Schizophrenia is a TH2 dominant autoimmune disease possibly against acetylcholine receptors of CNS

Schizophrenia is a very common psychiatric disorder. However, its etiology and pathogenesis is still unknown. Current theory saying that neurotransmitter imbalance such as serotonin or dopamine only provides limited effectiveness in schizophrenia treatment by drugs changing serotonin and dopamine concentration. Despite of such treatment, majority of schizophrenia patients still have very poor prognosis. Thus, the neurotransmitter imbalance theory is not correct. Here, I propose that schizophrenia is actually a TH2 dominant autoimmune disorder. The candidate of autoantigen could be acetylcholine receptors of CNS. My theory can explain the positive as well as negative symptoms of schizophrenia. By microarray analysis of PBMCS, one-tenth of the total 519 significantly expressed genes are immune-related genes. Among them, TH2 related genes are significantly up-regulated including IL-4, histidine decarboxylase, aldehyde dehydrogenase, CCR9, IgE Fc receptor, GATA2, serotonin receptor, phospholipase A2, and prostaglandin D2 synthase. Besides, TH1 and TH17 related genes are down-regulated including CXCL5, cathepsin C, and neutrophil related S100 binding proteins. The new theory sheds a light to better control this detrimental illness. Anti-inflammatory agents could be used to manage schizophrenia in the near future

Antipsychotic Response in the First Week Predicts Later Efficacy

Background and Aims: Time of onset of antipsychotic action is still a debated matter. We aimed to replicate and extend previous findings that early response can predict subsequent non-response. Methods: 86 acutely psychotic patients treated with haloperidol were studied. Results: A PANSS reduction = 23% at 1 week of treatment predicts response at 3 weeks, with a specificity of 84% and a sensitivity of 86%. Conclusion: Our results confirm that an early response to antipsychotic treatment accurately predicts the treatment effectiveness and extends it to a prediction performed as early as 1 week. Copyright (c) 2012 S. Karger AG, Base

Electroconvulsive therapy for agitation in schizophrenia: Meta-analysis of randomized controlled trials

Background: Agitation poses a significant challenge in the treatment of schizophrenia. Electroconvulsive therapy (ECT) is a fast, effective and safe treatment for a variety of psychiatric disorders, but no meta-analysis of ECT treatment for agitation in schizophrenia has yet been reported. Aims: To systematically evaluate the efficacy and safety of ECT alone or ECT-antipsychotics (APs) combination for agitation in schizophrenia. Methods: Systematic literature search of randomized controlled trials (RCTs) was performed. Two independent evaluators selected studies, extracted data about outcomes and safety with available data, conducted quality assessment and data synthesis. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to judge the level of the overall evidence of main outcomes. Results: Seven RCTs from China, including ECT alone (4 RCTs with 5 treatment arms, n=240) and ECT-APs combination (3 RCTs, n=240), were identified. Participants in the studies were on average 34.3(4.5) years of age and lasted an average of 4.3(3.1) weeks of treatment duration. All 7 RCTs were non-blinded, and were rated as low quality based on Jadad scale. Meta-analysis of the pooled sample found no significant difference in the improvement of the agitation sub-score of the Positive and Negative Syndrome Scale (PANSS) when ECT alone (weighted mean difference=-0.90, (95% confidence interval (CI): -2.91, 1.11), p=0.38) or ECT-APs combination (WMD=-1.34, (95%CI: -4.07, 1.39), p=0.33) compared with APs monotherapy. However, ECT alone was superior to APs monotherapy regarding PANSS total score (WMD=-7.13, I2=0%, p=0.004) and its excitement sub-score (WMD=-1.97, pI2=0%, p=0.004) and its excitement sub-score at 7 and 14 days (WMD=-1.97 to -1.92, p=0.002 to 0.0001) after ECT. The ECT-APs combination was superior to APs monotherapy with respect to the PANSS total score at treatment endpoint (WMD=-10.40, p=0.03) and 7 days (WMD=-5.01, p=0.02). Headache ( number-needed-to-harm (NNH)=3, 95%CI=2-4) was more frequent in the ECT alone group compared to AP monotherapy. According to the GRADE approach, the evidence levels of main outcomes were rated as ‘‘very low’’ (37.5%) and “low” (50%). Conclusion: Pooling of the data based on 7 RCTs from China found no advantage of ECT alone or ECT-APs combination in the treatment of agitation related outcomes in schizophrenia patients. However, ECT alone or ECT-APs combination were associated with significant reduction in the PANSS total score. High-quality RCTs are needed to confirm the current interpretations. Review registration number: CRD4201400668

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial

Background Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. Objective To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. Design A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up Setting Adult psychiatric services, treating people with schizophrenia. Participants Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. Interventions Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. Main Outcome Measures The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich’s Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. Results No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference –1.3, 95% confidence interval–2.5 to–0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation. Limitations The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. Conclusion Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies. Future Work Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge.</p

Recovery and serious mental illness: a review of current clinical and research paradigms and future directions

Introduction: Recovery from serious mental illness has historically not been considered a likely or even possible outcome. However, a range of evidence suggests the courses of SMI are heterogeneous with recovery being the most likely outcome. One barrier to studying recovery in SMI is that recovery has been operationalized in divergent and seemingly incompatible ways, as an objective outcome, versus a subjective process. Areas Covered: This paper offers a review of recovery as a subjective process and recovery as an objective outcome; contrasts methodologies utilized by each approach to assess recovery; reports rates and correlates of recovery; and explores the relationship between objective and subjective forms of recovery. Expert Commentary: There are two commonalities of approaching recovery as a subjective process and an objective outcome: (i) the need to make meaning out of one’s experiences to engage in either type of recovery and (ii) there exist many threats to engaging in meaning making that may impact the likelihood of moving toward recovery. We offer four clinical implications that stem from these two commonalities within a divided approach to the concept of recovery from SMI

Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia?

