The Preclinical Profile of DSR-141562: A Novel Phosphodiesterase 1 Inhibitor for the Treatment of Positive Symptoms, Negative Symptoms and Cognitive Impairments Associated with Schizophrenia.

Schizophrenia is characterized by a constellation of heterogeneous symptoms including hallucinations and delusions, motivational and social deficits, and cognitive impairments. Although positive symptoms have historically been the target for drug development, in recent years, attention has turned to cognitive and negative symptoms. Cognitive deficits in schizophrenia are associated with significant impairments in functional, social, and employment outcomes, and although they are widely researched and relatively well understood, there are no currently approved compounds to treat them. This chapter provides a selective review of the current status of approaches developed to improve cognition in schizophrenia. It covers pharmacological approaches as well as cognitive training and cognitive remediation techniques. It also explores the various study design issues and challenges that contribute to the difficulties in discovering reliable ways to improve the cognitive deficits present in schizophrenia.

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Performance of patients with different schizophrenia subtypes on the Synthetic House–Tree–Person Test

Social Behavior and Personality An International Journal ◽

10.2224/sbp.8408 ◽

2019 ◽

Vol 47 (11) ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

AiBao Zhou ◽

Pei Xie ◽

ChaoChao Pan ◽

Zhe Tian ◽

Junwei Xie

Keyword(s):

Negative Symptoms ◽

Positive Symptoms ◽

Study Results ◽

Symptom Type ◽

Positive And Negative Symptoms

We explored differences in performance on the Synthetic House–Tree–Person Test between people with mainly positive symptoms and those with mainly negative symptoms of schizophrenia and, further, aimed to provide a basis for the diagnosis of schizophrenia symptom type. Participants were 58 people receiving treatment for schizophrenia, and we asked them to complete the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Synthetic House–Tree–Person Test. There were significant differences in results on the Synthetic House–Tree–Person Test between the group with positive symptoms, the group with a mix of positive and negative symptoms, and the group with negative symptoms. There were 12 features of participants' drawings, such as big hands, which were correlated with hallucinations and delusions in positive symptoms, and 9 features, such as trees in a landscape, which were correlated with avolition and anhedonia in negative symptoms. Our study results suggest differences in performance on the Synthetic House–Tree–Person Test between these different symptom subtypes of schizophrenia; hence, the features that appear in drawings made during the test may contribute to the diagnosis of symptoms of people with schizophrenia.

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Evaluation of positive and negative symptoms in schizophrenia

Psychiatry and Psychobiology ◽

10.1017/s0767399x00003199 ◽

1986 ◽

Vol 1 (2) ◽

pp. 108-122 ◽

Cited By ~ 29

Author(s):

Nancy C. Andreasen ◽

William M. Grove

Keyword(s):

Negative Symptoms ◽

The United States ◽

Psychotic Symptoms ◽

Positive Symptoms ◽

University Of Iowa ◽

Normal Functions ◽

Subsequent Investigation ◽

The University ◽

The Relationship ◽

Positive And Negative Symptoms

SummaryMost investigators concur that schizophrenia is probably a heterogeneous group of disorders that share the common features of psychotic symptoms, partial response to neuroleptics, and a relatively poor outcome. The subdivision of schizophrenia into two subtypes, positive versus negative, has achieved wide acceptance throughout the world during recent years. This distinction has heuristic and theoretical appeal because it unites phenomenology, pathophysiology, and etiology into a single comprehensive hypothesis.In spite of its wide appeal, the distinction has a number of problems. These include the failure to distinguish between symptom syndromes and diseases; failure to deal with the mixed patient; failure to take longitudinal course into account; and failure to address conceptually and methodologically the distinction between positive and negative symptoms.This paper focuses primarily on the conceptual basis for two instruments designed to measure positive and negative symptoms, the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), originally described in 1982. Since their description, these scales have been used in a variety of other centers. These scales are based on the hypothesis that negative symptoms represent a deficit or diminution in normal psychological functions wliile positive symptoms represent an excess or distortion of normal functions. Reliability data are now available from Italy, Spain, and Japan which suggest that these scales can be used reliably in cultural settings outside the United States. The results of these studies are summarized in this paper. In addition, a replication study involving a new sample of 117 schizophrenics collected at the University of Iowa is described. In this second study of the SANS and SAPS, internal consistency is found to be quite high in the SANS. Thus negative symptoms appear to be more internally correlated with one another than are positive symptoms. The implications of this result are discussed. A principal components analysis is used to explore the relationship between positive and negative symptoms. While the study reported in 1982 suggested that positive and negative symptoms are negatively correlated, in the present study they appear to be uncorrelated. Overall, the results suggest that the SANS and SAPS are useful comprehensive instruments for the evaluation of positive and negative symptoms. The relationship between these symptoms and external validators such as cognitive functioning or CT scan abnormalities will be reported in a subsequent investigation.

