Predominant Negative Symptoms Research Articles

The management of patients with predominant negative symptoms in Slovakia: A 1-year longitudinal, prospective & multicentric cohort study.

The management of patients with predominant negative symptoms in Slovakia: A 1-year longitudinal, prospective & multicentric cohort study.

A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia.

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.

Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D

Insufficiency of vitamin D levels often occur in individuals with schizophrenia and first-episode psychosis (FEP). However, it is unknown whether this represents a biological predisposition, or it is essentially driven by illness-related alterations in lifestyle habits. Lower vitamin D has also been associated with adverse neurodevelopmental outcomes and predominant negative psychotic symptoms. This study aimed to investigate the contribution of polygenic risk score for circulating 25-hydroxyvitamin D concentration (PRS-vitD) to symptom presentation among individuals with FEP enrolled in the Athens First-Episode Psychosis Research Study (AthensFEP n = 205) and the Psychosis Incident Cohort Outcome Study (PICOS n = 123). The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale at baseline and follow-up assessments (AthensFEP: 4-weeks follow-up, PICOS: 1-year follow-up). Premorbid intelligence and adjustment domains were also examined as proxy measures of neurodevelopmental deviations. An inverse association between PRS-vitD and severity of negative symptoms, in particular lack of social motivation, was detected in the AthensFEP at baseline (adjusted R2 = 0.04, p < 0.001) and follow-up (adjusted R2 = 0.03, p < 0.01). The above observation was independently validated in PICOS at follow-up (adjusted R2 = 0.06, p < 0.01). No evidence emerged for a relationship between PRS-vitD and premorbid measures of intelligence and adjustment, likely not supporting an impact of lower PRS-vitD on developmental trajectories related to psychotic illness. These findings suggest that polygenic vulnerability to reduced vitamin D impairs motivation and social interaction in individuals with FEP, thereby interventions that encourage outdoor activities and social engagement in this patient group might attenuate enduring negative symptoms.

Multilevel evidence of MECP2-associated mitochondrial dysfunction and its therapeutic implications.

We present a male patient carrying a pathogenic MECP2 p. Arg179Trp variant with predominant negative psychiatric features and multilevel evidence of mitochondrial dysfunction who responded to the cariprazine treatment. He had delayed speech development and later experienced severe social anxiety, learning disabilities, cognitive slowing, and predominant negative psychiatric symptoms associated with rigidity. Clinical examinations showed multisystemic involvement. Together with elevated ergometric lactate levels, the clinical picture suggested mitochondrial disease, which was also supported by muscle histopathology. Exploratory transcriptome analysis also revealed the involvement of metabolic and oxidative phosphorylation pathways. Whole-exome sequencing identified a pathogenic MECP2 variant, which can explain both the dopamine imbalance and mitochondrial dysfunction in this patient. Mitochondrial dysfunction was previously suggested in classical Rett syndrome, and we detected related phenotype evidence on multiple consistent levels for the first time in a MECP2 variant carrier male. This study further supports the importance of the MECP2 gene in the mitochondrial pathways, which can open the gate for more personalized therapeutic interventions. Good cariprazine response highlights the role of dopamine dysfunction in the complex psychiatric symptoms of Rett syndrome. This can help identify the optimal treatment strategy from a transdiagnostic perspective instead of a classical diagnostic category.

A Study of Neurological Soft Signs and Cognition in Schizophrenia.