Growing interest in gut and digestive processes and their potential link to brain and peripheral based inflammation or biobehavioral phenotypes has led to an increasing number of basic and translational scientific reports focused on the role of gut microbiota within the context of neuropsychiatric disorders. However, the effect of dietary modification on specific gut metabolites, in association with immune, metabolic, and psychopathological functioning in schizophrenia spectrum disorders has not been well characterized. The short chain fatty acids (SCFA) acetate, butyrate, and propionate, major metabolites derived from fermentation of dietary fibers by gut microbes, interact with multiple immune and metabolic pathways. The specific pathways that SCFA are thought to target, are dysregulated in cardiovascular disease, type II diabetes, and systemic inflammation. Most notably, these disorders are consistently linked to an attenuated lifespan in schizophrenia. Although, unhealthy dietary intake patterns and increased prevalence of immune and metabolic dysfunction has been observed in people with schizophrenia; dietary interventions have not been well utilized to target immune or metabolic illness. Prior schizophrenia patient trials primarily focused on the effects of gluten free diets. Findings from these studies indicate that a diet avoiding gluten benefits a limited subset of patients, individuals with celiac disease or non-celiac gluten sensitivity. Therefore, alternative dietary and nutritional modifications such as high-fiber, Mediterranean style, diets that enrich the production of SCFA, while being associated with a minimal likelihood of adverse events, may improve immune and cardiovascular outcomes linked to premature mortality in schizophrenia. With a growing literature demonstrating that SCFA can cross the blood brain barrier and target key inflammatory and metabolic pathways, this article highlights enriching dietary intake for SCFA as a potential adjunctive therapy for people with schizophrenia

Getting better acquainted with Auditory Voice Hallucinations (AVHs): A need for clinical and social change

The phenomenon of hearing voices (AVHs) is very much a subject of current scientific interest, both clinically1 and socially. For a long time, auditory hallucinations—perceiving sounds without external stimuli (David, 2004)—were considered an obvious sign of schizophrenic or psychotic psychopathology (Goodwin et al., 1971; Larøi et al., 2012), but these days such an association is no longer taken for granted. Various recent studies in the areas of psychology, psychiatry, and neuroscience have brought a renewal of interest in AVHs. First of all, the move beyond Kraepelinian logic (van Os, 2009; Fusar-Poli et al., 2014) has led us to see AVHs as a phenomenon in their own right, and not just a characteristic of schizophrenia (Fernyhough, 2004). Furthermore, a number of studies in imaging techniques have allowed us to study the phenomenon live, as it occurs, collecting various new data (Shergill et al., 2000). On the other hand, psychological studies with attempts at modeling, have boosted the idea that AVHs are linked to the linguistic and verbal qualities of the subject, thus reducing the association between voice hallucinations and signs of pathology (Johns and van Os, 2001; Pearson et al., 2001; Stanghellini and Cutting, 2003). Other researchers have theorized that hearing voices is a different manifestation of self-awareness (Salvini and Bottini, 2011; Salvini and Quarato, 2011). Even DSM-5 has modified the importance it attaches to hallucinations, in fact although the 4th edition diagnosed “schizophrenia” simply on the basis of the symptom “hallucinations,” in the new edition hallucinations on their own are not considered a sufficient symptom to diagnose the specter of schizophrenia” (American Psychiatric Association, 2013). Many of those suffering from this condition are not under treatment and are not diagnosable in psychopathological terms, which asks ever more questions of health professionals (Iudici, 2015), and which brings with it the risk that the phenomenon of hearing voices may be considered pathological because of a lack of understanding of the problem. One direct implication of this risk concerns non-psychotic and non-schizophrenic hearers of voices who are afraid of being considered mad or disturbed, who very often live in fear for years without talking about it with anyone, although realizing that hearing voices causes no general maladjustment in their lives (Andrew et al., 2008). In the long term this can lead to feelings of alarm in some of them, and when such situations result in a visit to a clinic or a psychiatrist, there are often “suffering and conflicted confessions” about such experiences, especially by people who have never had psychiatric experience (Iudici and Gagliardo Corsi, 2017). These people consequently do not have appropriate information to help them understand their experiences (Faccio et al., 2013). This fact raises further doubts about the direct juxtaposition of auditory hallucinations and diagnoses of mental disturbance, and consequently our interest is in sensitizing clinicians to a broader interpretation of the phenomenon than the traditional view, highlighting the importance of considering more perspectives

The new-generation antipsychotics -integrating the neuropathology and pharmacology of schizophrenia

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