Persistent Symptoms Of Schizophrenia Research Articles

Pro-social and pro-cognitive effects of LIT-001, a novel oxytocin receptor agonist in a neurodevelopmental model of schizophrenia

Social and cognitive dysfunctions are the most persistent symptoms of schizophrenia. Since oxytocin (OXT) is known to play a role in social functions and modulates cognitive processes, we investigated the effects of a novel, nonpeptide, selective OXT receptor agonist, LIT-001, in a neurodevelopmental model of schizophrenia. Administration of methylazoxymethanol acetate (MAM; 22 mg/kg) on the 17th day of rat pregnancy is known to cause developmental disturbances of the brain, which lead to schizophrenia-like symptomatology in the offspring. Here, we examined the effects of acutely administered LIT-001 (1, 3, and 10 mg/kg) in MAM-exposed males and females on social behaviour, communication and cognition. We report that MAM-treated adult male and female rats displayed reduced social behaviour, ultrasonic communication and novel object recognition test performance. LIT-001 partially reversed these deficits, increasing the total social interaction time and the number of ‘positive’, highly-modulated 50 kHz ultrasonic calls in male rats. The compound ameliorated MAM-induced deficits in object discrimination in both sexes. Present results confirm the pro-social activity of LIT-001 and demonstrate its pro-cognitive effects following acute administration.

Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM\u2019Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial

BackgroundOne out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response.MethodsIn a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment.DiscussionThe results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia.Trial registrationClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016

Project e-MOTIPH: Patient Journey of patients with persistent symptoms of schizophrenia

The International Journal of Integrated Care (IJIC) is an online, open-access, peer-reviewed scientific journal that publishes original articles in the field of integrated care on a continuous basis.IJIC has an Impact Factor of 5.120 (2020 JCR, received in June 2021)

Understanding the course of persistent symptoms in schizophrenia: Longitudinal findings from the pattern study

The Pattern study was conducted to provide longitudinal observational data for individual patients with persistent symptoms of schizophrenia. Pattern is an international, multicenter, non-interventional, prospective cohort study of schizophrenia outpatients who were not considered to be in recovery. In the longitudinal phase reported herein, patients were assessed over 1 year using different clinical rating scales. Patient management followed routine local clinical practice. Primary outcome was disease state, defined by the Positive and Negative Syndrome Scale (PANSS), Negative Symptom Factor Score (NSFS), Positive Symptom Factor Score (PSFS), and Personal and Social Performance (PSP) Scale. In total, 1344 protocol-compliant patients (70.9% male) were included. Patients showed a high stability in disease state between consecutive study visits. Persistent negative persistent symptoms and symptomatic remission were the most prevalent and stable disease states. Patients in relapse generally transitioned to negative persistent symptoms or to symptomatic remission. PANSS, PSP, and quality of life ratings remained relatively stable. Relapses occurred in 10% of patients; probability of relapse was associated with younger age, extra-pyramidal symptoms, and more antipsychotic medications. Despite treatment, schizophrenia symptoms tend to remain stable over time, without overall improvement. One of the greatest challenges in schizophrenia is attainment of full symptom remission.

S118. CAN THE POSITIVE AND NEGATIVE SYNDROME SCALE (PANSS) DIFFERENTIATE REFRACTORY FROM NON-REFRACTORY SCHIZOPHRENIA? A FACTOR ANALYTIC INVESTIGATION BASED ON DATA FROM THE PATTERN COHORT STUDY

BackgroundTreatment Resistant Schizophrenia (TRS) and Non-Treatment Resistant Schizophrenia (NTRS) may represent different biological subtypes of schizophrenia but there are few studies which investigated the distinction between these groups in terms of psychopathology. In the present study, we used both Exploratory (EFA) and Confirmatory (CFA) Factor Analyses to investigate symptom dimensions in TRS in comparison with NTRS using the Positive and Negative Syndrome Scale (PANSS).MethodsData from 1429 patients who participated in the PATTERN study a Non- Intervention Prospective Study of Patients with Persistent Symptoms of Schizophrenia) was used. TRS was defined by proxy, based on the use of clozapine (TRS) whereas NTRS used non-clozapine antipsychotics (NTRS). EFA methods included the extraction of principal components and the Varimax rotation. The number of factors was chosen based on the Kaiser criterion. Factors items were considered valid when loadings were greater or equal to 0.5. The fit to the data was evaluated by CFA in comparison with well established PANSS models using fit indexes such as: NNFI (Non-Normed Fit Index), NFI (Normed fit Index), CFI (Comparative Fit Index), RMEA (Root-Mean-Square Error of Approximation). SPSS 23.0 and R version 3.2.2 were used for statistical analyses.ResultsDemographic data showed that, when compared with NTRS, patients with TRS showed an earlier age of onset, a longer duration of illness, higher PANSS positive scores, a higher duration of persistent positive and negative symptoms. There were no differences between groups in terms of the duration of untreated psychosis. The EFA yielded almost the same five-factor structure in both groups namely Negative, Positive, Affective, Disorganized/Cognitive and Excitation factors. CFA showed that both models do not fit completely to the data when compared with well known PANSS factor analytical models.DiscussionData from a large cross-national sample of 1429 patients of the Pattern study showed that TRS and NTRS patients have an almost identical factor structure when evaluated by the PANSS. These results are similar to a previous study with a smaller sample which has evaluated the dimensions of the PANSS in patients with refractory schizophrenia.