Neurological soft signs (NSS) are delicate neurological abnormalities that comprise deficits in motor coordination, problems with the sequencing of complex motor acts, and sensory integration difficulties. These are nonspecific with no specific localization in the brain. NSS are found in many patients with Schizophrenia. Cognitive dysfunctions are also present in more than two-thirds of patients with Schizophrenia. This study aims at assessing the NSS and its association with cognitive impairment in patients with Schizophrenia. A total of 100 Schizophrenia patients were included in the study. The Heidelberg scale was used for assessing the NSS. The Montreal Cognitive Assessment Scale(MoCA) for cognitive impairment, the Positive and Negative Syndrome Scale(PANSS) for Schizophrenia, and the Brief Psychiatric Rating Scale (BPRS) were used to assess the severity. Statistical analysis was performed by Pearson's Chi-square test, Kruskal-Wallis test, Wilcoxon rank testsand Spearman rank correlation along with mean and standard deviation. NSS were present in 68% (N=68) of the patients with motor coordination being maximally affected. Cognitive impairment was found in 73% (N=73) of patients with a MoCA score <26. Patients with predominant negative symptoms had higher NSS scores and lower MoCA scores. A "statistically significant" correlation was observed between cognitive impairment and NSS. Most patients with NSS and impaired cognition were in the "markedly ill" category of BPRS. A significant association was observed between cognitive deficits, negative symptoms, and NSS in Schizophrenia.NSS and cognitive dysfunctions are integral parts of Schizophrenia symptomdomains and need to be assessed as the negative symptoms and severity of illness are associated with NSS, especially problems with motor coordination and cognitive dysfunctions.

Single trajectory treatment response for predominant negative symptoms: Post-hoc analysis of a clinical trial with cariprazine and risperidone.

Examining the heterogeneity of negative symptoms of schizophrenia contributes to the identification of available treatment targets. Generally, prior evidence classified three to four symptom treatment response trajectory groups over the course of positive symptoms, yet, no evidence exists regarding the heterogeneity of medium-term response to predominant negative symptoms. The current post-hoc analysis aims to identify the heterogeneity in negative symptom treatment response trajectories among patients with predominant negative symptoms who received either cariprazine or risperidone for 26weeks. Treatment response was analyzed based on the: the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), and the Clinical Global Impression Severity (CGIS) and Improvement (CGII) scales. To identify subgroups of patients with a similar course of treatment response, group-based trajectory modelling was utilized. Results demonstrated that in comparison with competing models, a single trajectory best described the treatment response of patients with predominant negative symptoms. The results indicate that patients with predominant negative symptoms with over ten years of schizophrenia respond rapidly to adequate treatment and follow a course of steady improvement.

Cariprazine for negative symptoms in early psychosis: a pilot study with a 6-month follow-up.

Cariprazine, a novel antipsychotic drug that is a partial agonist with preferential binding to the D3 receptor, has demonstrated efficacy in clinical trials across all symptom domains, including negative symptoms, which can occur early in the course of psychotic illness. However, evidence, to date regarding its effects in early psychosis patients with primary negative symptoms has been limited. To evaluate the efficacy of cariprazine for negative symptoms in early psychosis patients. Demographic and clinical information of the study population were collected from the electronic records and PANSS scale administered at baseline, 3 and 6 months. Tolerability and discontinuation reasons, where applicable, were also recorded. Ten patients with early psychosis (four men and six women, mean age - 25.5 years) with prominent or predominant negative symptoms were treated with cariprazine (range 1.5 - 3 mg). Three patients discontinued cariprazine within the first 3 months due to patient choice, lack of response and non-compliance, respectively. In the remaining patients, there was a significant reduction in the mean negative PANSS score from baseline to 6 months (from 26.3 to 10.6), mean total PANSS score (from 81.4 to 43.3) and in the mean positive PANSS score (from 14.4 to 9.9) which correspond to a 53.1, 41.5, and 28.5% mean score reduction. This pilot study suggests that cariprazine is a safe and effective treatment in early psychosis, particularly for the alleviation of negative symptoms which remains an area of unmet treatment need.

