Positive And Negative Syndrome Scale Subscale Scores Research Articles

Clinical correlates and thyroid hormones of metabolic syndrome in first-episode and drug-naïve major depressive disorder outpatients with and without hyperglycemia: a comprehensive cross-sectional study

Hyperglycemia and metabolic syndrome (MetS) are common in patients with major depressive disorder (MDD). This study aimed to explore the prevalence and clinical factors of MetS in first-episode and drug-naïve MDD (FEDND) patients with and without hyperglycemia. A total of 1,718 FEDND patients’ symptoms were assessed using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS). Blood glucose levels, metabolic index, and thyroid hormones were measured during fasting. The prevalence of MetS in FEDND patients with hyperglycemia was 35.67 times higher than in FEDND patients without hyperglycemia. FEDND patients with MetS were older, had later age of onset, and were predominantly married than those without MetS (p < 0.05). Among FEDND patients without hyperglycemia, suicide attempts, severe anxiety, HAMD, HAMA, PANSS subscale scores, thyroid stimulating hormone, antithyroglobulin, and total cholesterol levels were all higher in patients with MetS than those without MetS (all p < 0.05). In FEDND patients without hyperglycemia, the combination of age and TgAb distinguished those patients with and without MetS. Our results suggest a high prevalence of MetS in FEDND patients with hyperglycemia. Several clinical variables and thyroid function-related hormones impact MetS in patients with FEDND.

Impact of Childhood Trauma and Adult Separation Anxiety Disorder on Quality of Life in Individuals with Schizophrenia.

Childhood trauma and anxiety disorders are common in individuals with schizophrenia. This study aimed to investigate the effects of childhood trauma and adult separation anxiety disorder on the quality of life of individuals with schizophrenia. This cross-sectional study included 111 individuals with schizophrenia and 85 control subjects. The separation anxiety symptom inventory (SASI), adult separation anxiety questionnaire (ASAQ), Positive and Negative Syndrome Scale (PANSS), childhood trauma questionnaire (CTQ), and World Health Organization quality of life questionnaire (WHOQoL-BREF) were administered to the participants. More individuals with schizophrenia than control subjects were unemployed and single (p<0.05). Individuals with schizophrenia scored significantly higher on the SASI, ASAQ, and CTQ (p<0.05), whereas the control subjects scored significantly higher on the WHOQoL-BREF (p<0.05). ASAQ scores had mild positive correlations with total PANSS and PANSS subscale scores, and moderate positive correlations with total CTQ, CTQ emotional subscale scores, and CTQ physical abuse subscale scores. A negative moderate correlation was found between ASAQ and total WHOQoL-BREF scores. Mediation analysis revealed that CTQ scores significantly affected total WHOQoL-BREF and ASAQ scores. The model pathway for ASAQ scores showed a significant direct and indirect effect of CTQ on the total WHOQoL-BREF scores. Childhood trauma predicts adult separation anxiety disorder, which partially mediates the impact of childhood trauma on quality of life in individuals with schizophrenia. Therapeutic interventions for adult separation anxiety disorder in individuals with schizophrenia and a history of childhood trauma may help increase their quality of life.

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.

Effectiveness of Lurasidone 80 mg in Patients with Schizophrenia: Results of an Open-Label, 12-Week Extension Study.

