Positive Symptoms Of Schizophrenia Research Articles

T177. CANNABIDIOL AS A POTENTIAL PREVENTATIVE TREATMENT IN A NEUREGULIN-1 MOUSE MODEL OF SCHIZOPHRENIA

BackgroundSchizophrenia is caused by interactions between genes of predisposition and environmental insults. The main pharmacological treatments for schizophrenia are antipsychotic drugs; however, these are associated with a range of side effects (weight gain, metabolic disease, diabetes), have limited treatment compliance, and do not work for approximately 30% of patients. Cannabidiol (CBD) is a non-psychoactive cannabinoid that has shown promise as an antipsychotic-like drug in both human and rodent studies, however its potential as a preventative drug via anti-inflammatory pathways has not yet been investigated. Brain maturation during adolescent development creates a window where CBD could potentially reverse later behavioural deficits via pathways such as anti-inflammation, and reverse the deficits caused by Δ⁹-tetrahydrocannabinol (THC), a psychoactive compound of the cannabis plant linked to the development of schizophrenia.Here we investigated the therapeutic potential of CBD administered in adolescence to protect against the development of schizophrenia-like behaviours, as well as whether CBD could protect against later sensitivity to THC. For this study we used a well-established genetic mouse model of schizophrenia (Nrg1 TM HET) that shows face, construct, and predictive validity for schizophrenia, and is also more susceptible to the effects of cannabinoids.MethodsIn this study, male Nrg1 TM HET mice and wild type (WT) mice were treated with 30 mg/kg of CBD or vehicle intraperitoneally for three weeks during adolescence (PND 35–60). Mice were tested CBD-free in adulthood (5–6 mo) in the open field task, which measures locomotion and anxiety (related to positive symptoms in schizophrenia); social interaction, which measures mouse interactions (relevant to negative symptoms); pre-pulse inhibition (PPI), which measures sensorimotor gating (deficits also found in schizophrenia patients); and fear conditioning, which measures associative learning and memory. Mice were then treated after one week washout with either 3 mg/kg of THC or vehicle, and run in a battery of open field, social interaction, and PPI tests. Brains and bloods were collected to investigate neuroinflammation after another week of washout. Western blots were used to investigate Iba1 levels, while ELISA was used to investigate levels of cytokines IL-10, IL-1B, and TNF-a.ResultsCBD treatment significantly reduced anxiety in Nrg1 TM HET mice but not WT mice, however it had no effect on locomotion in either group in the open field task. CBD treatment lowered the frequency of total social interaction in both genotypes, and reduced the frequency of social interactions of Nrg1 TM HET to WT levels. CBD reduced PPI in Nrg1 TM HET mice but not WT mice, and Nrg1 TM HET mice had lower overall PPI than WT mice. There was no effect of CBD on fear-associated memory. CBD effects on THC sensitivity in these mice are ongoing, as are brain cytokine and protein analyses.DiscussionThese results suggest that Nrg1 TM HET mice are more susceptible to the effects of chronic CBD in adolescence, despite a significant washout. This confirms previous data from our laboratory demonstrating increased susceptibility of Nrg1 TM HET male mice to cannabinoid constituents, and suggests persistent brain changes following adolescent exposure to CBD. Potential reasons for these persistent changes include an altered neuroinflammatory profile in Nrg1 TM HET mice. CBD has previously been shown to be anxiolytic in other studies and our results confirm its potential as an anxiolytic, particularly in our model of schizophrenia.