Antipsychotic-induced akathisia in adults with acute schizophrenia: A systematic review and dose-response meta-analysis

Antipsychotic-induced akathisia is severely distressing. We aimed to investigate relationships between antipsychotic doses and akathisia risk. We searched for randomised controlled trials that investigated monotherapy of 17 antipsychotics in adults with acute schizophrenia until 06 March 2022. The primary outcome was the number of participants with akathisia, which was analysed with odds ratios (ORs). We applied one-stage random-effects dose-response meta-analyses using restricted cubic splines to model the dose-response relationships. We included 98 studies (343 dose arms, 34,225 participants), most of which were short-term and had low-to-moderate risk of bias. We obtained data on all antipsychotics except clozapine and zotepine. In patients with acute exacerbations of chronic schizophrenia, from moderate to high certainty of evidence, our analysis showed that sertindole and quetiapine carried negligible risks for akathisia across examined doses (flat curves), while most of the other antipsychotics had their risks increase initially with increasing doses and then either plateaued (hyperbolic curves) or continued to rise (monotonic curves), with maximum ORs ranging from 1.76 with 95% Confidence Intervals [1.24, 2.52] for risperidone at 5.4 mg/day to OR 11.92 [5.18, 27.43] for lurasidone at 240 mg/day. We found limited or no data on akathisia risk in patients with predominant negative symptoms, first-episode schizophrenia, or elderly patients. In conclusion, liability of akathisia varies between antipsychotics and is dose-related. The dose-response curves for akathisia in most antipsychotics are either monotonic or hyperbolic, indicating that higher doses carry a greater or equal risk compared to lower doses.

Psychiatric Inpatient Healthcare Resource Utilization and Treatment Patterns Among Patients With Predominant Negative Symptoms in Schizophrenia

AbstractIntroductionCurrently approved treatments for schizophrenia (antipsychotics) have demonstrated effectiveness for treating positive symptoms; however, these agents are largely ineffective in treating other domains. Negative symptoms, including avolition, alogia, blunted affect, and asociality, are difficult to treat, and often persist despite adequate control of positive symptoms. Additionally, some patients experience “predominant” (moderate-to-severe negative symptoms that have greater relative severity than co-occurring positive symptoms) or “prominent” (severity of negative symptoms [moderate-to-severe] without any reference to positive symptoms) negative symptoms. These symptoms are known to have great impact on patient social functioning and quality of life, and are associated with poorer clinical course and outcomes for patients. Here, we examined inpatient healthcare resource utilization in patients with schizophrenia experiencing predominantly negative symptoms (PNS).MethodsDe-identified data were extracted from electronic health records in the NeuroBlu Database across 25 US mental healthcare providers. Positive and negative symptom data were derived from free-text records using natural language processing. PNS was defined as the presence of three or more negative symptoms and three or fewer positive symptoms at first clinical contact following schizophrenia diagnosis. Groups were balanced for baseline demographic and clinical characteristics by minimizing the generalized Mahalanobis distance and compared using chi-square and t-tests. Treatment patterns were visualized using Sankey diagrams.ResultsA total of 4444 patients with schizophrenia were identified and 8% were classified as PNS. A balanced cohort of 720 patients (50% PNS) was generated. Patients with PNS were more likely to be hospitalized in the 12 months following diagnosis (PNS: 76%, non-PNS: 60%, χ2: 22.5, p &lt; 0.001) and were switched to a second-line antipsychotic after a shorter first-line treatment duration. The most frequently prescribed antipsychotics differed between groups (PNS: risperidone, aripiprazole, haloperidol; non-PNS: risperidone, olanzapine, other atypical).DiscussionThis study demonstrates that negative symptoms in schizophrenia may be associated with worse illness course and higher healthcare resource utilization. There remains a need for new treatment options for patients with persistent, prominent, or predominant negative symptoms which specifically improve this historically hard-to-treat and assess symptom domain.FundingSunovion Pharmaceuticals, Inc.