To evaluate the effectiveness and safety of lurasidone 80 mg/day (versus the 40 mg/day dose) during a 12-week, open-label extension study in patients with an acute exacerbation of schizophrenia who had completed a 6-week double-blind study of lurasidone. A total of 289 adult patients with schizophrenia completed the double-blind study and enrolled in the 12-week extension study. Lurasidone was flexibly dosed at 40 or 80 mg/day. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) subscale scores, Clinical Global Impression-Severity Scale (CGI-S), and Calgary Depression Scale for Schizophrenia (CDSS), analyzed based on last observation carried forward (LOCF-endpoint). Safety/tolerability assessments included adverse events, body weight, laboratory tests, and discontinuation due to adverse events. Mean endpoint change was greater for lurasidone in modal doses of 80 mg/d (N=136) vs 40 mg/d (N=153) on the PANSS positive subscale (-3.0 vs -2.3), PANSS negative subscale (-1.9 vs -1.7), PANSS General Psychopathology subscale (-5.1 vs -3.8), the CGI-S score (-0.5 vs -0.4), and the CDSS score (-0.7 vs -0.1). Discontinuation rates due to adverse events on lurasidone modal 80 mg/d vs 40 mg/d were 4.4% vs 7.2%; and the most common adverse events in the modal 80 mg/d group were nasopharyngitis, 7.4% (vs 4.6% on modal 40 mg/d), constipation, 5.9% (vs 2.0%), and headache, 5.9% (vs 2.0%). In patients with acute schizophrenia treated with lurasidone 40 mg/d, increasing the dose to 80 mg/d was well tolerated, and was associated with greater improvement in PANSS subscale scores compared to continued treatment with a dose of 40 mg/d.

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation.

BACKGROUNDCognitive impairments are core characteristics of schizophrenia, but are largely resistant to current treatments. Several recent studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dor-solateral prefrontal cortex (DLPFC) can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients. However, results are inconsistent across studies.AIMTo examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia.METHODSForty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC (n = 25) or sham stimulation (n = 22) on weekdays for four consecutive weeks. Patients performed the pattern recognition memory (PRM) task from the Cambridge Neuropsychological Test Automated Battery at baseline, at the end of rTMS treatment (week 4), and 4 wk after rTMS treatment (week 8). Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS).RESULTSThere were no significant differences in PRM performance metrics, SANS total score, SANS subscores, PANSS total score, and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period, but PRM performance metrics (percent correct and number correct) and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group (all P < 0.05). Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment. Moreover, the improvement in visual memory was correlated with the reduction in negative symptoms at week 8. In contrast, there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8 (all P > 0.05).CONCLUSIONHigh-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia, but these effects are delayed, potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

Add-On Pramipexole for the Treatment of Schizophrenia and Schizoaffective Disorder: A Randomized Controlled Trial.

Objective: Several small clinical trials have reported that the dopamine agonist pramipexole was beneficial in treating patients with schizophrenia. A confirmatory trial was conducted to test this hypothesis.Methods: This 16-week, multicenter, double-blind, randomized, placebo-controlled study included 200 subjects meeting DSM-IV-TR criteria for schizophrenia or schizoaffective disorder. Patients were randomized to receive either pramipexole (0.75 mg twice daily, n = 100) or placebo (n = 100) as an add-on to their regular antipsychotic treatment. The primary outcome measure was the total score on the Positive and Negative Syndrome Scale (PANSS); secondary outcome measures included PANSS subscale and cognitive functioning scores. Recruitment was performed in 30 sites in Romania and 1 site in the Republic of Moldova between January and June 2011.Results: Analysis of covariance models showed no significant difference between pramipexole and placebo for total PANSS (P > .99) and PANSS positive (P > .99), negative (P = .73), and general psychopathology (P = .99) subscale scores. Changes in Clinical Global Impressions-Severity of Illness scale and Brief Assessment of Cognition in Schizophrenia scores showed no significant difference between pramipexole and placebo.Conclusions: The results of this large randomized controlled trial indicated that pramipexole was not efficacious as an add-on to antipsychotic medications for schizophrenia.Trial Registration: ClinicalTrials.gov identifier NCT01320982.

A Real Environment Based Virtual Reality Psychosocial Treatment May Help Patients with Schizophrenia to Increase Social Functioning: A Preliminary Study.

