Family psychoeducation in schizophrenia and schizophrenia related disorder, treatment compliance, and suicidal risk reduction: questions about their relationship from a naturalistic observation.

Introduction: The Profamille V3.2 multi-family psycho-educational program directed at caregivers of relatives with schizophrenia or schizophrenia related disorder has been shown to decrease the annual prevalence of suicide attempts. It has been reported that psychoeducation of families can sometimes improve compliance with treatment. This study investigates whether the Profamille program improves compliance and thus reduces the risk of suicide among patients. Method: This is a retrospective study of 179 groups of family caregivers, encompassing 1946 participants enrolled in Module 1 of the Profamille program and followed up one year after completion of the module. Evaluations were conducted using questionnaires filled out by family caregivers at three distinct times: prior to beginning the program, upon its completion, and again one year following its conclusion. The annual prevalence of suicide attempts was measured both before the program began and one year after its conclusion, while compliance to treatment was evaluated at the start and end of the program. Result: After the Profamille program, the annual prevalence of suicide attempts fell by a factor of 2 (p-value = 0.00002) and patient compliance improved (p-value <0.000001). This reduction in suicide attempts was observed independently of improved compliance. Compliance seems to have an additional effect, but only after participation in the program. Conclusion: The Profamille program reduces patients' risk of suicide even when patients are not taking the treatment. When family psychoeducation is not proposed in schizophrenia or schizophrenia related disorder, this can represent a loss of chance for patients.

Improving social function with real-world social-cognitive remediation in schizophrenia: Results from the RemedRugby quasi-experimental trial.

BACKGROUND: Functional capacity (FC) has been identified as a key outcome to improve real-world functioning in schizophrenia. FC is influenced by cognitive impairments, negative symptoms, self-stigma and reduced physical activity (PA). Psychosocial interventions targeting FC are still under-developed. METHODS: we conducted a quasi-experimental study evaluating the effects of an exercise-enriched integrated social cognitive remediation (SCR) intervention (RemedRugby [RR]) compared with an active control group practicing Touch Rugby (TR). To our knowledge, this is the first trial to date evaluating the effectiveness of such a program provided in a real-life environment. RESULTS: Eighty-seven people with schizophrenia were included and allocated to either the RR group (n = 57) or the TR group (n = 30) according to the routine clinical practice of the recruiting center. Outcomes were evaluated at baseline and post-treatment in both groups and after 6 months of follow-up in the RR group using standardized scales for symptom severity, social functioning, self-stigma, and a large cognitive battery. After treatment we observed moderate to large improvements in social function (Personal and Social Performance Scale [PSP], p < 0.001, d = 1.255), symptom severity (Positive and Negative Syndrome Scale [PANSS] negative, p < 0.001, d = 0.827; PANSS GP, p < 0.001, d = 0.991; PANSS positive, p = 0.009, d = 0.594), verbal abstraction (p = 0.008, d = 0.554), aggression bias (p = 0.008, d = 0.627), and self-stigma (stereotype endorsement, p = 0.019, d = 0.495; discrimination experiences, p = 0.047; d = 0.389) that were specific to the RR group and were not observed in participants playing only TR. Effects were persistent over time and even larger between post-treatment and follow-up. CONCLUSIONS: Exercise-enriched integrated SCR appears promising to improve real-life functioning in schizophrenia. Future research should investigate the potential effects of this intervention on neuroplasticity and physical fitness.

[Effect of High Council for Public Health on September 28th 2012 recommendation about antipapillomavirus vaccination on antipapillomavirus and trivalent or tetravalent DTP or DTCP co-vaccination in South Western France]. / Impact de l'avis du Haut conseil à la santé publique du 28 septembre 2012 à propos de la vaccination antipapillomavirus : une étude de l'évolution de la co-délivrance des vaccins antipapillomavirus et vaccin tri ou tétravalent DTP ou DTCP en Midi-Pyrénées.