Clinical Global Impression of Cariprazine in Negative Symptom Schizophrenia Patients: Comparison of clinical trial data vs. real-world evidence

IntroductionThere is an increasing need to understand the effectiveness of novel medications in real-world context since despite being the gold standard, double-blind trials have their own limitations as well. Clinical Global Impression is a simple tool for clinicians to assess the severity of an illness (CGI-Severity) as well as to rate how much the patient’s disorder has improved or worsened relative to baseline (CGI-Improvement). In this poster, cariprazine, a third-generation antipsychotic medication that was found to be effective in the treatment of negative symptoms in schizophrenia will be evaluated.ObjectivesTo compare the effectiveness of cariprazine in clinical trial vs real-world setting via the CGI-S and CGI-I scales in negative symptom schizophrenia patients.MethodsWe compared the results of a clinical trial (Németh et al. Lancet 2017; 389:1103-13) and an observational study (Rancans et al. Int Clin Psychopharmacol. 2021;36(3):154-161). The latter was an open-label, flexible-dose, 16-week, observational study of cariprazine involving 116 outpatients in Latvia. Adult patients who have been diagnosed with schizophrenia, exhibited negative symptoms based on clinical judgement, were at least mildly ill according to the CGI-S scale and have not previously received cariprazine were eligible to take part in the study. Dosing of cariprazine was based on clinical judgement. The clinical trial was a randomized, double-blind, multi-centred, 26-week study with adults aged 18–65 years with long-term (&gt;2 year), stable schizophrenia and predominant negative symptoms (&gt;6 months). Patients were randomly assigned to monotherapy with cariprazine 4.5 mg/day or risperidone 4.0 mg/day.Results116 patients on flexible dose cariprazine (observational study) were compared with 227 patients on cariprazine 4.5 mg/day and 229 on risperidone 4.0 mg/day (clinical trial). Baseline severity of illness as measured by the CGI-S was between moderately and markedly ill in all three groups. By the end of the 26-week trial, cariprazine reduced the CGI-S score significantly (LS Mean Change: -0.9, p&lt;0.01). In contrast, the risperidone group achieved only -0.7-point change from baseline. In the observational study, cariprazine also achieved significant change (-0.9, p&lt;0.001) but by week 16. In terms of improvement, patients on cariprazine improved minimally to much in both the clinical trial and real-world setting.ConclusionsThe effectiveness of cariprazine in clinical trial and real-world setting do not seem to differ as measured by the scales in negative symptom patients.Disclosure of InterestE. Rancans Grant / Research support from: Gedeon Richter, Lundbeck, Consultant of: Abbvie, Gedeon Richter, Grindex, Janssen Cilag, Lundbeck, Servier, Zentiva, Speakers bureau of: Abbvie, Gedeon Richter, Grindex, Janssen Cilag, Lundbeck, Servier, Zentiva, Z. Dombi Employee of: Gedeon Richter Plc., R. Csehi Employee of: Gedeon Richter Plc., G. Németh Employee of: Gedeon Richter Plc.

The Role of Glutamatergic Gene Polymorphisms in the Clinical Phenotypes of Schizophrenia.

Personal variations in genetic risk for schizophrenia relate to its phenotypic heterogeneity-both in disorder development and clinical manifestations. Abnormal glutamatergic neurotransmitter system functioning is integrated in the pathogenesis of schizophrenia. A sample of 805 Russian schizophrenia patients from the Siberian Federal region was investigated. We examined the association of 39 single nucleotide polymorphisms in eight genes (GRIN2A, GRIN2B, SLC1A2, SLC1A3, SLC17A7, GRM3, GRM7, and GRM8) involved in the glutamatergic system with the development of clinical heterogeneity of schizophrenia. The MassARRAY Analyzer 4 was used for genotyping. GRIN2A rs11644461, rs8057394 and GRIN2B rs7313149 are associated with the continuous type of schizophrenia. The GRIN2A rs8057394*G allele is a relative risk factor (p = 0.019) for developing the continuous type of schizophrenia. We found a nominally significant association between negative symptoms of schizophrenia and SLC17A7 rs62126236. The SLC17A7 rs62126236*T allele has a protective effect (p = 0.039) against predominant negative symptoms in schizophrenia. The total Positive and Negative Syndrome Scale (PANSS) scores were significantly associated with GRIN2A rs9788936 after adjusting for multiple testing (p = 0.001). In this study the contribution of the glutamatergic gene polymorphisms to the clinical heterogeneity of schizophrenia has been demonstrated.

Identifying risk factors for predominant negative symptoms from early stages in schizophrenia: A longitudinal and sex-specific study in first-episode schizophrenia patients.