Effects of transcranial direct current stimulation on working memory and negative symptoms in schizophrenia: a phase II randomized sham-controlled trial

BackgroundThe lack of efficacy of pharmacological treatments for cognitive and negative symptoms in schizophrenia highlights the need for new interventions. We investigated the effects of tDCS on working memory and negative symptoms in patients with schizophrenia. MethodDouble-blinded, randomized, sham-controlled clinical trial, investigating the effects of 10 sessions of tDCS in schizophrenia subjects. Stimulation used 2 mA, for 20 min, with electrodes of 25 cm2 wrapped in cotton material soaked in saline solution. Anode was positioned over the left DLPFC and the cathode in the contralateral area. Twenty-four participants were assessed at baseline, after intervention and in a three-months follow-up. The primary outcome was the working memory score from MATRICS and the secondary outcome the negative score from PANSS. Data were analyzed using generalized estimating equations. ResultsWe did not find group ∗ time interaction for the working memory (p = 0.720) score or any other cognitive variable (p > 0.05). We found a significant group ∗ time interaction for PANSS negative (p < 0.001, d = 0.23, CI.95 = −0.59–1.02), general (p = 0.011) and total scores (p < 0.001). Exploratory analysis of PANSS 5 factors suggests tDCS effect on PANSS negative (p = 0.012), cognitive (p = 0.016) and depression factors (p = 0.029). ConclusionThe results from this trial highlight the therapeutic effects of tDCS for treatment of persistent symptoms in schizophrenia, with reduction of negative symptoms. We were not able to confirm the superiority of active tDCS over sham to improve working memory performance. Larger sample size studies are needed to confirm these findings.

Burden of illness of people with persistent symptoms of schizophrenia: A multinational cross-sectional study.

Few studies have examined the impact of persistent symptoms of schizophrenia, especially with respect to patient-reported outcomes (PROs), carer burden and health economic impact. Analyse data relating to burden and severity of illness, functional impairment and quality of life for patients with persistent symptoms of schizophrenia. A cohort of stable outpatients with persistent symptoms of schizophrenia across seven countries were assessed in a multicentre, non-interventional, cross-sectional survey and retrospective medical record review using PRO questionnaires, clinical rating scales and carer questionnaires. Overall, 1,421 patients and 687 carers were enrolled. Approximately two-thirds of patients had moderate/mild schizophrenia with more severe negative symptoms predominating. Patients showed impaired personal/social functioning and unsuitability for work correlated with various patient factors, most notably symptom-related assessments. Quality-of-life assessments showed 25% to ⩾30% of patients had problems with mobility, washing or dressing. Carer burden was also considerable, with carers having to devote an average of 20.5 hours per week and notable negative impact on quality-of-life measures. Healthcare resource utilisation for in-hospital, outpatient and other care provider visits was significant. These results demonstrate the significant burden of schizophrenia for patients, carers and society and highlight the need for improved treatment approaches.

Study suggests benefits of raloxifene in women with schizophrenia symptoms

A 120‐mg daily dose of the selective estrogen receptor modulator raloxifene significantly reduced illness severity when used with an antipsychotic in adult women with persistent symptoms of schizophrenia, a new study has found. The study's lead author pointed out that the results demonstrate the potential importance of hormonal factors in women who have not responded adequately to conventional treatment for psychotic illness. Study results were published online July 20 in JAMA Psychiatry.