T13. CORNEAL CONFOCAL MICROSCOPY DETECTS NEURAL CHANGES IN SCHIZOPHRENIA

BackgroundA combination of neurodevelopmental and degenerative neural changes are likely to underpin positive and negative symptoms in schizophrenia. However, there are currently no validated biomarkers to accurately quantify the extent of neural changes in schizophrenia.Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique that has been used to demonstrate in vivo corneal nerve fiber abnormalities in a range of peripheral neuropathies and central neurodegenerative disorders including Parkinson’s disease, multiple sclerosis and dementia.We wished to test the hypothesis that corneal nerve abnormalities occur in patients with schizophrenia, particularly those with negative symptoms and cognitive impairment.MethodsPatients with DSM-V schizophrenia without other causes of peripheral neuropathy other than metabolic syndrome underwent assessment of clinical ratings (Positive and Negative Symptoms Scale (PANSS), cognitive function (Montreal Cognitive Assessment (MOCA) and Corneal confocal microscopy (CCM), vibration perception threshold (VPT) and sudomotor function testing.Healthy controls underwent the same assessments apart from PANSS.Results55 subjects without (n=38) and with schizophrenia (n=17) with comparable mean age (35.7±8.5 vs 35.6±12.2, P=0.96) were studied.Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02) and lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02) compared with healthy controls.The proportion of gender, systolic and diastolic blood pressure, HbA1c, cholesterol, triglyceride and High Density Lipoproteins were comparable between the two groups.Patients with schizophrenia had significantly lower corneal nerve fibre density (CNFD, fibers/mm2) (35.6±6.5 vs 23.5±7.8, p<0.0001), branch density (CNBD, branches/mm2) (98.1±30.6 vs 34.4±26.9, p<0.0001), and fibre length (CNFL, mm/mm2) (24.2±3.9 vs 14.3±4.7, p<0.0001) compared with healthy controls but no difference in peripheral neuropathy assessed by VPT and sudomotor function testing.The area under the Receiver Operating Characteristic Curve (95% CI) of CNFD, CNBD, CNFL to distinguish patients with schizophrenia from healthy controls were 87.0% (76.8–98.2%), 93.2% (84.2–102.3%), 93.2% (84.4–102.1%), respectively.DiscussionThese preliminary results:support the hypothesis that corneal nerve abnormalities occur in schizophrenia;corneal confocal microscopy has high diagnostic capability to distinguish subjects with schizophrenia from healthy controls;provide evidence to support the potential application of corneal confocal microscopy as a non-invasive technique to detect neural change in schizophrenia.

S190. WHEN WORDS AREN’T ENOUGH: DANCE/MOVEMENT THERAPY AND SCHIZOPHRENIA

BackgroundDance/Movement Therapy (DMT) is a language that transcends the verbal realm. This facet of communicating through dance and movement is significant particularly when the population you are working with often communicates in ways that are creative, unique, and not necessarily conventional. This is often the case when working with people who have been diagnosed on the schizophrenia spectrum. Although they fall under the same diagnosis, positive and negative symptoms of schizophrenia are embodied in quite different ways; as their names indicate, positive and negative symptoms are dichotomous and fall on opposite ends of a movement spectrum.MethodsWe will explore the many bodily manifestations of schizophrenia and DMT approaches to best support the specific needs associated with this complex diagnosis. The co-facilitators have each engaged in their own clinical practice and research exploring how DMT interventions can best serve the population in grounding, thought and behavioral organization, ego strengthening, and development of interpersonal relationships. As one can imagine, having a diagnosis of schizophrenia can be isolating and interrupt healthy relationship development due to stigmatization. The co-facilitators have found DMT to be a humanizing factor in this often dehumanized population. The use of creativity with people with schizophrenia allows the psychotherapeutic relationship to focus on personal strengths, individuality, and unconditional acceptance.ResultsDance/movement therapists assess patient functioning through non-verbal indicators in everyday behavior, postural and gestural patterns, and qualitative elements that emerge during therapeutic interactions. Oftentimes, their experiences with positive symptomatology affect their ability to relate in a shared reality base with others not experiencing these positive symptoms. Single-session DMT interventions have supported a decrease in psychological distress, and positive and negative symptomatology for people with schizophrenia in an inpatient psychiatric facility (Biondo, 2019).Within a group DMT approach to treatment, dance/movement therapist considers movement and body-based experiences, as natural and effective sources of self-awareness and expression, which can illuminate the interrelationships between the many dimensions of human behavior (Bryl, 2018). This approach integrates movement techniques, creative embodiment, the non-verbal aspects of self-awareness and interpersonal communication and targets core specific features of chronic schizophrenia and negative symptomatology. As such it provides links to outcomes directly related to affective, cognitive, behavioral, and functional processes in the treatment for schizophrenia in residual stages (Bryl, 2018).DiscussionSchizophrenia can manifest through many different representations: with positive and/or negative symptoms, and with acute episodes or chronicity. The diagnosis will interrupt healthy ego strength, the ability to relate with others, and the ability to function without supports. Dance/movement therapy is a wonderful approach to working with this population in its many forms, as it addresses the psychological, cognitive, social, and functional levels of participants. Although positive and negative symptoms often manifest quite differently on a movement level, DMT has the ability to support the many needs of those diagnosed with schizophrenia. The many limitations of psychopharmacological interventions for people with schizophrenia are evidence that inclusive, strengths-based, and body-informed therapy options would greatly benefit this population.