INTRODUCTION: Antipapillomavirus vaccination is used to prevent genital infection by papilloma virus, responsible for a high morbidity. In France, the High Council for Public Health published on September 28th 2012 a new guideline decreasing the age of vaccination from 16 to between 11 to 14 allowing a joint vaccination with mandatory tetravalent or trivalent (against diphtheria, tetanus, pertussis and poliomyelitis Tdap-IPV or Td/IPV booster) vaccination. Our study aimed to assess if this guideline changed the rate of joint vaccinations. METHODS: A descriptive before/after study was conducted on French health insurance reimbursement database at the regional level (Midi-Pyrénées area). The study period comprised 1 year before and 1 year after the publication of the new guideline. We assess the rate of co-vaccinations in these 2 periods and compared them by a Chi2 test. RESULTS: On the study period, 35,647 vaccines were reimbursed corresponding to 18,230 complete vaccinations. Concerning co-vaccinations, 3287 were reimbursed: 1406 (16.4%) before the publication of the guideline and 1881 (19.4%) after (P<0.01). DISCUSSION: The new guideline was accompanied by a rapid increase in the rate of co-vaccinations. It did not diminish the rate of vaccination by antipapillomavirus.

Targeted calretinin expression in granule cells of calretinin-null mice restores normal cerebellar functions.

Ca2 binding proteins such as calretinin, characterized by the presence of EF-hand motifs that bind Ca2+ ions, are involved in the shaping of intraneuronal Ca2+ fluxes. In the cerebellar cortex, information processing tightly relies on variations in intracellular Ca2+ concentration in Purkinje and granule cells. Calretinin-deficient (Cr-/-) mice present motor discoordination, suggesting cellular and network cerebellar dysfunctions. To determine the cell specificity of these alterations, we constructed transgenic Cr-/- mice exhibiting a selective reexpression of calretinin in granule cells through the promoter function of the GABAA receptor alpha6 subunit gene. Normal granule cell excitability and wild-type Purkinje cell firing behavior in awake mice were restored while the emergence of high-frequency oscillations was abolished. Behavioral analysis of these calretinin-rescue mice revealed that normal motor coordination was restored as compared with Cr-/- mice. These results demonstrate that calretinin is required specifically in granule cells for correct computation in the cerebellar cortex and indicate that the finetuning of granule cell excitability through regulation of Ca2+ homeostasis plays a crucial role for information coding and storage in the cerebellum.

Activation of protein kinase C and inositol 1,4,5-triphosphate receptors antagonistically modulate voltage-gated sodium channels in striatal neurons.

Regulation of voltage-gated sodium channels is crucial to firing patterns that constitute the output of medium spiny neurons (MSN), projecting neurons of the striatum. This modulation is thus critical for the final integration of information processed within the striatum. It has been shown that the adenylate cyclase pathway reduces sodium currents in MSN through channel phosphorylation by cAMP-dependent protein kinase. However, it is unknown whether a phospholipase C (PLC)-mediated signaling cascade could also modulate voltage-gated sodium channels within MSN. Using the whole-cell patch clamp technique, we investigated the effects of activation of two key components in PLC-mediated signaling cascades: protein kinase C (PKC) and inositol-1,4,5-triphosphate (IP(3)) receptors on voltage-dependent sodium current. Cellular dialysis with phorbol 12-myristate 13-acetate, an activator of PKC, significantly reduced peak sodium current amplitude, while adenophostin A, an activator of IP(3) receptors, significantly increased peak sodium current amplitude. This effect of adenophostin was abolished by calcium chelation or by FK506, an inhibitor of calcineurin. These results suggest an antagonistic role of PKC and IP(3) in the modulation of striatal voltage-gated sodium channels, peak current amplitude being decreased through phosphorylation by PKC and increased through dephosphorylation by calcineurin.

Effects of remifentanil on N-methyl-D-aspartate receptor: an electrophysiologic study in rat spinal cord.

