Social Cognition and Interaction Training (SCIT) versus Training in Affect Recognition (TAR) in patients with schizophrenia: A randomized controlled trial.

INTRODUCTION: Training in Affect Recognition (TAR) is a "targeted" and computer-aided program that has been shown to effectively attenuate facial affect recognition deficits and improve social functioning in patients with schizophrenia. Social Cognition and Interaction Training (SCIT) is a group "broad-based" intervention, that has also been shown to improve emotion recognition, theory of mind (ToM), and social functioning. To date, no study has compared the efficacy of two different social cognitive interventions. OBJECTIVES: We aim to compare the efficacy of TAR and SCIT on schizophrenia patients' performance on facial affect recognition, theory of mind, attributional style and social functioning before, after treatment, and three months thereafter. METHODS: One hundred outpatients with a diagnosis of schizophrenia were randomly assigned to the TAR or SCIT condition and completed pre- (T0) and posttreatment (T1) assessments and a 3-month follow up (T2) of emotion recognition (ER-40), theory of mind (Hinting Task), attributional style (AIHQ) and social functioning (PSP). RESULTS: The entire sample, receiving TAR or SCIT, showed improvements in theory of mind, attributional style, clinical symptoms and social functioning. This effect was maintained at three-months. The TAR intervention was more efficacious than the SCIT program in improving the recognition of facial emotions (ER-40). The TAR intervention also demonstrated a lower drop-out rate than the SCIT intervention. CONCLUSIONS: There were improvements in social cognition, symptomatology and functioning of patients in the entire sample, receiving SCIT or TAR. Both TAR and SCIT appear as valuable treatments for people with schizophrenia and social cognitive deficits.

Muscarinic modulation of TREK currents in mouse sympathetic superior cervical ganglion neurons.

Muscarinic receptors play a key role in the control of neurotransmission in the autonomic ganglia, which has mainly been ascribed to the regulation of potassium M-currents and voltage-dependent calcium currents. Muscarinic agonists provoke depolarization of the membrane potential and a reduction in spike frequency adaptation in postganglionic neurons, effects that may be explained by M-current inhibition. Here, we report the presence of a riluzole-activated current (IRIL ) that flows through the TREK-2 channels, and that is also inhibited by muscarinic agonists in neurons of the mouse superior cervical ganglion (mSCG). The muscarinic agonist oxotremorine-M (Oxo-M) inhibited the IRIL by 50%, an effect that was abolished by pretreatment with atropine or pirenzepine, but was unaffected in the presence of himbacine. Moreover, these antagonists had similar effects on single-channel TREK-2 currents. IRIL inhibition was unaffected by pretreatment with pertussis toxin. The protein kinase C blocker bisindolylmaleimide did not have an effect, and neither did the inositol triphosphate antagonist 2-aminoethoxydiphenylborane. Nevertheless, the IRIL was markedly attenuated by the phospholipase C (PLC) inhibitor ET-18-OCH3. Finally, the phosphatidylinositol-3-kinase/phosphatidylinositol-4-kinase inhibitor wortmannin strongly attenuated the IRIL , whereas blocking phosphatidylinositol 4,5-bisphosphate (PIP2 ) depletion consistently prevented IRIL inhibition by Oxo-M. These results demonstrate that TREK-2 currents in mSCG neurons are inhibited by muscarinic agonists that activate M1 muscarinic receptors, reducing PIP2 levels via a PLC-dependent pathway. The similarities between the signaling pathways regulating the IRIL and the M-current in the same neurons reflect an important role of this new pathway in the control of autonomic ganglia excitability.

Lipophilic toxins analyzed by liquid chromatography-mass spectrometry and comparison with mouse bioassay in fresh, frozen, and processed molluscs.

The search for alternative methods to the mouse bioassay (MBA) has intensified over recent years. The present work analyzes seven different species of shellfish (clams, small scallops, small clams, mussels, oysters, cockles, and edible whelks) in fresh, frozen boiled, and canned presentations using liquid chromatography-mass spectrometry (LC-MS/MS), and the results are compared with the same samples analyzed through MBA. The toxins studied were OA, DTX1, DTX2, YTX, PTX2, and AZA1, which are legislated in the EU, and SPX1, which is not regulated yet. Consistent results between LC-MS/MS and MBA were found in 69% of the samples, whereas 26% of MBA showed "false-positive" results with respect to the toxins analyzed. No "false negatives" were observed. The possibility of LC-MS/MS as an alternative or complementary technique to MBA is discussed.

Characteristics of palytoxin-induced cytotoxicity in neuroblastoma cells.