M96. A NEW ASSESSMENT TOOL FOR FORMAL THOUGHT DISORDER IN SCHIZOPHRENIA: DOKUZ EYLUL THOUGHT DISORDER SCALE

BackgroundCurrent scales of formal thought disorder (FTD) in schizophrenia have been shown to hold considerable inadequacies: 1. The concept of FTD is usually limited to positive and negative symptoms of schizophrenia 2. There is no much consideration about pragmatic disturbances. 3. There are significant inconsistencies in measurements of posFTD and negFTD dimensions (eg, merely focusing on the positive dimension); 4. As to the comprehensive scales of posFTD and negFTD, administration or assessment is time-consuming for routine clinical use and they are not user friendly. Besides, some of the FTD scales include the utilization of materials such as pictures, figures, or extended structured interviews to be able to provide speech samples of the patient. Developing a new FTD assessment tool that can be practically applied in clinic might help clinicans in diagnosis, treatment and follow-up. The aim of our study was to develop a new scale for assessment of FTD and evaluate the reliability and validity of this scale. We named our new FTD scale as Dokuz Eylul Thought Disorder Scale (DETDS). The originality of this scale is based on the fact that it involves assessment of pragmatic comprehension as well as positive and negative FTD and it can be administered and scored practically in routine clinical examination.MethodsThis study included 130 patients with schizophrenia and 35 controls. For assessing the reliability of this new scale, internal consistency, test-retest and interrater reliability analyses were conducted. The validity of the scale was assessed with concurrent validity and factor analysis methods.ResultsIn the study, Cronbach’s was 0.86. The new scale has a good test-retest (r=0.83) and interrater (ICC=0.985) reliability. The posFTD subscale of the new scale showed high correlation with the posFTD subscale of the Scale for the Assessment of Positive Symptoms (SAPS) (r=0.95, p<0.001) and negFTD subscale of our scale showed high correlation with the alogia subscale of the Scale for the Assessment of Negative Symptoms (SANS) (r=0.95, p<0.001) and impoverishment of thought subscale of the Thought and Language Index (TLI) (r=0.66, p<0.001). The factor analysis revealed a 3-factor solution which explained 74.6% of the variance: 1. Positive Formal Thought Disorder, 2. Negative Formal Thought Disorder, 3. Pragmatic Comprehension Disorder.DiscussionOur findings showed that DETDS is a reliable and valid scale which can be used in assessing FTD in patients with schizophrenia in routine clinical use. Unlike most scales of FTD that are available in the literature, but similar to SANS, SAPS, and PANSS, it is practical to use because it is based on clinical interview. Another strength of DETDS is that it intensifies the posFTD and negFTD dimensions and scores them hierarchically in terms of severity. The fact that the new scale covers pragmatic comprehension disorders also presents an innovation to the literature.

