Development and validation of the Symptomatic Transdiagnostic Test (S2T).

INTRODUCTION: The categorical approach in psychiatry has received many criticisms. Modern research tends to develop a transdiagnostic approach. However, transdiagnostic works lack an overall understanding and focus mainly on anxiety and depression. The aim of the present study was to develop an easy to use tool to evaluate multiple dimensions opening the way for further research in the transdiagnostic approach. This will allow researchers to quickly assess the efficacy of psychotherapeutic interventions on multiple psychopathological dimensions. METHOD: First, we identified the main symptoms of psychopathology in a sample of mental healthcare workers. Second, we developed the Symptomatic Transdiagnostic Test (S2T) to assess the main symptoms of psychopathology. Third, we evaluated its psychometric properties (exploratory and confirmatory factor analysis, internal consistency) in three non-clinical samples and one clinical sample. RESULTS: The 66-item S2T included eleven factors referring to: i) negative thoughts and mood; ii) psycho-traumatic and maladaptive symptoms; iii) addiction symptoms; iv) disturbed eating behavior; v) disturbed perception and behavior; vi) panic and agoraphobia; vii) emotional lability; viii) dejection; ix) neurodevelopmental manifestations; x) anxiety and xi) psychic hyperactivity. We found a high internal consistency for the general scale (α=0.96) and the subscales. We found a good concurrent validity. As expected, we found higher levels of symptoms within the clinical population as compared to the non-clinical samples, except for addiction symptoms and disrupted eating behavior. We found negative associations between the symptomatic dimensions and psychological skills. CONCLUSION: The S2T is a relevant tool for clinicians and researchers to assess the psychopathological profile. The main psychopathological symptoms are negatively related to the psychological skills.

Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells.

OBJECTIVES: Polycystin-1 (PC1), a signalling receptor regulating Ca(2+)-permeable cation channels, is mutated in autosomal dominant polycystic kidney disease, which is typically characterized by increased cell proliferation. However, the precise mechanisms by which PC1 functions on Ca(2+) homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non-capacitative Ca(2+) entry (NCCE) and Ca(2+) oscillations, with downstream effects on cell proliferation. RESULTS AND DISCUSSION: By employing RNA interference, we show that depletion of endogenous PC1 in HEK293 cells leads to an increase in serum-induced Ca(2+) oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca(2+) oscillations and cell proliferation are increased in PC1-mutated kidney cystic cell lines, but both abnormal features are reduced in cells that exogenously express PC1. Notably, blockers of the NCCE pathway, but not of the CCE, blunt abnormal oscillation and cell proliferation. Our study therefore provides the first demonstration that PC1 modulates Ca(2+) oscillations and a molecular mechanism to explain the association between abnormal Ca(2+) homeostasis and cell proliferation in autosomal dominant polycystic kidney disease.

Mitochondrial dysfunction and death in motor neurons exposed to the glutathione-depleting agent ethacrynic acid.

This study investigated the mechanisms of toxicity of glutathione (GSH) depletion in one cell type, the motor neuron. Ethacrynic acid (EA) (100 microM) was added to immortalized mouse motor neurons (NSC-34) to deplete both cytosolic and mitochondrial glutathione rapidly. This caused a drop in GSH to 25% of the initial level in 1 h and complete loss in 4 h. This effect was accompanied by enhanced generation of reactive oxygen species (ROS) with a peak after 2 h of exposure, and by signs of mitochondrial dysfunction such as a decrease in 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide (MTT) (30% less after 4 h). The increase in ROS and the MTT reduction were both EA concentration-dependent. Expression of heme oxygenase-1 (HO-1), a marker of oxidative stress, also increased. The mitochondrial damage was monitored by measuring the mitochondrial membrane potential (MMP) from the uptake of rhodamine 123 into mitochondria. MMP dropped (20%) after only 1 h exposure to EA, and slowly continued to decline until 3 h, with a steep drop at 5 h (50% decrease), i.e. after the complete GSH loss. Quantification of DNA fragmentation by the TUNEL technique showed that the proportion of cells with fragmented nuclei rose from 10% after 5 h EA exposure to about 65% at 18 h. These results indicate that EA-induced GSH depletion rapidly impairs the mitochondrial function of motor neurons, and this precedes cell death. This experimental model of oxidative toxicity could be useful to study mechanisms of diseases like spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS), where motor neurons are the vulnerable population and oxidative stress has a pathogenic role.