Seven schizophrenia patients who have been admitted to the Schizophrenia Outpatient Unit of Dokuz Eylül University School of Medicine and met the diagnosis of schizophrenia according to DSM-V diagnostic criteria were included in the study. Psychosocial functionality level was assessed by PSP (Personal and Social Performance Scale), positive and negative symptom severity with PANSS (Positive and Negative Syndrome Scale), and social skills with SSC (Social Skills Checklist). VRPTP was continued for a total of 10 sessions and twice a week during five weeks. In this study, a real-environment-based VR-PTP for schizophrenia patients was developed. In the sessions, there were different realenvironment- based VR contents including social interaction components such as cafe, market, bazaar, public transportation. There was a statistically significant difference between the PSP scores before and after the VR application (p=0.018). None of the patients reported motion sickness during VR sessions due to the immersive nature of VR. There was no significant difference between pre and post VR PANSS total and subscale scores. In this preliminary study, we discovered that realenvironment- based VR-PTP is effective for improving the social skills of patients with schizophrenia. Cognitive enhancement programs and psychosocial functionality therapies may be carried out using virtual reality in the near future. VR can assist patients in coping with their symptoms and day-to-day challenges.

An exploratory evaluation of predictors of duration of untreated psychosis in first-episode psychosis in lower income patients

A longer duration of untreated psychosis (DUP) may adversely affect the course and impact of the illness. Little is known about predictors of duration of untreated psychosis in lower socioeconomic strata (SES) in urban India. We examined variables associated with DUP in 60 urban lower SES patients diagnosed with first-episode, untreated psychosis. Instruments used included the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF), the UCLA Social Attainment Scale (SAS), and the Stigma Subscale from the Family Interview Schedule. The mean age of the sample was 30.5 years. The sample was 50% male. Most patients (90%) were living in a nuclear family. The median DUP was 120 days. DUP was <6 months in 31.7% of the sample and >2 years in 23.3%. A third of the sample had been taken to faith healers before being brought into medical care. DUP was not significantly associated with age, sex, religion, education, family history of mental illness, marital status, employment status, income, substance use, PANSS subscale and total scale scores, and GAF scores. Presence of an antecedent stressor, acute onset of psychosis, presence of medical co-morbidities, lower stigma scores, and higher SAS scores were significantly associated with shorter DUP.

The Role of Butyric Acid in Treatment Response in Drug-Naïve First Episode Schizophrenia.

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's < 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's < 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.

Animal-Assisted Therapy in Middle-Aged and Older Patients With Schizophrenia: A Randomized Controlled Trial.

Objective: Animal-assisted therapy (AAT) has the potential to improve the symptomology, negative emotions, and level of well-being in older adults, as well as patients with mental illness. However, there remains limited evidence supporting the treatment efficacy of AAT in middle-aged and older adults with schizophrenia. Therefore, this study implemented a randomized controlled trial to assess the efficacy of a 12-week AAT psychological intervention with dogs for middle-aged and older patients with chronic schizophrenia in a clinical setting.Method: Patients, age ≥ 40 years, with chronic schizophrenia were allocated randomly to either the AAT group or control group. Patients in the AAT group received an additional hour -long AAT session every week for 12 weeks. Patients in the control group received the usual treatment plus an hour long non-animal related intervention. All patients were assessed based on primary outcome measures before and after the 12-week intervention, including the Positive and Negative Syndrome Scale (PANSS), Depression Anxiety Stress Scales Assessment (DASS), and Chinese Happiness Inventory (CHI).Results: Patients who received AAT had greater improvements in the PANSS and DASS-stress subscale scores than the control group (p < 0.05). The effect was small (success ratio different, SRD = 0.25) for the PANSS and the DASS-stress subscale (SRD = 0.15). There were no significant differences in the change scores of the CHI between the AAT and control groups (p = 0.461).Conclusions: AAT seemed to be effective in reducing psychiatric symptoms and stress levels of middle-aged and older patients with schizophrenia. AAT could be considered as a useful adjunctive therapy to the usual treatment programs.

Long acting aripiprazole influences cognitive functions in recent onset schizophrenia.

Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with catechol-O-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia. This study examined the short-term influence of aripiprazole long-acting injectable (LAI) as well as of COMT, MTHFR, and SERT gene polymorphisms and their interactions on clinical features and cognitive functions in inpatients with recent onset schizophrenia. This study included 98 inpatients suffering from recent onset schizophrenia diagnosed according to DSM-5 criteria. Three months after initiating aripiprazole LAI, the severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), while cognitive functions were measured by 5-KOG test for cognition. Genotypes of SERT, MTHFR, and COMT gene were determined by different polymerase chain reaction (PCR) methods. Three-month aripiprazole LAI treatment was associated with a statistically significant change of PANSS total (p<0.001) and subscale scores as well as cognitive parameters of delayed recall (p<0.03), attention (p<0.01), and executive functions in the form of less perseverations (p<0.03), without influencing other examined cognitive functions. However, it significantly influenced composite cognitive score (p<0.02). In regard to the investigated genetic polymorphisms, we established a positive association between the COMT polymorphism (M/M allele carriers) and attention (p<0.01). Additionally, we also established a positive association between the COMT - MTHFR interaction and attention (p<0.02), as well as perseveration item belonging to executive functions (p<0.01). Two other investigated polymorphisms (MTHFR and SERT) were not significantly associated with cognitive indices. Investigated genetic polymorphisms and their interactions were not associated with PANSS scores. Our findings suggest that aripiprazole LAI improves individual cognitive functions in recent onset schizophrenia. Investigated COMT polymorphism (Met/Met genotype), as well as the COMT-MTHFR interaction, were positively associated with attention and executive functioning (perseveration), potentially implying COMT's biomarker potential in terms of cognition in schizophrenia.

Effect of Sodium Benzoate vs Placebo Among Individuals With Early Psychosis

There is evidence that sodium benzoate (BZ) may be an effective adjunctive treatment for schizophrenia. The clinical efficacy of BZ has been investigated in chronic schizophrenia; however, the efficacy of this agent has not been studied in individuals with early psychosis. To examine the clinical efficacy of the adjunctive use of BZ for symptoms in people with early psychosis. Using a placebo-controlled double-masked parallel-group design, this randomized clinical trial was conducted from August 2015 to July 2018. Participants aged between 15 and 45 years experiencing early psychosis were enrolled from 5 major clinical sites in Queensland, Australia. Data analysis was conducted from October 2018 to February 2020. Participants were randomized 1:1 (50 participants in each group) to receive 500 mg of sodium benzoate twice daily or placebo for 12 weeks. The primary efficacy outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks. The key secondary efficacy measures were (1) the Clinical Global Impression score, (2) the Hamilton Depression Rating Scale for depression, (3) functioning as assessed by the clinician-rated Global Assessment of Function, and (4) the Assessment of Quality of Life Scale. The PANSS subscale scores and impact on selected amino acid concentrations were also assessed. The study comprised 100 participants with a mean (SD) age of 21.4 (4.1) years, of whom 73 (73%) were male individuals. The mean (SD) baseline PANSS score was 75.3 (15.4). We found no improvement in total PANSS score in the BZ group compared with the placebo group. The end result of least-squares mean difference (SE) for total PANSS was -1.2 (2.4) (P = .63). There were no differences in any subscales of the PANSS, any secondary measures, nor any amino acid concentrations. The dose of BZ was well tolerated without any clinically significant treatment-emergent adverse event differences between BZ and placebo groups. In this randomized clinical trial, there was no evidence that adjunctive use of 500 mg of BZ twice daily is an effective treatment for individuals with early psychosis. anzctr.org.au Identifier: ACTRN12615000187549.

A randomized-controlled trial of blonanserin and olanzapine as adjunct to antipsychotics in the treatment of patients with schizophrenia and dopamine supersensitivity psychosis: The ROADS study.

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.