Understanding the impact of persistent symptoms in schizophrenia: Cross-sectional findings from the Pattern study

BackgroundThe high societal burden of schizophrenia is largely caused by the persistence of symptoms and accompanying functional impairment. To date, no studies have specifically assessed the course of persistent symptoms or the individual contributions of positive and negative symptoms to patient functioning. The cross-sectional analysis of the Pattern study provides an international perspective of the burden of schizophrenia. MethodsClinically stable outpatients from 140 study centers across eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom) were assessed using clinical rating scales: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Personal and Social Performance (PSP) Scale. Additional measures included patient-reported outcomes, patient socio-demographic variables, living situation, employment and resource use. ResultsOverall, 1379 patients were assessed and analyzed and had similar sociodemographic characteristics across countries, with 61.6% having persistent positive and/or negative symptoms. Positive and negative symptoms had been persistent for a mean of 9.6 and 8.9years (SD: 8.8 and 9.6), respectively. Approximately 86% of patients had a functional disability classified as greater than mild. Patients with a higher PANSS Negative Symptom Factor Score were more likely to have a poorer level of functioning. ConclusionsThis analysis examines individual contributions of persistent positive and negative symptoms on patient functioning in different countries. A high prevalence of patients with persistent symptoms and functional impairment was a consistent finding across countries. Longitudinal observations are necessary to assess how to improve persistent symptoms of schizophrenia and overall patient functioning.

P.3.b.028 Understanding the impact of persistent symptoms in schizophrenia: cross-sectional findings from the Pattern study

P.3.b.028 Understanding the impact of persistent symptoms in schizophrenia: cross-sectional findings from the Pattern study

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of High-Dose Quetiapine in Patients With Persistent Symptoms of Schizophrenia or Schizoaffective Disorder

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of High-Dose Quetiapine in Patients With Persistent Symptoms of Schizophrenia or Schizoaffective Disorder

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of High-Dose Quetiapine in Patients With Persistent Symptoms of Schizophrenia or Schizoaffective Disorder

Quetiapine is often prescribed at higher than approved doses. We investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d. A trial was carried out from October 2003-September 2005 in 19 referral centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were randomized on the basis of persistent symptoms of moderate severity (< 30% improvement in total Positive and Negative Syndrome Scale score after ≥ 4 weeks of quetiapine). The 8 week, double-blind study compared continuation of quetiapine 800 mg/d (n = 43) versus 1,200 mg/d (n = 88). The primary outcome measure was emergent or worsening parkinsonism (Simpson-Angus Scale). Secondary outcomes were adverse events, metabolic side effects, and symptom severity. Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and > 800-mg/d groups, respectively. Emergent or deteriorating parkinsonism in the high-dose group was 3.1% greater (95% CI, -7.8% to 14.0%; P = .76) than in the 800-mg/d group, a value that was within the a priori limit of 16% defined as noninferiority. Both doses of quetiapine were safe and well tolerated. Weight gain was greater in the high-dose group (1.7 kg over 12 weeks; ≥ 7% body weight, n = 11 [12.5%]) versus the 800-mg/d group (1.1 kg over 12 weeks; ≥ 7% body weight, n = 4 [9.3%]). The mean adjusted difference in weight gain (1.3 kg) was greater in the high-dose group (95% CI, 0.0-2.5; P = .044). Symptom severity declined, with no significant difference between groups. The results did not demonstrate any advantage for use of quetiapine outside the approved dose range. www.clinicaltrials.gov Identifier: NCT00328978.

Cognitive-Behavioral Therapy for Medication-Resistant Schizophrenia: A Review

Research meta-analyses have found that cognitive-behavioral therapy (CBT) is beneficial for persistent symptoms of schizophrenia. This review describes and updates the evidence base for this statement. A review of the existing literature (Medline, PsychInfo, and Embase) was carried out according to the guidelines for systematic reviews. Based on the findings of this review, the updated conclusion is that CBT has emerged as an effective adjuvant to antipsychotic medication in the treatment of persistent symptoms of schizophrenia. Studies of the use of CBT in the prodromal phase of psychosis and in combination with family therapy are currently underway. (Reprinted with permission from Journal of Psychiatric Practice 2008; 14:22–33)

A randomized controlled trial of cognitive-behavior therapy for persistent symptoms in schizophrenia: A five-year follow-up

Meta-analyses of randomized controlled trials support the efficacy of cognitive behavioral therapy (CBT) in the treatment of symptoms of schizophrenia refractory to antipsychotic medication. This article addresses the issue of medium term durability. A five-year follow-up was undertaken of a sample of 90 subjects who participated in a randomized controlled trial of CBT and befriending (BF). Patients received routine care throughout the trial and the follow-up period. Intention to treat multivariate analysis was performed by an independent statistician following multiple imputation of missing data. Fifty-nine out of ninety patients were followed up at 5 years (CBT = 31, BF = 28). In comparison to BF and usual treatment, CBT showed evidence of a significantly greater and more durable effect on overall symptom severity (NNT = 10.36, CI − 10.21, 10.51) and level of negative symptoms (NNT = 5.22, CI − 5.06 − 5.37). No difference was found between CBT and BF on either overall symptoms of schizophrenia or depression. The initial cost of an adjunctive course of CBT for individuals with medication refractory schizophrenia may be justified in light of symptomatic benefits that persist over the medium term.