People with schizophrenia and predominant negative symptoms (PNS) present a different clinical and functional profile from those without such symptomatology. Few studies have examined the risk factors and the incidence of PNS in first-episode schizophrenia patients (FES) and differentiating by sex. This study aims to assess prevalence, demographic and clinical characteristics related to PNS from early stages and to study if there are sex-specific features in terms of developing PNS. In a sample of 121 FES patients derived from a multicentre and naturalistic study, those who developed PNS at 12-months were identified. Environmental, clinical, functional, and cognitive ratings were examined longitudinally. Binary logistic regressions were applied to detect baseline risk factors for developing PNS at one-year follow-up. In the present FES cohort, 24.8% of the patients (n=30) developed PNS (20% of the women, 27.6% of the men). Compared to non-PNS (75.2%, n=91), at baseline, PNS group had more negative (t=-6.347; p<0.001) and depressive symptoms (t=-5.026; p<0.001), poorer premorbid adjustment (t=-2.791; p=0.006) and functional outcome (t=-2.649; p<0.001), more amotivation (t=-7.333; p<0.001), more expressivity alterations (t=-4.417; p<0.001), worse cognitive reserve (t=2.581; p<0.011), a lower estimated intelligent quotient (t=2.417; p=0.017), worse verbal memory (t=2.608; p=0.011), and worse fluency (t=2.614; p=0.010). Regressions showed that the premorbid adjustment was the main predictor of PNS in females (p=0.007; Exp(B)=1.106) while in males were a worse verbal memory performance (p=0.031; Exp(B)=0.989) and more alterations in the motivation domain (p=0.001; Exp(B)=1.607). A different baseline clinical profile and notable risk factors differences in the development of PNS between males and females were found. Results suggest that sex may be an important confounder in studies comparing schizophrenia patients with predominant and non-predominant negative symptomatology.

Time course of significantly greater improvement in global illness-severity with cariprazine versus risperidone in schizophrenia patients with predominant negative symptoms

Time course of significantly greater improvement in global illness-severity with cariprazine versus risperidone in schizophrenia patients with predominant negative symptoms

A study of association between serum testosterone levels and clinical aspects of schizophrenia

Background: Sex disparities in schizophrenia especially in negative symptoms may be related to the action of sex steroid hormones. Objective: The purpose of this study was to analyze relationship of serum testosterone levels with respect to clinical psychopathology laying emphasis on negative symptoms in male patients with schizophrenia. Material and Methods: The study population consisted of two hundred male schizophrenia patients and fifty- age matched healthy individuals. Sociodemographic data and history of illness were noted in semi-structured proforma. Clinical psychopathology was assessed by Positive and Negative Syndrome Scale (PANSS). Drug Induced Extrapyramidal Symptoms Scale (DIEPSS) and Calgary Depression Scale for Schizophrenia (CDSS) were also used to exclude the effects of extrapyramidal symptoms and depression. Serum testosterone level was measured by chemiluminescence method. Data were analyzed by chi square test (x2) and z-test. Pearson’s correlation analysis was used for association of testosterone level with PANSS sub-scale scores. Results: Mean testosterone level was significantly lower in schizophrenia patients (381.90±158.29; p ˭ 0.001) as compared to healthy subjects (520.51±145.94). A significant inverse association was detected between PANSS negative sub scale scores and testosterone levels (r ˭ -0.211, p ˭ 0.034). There was no correlation with other PANSS sub scale items (i.e., positive symptoms, general psychopathology and total scores), age of onset and disease duration. Conclusion: The present study indicates that lower level of testosterone may have a role in presentation of negative symptoms in schizophrenia, and the pathophysiological processes of disease affected the testosterone levels. Therefore, clinicians are advised to monitor levels of testosterone in patients with predominant negative symptoms of schizophrenia and enquire about sexual dysfunction and infertility. Lower level of sex steroids is a point of concern as these patients are at high risk of osteoporosis and cardiovascular co-morbidities. In near future therapeutic strategies targeting testosterone could be useful in ameliorating the negative symptoms of disease.

