Guillaume Fond

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: Systematic review and meta-analysis

To perform a meta‐analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was to analyze factors possibly moderating heterogeneity.

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review

To provide a systematic review of the literature regarding the efficacy of anti‐inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders].

The "psychomicrobiotic": Targeting microbiota in major psychiatric disorders: A systematic review.

The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the hosts brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.

EEG neurofeedback treatments in children with ADHD: an updated meta-analysis of randomized controlled trials

Objective: We undertook a meta-analysis of published Randomized Controlled Trials (RCT) with semi-active control and sham-NF groups to determine whether Electroencephalogram-neurofeedback (EEG-NF) significantly improves the overall symptoms, inattention and hyperactivity/impulsivity dimensions for probably unblinded assessment (parent assessment) and probably blinded assessment (teacher assessment) in children with Attention Deficit Hyperactivity Disorder (ADHD). Data sources: A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis. Data extraction: Effect sizes for ADHD symptoms were expressed as standardized mean differences (SMD) with 95% confidence intervals. Results: Five identified studies met eligibility criteria, 263 patients with ADHD were included, 146 patients were trained with EEG-NF. On parent assessment (probably unblinded assessment), the overall ADHD score (SMD = −0.49 [−0.74, −0.24]), the inattention score (SMD = −0.46 [−0.76, −0.15]) and the hyperactivity/impulsivity score (SMD = −0.34 [−0.59, −0.09]) were significantly improved in patients receiving EEG-NF compared to controls. On teacher assessment (probably blinded assessment), only the inattention score was significantly improved in patients receiving EEG-NF compared to controls (SMD = −0.30 [−0.58, −0.03]). Conclusions: This meta-analysis of EEG-NF in children with ADHD highlights improvement in the inattention dimension of ADHD symptoms. Future investigations should pay greater attention to adequately blinded studies and EEG-NF protocols that carefully control the implementation and embedding of training.

The Promise of Biological Markers for Treatment Response in First-Episode Psychosis: A Systematic Review

Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded-beside markers for metabolism of antipsychotics-no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results.

A further evaluation of decision-making under risk and under ambiguity in schizophrenia.

Abnormal decision-making has been described as a key-concept to understand some behavioral disturbances in schizophrenia. However, whether schizophrenia patients display impairments in profitable decision-making on experimental designs is still controversial (1) to assess performance on decision-making paradigms under ambiguity and under risk conditions in a large sample of schizophrenia patients and (2) to study the impact of clinical variables on decision-making performance in schizophrenia. The Iowa gambling task (IGT) and the game of dice task (GDT) were administered to assess, respectively, decision-making under ambiguity and under risk in 63 schizophrenia patients and 67 healthy controls. In addition, clinical variables (e.g., schizophrenic symptoms, self-reported depression, and impulsivity) were evaluated using appropriate questionnaires the same day. Pharmacological treatments were reported. Schizophrenia patients had impaired performances on both IGT and GDT tasks. No correlation between the decision-making tasks performance and clinical variables was found. Lower gains on the GDT were associated with executive dysfunctioning in schizophrenia. These findings give evidence that schizophrenia patients display impairments in both decision-making under ambiguity and under risk.

Fasting in mood disorders: neurobiology and effectiveness. A review of the literature

Clinicians have found that fasting was frequently accompanied by an increased level of vigilance and a mood improvement, a subjective feeling of well-being, and sometimes of euphoria. Therapeutic fasting, following an established protocol, is safe and well tolerated. We aim in this article to explore the biological mechanisms activated during fasting that could have an effect on brain function with particular focus on mood (we do not discuss here the mechanisms regulating eating behavior) and to provide a comprehensive review on the potential positive impact of therapeutic fasting on mood. We explored Medline, Web of Science and PsycInfo according to the PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-Analysis). The initial research paradigm was: [(fasting OR caloric restriction) AND (mental health OR depressive disorders OR mood OR anxiety)]. Many neurobiological mechanisms have been proposed to explain fasting effects on mood, such as changes in neurotransmitters, quality of sleep, and synthesis of neurotrophic factors. Many clinical observations relate an early (between day 2 and day 7) effect of fasting on depressive symptoms with an improvement in mood, alertness and a sense of tranquility reported by patients. The persistence of mood improvement over time remains to be determined.