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Paliperidone to Treat Psychotic Disorders

Neurology International ◽

10.3390/neurolint13030035 ◽

2021 ◽

Vol 13 (3) ◽

pp. 343-358

Author(s):

Hormazd D. Minwalla ◽

Peter Wrzesinski ◽

Allison Desforges ◽

Joshua Caskey ◽

Brittany Wagner ◽

...

Keyword(s):

Cognitive Impairment ◽

Schizoaffective Disorder ◽

Negative Symptoms ◽

Psychotic Disorders ◽

Drug Information ◽

The United States ◽

Mental Illnesses ◽

Positive Symptoms ◽

Review Of The Literature ◽

Second Generation Antipsychotics

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysregulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder.

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Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis

EClinicalMedicine ◽

10.1016/j.eclinm.2021.100909 ◽

2021 ◽

Vol 36 ◽

pp. 100909

Author(s):

Gonzalo Salazar de Pablo ◽

Filippo Besana ◽

Vincenzo Arienti ◽

Ana Catalan ◽

Julio Vaquerizo-Serrano ◽

...

Keyword(s):

High Risk ◽

Negative Symptoms ◽

Meta Analysis ◽

Positive Symptoms ◽

Clinical High Risk ◽

Longitudinal Outcome

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Anti-DNA antibodies in the blood of patients with schizophrenia possess DNA-hydrolyzing activity

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.628 ◽

2016 ◽

Vol 33 (S1) ◽

pp. s247-s248

Author(s):

E. Ermakov ◽

L. Smirnova ◽

L. Sinyanskii ◽

D. Dobrygina ◽

A. Semke ◽

...

Keyword(s):

Statistical Analysis ◽

Infectious Diseases ◽

Negative Symptoms ◽

Clinical Symptoms ◽

Dnase Activity ◽

Positive Symptoms ◽

Linear Forms ◽

Dna Antibodies ◽

Competing Interest ◽

Positive And Negative Symptoms

IntroductionAutoantibodies (Abs) to different neuronal receptors and DNA were detected in the blood of patients with schizophrenia. Abs hydrolyzing DNA were detected in pool of polyclonal autoantibodies in autoimmune and infectious diseases, such catalytic Abs were named abzymes.ObjectivesTo investigate the level of anti-DNA antibodies and DNA-hydrolyzing activity of IgG from the serum of patients with schizophrenia depending on leading clinical symptoms.Aims– To measure the concentration of anti-DNA Abs in serum of patients with leading positive and negative symptoms;– to determine DNA-hydrolyzing activity of IgG.MethodsIn our study, 51 patients were included. The levels of antiDNA Abs were determined using ELISA. DNA-hydrolyzing activity was detected as the level(%) of supercoiled pBluescript DNA transition in circular and linear forms. Statistical analysis was performed in “Statistica 9.0”.ResultsAnti-DNA Abs of patients with schizophrenia not only bind DNA, but quite efficiently hydrolyze the substrate. IgG of patient with schizophrenia were shown to possess DNA hydrolyzing activity. It should be noted that DNAase activity of IgG in patients with schizophrenia with a negative symptoms was significantly higher, than in patients with positive symptoms (Table 1).ConclusionsThe data show a correlation with the level of DNase activity and leading symptoms of patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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PMH56 Negative Symptoms Have Greater Impact on Functioning Than Positive Symptoms in Schizophrenia: Analysis of Catie Data