T167. QUALITATIVE DIFFERENCES IN LONG ACTING INJECTABLE ANTIPSYCHOTIC MEDICATIONS AMONG SCHIZOPHRENIA PATIENTS

BackgroundThe purpose of this presentation is to investigate qualitative differences associated with treatment of Schizophrenia spectrum disorder patients with long acting injectable (LAI) antipsychotics, including adverse effects and efficacy.MethodsLiterature around LAI antipsychotics and their comparative data was reviewed and evaluated via all electronic databases up to December 2018.ResultsMetabolic, hepatic and cardiovascular complications in olanzapine treatment have been the major concern in most studies, despite the effectiveness of the medication, as coronary heart disease is strongly associated with a decrease in the life expectancy of schizophrenia patients (coupled with higher levels of smoking and malnutrition). Treatment with risperidone was associated with a worsening of depressive affect and suicidal ideation (except prolactin-related and extrapyramidal adverse effects), as well as sexual dysfunction. Hyperprolactinemia, extrapyramidal / neurological symptoms, and sexual dysfunction were the major problems with haloperidol treatment despite a good efficacy profile with respect to positive symptoms of schizophrenia. Sporadic effectiveness, agitation and, to a lesser extent, weight gain were some of the concerns in palimperidone treatment. Aripiprazole treatment was associated with a comparatively milder and in the long term more preferable adverse effect profile, while exhibiting similarly high levels of efficacy with olanzapine in controlling schizophrenia symptoms, but with a reported relatively higher rate in treatment discontinuation (drop-outs) in comparison to olanzapine and haloperidol in case of schizophrenia (in contrast to schizoaffective disorder in which high levels of both compliance and effectiveness are exhibited).DiscussionThe need for an individualized approach in psychiatric treatment highlighted so that the needs of each patient be taken into account by the therapist in choosing the optimal treatment within a given time frame.

S111. A REAL ENVIRONMENT BASED VIRTUAL REALITY APPLICATION TO IMPROVE PHYSICAL HEALTH OF PATIENTS WITH SCHIZOPHRENIA

BackgroundPhysical illnesses such as hypertension, diabetes, and cardiovascular diseases are much more common in patients with schizophrenia compared to general population. Besides the rate of schizophrenia patients benefiting from general health services have been quite low. These physical illnesses don’t only cause bad prognosis but also decrease the quality of life and increase the risk of early death. Many schizophrenia studies in recent years have found that patients with schizophrenia have died very early compared to normal population. The most important reasons of developing physical illnesses in schizophrenia are decrease in physical activity, nutrition problems, weight gain, smoking cigarettes, alcohol and substance abuse, unhealthy lifestyles.Emerging new technologies may lead to the discovery of new treatment techniques in psychiatric disorders and related problems. Virtual reality (VR) as one of these new technologies, is composed of imitated real environments on computers. Most of virtual reality environments are about visual experiences by means of computer screen. Virtual reality is used for presenting reality experience and it is a 3D computer program of existing or non-existing environments. Although virtual reality in treatment of schizophrenia is new to the science, it has promising results to improve positive symptoms of schizophrenia. Also, VR technology may be useful to improve psychosocial functioning among the patients with schizophrenia. The aim of this study is to investigate the effect of VR physical health program on physical health parameters such as nutrition, psychomotor activity, smoking cigarettes and lifestyle.MethodsPatients who met DSM-V schizophrenia diagnostic criteria from Dokuz Eylül University School of Medicine, Schizophrenia and Psychosis Outpatient Clinic were included into the study. In this study, a virtual reality laboratory has been established and physical health improvement program by using virtual reality technology with real life experiences has been developed for patients with schizophrenia.ResultsNone of the patients reported motion sickness due to exposure to real environment during or after immersive process of VR. There were significant changes regarding the physical health parameters.DiscussionVR physical health program may be useful to improve physical health-related problems such as obesity, psychomotor inactivity and smoking cigarettes.

