Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram.

OBJECTIVE: This double-blind, sham-controlled trial investigated the effects of two daily tDCS sessions over a 5-day period in treatment-resistant depression. METHOD: Twenty-four treatment-resistant depressed patients received two daily sessions of active or sham anodal tDCS to the left prefrontal cortex (2 mA, 10 sessions over 1 week). Depression severity, psychomotor retardation and cognitive function were assessed. RESULTS: Active tDCS was not significantly superior to sham tDCS on the HDRS at week 4, as well as on the MADRS and SRRS scales, and on neuropsychological tests. Response rates were not significantly higher with active tDCS. tDCS was well tolerated, with mild adverse events limited to transient scalp discomfort. CONCLUSION: tDCS did not induce clinically relevant antidepressant effect in active and sham stimulation groups. There was no impact on psychomotor and neuropsychological functioning. SIGNIFICANCE: tDCS efficacy on specific symptom profiles in pharmacotherapy-resistant depression is limited. The use of optimized stimulation protocol and longer period of follow up may valuably contribute to specify the place of tDCS in treatment-resistant depression.

[Sexual dysfunction and depression: Validity of a French version of the ASEX scale]. / Validation française de l'échelle psychométrique ASEX d'évaluation des troubles sexuels dans la dépression.

BACKGROUND: Since the Beck study (1967), it is well known that sexual dysfunction is particularly prevalent in depressive patients compared to the general population, at 70% and 30% respectively. Depression, psychotropics and antidepressants are responsible for altering sexuality, and patients are considerably affected by these symptoms that dramatically decrease their quality of life. Screening for sexual dysfunctions seems essential, and a scale such as the Arizona Sexual Experience Scale (ASEX) may help practitioners. The English version of this scale was validated in 2000 (McGahuey et al. [9]), and is widely used in scientific research. The aim of this study was to assess the validity of the French version of the ASEX scale. METHODS: Following authorization from the University of Arizona, the ASEX scale was translated into French by our team at the University hospital of Besançon (France), by the back translation technique, and then checked by a professional translator. ASEX, Mini International Neuropsychiatric Interview (MINI), Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) were filled out by 37 depressed inpatients, and ASEX and PHQ-9 by 64 controls (hospital employees, residents and students at the University of Besançon), and again one to two weeks later. Bivariate correlations were performed using total ASEX scores to determine the test-retest reliability. Internal consistency of the ASEX scale was assessed using Cronbach's alpha analysis. Analyses of variance (Anova) were performed to determine the validity of the ASEX scale to compare patients to controls for total ASEX score and for individual ASEX item scores. In order to determine whether the ASEX criteria accurately reflect sexual dysfunction (determined by the HDRS rating or self-report), positive and negative predictive value and sensitivity and specificity were measured. To determine how well the total ASEX score differentiates between individuals with sexual dysfunction and those without, a Receiver Operating Characteristic (ROC) analysis was performed. We expected similar results between the French version of the ASEX scale and the original one (McGahuey and al., 2000). RESULTS: Patients and controls were similar in terms of sex and age. The test-retest reliability was good, and the internal consistency was excellent using Cronbach's alpha analysis (alpha=0.9451). Analyses of variance (Anova) showed strong differences between the two groups, confirming the validity of the ASEX scale to compare patients to controls for total ASEX score and individual ASEX item scores. Positive and negative predictive values were respectively 89.66% (PPV) and 85.33% (NPV). Specificity and sensitivity were respectively 95.31% (Sp) and 70.27% (Se). The ROC analysis showed the area under the curve (AUC=0.8457) and the best ASEX criteria to demonstrate that sexual dysfunction had been correctly identified (total ASEX score ≥ 18). CONCLUSION: This study assessed the validity and reliability of the French version of the ASEX scale. These findings demonstrate the highly acceptable psychometric properties of ASEX in patients with depression.

[French guidelines on the use of repetitive transcranial magnetic stimulation (rTMS): safety and therapeutic indications]. / Recommandations françaises sur l'utilisation de la stimulation magnétique transcrânienne répétitive (rTMS) : règles de sécurité et indications thérapeutiques.

During the past decade, a large amount of work on transcranial magnetic stimulation (TMS) has been performed, including the development of new paradigms of stimulation, the integration of imaging data, and the coupling of TMS techniques with electroencephalography or neuroimaging. These accumulating data being difficult to synthesize, several French scientific societies commissioned a group of experts to conduct a comprehensive review of the literature on TMS. This text contains all the consensual findings of the expert group on the mechanisms of action, safety rules and indications of TMS, including repetitive TMS (rTMS). TMS sessions have been conducted in thousands of healthy subjects or patients with various neurological or psychiatric diseases, allowing a better assessment of risks associated with this technique. The number of reported side effects is extremely low, the most serious complication being the occurrence of seizures. In most reported seizures, the stimulation parameters did not follow the previously published recommendations (Wassermann, 1998) [430] and rTMS was associated to medication that could lower the seizure threshold. Recommendations on the safe use of TMS / rTMS were recently updated (Rossi et al., 2009) [348], establishing new limits for stimulation parameters and fixing the contraindications. The recommendations we propose regarding safety are largely based on this previous report with some modifications. By contrast, the issue of therapeutic indications of rTMS has never been addressed before, the present work being the first attempt of a synthesis and expert consensus on this topic. The use of TMS/rTMS is discussed in the context of chronic pain, movement disorders, stroke, epilepsy, tinnitus and psychiatric disorders. There is already a sufficient level of evidence of published data to retain a therapeutic indication of rTMS in clinical practice (grade A) in chronic neuropathic pain, major depressive episodes, and auditory hallucinations. The number of therapeutic indications of rTMS is expected to increase in coming years, in parallel with the optimisation of stimulation parameters.

Modulation of p53 transcriptional activity by PRIMA-1 and Pifithrin-alpha on staurosporine-induced apoptosis of wild-type and mutated p53 epithelial cells.

We recently argued for a major role of p53 in staurosporine(ST)-induced apoptosis of immortalized epithelial cells, depending on their p53 status. Here, we studied the effects of PRIMA-1 (p53 reactivation and induction of massive apoptosis) and Pifithrin-alpha (p fifty-three inhibitor) in combination with ST to reinforce our previous results by respectively restoring or inhibiting the p53 transcriptional activity in different cell lines.PRIMA-1 does modify neither expression of apoptosis-related proteins nor the percentage of wild-type p53 HeLa and CaSki cells with [symbol: see text]delta psi m and DNA cleavage, whilst it increases by 45% Bax expression and apoptosis of mutated p53 C33A cells. Pifithrin-alpha, does modify neither Bax expression nor apoptosis level of C33A cells, but readily inhibits both [symbol: see text]delta psi m and DNA fragmentation of p53wt cells with decreasing Bax expression. These data support the evidence that PRIMA-1 could be a good candidate, as an anti-cancer drug targeting mutant p53, in order to increase ST efficiency. Moreover, Pifithrin-alpha could be used in combination with ST and PRIMA-1 to prevent side effects of anti-tumor therapies in cells expressing mutant P53.