass spectra of previously described endogenous digitalis- like factors (EDLF) from animals. This would suggest that ubiquitously distributed MCS factors may function as putative endogenous regulatory substances of Na,K-ATPase and possibly of other ATPases. With the symmetric display of several equivalent carbonyl or hydroxy groups, the structure of MCS factors is particularly suited for interactions with proteins and other bio-molecules. This could explain the high biological activity and the unusual properties of the MCS factors. (C) 2002 Elsevier Science B.V. All rights reserved

Characterization of the macrocyclic carbon suboxide factors as potent Na,K-ATPase and SR Ca-ATPase inhibitors

Recently discovered macrocyclic carbon suboxide (MCS) factors with the general formula (C3O2)(n) were found to strongly inhibit rabbit and rat Na,K-ATPase as well as SR Ca-ATPase. Highly active MCS factors were obtained by a base/acid treatment of their lipophilic precursor isolated from plants. In the ESI-MS spectra, the dominant molar mass ion of 431 Da corresponds to a 1:1 complex of the carbon suboxide hexamer (n = 6; M-r = 408 Da) with a Na+ ion. Additional mass ions identified in positive and negative ion mode were assigned as complexes of the MCS hexamer (n = 6) and octamer (n = 8) with Na+ or with TFA(-) in various ratios. The dominant mass ion values of these active MCS factors from plants are also found in mass spectra of previously described endogenous digitalis- like factors (EDLF) from animals. This would suggest that ubiquitously distributed MCS factors may function as putative endogenous regulatory substances of Na,K-ATPase and possibly of other ATPases. With the symmetric display of several equivalent carbonyl or hydroxy groups, the structure of MCS factors is particularly suited for interactions with proteins and other bio-molecules. This could explain the high biological activity and the unusual properties of the MCS factors. (C) 2002 Elsevier Science B.V. All rights reserved

Accuracy of stereotaxic positioning of transcranial magnetic stimulation

In cognitive neuroscience, optically tracked frameless stereotaxic navigation has been successfully used to precisely guide transcranial magnetic stimulation (TMS) to desired cortical areas for brain-mapping purposes. Thereby, potential sources of imprecision are the fixation of a reference frame to the head of the subject and the referencing procedure according to certain landmarks (LM). The aim of our study was to evaluate the accuracy of frameless stereotaxic coil positioning in a standard experimental setting. A parameter for accuracy is the reproducibility of LM coordinates. In order to test the stability of the referencing for stereotaxic positioning within a single TMS session (within-session stability), the coordinates of six predefined facial LM in nine subjects were recorded first after the initial registration and second after a 20 minutes TMS session. The two sets of coordinates were then compared. The reliability of the positioning coordinates between different TMS sessions (inter-session repeatability) was addressed by registering the subjects LM coordinates in two independent TMS sessions. The variance of the recorded coordinates was analyzed. Altogether, LM were registered 1728 times (192 measures per subject). Within-session stability: The mean Euclidean distance (MED) between the LM position coordinates before and after a TMS session was 1.6 mm, when pooling over all LM. Inter-session repeatability: The MED between the LM positions recorded after the reference procedures of two different sessions showed an average deviation of 2.5 mm. In conclusion, optically tracked frameless stereotaxic coil positioning is from the technical viewpoint of high stability and repeatability. It is therefore a precise method for TMS brain mapping studies or for repeated TMS treatments, with the need of topographically exact stimulation