Controlled sleep deprivation as an experimental medicine model of schizophrenia: An update

In recent years there has been a surge of interest and corresponding accumulation of knowledge about the role of sleep disturbance in schizophrenia. In this review, we provide an update on the current status of experimentally controlled sleep deprivation (SD) as an experimental medicine model of psychosis, and also consider, given the complexity and heterogeneity of schizophrenia, whether this (state) model can be usefully combined with other state or trait model systems to more powerfully model the pathophysiology of psychosis. We present evidence of dose-dependent aberrations that qualitatively resemble positive, negative and cognitive symptoms of schizophrenia as well as deficits in a range of translational biomarkers for schizophrenia, including prepulse inhibition, smooth pursuit and antisaccades, following experimentally controlled SD, relative to standard sleep, in healthy volunteers. Studies examining the combination of SD and schizotypy, a trait model of schizophrenia, revealed only occasional, task-dependent superiority of the combination model, relative to either of the two models alone. Overall, we argue that experimentally controlled SD is a valuable experimental medicine model of schizophrenia to advance our understanding of the pathophysiology of the clinical disorder and discovery of more effective or novel treatments. Future studies are needed to test its utility in combination with other, especially state, model systems of psychosis such as ketamine.

TDCS and Cognitive Training for Treatment of Schizophrenia Symptoms

Perceptual models of positive symptoms in schizophrenia include hyper-excitability of auditory/verbal perceptual systems (in left temporoparietal junction; l-TPJ), and hypo-excitability of cognitive control which normally inhibits or reattributes perceptual misrepresentations (in right ventrolateral prefrontal cortex; r-VLPFC). Inhibitory stimulation of l-TPJ has been shown to reduce positive symptoms of schizophrenia, but r-VLPFC has not been targeted previously.

Overweighting of Initial Motion Information Correlates With Severity of Positive Symptoms in Schizophrenia

Recent predictive coding accounts suggest that alterations in how prior knowledge and new sensory inputs are integrated in perception and inference may be implicated in the emergence of delusions and hallucinations. We tested this model by manipulating the precision of sequentially-presented visual motion information, hypothesizing that the severity of positive symptoms would correlate with a bias towards the direction of initial motion.

Variability in Response to Noninvasive Brain Stimulation in Schizophrenia Spectrum Disorders

While initial reports had been promising, more recent studies have questioned the efficacy of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) as add-on treatment of persistent positive symptoms in schizophrenia. One argument that is widely shared is that brain stimulation only works in a subgroup of patients, although this assumption is rarely tested explicitly.

Current Treatment Options and Emerging Agents for Schizophrenia.

The currently available antipsychotics mostly treat the positive symptoms of schizophrenia and have at least one adverse effect as a potential liability. Encouraging data suggest potential efficacy for a variety of new agents for the treatment of total symptoms and/or specific symptom domains of schizophrenia. Mechanisms of action that are under investigation include dopamine D3 antagonism/serotonin 5-HT1A partial agonism; combined dopamine, serotonin, and glutamate modulation; phosphodiesterase 10A inhibition; trace amine-associated receptor-1 (TAAR1) agonism plus 5-HT1A agonism; 5-HT2A inverse agonism; sigma-2/5-HT2A antagonism; D-amino acid oxidase (DAAO) inhibition; glycine transporter-1 inhibition; vesicular monoamine transporter-2 antagonism; mu opioid antagonism added to olanzapine; and novel long-acting injectable antipsychotic formulations. It is hoped that ongoing and recently completed trials for agents with known and/or novel mechanisms of action will lead to approved treatments that effectively target the various symptom domains of schizophrenia, minimize the risk for a broad range of clinically relevant adverse effects, and improve functional outcomes for patients. Some novel treatments have already received approval for use in patients with schizophrenia. This brief report discusses recently approved novel agents and potential new treatment options for schizophrenia that are being investigated.

Noncanonical, Dopamine-Dependent Long-Term Potentiation at Hippocampal Output Synapses in a Rodent Model of First-Episode Psychosis.