Predicting Recovery From Schizophrenia: A Retrospective Comparison of Characteristics at Onset of People With Single and Multiple Episodes

A retrospective study was designed to determine whether socio-demographic and clinical factors at onset, previously shown to relate to outcome, differentiated those with a single episode with no persistent symptoms of schizophrenia from other outcome groups. In a geographically determined sample of 436 people with schizophrenia spectrum disorder and a minimum followup period of at least 6 years, 68 people (15.6%) had a single episode with complete remission. The single episode group differed significantly from the rest of the sample at onset on nine variables. On a logistic regression, employment status independently predicted single episodes. Although those with single episodes differed from the rest of the sample on a number of variables, they did not differ significantly at onset from the other better outcome group (repeated episodes without persistent symptoms) on any variables with the exception of insight. Two possibilities are considered: (1) the two better outcome groups differed very little at onset but subsequent treatment or experiences accounted for the differences in outcome; or (2) important differences, not routinely assessed at onset, influenced outcome. The implications of these findings for research into the prevention of relapse in psychosis are considered.

Antihostility Effects of Adjunctive Divalproex

Back to table of contents Previous article Next article LettersFull AccessAntihostility Effects of Adjunctive DivalproexLeslie Citrome, M.D., M.P.H.Leslie CitromeSearch for more papers by this author, M.D., M.P.H.Published Online:1 Sep 2004https://doi.org/10.1176/appi.ps.55.9.1068-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail In Reply: Dr. Eilers makes the excellent point that our report of the specific antihostility effect of adjunctive valproate (given as divalproex) cannot be easily generalizable to a state hospital population. Adjunctive valproate in such settings is not usually used at the "front end" of treatment but at the "back end" when other treatments have failed. Moreover, the trial specifically excluded patients who were treatment refractory.No reports have been published of controlled trials of sufficient magnitude to adequately answer the question of whether or not adjunctive valproate is useful for patients with persistent symptoms of schizophrenia or persistent aggressive behavior (1). The high rate of use of adjunctive valproate among patients with schizophrenia in hospitals operated by the New York State Office of Mental Health (2) is indeed astonishing and is probably comparable to rates in similar settings across the country. This widespread use of adjunctive valproate does not necessarily mean that the strategy is effective, and further research is needed. Trials of longer duration and with more chronically ill patients will be needed to test this treatment approach. As noted, our study did not provide support for a specific antihostility effect for co-prescribed valproate beyond the first week of treatment.The parent study was valuable because it provided evidence that the major effect of adjunctive valproate appears to be on the positive symptoms of schizophrenia (3). No differences were found in the use of adjunctive lorazepam between the monotherapy and combination groups, which reduces the possibility that the ameliorative effect of valproate was by a general sedative effect. In our post hoc analysis we specifically included the presence or absence of sedation in the statistical model, as well as adjunctive use of potentially sedating rescue medication. Although the possibility of a type I error is always present, the general methodology employed is similar to that used in other published studies by our group, including a preplanned analysis that had obvious face validity in demonstrating the advantage of clozapine as an antihostility agent (4).These issues are important for clinicians working in public-sector psychiatry, where we have the daunting responsibility of managing patients with serious and persistent mental illness, whose illness is often refractory to standard treatment approaches and who may exhibit persistent aggressive behavior. Readers of Psychiatric Services are the ideal audience for this type of open debate. More research in this area is needed.

Hippocampal Dysfunction Shown in Schizophrenia

Cognitive deficits such as inattention and memory impairment are persistent symptoms in schizophrenia that respond poorly to treatment, contribute to poor prognosis, and have been associated with impaired activation of the dorsolateral prefrontal cortex (DLPFC). These researchers used a novel technique involving positron emission tomography to study prefrontal cortical and hippocampal function during episodic memory retrieval in 13 schizophrenics and 8 controls. Both schizophrenic patients …