Antipsychotic drugs: Pro-cancer or anti-cancer? A systematic review

INTRODUCTION Important data was recently published on the potential genotoxic or carcinogenic effects of antipsychotics, as well as on their cytotoxic properties on cancer cells, that must be considered by psychiatrists in the benefit/risk ratio of their prescriptions. AIM OF THE STUDY To answer whether or not antipsychotics, as a class or only some specific molecules, may influence cancer risk among treated patients. METHODS ELIGIBILITY CRITERIA: All studies (in vitro, animal studies and human studies) concerning effects of antipsychotic drugs on cancer development were included. The search paradigm [neoplasms AND (antipsychotic agents OR neuroleptic OR phenothiazine)] was applied to Medline (1966-present) and Web of Science (1975-present). RESULTS Ninety-three studies were included in the qualitative synthesis. Results can be summarized as follows: (1) patients with schizophrenia may be less likely to develop cancer than the general population, (2) antipsychotics as a class cannot be considered at the moment as at risk for cancer, even if some antipsychotics have shown carcinogenic properties among rodents, (3) phenothiazines seem to have antiproliferative properties that may be useful in multidrug augmentation strategies in various cancer treatments, but their bad tolerance may decrease usage amongst non-psychotic patients, and (4) clozapine appears to have a separate status given that this molecule shows antiproliferative effects implied in agranulocytosis as well as a potential increased risk for leukemia. CONCLUSION Benefit/risk ratio regarding cancer risk is in favor of treating patients with schizophrenia with antipsychotic drugs. The practicing clinician should be reassuring on the subject of cancer risk due to antipsychotic drugs.

La thérapie d’acceptation et d’engagement

INTRODUCTION Acceptance and commitment therapy (ACT) is a third generation of cognitive-behavioral therapies. The point is to help patients to improve their psychological flexibility in order to accept unavoidable private events. Thus, they have the opportunity to invest energy in committed actions rather than struggle against their psychological events. OBJECTIVES OF THE STUDY (i) To present the ACT basic concepts and (ii) to propose a systematic review of the literature about effectiveness of this kind of psychotherapy. METHOD (i) The core concepts of ACT come from Monestès (2011), Schoendorff (2011), and Harris (2012); (ii) we conducted a systematic review of the literature using the PRISMAs criteria. The research paradigm was « acceptance and commitment therapy AND randomized controlled trial ». The bases of the MEDLINE, Cochrane and Web of science have been checked. RESULTS Overall, 61 articles have been found, of which, after reading the abstracts, 40 corresponded to the subject of our study. (I) Psychological flexibility is established through six core ACT processes (cognitive defusion, acceptance, being present, values, committed action, self as context), while the therapist emphasizes on experiential approach. (II) Emerging research shows that ACT is efficacious in the psychological treatment of a wide range of psychiatric problems, including psychosis, depression, obsessive-compulsive disorder, trichotillomania, generalized anxiety disorder, post-traumatic stress disorder, borderline personality disorder, eating disorders. ACT has also shown a utility in other areas of medicine: the management chronic pain, drug-dependence, smoking cessation, the management of epilepsy, diabetic self-management, the management of work stress, the management of tinnitus, and the management of multiple sclerosis. Meta-analysis of controlled outcome studies reported an average effect size (Cohens d) of 0.66 at post-treatment (n=704) and 0.65 (n=580) at follow-up (on average 19.2 weeks later). In studies involving comparison between ACT and active well-specified treatments, the effect size was 0.48 at post (n=456) and 0.62 at follow-up (n=404). In comparisons with waist list, treatment as usual, or placebo treatment, the effect sizes were 0.99 at post (n=248) and 0.71 at follow-up (n=176). Furthermore, ACT studies pointed out learning specific skills, such as decreasing experiential avoidance, increasing cognitive defusion, acceptance and contact with the present moment. Finally, all ACT studies showed an improved quality of life. DISCUSSION The loss of psychological flexibility is the origin of the pain caused by psychiatric disorders and chronic diseases. This is why other studies are needed to investigate ACTs full potential.

Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate.

Recent studies have shown a strong link between Toxoplasma gondii infection and psychiatric disorders, especially schizophrenia and bipolar disorders (odd ratio ≈2.7 for each disorder). Antipsychotic drugs and mood stabilizers may have anti-toxoplasmic activity that potentially may be associated with better effectiveness in these disorders, but previous results have been few in number and conflicting. We therefore sought to determine which daily prescribed antipsychotics and mood stabilizer have the best anti-toxoplasmic activity during the development phase of the parasite. In the present study, we examined the effects of commonly used antipsychotic drugs (amisulpride, cyamemazine, fluphenazine, haloperidol, levomepromazine, loxapine, olanzapine, risperidone and tiapride) and one mood-stabilizing agent (valproate) on toxoplasmic activity. We replicated that fluphenazine has a high anti-toxoplasmic activity, but it does not seem to be a phenothiazine-specific class effect: indeed, we found that another first-generation antipsychotic, zuclopenthixol, has a high anti-toxoplasmic activity. Valproate, tiapride and amisulpride have no anti-toxoplasmic activity on parasite growth, and the other antipsychotic drugs showed low or intermediate anti-toxoplasmic activity. As it is not possible to know the intracellular concentrations of antipsychotics in the brain, further clinical studies are warranted to determine whether these in vitro findings have potential implications in treatment of toxo-positive patients with schizophrenia. These findings may be potentially relevant for the choice of the first-line antipsychotic drug or mood stabilizer in previously infected patients.