Cognitive deficits and positive symptoms in schizophrenia have both been linked to hippocampal dysfunction. Recently, subregion-specific aberrant and maladaptive hippocampal synaptic plasticity has been suggested as one of the mechanistic underpinnings. The subiculum is the final output hub of the hippocampus and orchestrates hippocampal information transfer to other brain regions. While most CA1 pyramidal neurons show regular-spiking behavior, subicular output neurons comprise bursting and regular-firing pyramidal cells. These two cell types target different brain regions and express unique forms of synaptic plasticity. Here, we used a single systemic application of the noncompetitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 to model first-episode psychosis in rats and studied long-term potentiation (LTP) in subicular regular-firing cells in acute hippocampal slices. Previously, we have reported a facilitation of a presynaptic, late-onset LTP in subicular bursting pyramidal cells after systemic NMDAR antagonism. Here, we show that single systemic NMDAR antagonist application also facilitates the induction of a noncanonical, but postsynaptic NMDAR-independent LTP in ventral subicular but not in CA1 regular-firing pyramidal cells. This form of LTP was dependent on D1/D5 dopamine receptor activation. Activation of D1/D5 dopamine receptors by a specific agonist mimicked and occluded LTP induced by electrical high-frequency stimulation (HFS). Furthermore, our results indicate that this form of LTP relies on postsynaptic Ca2+ signaling and requires the activation of protein kinase A. Considering the pivotal role of the subiculum as information gatekeeper between the hippocampus and other brain regions, this aberrant LTP in ventral subicular regular-firing neurons is expected to interfere with physiological hippocampal output processing and might thereby contribute to hippocampal dysfunction in psychotic events.

Apophenia as the disposition to false positives: A unifying framework for openness and psychoticism.

Positive symptoms of schizophrenia and its extended phenotype-often termed psychoticism or positive schizotypy-are characterized by the inclusion of novel, erroneous mental contents. One promising framework for explaining positive symptoms involves apophenia, conceptualized here as a disposition toward false-positive errors. Apophenia and positive symptoms have shown relations to openness to experience (more specifically, to the openness aspect of the broader openness/intellect domain), and all of these constructs involve tendencies toward pattern seeking. Nonetheless, few studies have investigated the relations between psychoticism and non-self-report indicators of apophenia, let alone the role of normal personality variation. The current research used structural equation models to test associations between psychoticism, openness, intelligence, and non-self-report indicators of apophenia comprising false-positive error rates on a variety of computerized tasks. In Sample 1, 1,193 participants completed digit identification, theory of mind, and emotion recognition tasks. In Sample 2, 195 participants completed auditory signal detection and semantic word association tasks. Psychoticism and the openness aspect were positively correlated. Self-reported psychoticism, openness, and their shared variance were positively associated with apophenia, as indexed by false-positive error rates, whether or not intelligence was controlled for. Apophenia was not associated with other personality traits, and openness and psychoticism were not associated with false-negative errors. Findings provide insights into the measurement of apophenia and its relation to personality and psychopathology. Apophenia and pattern seeking may be promising constructs for unifying the openness aspect of personality with the psychosis spectrum and for providing an explanation of positive symptoms. Results are discussed in the context of possible adaptive characteristics of apophenia as well as potential risk factors for the development of psychotic disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Effect of Amisulpride on Hippocampal Neurogenesis in an Experimental Model of Stressed Rats

Rationale: Amisulpride (Sanofi) is atypical antipsychotic against both positive and negative symptoms of schizophrenia . Efficacy is observed against negative symptoms in a low dose range of ( 50-300 mg / day ) while in positive symptoms is observed in a high dose range ( 800-1200 mg / day ) Boyer et al ,( 1994 ). It is a selective and potent antagonist at dopamine D2 and D3 receptors. Also it appears to have a useful potential for treatment of depression Boyer et al ,(1999). Objectives: The current study investigated that amisulpride has antidepressant properties over a range of doses in two procedures namely the Forced Swim Test (FST) Porso et al,(1978) and immune-histopathology of Ki67. Also the effect of high versus low dose of amisulpride on hippocampal neurogenesis in male Wistar Han albino rats. Results: There is an increase of immobility time in seconds in CSS group compared with Control group with Mean ± SD (67.00±8.623 and 3.333±1.670 respectively) with P treatment with oral Amisulpride 5 ,10 mg/kg/day result in insignificant increase in Ki-67 immunostained cells in SVZ, with the maximum statistically increase with 20 mg/kg/day, with means (15.78,13.38 and 28.00 respectively )compared with CSS (Mean 8.000 ) with P values of 0.5108 ,0.8187and 0.0009 respectively and F (4,40)=6.628.