Cation fluxes appear to play a key role in palytoxin-induced signal. There are other cellular targets that have not been described as well as the biochemical signaling cascades that transmit palytoxin-stimulated signals remain to be clarified. Since modifications of cations, mainly calcium, are generally associated to cell death or apoptosis, we wanted to further evaluate the effect of palytoxin on cell death. Then, in vitro cytotoxic effects of palytoxin were characterized on human neuroblastoma cells. By using several techniques, we studied markers of cell death and apoptosis, such as cell detachment, mitochondrial membrane potential, caspases, DNA damage, LDH leakage, propidium iodide uptake, F-actin depolymerization and inhibition of cellular proliferation. Results show that palytoxin triggers a series of toxic responses; it inhibits cell proliferation, induces cell rounding, detachment from the substratum and F-actin disruption. Among the apoptotic markers studied we only detected fall in mitochondrial membrane potential. Neither caspases activation nor chromatin condensation or DNA fragmentation were observed in palytoxin-treated cells.

Spontaneous bursting and rhythmic activity in the cuneate nucleus of anaesthetized rats.

Spontaneous and rhythmic neuronal activity in dorsal column nuclei has long been identified in anesthetized cats. Here, we have studied the spontaneous behavior of cuneate cells in anesthetized rats through extracellular recording, showing that most cuneate neurones recorded (155 of 185) fired spontaneously. Overall, 74% of these spontaneously firing neurones were single-spiking and 26% were bursting. Cells were considered "bursting" when more than 50% of the spontaneous spikes belonged to bursts. Nevertheless, occasional bursts were seen in 33% of spontaneous cuneate cells which were classified as single-spiking. Rhythmic firing was observed in about 14% of both spontaneously bursting and single-spiking cells, and these cells were located close to the obex (+/-0.5 mm). Although the spike-frequency was mostly in the range 0-15 spikes/s, spontaneous rhythmic activity was circumscribed mainly to the alpha/beta-like range, both in single-spiking (26.1+/-3.6 Hz, n=16) and bursting cells (19.5+/-4.1 Hz, n=6). Lemniscal stimulation often activated several antidromic units with the same latency. About 65% of cuneolemniscal cells were spontaneously active and of these, 83% were single-spiking and 11% rhythmic (all single-spiking). In cells that were not antidromically activated from the medial lemniscus, short latency orthodromic responses consistent with excitation by recurrent lemniscal collaterals were often observed following lemniscal activation. Interestingly, only cells completely unresponsive to lemniscal stimulation showed rhythmic bursting. Most spontaneous cells responded with a burst to natural receptive field stimulation, while rhythmic cells became temporally arrhythmic. These results demonstrate, for the first time, that rat cuneate neurones can fire bursts spontaneously. Besides, this bursting activity can be rhythmic. These two properties, and the fact that groups of cuneolemniscal cells share the same conduction velocity, probably imply the reinforcement of temporal and spatial summation at their targets when they are synchronously recruited by the stimulation of overlapping receptive fields.

Newly developed blockers of the M-current do not reduce spike frequency adaptation in cultured mouse sympathetic neurons.

The M-current (I(K(M))) is believed to modulate neuronal excitability by producing spike frequency adaptation (SFA). Inhibitors of M-channels, such as linopirdine and 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE991), enhance depolarization-induced transmitter release and improve learning performance in animal models. As such, they are currently being tested for their therapeutic potential for treating Alzheimer's disease. The activity of these blockers has been associated with the reduction of SFA and the depolarization of the membrane observed when I(K(M)) is inhibited. To test whether this is the case, the perforated patch technique was used to investigate the capacity of I(K(M)) inhibitors to alter the resting membrane potential and to reduce SFA in mouse superior cervical ganglion neurons in culture. Linopirdine and XE991 both proved to be potent blockers of I(K(M)) when the membrane potential was held at -30 mV (IC(50) 2.56 and 0.26 microM, respectively). However, their potency gradually declined upon membrane hyperpolarization and was almost null when the membrane potential was kept at -70 mV, indicating that their blocking activity was voltage dependent. Nevertheless, I(K(M)) could be inhibited at these hyperpolarized voltages by other inhibitors such as oxotremorine-methiodide and barium. Under current-clamp conditions, neither linopirdine (10 microM) nor XE991 (3 microM) was effective in reducing the SFA and both provoked only a small slowly developed depolarization of the membrane (2.27 and 3.0 mV, respectively). In contrast, both barium (1 mM) and oxotremorine-methiodide (10 microM) depolarized mouse superior cervical ganglion neurons by about 10 mV and reduced the SFA. In contrast to classical I(K(M)) inhibitors, the activity of linopirdine and XE991 on the I(K(M)) is voltage dependent and, thus, these newly developed I(K(M)) blockers do not reduce the SFA. These results may shed light on the mode of action of these putative cognition enhancers in vivo.