138 Efficacy and Safety of SEP-363856, a Novel Psychotropic Agent with a Non-D2 Mechanism of Action, in the Treatment of Schizophrenia

SEP-363856 is a novel psychotropic agent that has shown broad efficacy in animal models of schizophrenia and depression. Its antipsychotic effects appear to be mediated by agonist activity at both trace amine-associated receptor 1 (TAAR1) and 5-HT1A receptors. Notably, SEP-363856 does not bind to any dopaminergic, serotonergic (except 5-HT1A), glutamatergic, or other neuroreceptors thought to mediate the effects of currently available antipsychotics. The aim of this study was to evaluate the efficacy and safety of SEP-363856 in acutely symptomatic patients with schizophrenia. Patients aged 18-40 years meeting DSM-5 criteria for schizophrenia (PANSS total score ≥80) were randomized, double-blind, to 4-weeks of flexible-dose SEP-363856 (50 or 75 mg/d) or placebo. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total score (primary), PANSS subscale scores, and the Clinical Global Impressions-Severity (CGI-S) score. Change from baseline in primary and secondary measures were analyzed using a mixed model for repeated measures (MMRM) analysis. Study treatment groups were similar at baseline: SEP-363856 (N=120; male, 64.2%; mean age, 30.0 years; PANSS total score, 101.4) and placebo (N=125; male, 63.2%; mean age, 30.6 years; PANSS total score, 99.7). Least-squares (LS) mean reduction from baseline to week 4 was significantly greater for SEP-363856 vs. placebo on the PANSS total score (-17.2 vs. -9.7; P=0.001; effect size, 0.45), PANSS positive subscale score (-5.5 vs. -3.9; P=0.019; effect size, 0.32), PANSS negative subscale score (-3.1 vs. -1.6; P=0.008; effect size, 0.37), PANSS general psychopathology subscale score (-9.0 vs. -4.7; P<0.001; effect size, 0.51), and the CGI-Severity score (-1.0 vs. -0.5; P<0.001; effect size, 0.52). Discontinuation rates for SEP-363856 vs. placebo were similar overall (21.7% vs. 20.8%) and due to an adverse event (8.3% vs. 6.4%). Change in weight, lipids, glucose and prolactin was similar in SEP-363856 and placebo groups. Adverse events occurring with an incidence ≥2% on SEP-363856 or placebo (with SEP-363856 incidence higher than placebo) were: somnolence (6.7% vs. 4.8%), agitation (5.0% vs. 4.8%), nausea (5.0% vs. 3.2%), diarrhea (2.5% vs. 0.8%), and dyspepsia (2.5% vs. 0%). The proportion of patients who reported any extrapyramidal symptom was 3.3% on SEP-363856 and 3.2% on placebo. In this placebo-controlled study, treatment with SEP-363856, a novel psychotropic agent, was associated with statistically significant and clinically meaningful improvement in schizophrenia symptoms as demonstrated by endpoint change in PANSS total and subscale scores, and CGI-Severity scores. Safety and tolerability findings for SEP-363856 were in general similar to placebo. In particular, SEP-363856 was not associated with extrapyramidal symptoms, akathisia, or hyperprolactinemia, consistent with its non-D2 mechanism of action. NCT02969382. Supported by funding from Sunovion Pharmaceuticals Inc.