Potential therapeutic antipsychotic effects of Naringin against ketamine-induced deficits in rats: Involvement of Akt/GSK-3β and Wnt/β-catenin signaling pathways

AimSchizophrenia is a chronic, disabling and one of the major neurological illnesses affecting nearly 1% of the global population. Currently available antipsychotic medications possess limited effects. The current research aimed at investigating potential therapeutic add-on benefit to enhance the effects of clozapine anti-schizophrenic. Main methodsTo induce schizophrenia, ketamine was administered at a dose of 25 mg/kg i.p. for 14 consecutive days. Naringin was administered to Wistar rats at a dose of 100 mg/kg orally, alone or in combination with clozapine 5 mg/kg i.p from day 8 to day 14. Furthermore, behavioral tests were conducted to evaluate positive, negative and cognitive symptoms of schizophrenia. In addition, neurotransmitters' levels were detected using HPLC. Moreover, oxidative stress markers were assessed using spectrophotometry. Furthermore, apoptotic and wnt/β-catenin pathway markers were determined using western blotting (Akt, GSK-3β and β-catenin), colorimetric methods (Caspase-3) and immunohistochemistry (Bax, Bcl2 and cytochrome c). Key findingsKetamine induced positive, negative and cognitive schizophrenia symptoms together with neurotransmitters' imbalance. In addition, ketamine treatment caused significant glutathione depletion, lipid peroxidation and reduction in catalase activity. Naringin and/or clozapine treatment significantly attenuated ketamine-induced schizophrenic symptoms and oxidative injury. Additionally, ketamine provoked apoptosis via increasing Bax/Bcl2 expression, caspase-3 activity, and Cytochrome C and Akt protein expression while naringin/clozapine treatment significantly inhibited this apoptotic effect. Moreover, naringin activated the neurodevelopmental wnt/β-catenin signaling pathway evidenced by increasing pGSK-3β and reducing pβ-catenin protein expression. SignificanceThese findings may suggest that naringin possesses a potential therapeutic add-on effect against ketamine-induced schizophrenia.

Psychotic Experiences in Schizophrenia and Sensitivity to Sensory Evidence.

Perceptual inference depends on an optimal integration of current sensory evidence with prior beliefs about the environment. Alterations of this process have been related to the emergence of positive symptoms in schizophrenia. However, it has remained unclear whether delusions and hallucinations arise from an increased or decreased weighting of prior beliefs relative to sensory evidence. To investigate the relation of this prior-to-likelihood ratio to positive symptoms in schizophrenia, we devised a novel experimental paradigm which gradually manipulates perceptually ambiguous visual stimuli by disambiguating stimulus information. As a proxy for likelihood precision, we assessed the sensitivity of individual participants to sensory evidence. As a surrogate for the precision of prior beliefs in perceptual stability, we measured phase duration in ambiguity. Relative to healthy controls, patients with schizophrenia showed a stronger increment in congruent perceptual states for increasing levels of disambiguating stimulus evidence. Sensitivity to sensory evidence correlated positively with the individual patients' severity of perceptual anomalies and hallucinations. Moreover, the severity of such experiences correlated negatively with phase duration. Our results indicate that perceptual anomalies and hallucinations are associated with a shift of perceptual inference toward sensory evidence and away from prior beliefs. This reduced prior-to-likelihood ratio in sensory processing may contribute to the phenomenon of aberrant salience, which has been suggested to give rise to the false inferences underlying psychotic experiences.

Reward anticipation in schizophrenia: A coordinate-based meta-analysis

Reward processing impairments have been linked with positive and negative symptoms of schizophrenia. Here, we performed a coordinate-based meta-analysis that combined eleven BOLD-fMRI studies comparing reward anticipation signals between schizophrenia patients and healthy controls. We observed a reduced difference in activation in schizophrenia patients within a frontal-striatal network. Meta-regressions revealed that this functional signature was linked to the severity of psychotic symptoms and persisted even after controlling for the dose of antipsychotic medications.