BACKGROUND: Remifentanil hydrochloride contained in Ultiva (GlaxoSmithKline, Genval, Belgium) has been incriminated in difficult postoperative pain management, promotion of hyperalgesia, and direct N-methyl-D-aspartate (NMDA) receptor activation, but the involved mechanisms have remained unclear. In the current study, the authors investigated the effects of remifentanil hydrochloride, with and without its vehicle, glycine, on the activation of NMDA receptors and the modulation of NMDA-induced current on neurons inside the lamina II from the dorsal horn of rat spinal cord. METHODS: To test these effects, whole cell patch clamp recordings were conducted on acute rat lumbar spinal cord slices. Considering that both components of Ultiva (remifentanil hydrochloride and glycine) could be involved in NMDA receptor activation, experiments were performed first with remifentanil hydrochloride, second with glycine, and third with the two components within Ultiva. RESULTS: Remifentanil hydrochloride does not induce any current, whereas 3 mm glycine induced a current that was abolished by the specific NMDA glutamate site antagonist D-2-amino-5-phosphonovalerate. Ultiva (remifentanil hydrochloride with its vehicle, glycine) also evoked an inward current that was abolished by D-2-amino-5-phosphonovalerate and not significantly different from the glycine-induced current. Application of remifentanil hydrochloride potentiated the NMDA-induced inward current, and this potentiation was abolished by the mu-opioid receptor antagonist naloxone. CONCLUSION: These results show that remifentanil hydrochloride does not directly activate NMDA receptors. The NMDA current recorded after application of Ultiva is related to the presence of glycine. Induced NMDA current is potentiated by application of remifentanil hydrochloride through a pathway involving the mu-opioid receptor.

Intracellular calcium regulation by burst discharge determines bidirectional long-term synaptic plasticity at the cerebellum input stage.

Variations in intracellular calcium concentration ([Ca2+]i) provide a critical signal for synaptic plasticity. In accordance with Hebb's postulate (Hebb, 1949), an increase in postsynaptic [Ca2+]i can induce bidirectional changes in synaptic strength depending on activation of specific biochemical pathways (Bienenstock et al., 1982; Lisman, 1989; Stanton and Sejnowski, 1989). Despite its strategic location for signal processing, spatiotemporal dynamics of [Ca2+]i changes and their relationship with synaptic plasticity at the cerebellar mossy fiber (mf)-granule cell (GrC) relay were unknown. In this paper, we report the plasticity/[Ca2+]i relationship for GrCs, which are typically activated by mf bursts (Chadderton et al., 2004). Mf bursts caused a remarkable [Ca2+]i increase in GrC dendritic terminals through the activation of NMDA receptors, metabotropic glutamate receptors (probably acting through IP3-sensitive stores), voltage-dependent calcium channels, and Ca2+-induced Ca2+ release. Although [Ca2+]i increased with the duration of mf bursts, long-term depression was found with a small [Ca2+]i increase (bursts <250 ms), and long-term potentiation (LTP) was found with a large [Ca2+]i increase (bursts >250 ms). LTP and [Ca2+]i saturated for bursts >500 ms and with theta-burst stimulation. Thus, bursting enabled a Ca2+-dependent bidirectional Bienenstock-Cooper-Munro-like learning mechanism providing the cellular basis for effective learning of burst patterns at the input stage of the cerebellum.

Fast oscillation in the cerebellar cortex of calcium binding protein-deficient mice: a new sensorimotor arrest rhythm.

Fast oscillations (>100 Hz) may serve physiological roles when regulated properly. They may also appear in pathological conditions. In cerebellum, 160 Hz oscillation emerge in mice lacking calbindin and/or calretinin, two proteins devoted to calcium buffering in Purkinje and granule cells, respectively. Here, we review the pharmacological and spatiotemporal properties of this fast cerebellar oscillation and the related Purkinje cell firing behaviour in alert mice. We show that this oscillation is highly synchronized along the parallel fiber beam and reversibly inhibited by gap junctions, GABA(A) and NMDA receptors blockers. Cutaneous stimulation of the whisker region transiently suppressed the oscillation which shows in some aspects similarities with cerebral "resting" rhythmic activities of wakefulness arresting to sensory or motor information such as alpha and mu rhythms. The Purkinje cells of these mutants present an increased simple spike firing rate, rhythmicity and synchronicity, and a decreased complex spike duration and subsequent pause. Both simple and complex spikes may be tightly phase-locked with the oscillation. Contrastingly, on slice recordings, the intrinsic membrane properties of Purkinje cell are similar in wild type mice and in mice lacking calbindin. The role played by this fast cerebellar oscillation in the emergence of ataxia is yet to be solved.

Altered neuronal excitability in cerebellar granule cells of mice lacking calretinin.

Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mm of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore the calcium-buffering capacity. A proposed mathematical model demonstrates that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium-buffering capacity resulting from the absence of calretinin. This result suggests that calcium-binding proteins modulate intrinsic neuronal excitability and may therefore play a role in information processing in the CNS.