Challenges and Considerations in Treating Negative and Cognitive Symptoms of Schizophrenia Spectrum Disorders

The prototypical patient with schizophrenia spectrum disorders (SSDs) is often thought to possess positive symptoms. However, patients with SSDs can present with predominantly negative and cognitive symptoms, which can create diagnostic and treatment challenges. A 33-year-old female veteran presented to the emergency department with diminished speech output, markedly blunted affect, tangential speech, was not oriented to situation, and appeared to be responding to internal stimuli. Following inpatient admission, the veteran was diagnosed with schizoaffective disorder, which was misdiagnosed as major depressive disorder and borderline personality disorder during her military service. She was initially treated with olanzapine injections and psychotherapy but continued to experience worsening symptoms, resulting in multiple hospitalizations. After starting clozapine, she demonstrated marked improvement and continued with outpatient mental health care. Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for the patient. Clozapine is a promising treatment for addressing these symptoms. This case demonstrates how careful multidisciplinary evaluations, review of health records, collateral information from family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.

Negative symptoms correlate with altered brain structural asymmetry in amygdala and superior temporal region in schizophrenia patients.

Negative symptoms play an important role in development and treatment of schizophrenia. However, brain changes relevant to negative symptoms are still unclear. This study examined brain structural abnormalities and their asymmetry in schizophrenia patients and the association with negative symptoms. Fifty-nine schizophrenia patients and 66 healthy controls undertook structural brain scans. Schizophrenia patients were further divided into predominant negative symptoms (PNS, n = 18) and non-PNS (n = 34) subgroups. Negative symptoms were assessed by the Negative Symptom Assessment (NSA). T1-weighted images were preprocessed with FreeSurfer to estimate subcortical volumes, cortical thickness and surface areas, asymmetry Index (AI) was then calculated. MANOVA was performed for group differences while partial correlations in patients were analyzed between altered brain structures and negative symptoms. Compared to healthy controls, schizophrenia patients exhibited thinner cortices in frontal and temporal regions, and decreased leftward asymmetry of superior temporal gyrus (STG) in cortical thickness. Patients with PNS exhibited increased rightward asymmetry of amygdala volumes than non-PNS subgroup. In patients, AI of cortical thickness in the STG was negatively correlated with NSA-Emotion scores (r = −0.30, p = 0.035), while AI of amygdala volume was negatively correlated with NSA-Communication (r = −0.30, p = 0.039) and NSA-Total scores (r = −0.30, p = 0.038). Our findings suggested schizophrenia patients exhibited cortical thinning and altered lateralization of brain structures. Emotion and communication dimensions of negative symptoms also correlated with the structural asymmetry of amygdala and superior temporal regions in schizophrenia patients.

Depressive Symptoms and PANSS Symptom Dimensions in Patients With Predominant Negative Symptom Schizophrenia: A Network Analysis.

IntroductionSchizophrenia is a severe psychiatric disorder with a large symptomatic heterogeneity. Moreover, many patients with schizophrenia present with comorbid psychiatric symptoms or disorders. The relation between depressive symptoms and negative symptoms, such as blunted affect, alogia, anhedonia, asociality and avolition, is particularly intriguing. The negative symptoms can be primary or secondary of depression or overlapping with depressive symptoms. The aim of the present network analysis was to better understand the interactions between depressive symptoms and the different symptoms of schizophrenia and to investigate whether negative symptoms and depressive symptoms can be better delineated.MethodsA network analysis on the baseline item scores of the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) from the cariprazine-risperidone study in patients with predominant negative symptoms (PNS) was performed. The connections between all these symptoms (PANSS and CDSS) were investiged: node strength and network centrality were estimated and the Mohr 5-factor model of the PANSS was applied to test the validity of its different symptoms clusters.ResultsAcross 460 patients with schizophrenia and PNS, the most central symptom (largest node strength) was depression (PANSS) followed by depression (CDSS), anxiety, lack of judgment and insight and tension. The PANSS negative symptom cluster together and was only poorly connected with CDSS depresson symptoms. The Mohr 5 factor model was clearly recognized in the overall clustering of symptoms.ConclusionThis network analysis suggests that depression and anxiety symptoms are the most central in this PNS patient population, despite the baseline low depression scores, and that negative symptoms are a clearly independent symptom cluster that can be delineated from depressive symptoms.

