Event-related potentials and use of psychotropic medication in major psychiatric disorders

Background: Attention deficits measured using event-related potentials (ERPs) have been frequently reported in several major psychiatric disorders, e.g. mood disorder (MD), psychotic disorder (PD) and substance use disorder (SUD). However, comparisons between these specific categories are lacking. Here we investigated if electrophysiological parameters of basic information processing are associated with the above-mentioned categories of psychiatric disorders, or instead were associated with general psychopathology. Methods: 579 subjects with MD, PD or SUD and healthy controls (HC) were included. Participants were tested in a passive auditory and an active visual oddball paradigm to assess mismatch negativity (MMN), P3A and P3B amplitudes. Additionally, we examined associations between these measures and psychoactive medication treatments. Results: All patients had significantly lower P3B amplitudes compared to healthy controls, while only SUD patients had lower P3A amplitudes than MD, PD and HC. PD patients also produced significantly less MMN than both MD and SUD patients. Additionally, we found significantly higher P3B amplitude in HC compared to patients without psychopharmacological treatment and patients treated with two or more psychoactive compounds (polypharmacy), but no significant associations with medication on P3A and MMN amplitudes. Conclusions: Our results add to the theory that P3B deficits are associated with general psychopathology, whereas P3A and MMN deficits appear to be associated with substance abuse and psychotic disorders respectively

Associations between psychotropic drugs and rsEEG connectivity and network characteristics: a cross-sectional study in hospital-admitted psychiatric patients

INTRODUCTION: Resting-state EEG (rsEEG) characteristics, such as functional connectivity and network topology, are studied as potential biomarkers in psychiatric research. However, the presence of psychopharmacological treatment in study participants poses a potential confounding factor in biomarker research. To address this concern, our study aims to explore the impact of both single and multi-class psychotropic treatments on aforementioned rsEEG characteristics in a psychiatric population. METHODS: RsEEG was analyzed in a real-world cross-sectional sample of 900 hospital-admitted psychiatric patients. Patients were clustered into eight psychopharmacological groups: unmedicated, single-class treatment with antipsychotics (AP), antidepressants (AD) or benzodiazepines (BDZ), and multi-class combinations of these treatments. To assess the associations between psychotropic treatments and the macroscale rsEEG characteristics mentioned above, we employed a general linear model with post-hoc tests. Additionally, Spearman's rank correlation analyses were performed to explore potential dosage effects. RESULTS: Compared to unmedicated patients, single-class use of AD was associated with lower functional connectivity in the delta band, while AP was associated with lower functional connectivity in both the delta and alpha bands. Single-class use of BDZ was associated with widespread rsEEG differences, including lower functional connectivity across frequency bands and a different network topology within the beta band relative to unmedicated patients. All of the multi-class groups showed associations with functional connectivity or topology measures, but effects were most pronounced for concomitant use of all three classes of psychotropics. Differences were not only observed in comparison with unmedicated patients, but were also evident in comparisons between single-class, multi-class, and single/multi-class groups. Importantly, multi-class associations with rsEEG characteristics were found even in the absence of single-class associations, suggesting potential cumulative or interaction effects of different classes of psychotropics. Dosage correlations were only found for antipsychotics. CONCLUSION: Our exploratory, cross-sectional study suggests small but significant associations between single and multi-class use of antidepressants, antipsychotics and benzodiazepines and macroscale rsEEG functional connectivity and network topology characteristics. These findings highlight the importance of considering the effects of specific psychotropics, as well as their interactions, when investigating rsEEG biomarkers in a medicated psychiatric population

The HBP1 tumor suppressor is a negative epigenetic regulator of MYCN driven neuroblastoma through interaction with the PRC2 complex

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Raloxifene augmentation in men and women with a schizophrenia spectrum disorder:A study protocol

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered

RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate dependency factor further supported by growth inhibition upon in vitro knockdown and accelerated tumor formation in a neuroblastoma zebrafish model coexpressing human RRM2 with MYCN. Forced RRM2 induction alleviates excessive replicative stress induced by CHK1 inhibition, while high RRM2 expression in human neuroblastomas correlates with high CHK1 activity. MYCN-driven zebrafish tumors with RRM2 co-overexpression exhibit differentially expressed DNA repair genes in keeping with enhanced ATR-CHK1 signaling activity. In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential

Ordre sportif local et stratégies d'acteurs : évolution des relations municipalité OMS à Grenoble, à propos du sport d'élite, durant la période 1983-1995

Backgrounds and aims: Pathological gambling, a common psychiatric disorder, has many similarities with substance use disorders. Relapse, an important element in addictive disorders, however, has seldom been studied in pathological gambling. Hence, in analogy with previous research studies examining the role of self-report and neurocognitive measures on relapse in substance dependent patients, the present pilot study was executed. Methods: Twenty-two pathological gamblers and 31 healthy controls took part in this research. They filled in self-report questionnaires measuring impulsive personality (Barratt Impulsiveness Scale, Sensitivity to Punishment and Sensitivity to Reward Questionnaires) and performed neurocognitive tasks measuring impulsivity, decision-making and attentional bias (Iowa Gambling Task, Delay Discounting Task, Stroop Gambling Task). Twelve months later gambling activity was re-examined. Results: Analyses showed that PGs who relapsed (n = 13) did not differ on self-report and neurocognitive measures of impulsivity with PGs who did not relapse (n = 9). However, both groups did differ in age at onset. Finally, healthy controls and PGs differed in some (Barratt Impulsiveness Scale, Stroop Gambling Task), but not all impulsivity measures (Delay Discounting Task, Iowa Gambling Task, Sensitivity to Punishment and Sensitivity to Reward Questionnaires). Conclusions: One-year relapse in pathological gamblers is not predicted by self-report and or neurocognitive measures of impulsivity and decision-making. The similarities in performances between pathological gamblers and healthy controls illustrate the relative health of the examined pathological gamblers. This last finding supports the idea that subtypes of pathological gamblers exist so that different treatment strategies might be necessary

Cellular senescence in neuroblastoma

Neuroblastoma is a tumour that arises from the sympathoadrenal lineage occurring predominantly in children younger than five years. About half of the patients are diagnosed with high-risk tumours and undergo intensive multi-modal therapy. The success rate of current treatments for high-risk neuroblastoma is disappointingly low and survivors suffer from multiple therapy-related long-term side effects. Most chemotherapeutics drive cancer cells towards cell death or senescence. Senescence has long been considered to represent a terminal non-proliferative state and therefore an effective barrier against tumorigenesis. This dogma, however, has been challenged by recent observations that infer a much more dynamic and reversible nature for this process, which may have implications for the efficacy of therapy-induced senescence-oriented treatment strategies. Neuroblastoma cells in a dormant, senescent-like state may escape therapy, whilst their senescence-associated secretome may promote inflammation and invasiveness, potentially fostering relapse. Conversely, due to its distinct molecular identity, senescence may also represent an opportunity for the development of novel (combination) therapies. However, the limited knowledge on the molecular dynamics and diversity of senescence signatures demands appropriate models to study this process in detail. This review summarises the molecular knowledge about cellular senescence in neuroblastoma and investigates current and future options towards therapeutic exploration