Efficacy and Safety of Lumateperone for Treatment of Schizophrenia

Individuals living with schizophrenia are affected by cardiometabolic, endocrine, and motor adverse effects of current antipsychotic medications. Lumateperone is a serotonin, dopamine, and glutamate modulator with the potential to treat schizophrenia with few adverse effects. To examine the efficacy and safety of lumateperone for the short-term treatment of schizophrenia. This randomized, double-blind, placebo-controlled, phase 3 clinical trial was conducted from November 13, 2014, to July 20, 2015, with data analyses performed from August 13 to September 15, 2015. Patients with schizophrenia who were aged 18 to 60 years and were experiencing an acute exacerbation of psychosis were enrolled from 12 clinical sites in the United States. Patients were randomized 1:1:1 (150 patients in each arm) to receive lumateperone tosylate, 60 mg; lumateperone tosylate, 40 mg (equivalent to 42 or 28 mg, respectively, of the active moiety lumateperone); or placebo once daily for 4 weeks. The prespecified primary efficacy end point was mean change from baseline to day 28 in the Positive and Negative Syndrome Scale (PANSS) total score vs placebo. The key secondary efficacy measure was the Clinical Global Impression-Severity of Illness (CGI-S) score. The PANSS subscale scores, social function, safety, and tolerability were also assessed. The study comprised 450 patients (mean [SD] age, 42.4 [10.2] years; 346 [77.1%] male; mean [SD] baseline PANSS score, 89.8 [10.3]; mean [SD] baseline CGI-S score, 4.8 [0.6]). In the prespecified modified intent-to-treat efficacy analysis (n = 435), 42 mg of lumateperone met the primary and key secondary efficacy objectives, demonstrating a statistically significant improvement vs placebo from baseline to day 28 on the PANSS total score (least-squares mean difference [LSMD], -4.2; 95% CI, -7.8 to -0.6; P = .02; effect size [ES], -0.3) and the CGI-S (LSMD, -0.3; 95% CI, -0.5 to -0.1; P = .003; ES, -0.4). For 28 mg of lumateperone, the LSMD from baseline to day 28 was -2.6 (95% CI, -6.2 to 1.1; P = .16; ES, -0.2) on the PANSS total score and -0.2 (95% CI, -0.5 to 0.0; P = .02; ES, -0.3) on the CGI-S. Both lumateperone doses were well tolerated without clinically significant treatment-emergent motor adverse effects or changes in cardiometabolic or endocrine factors vs placebo. Lumateperone demonstrated efficacy for improving the symptoms of schizophrenia and had a favorable safety profile. ClinicalTrials.gov identifier: NCT02282761.

Adjunctive Memantine Treatment of Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Study.

This double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of memantine augmentation to standard regimen of antipsychotic treatment on psychotic symptoms and cognitive function in individuals with chronic schizophrenia for 8 weeks. Forty stabilized individuals with chronic schizophrenia were randomized in a 1:1 ratio to memantine (20 mg/d) and control (placebo) groups, along with their antipsychotic regimen for 8 weeks. The efficacy of treatment was assessed by the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition Scale, and the safety was measured by the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale at baseline and at weeks 4 and 8. No significant differences were observed in demographic or clinical variables between both groups at baseline. During the study, all subscales and total scores of PANSS decreased significantly within both groups, except the subscale score in memantine, which was found to be positive. Reduction in general subscale and total scores of PANSS was significantly higher in the control group compared with the memantine group. All subscale scores of the Brief Assessment of Cognition Scale increased significantly only in the memantine group. The increase in the Verbal Memory, Working Memory, Verbal Fluency Letter, and Verbal Fluency Total subscale scores was significantly higher in the memantine group than in the control group. There was no significant difference in the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale scores between the 2 groups during the study. This study showed that adjunctive memantine to antipsychotic regimen improved the verbal memory, learning, verbal letter fluency, and working memory without improvement on psychotic symptoms in individuals with chronic schizophrenia.

Examination of formal thought disorder and its clinical correlates with the Turkish Version of the Thought and Language Disorder Scale (TALD-TR) in schizophrenia

BackgroundFormal thought disorder (FTD) is considered to be a fundamental feature of schizophrenia. This study aims to analyze psychometric properties of the Turkish version of “Thought and Language Disorder Scale (TALD)” and investigate the relationship between FTD and various clinical characteristics in patients with schizophrenia. MethodsTALD was adapted into Turkish and applied to a total of 149 participants of which 114 had DSM-5 psychiatric diagnoses (schizophrenia N = 70, mania N = 20, depression N = 24) and 35 were healthy controls. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression were administered to detect illness severity. ResultsThe principal component analyses revealed that the Turkish version of TALD (TALD-TR) consisted of four factors including the Objective Positive (OP), Subjective Negative (SN), Objective Negative (ON) and Subjective Positive (SP) symptom dimensions which were in line with the original TALD factorial structure. It was concluded that TALD-TR shows strong construct validity and high interrater reliability. The correlation analyses with TALD-TR and PANSS showed that there are positive correlations between the TALD-TR total score and the PANSS total and subscale scores. Each diagnostic group showed the distinct pattern of FTD. The mania group exhibited the highest mean total score in the OP, whereas the schizophrenia group exhibited the highest mean total score in the ON factor. In the schizophrenia group, the severity of FTD correlated positively with duration of illness and negatively with age at onset of illness. ConclusionAdaptation of TALD into different languages seems to be possible, bringing in an international tool for research on FTD.