Aberrant effective connectivity is associated with positive symptoms in first-episode schizophrenia

Schizophrenia is a neurodevelopmental psychiatric disorder thought to result from synaptic dysfunction that affects distributed brain connectivity, rather than any particular brain region. While symptomatology is traditionally divided into positive and negative symptoms, abnormal social cognition is now recognized a key component of schizophrenia. Nonetheless, we are still lacking a mechanistic understanding of effective brain connectivity in schizophrenia during social cognition and how it relates to clinical symptomatology. To address this question, we used fMRI and dynamic causal modelling (DCM) to test for abnormal brain connectivity in twenty-four patients with first-episode schizophrenia (FES) compared to twenty-five matched controls performing the Human Connectome Project (HCP) social cognition paradigm. Patients had not received regular therapeutic antipsychotics, but were not completely drug naïve. Whilst patients were less accurate than controls in judging social stimuli from non-social stimuli, our results revealed an increase in feedforward connectivity from motion-sensitive V5 to posterior superior temporal sulcus (pSTS) in patients compared to matched controls. At the same time, patients with a higher degree of positive symptoms had more disinhibition within pSTS, a region computationally involved in social cognition. We interpret these findings the framework of active inference, where increased feedforward connectivity may encode aberrant prediction errors from V5 to pSTS and local disinhibition within pSTS may reflect aberrant encoding of the precision of cortical representations about social stimuli.

Toxoplasma gondii Infection and Clinical Characteristics of Patients With Schizophrenia: A Systematic Review and Meta-analysis

Abstract Schizophrenia is associated with an increased prevalence of IgG antibodies against Toxoplasma gondii (T. gondii seropositivity), whereby the infection seems to precede the disorder. However, it remains unclear whether a T. gondii infection affects clinical characteristics of schizophrenia. Therefore, a systematic review and meta-analysis was conducted following PRISMA guidelines examining the association between T. gondii seropositivity and severity of total, positive, or negative symptoms or age of onset in schizophrenia. PubMed, Embase, and PsycInfo were systematically searched up to June 23, 2019 (PROSPERO #CRD42018087766). Random-effects models were used for analysis. Furthermore, the influence of potential moderators was analyzed. Indications for publication bias were examined. From a total of 934 reports, 13 studies were included. No overall effect on severity of total, positive, or negative symptoms was found. However, in patients with a shorter duration of illness T. gondii seropositivity was associated with more severe positive symptoms (standardized mean difference [SMD] = 0.32; P &amp;lt; .001). Similar but smaller effects were seen for total symptoms, while it was absent for negative symptoms. Additionally, a significantly higher age of onset was found in those with T. gondii seropositivity (1.8 y, P = .015), although this last finding was probably influenced by publication bias and study quality. Taken together, these findings indicate that T. gondii infection has a modest effect on the severity of positive and total symptoms in schizophrenia among those in the early stages of the disorder. This supports the hypothesis that T. gondii infection is causally related to schizophrenia, although more research remains necessary.

Successful treatment of auditory hallucinations in a schizophrenia patient with clonidine

Many reports show evidence of the disruption of central noradrenergic activity in the etiology of schizophrenia. A few studies show positive effects of a specific α2-agonist, clonidine, on cognition and on positive and negative symptoms of schizophrenia. In this report, we tried clonidine for the treatment of auditory hallucinations in a patient with schizophrenia who had low compliance with antipsychotic treatment. At the end of seven days, auditory hallucinations decreased dramatically. Moreover, almost all auditory hallucinations disappeared at 6-months follow-up. This is the first case report showing the efficacy of clonidine monotherapy on auditory hallucinations in schizophrenia. However, the mechanism of action of clonidine remains hypothetical. The dramatic improvement observed in this case in the absence of any adverse effects suggests that controlled trials of the effect of clonidine on auditory hallucinations may be of clinical importance.