Alexandra Macgregor

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.

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.

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.

Prevalence and Smoking Behavior Characteristics of Nonselected Smokers With Childhood and/or Adult Self-Reported ADHD Symptoms in a Smoking-Cessation Program A Cross-Sectional Study

Background: ADHD involves impairing core symptoms of inattention and hyperactivity/impulsivity in children (childhood ADHD = CH) that may persist in adulthood (adult ADHD = AD). Conflicting findings have been found regarding AD prevalences among adult smokers, and it is unclear whether AD is associated with a more severe smoking behavior in adulthood. Objective: The aim of this article is (a) to determine CH and AD prevalences in a nonselected sample of adult smokers, (b) to describe the characteristics of smokers with ADHD symptoms versus those without, and (c) to determine whether CH and/or AD symptoms are risk factors for more severe smoking in adulthood. Method: Three hundred and seventy-three participants aged 18 years and over were prospectively recruited in a smoking-cessation unit. Participants were classified as “no ADHD symptoms,” “CH symptoms,” or “AD symptoms” according to their baseline score on the Wender Utah Rating Scale (WURS) alone (for CH symptoms) and WURS combined to the Adult Self Report Scale (ASRS) for AD symptoms. Other clinical variables were reported at first consultation. Results: (a) CH symptoms were reported in 15.3% (57/373) of the total sample, 42.1% (24/57) of whom also had persistent ADHD symptoms in adulthood (prevalence of AD was 24/373 = 6.4%). (b) In comparison with participants without ADHD symptoms, smokers with ADHD symptoms consume significantly more tobacco, but ADHD symptoms were no longer significantly associated with the daily number of smoked cigarettes after adjustment for sociodemographic variables. No significant association was found between the two groups and age at the first cigarette, age at onset daily smoking, and nicotine dependence. (c) Participants were categorized into three groups: Group 1 without ADHD symptoms lifetime (NH; n = 316), Group 2 with childhood history of ADHD symptoms (CH; n = 33), and Group 3 with Adult ADHD symptoms (AD; n = 24). The association with tobacco consumption (>20 cigarettes/day) was significant for CH only (p = .02). After adjustment for gender, age, professional status, and educational level, this association was not longer significant. Conclusion: Childhood and adult ADHD symptoms are both highly prevalent among nonselected smokers but our study failed to show more severe smoking characteristics among these participants after adjustment with sociodemographic variables.

D2 and D3 dopamine receptor affinity predicts effectiveness of antipsychotic drugs in obsessive-compulsive disorders: a metaregression analysis

Rationale and objectiveThe relationship between clinically effective antipsychotic drugs in obsessive–compulsive disorders (OCD) and binding affinities to cloned dopamine and serotonin receptor subtypes was analyzed in an effort to clarify the contribution of individual receptor subtypes to medication response.MethodsMeta-analysis was used to update previous meta-analyses of effectiveness data of add-on antipsychotic drugs to selective serotonin reuptake inhibitors (SSRIs) in OCD. Twelve previously analyzed randomized controlled trials (RCTs) and one new RCT were included. We performed a metaregression using a mixed-effect model to examine the association between antipsychotic’s effectiveness and receptor affinity.ResultsA total of 5 treatment arms obtained from 13 RCTs (431 patients) were included in our study. The results of our metaregression showed a significant association between D2 and D3 dopamine receptor affinities and effectiveness in OCD (respectively, slope = −0.36, p = 0.01; and slope = −0.50, p = 0.01) whereas other dopamine receptors and serotonin receptors were not significantly associated.ConclusionsThese observations suggest that increasing D2 and D3 dopamine receptor binding affinities enhances antipsychotics’ effectiveness in obsessive–compulsive disorders.

Treating patients with schizophrenia deficit with erythropoietin

This systematic review summarizes and critically appraises the literature on the effect of erythropoietin (EPO) in schizophrenia patients and the pathophysiological mechanisms that may explain the potential of its use in this disease. EPO is mainly known for its regulatory activity in the synthesis of erythrocytes and is frequently used in treatment of chronic anemia. This cytokine, however, has many other properties, some of which may improve the symptoms of psychiatric illness. The review follows the preferred reporting items for systematic reviews and meta‐analysis (PRISMA) statement guidelines. Three databases (Medline, Web of Science, and Cochrane) were searched combining the search terms ‘erythropoietin AND (psychotic disorders OR schizophrenia)’. Seventy‐eight studies were included in qualitative synthesis, a meta‐analytic approach being prohibited. The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment, such as neurotransmission regulation, neuroprotection, modulation of inflammation, effects on blood–brain barrier permeability, effects on oxidative stress and neurogenesis. Several potentially detrimental side‐effects of EPO therapy, such as increased risk of thrombosis, cancer, increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO. Overall, because the available data are inconclusive, further efforts in this field are warranted.

La phobie du sang-injection-accident: spécificités psychophysiologiques et thérapeutiques

INTRODUCTION Seventy-five percent of patients with blood-injection-injury phobia (BII-phobia) report a history of fainting in response to phobic stimuli. This specificity may lead to medical conditions remaining undiagnosed and untreated, incurring considerable cost for the individual and society. The psychophysiology of BII-phobia remains poorly understood and the literature on effective treatments has been fairly sparse. Aims of the systematic review: to synthesize the psychophysiology of BII-phobia and to propose a systematic review of the literature on effectiveness of different treatments evaluated in this indication. RESULTS Firstly, the most distinct feature of the psychophysiology of BII-phobia is its culmination in a vasovagal syncope, which has been described as biphasic. The initial phase involves a sympathetic activation as is typically expected from fear responses of the fight-flight type. The second phase is characterized by a parasympathetic activation leading to fainting, which is associated with disgust. Subjects with syncope related to BII-phobia have an underlying autonomic dysregulation predisposing them to neurally mediated syncope, even in the absence of any blood or injury stimulus. Many studies report that BII-phobic individuals have a higher level of disgust sensitivity than individuals without any phobia. Secondly, behavioral psychotherapy techniques such as exposure only, applied relaxation, applied tension, and tension only, have demonstrated efficacy with no significant difference between all these techniques. The disgust induction has not improved effectiveness of exposure. CONCLUSION We have explained the psychophysiology of BII-phobia, the understanding of which is required to study and validate specific techniques, in order to improve the prognosis of this disorder, which is a public health issue.

Apathy in schizophrenia: A review of neuropsychological and neuroanatomical studies

Apathy is a multidimensional symptom composed of cognitive, behavioral, and emotional facets including impaired motivation and reduced goal-directed behavior. Apathy belongs to schizophrenias negative symptomatology which has received increased attention over the last years including a growing interest in the assessment and the consequences of apathy. Nevertheless, the pathological mechanisms are still insufficiently explored as well as the multidimensional aspect of this symptom. The aim of this article is to provide a review of the main measures used to explore apathy in schizophrenia as well as the cognitive and neural correlates of apathy while taking into account the multidimensionality of this symptom. Studies have shown important correlations between apathy, executive functions and specific brain regions such as the anterior cingulate cortex, orbitofrontal cortex and the ventral and dorsal striatum. Nevertheless, most studies have neglected the multidimensional aspect of apathy, which is assessed as a single-dimension concept. These and other limitations are discussed as well as the main strengths of the current evidence on apathy in schizophrenia.