A rare case of early onset childhood schizophrenia with predominant negative symptoms

Early onset childhood schizophrenia (&lt;13 years) is often a rare disorder with an estimated prevalence of 1 in 30,000 children. The disease is characterized by hallucinations, delusions and cognitive impairments. It tends to present insidiously with a premorbid period of developmental delay or regression with declining academics. Often, the diagnosis of early onset schizophrenia is missed or sometimes misdiagnosed as pervasive developmental disorders. We here present a rare case of 10-year-old boy who showed behavioural abnormalities suggestive of psychosis.

Emerging Treatments in Schizophrenia.

Although antipsychotics have been available for almost 70 years and greatly improved outcomes for individuals with schizophrenia, all currently available options derive their efficacy from blockade of dopaminergic receptors. However, this mechanism of action leaves many symptoms unresolved and is associated with a significant side effect burden. The mechanisms underlying schizophrenia, which were initially thought to be related to excessive presynaptic dopamine in specific areas of the brain, are now understood to be much more complex and involve structural and molecular changes throughout brain circuits. Consequently, drug discovery efforts have sought new targets in the search for safer and more effective medications that can improve symptoms of schizophrenia and psychosis, including trace amine-associated receptors (TAARs), muscarinic receptors, and serotonergic receptors. Positive phase 2 trial results indicating efficacy and safety of the TAAR1 agonist ulotaront (SEP-363856) and of the muscarinic M1/M4 agonist KarXT (xanomeline plus trospium) for total, positive, and negative symptoms in patients with acute exacerbation of schizophrenia, and of the serotonin 5-HT2A agonist/antagonist pimavanserin in patients with schizophrenia and predominant negative symptoms for negative symptom control are encouraging. Taken together, these data indicate in the context of ongoing phase 3 trial programs that patients with schizophrenia may soon have access to the first non-D2 blocking medication, which could drastically change the treatment landscape and improve outcomes for many of the individuals with schizophrenia who do not fully respond to or cannot tolerate currently available antipsychotic agents that currently all act via postsynaptic dopamine D2 receptor blockade.

Emerging Treatments in Schizophrenia.

Although antipsychotics have been available for almost 70 years and greatly improved outcomes for individuals with schizophrenia, all currently available options derive their efficacy from blockade of dopaminergic receptors. However, this mechanism of action leaves many symptoms unresolved and is associated with a significant side effect burden. The mechanisms underlying schizophrenia, which were initially thought to be related to excessive presynaptic dopamine in specific areas of the brain, are now understood to be much more complex and involve structural and molecular changes throughout brain circuits. Consequently, drug discovery efforts have sought new targets in the search for safer and more effective medications that can improve symptoms of schizophrenia and psychosis, including trace amine-associated receptors (TAARs), muscarinic receptors, and serotonergic receptors. Positive phase 2 trial results indicating efficacy and safety of the TAAR1 agonist ulotaront (SEP-363856) and of the muscarinic M1/M4 agonist KarXT (xanomeline plus trospium) for total, positive, and negative symptoms in patients with acute exacerbation of schizophrenia, and of the serotonin 5-HT2A agonist/antagonist pimavanserin in patients with schizophrenia and predominant negative symptoms for negative symptom control are encouraging. Taken together, these data indicate in the context of ongoing phase 3 trial programs that patients with schizophrenia may soon have access to the first non-D2 blocking medication, which could drastically change the treatment landscape and improve outcomes for many of the individuals with schizophrenia who do not fully respond to or cannot tolerate currently available antipsychotic agents that currently all act via postsynaptic dopamine D2 receptor blockade.