Predictors of psychotic symptoms among young people with special educational needs.

Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.AimsTo examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability. Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS). The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54-1.4, all P &lt; 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3-9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6-50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97. Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.Declaration of interestNone.

Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia

BackgroundKetamine has been used to probe the biology of psychosis and cognitive dysfunction in humans. High levels of ketamine abuse are associated with persisting psychosis (KPP) in a minority of users. However, relatively little is known about cognitive function among KPP patients and whether the cognitive impairments associated with KPP resemble those of schizophrenia (SZ). MethodsWe recruited 149 treatment-seeking patients, including nonpsychotic ketamine users (KNP, n=51), KPP (n=23), and SZ (n=75) patients. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychopathology and the Cogstate Brief Battery to assess cognitive function including psychomotor processing speed, attention, working memory, verbal and visual learning and memory, spatial problem solving, and social-emotional cognition. ResultsKetamine-dependent patients had an extensive history of ketamine use (average duration=7.1±4.2years, average consumption=3.8±2.7g per day). Although KPP patients used relatively less average ketamine daily dose than KNP patients, KPP patients exhibited significantly greater total PANSS score and subscale scores, while these scores in KPP and SZ patients did not differ significantly. After adjusting for demographic characteristics and antipsychotic dose, KPP and SZ patients showed impairments in spatial problem solving and verbal memory compared to KNP patients, but KPP and SZ patients did not significantly differ from each other. ConclusionThese data suggest that the symptom profile and cognitive impairments associated with persisting psychosis due to chronic heavy ketamine abuse resemble those of schizophrenia, while KNP patients showed significantly less severe symptom profile and cognitive impairment than KPP and SZ.

Adolescents at ultra-high risk of psychosis in Italian neuropsychiatry services: prevalence, psychopathology and transition rate.

Studies in adolescents on ultra-high risk (UHR) and basic symptoms (BS) criteria for psychosis prediction are scarce. In Italy, early interventions in psychosis are less widespread than in other European countries. In the present study, we (1) assessed the clinical relevance of a UHR diagnosis [according to the comprehensive assessment of at-risk mental states (CAARMS) criteria] to promote the implementation of specific services for UHR adolescents into the Italian health care system; (2) described severity of positive, negative, general, and basic symptoms in UHR adolescents compared to adolescents with first-episode psychosis (FEP) and non-UHR adolescents (i.e., individuals who did not meet CAARMS criteria for UHR or FEP); and (3) investigated the predictive validity of UHR criteria in relation to BS criteria. Seventy-nine adolescents (aged 13-18years) were assessed with the CAARMS, the positive and negative syndrome scale (PANSS), and the schizophrenia proneness instrument, child and youth version (SPI-CY). Both UHR (n=25) and FEP (n=11) had significantly higher PANSS subscale scores compared to non-UHR (n=43). UHR had significantly lower PANSS-positive symptom scores than FEP, but similar global functioning and PANSS-negative symptoms and general psychopathology scores. Compared to non-UHR, both FEP and UHR had more severe thought and perception BS disturbances, and significantly more often met BS criteria. After 12months, 2 of 20 (10%) UHR had transitioned to psychosis. They also met both BS criteria. Given the uncertain outcome of UHR adolescents, future research is needed to determine whether the combined assessment of BS with UHR symptoms can improve the accuracy of psychosis prediction in adolescence.