Value in Health ◽

10.1016/j.jval.2011.08.355 ◽

2011 ◽

Vol 14 (7) ◽

pp. A296-A297 ◽

Cited By ~ 1

Author(s):

J. Rabinowitz ◽

G. Garibaldi ◽

S. Levine ◽

D. Bugarski-Kirola ◽

C. Berardo ◽

...

Keyword(s):

Negative Symptoms ◽

Positive Symptoms

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Family burden in schizophrenia: the influence of age of onset and negative symptoms

Trends in Psychiatry and Psychotherapy ◽

10.1590/2237-6089-2015-0082 ◽

2016 ◽

Vol 38 (2) ◽

pp. 96-99 ◽

Cited By ~ 8

Author(s):

Lucas M. Mantovani ◽

Rodrigo Ferretjans ◽

Iara M. Marçal ◽

Amanda M. Oliveira ◽

Fernanda C. Guimarães ◽

...

Keyword(s):

Negative Symptoms ◽

Age Of Onset ◽

Linear Regression Analysis ◽

Disease Onset ◽

Family Burden ◽

Positive Symptoms ◽

Subjective Burden ◽

Sociodemographic Variables ◽

Objective Burden ◽

Positive And Negative Symptoms

Abstract Objectives: To investigate the determinants of family burden in a sample of patients with schizophrenia and their caregivers. Methods: Thirty-one stable patients with schizophrenia and their main caregivers were recruited. Sociodemographic variables were assessed in a semi-structured interview, and positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed with the Schizophrenia Cognition Rating Scale (SCoRS). Levels of burden on caregivers were assessed with the Family Burden Interview Schedule (FBIS). Interactions among variables were analyzed using Pearson correlations and linear regression analysis. Results: Objective and subjective FBIS scores were 1.9 (standard deviation [SD] = 0.5) and 2.4 (SD = 0.6) respectively. Objective burden correlated positively with positive and negative symptoms, and cognitive impairment. Subjective burden correlated positively with positive symptoms and negatively with mean age of disease onset. Positive, negative and cognitive symptoms accounted for 47.6% of the variance of objective burden, with negative symptoms accounting independently for 30.3%. Age of onset, parents as caregivers and positive symptoms accounted for 28% of the variance of subjective burden, with age of onset independently explaining 20.3%. Conclusion: Patients' clinical and sociodemographic variables are important determinants of family burden in schizophrenia. Objective burden is predicted by symptoms, particularly negative ones. Subjective burden is predicted by symptoms and sociodemographic variables, particularly age of disease onset.

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Symptômes Positifs Et Négatifs De La Schizophrénie: Une Mise à jour

The Canadian Journal of Psychiatry ◽

10.1177/070674379403900704 ◽

1994 ◽

Vol 39 (7) ◽

pp. 407-414 ◽

Cited By ~ 11

Author(s):

Marc-André Roy ◽

Xavier Devriendt

Keyword(s):

Cognitive Deficits ◽

Negative Symptoms ◽

Three Dimensions ◽

Positive Symptoms ◽

Research Questions

The purpose of this article is to summarize the results of studies examining the validity of the positive and negative sub-types of schizophrenia as proposed by Crow. The authors summarized Crow's model's predictions in the form of 12 research questions and examined whether its predictions were confirmed. The following predictions are generally confirmed by the data collected: (i) it is possible to measure negative symptoms with accuracy; (ii) the negative symptoms predict a deterioration; (Hi) the negative symptoms are generally correlated with overall cognitive deficits; (iv) each dimension appears to have distinct neurobiological substrata. However, several elements of the Crow model are not supported by the data collected. Among the necessary modifications, the most important are as follows: (i) it appears more productive to conceive of the negative symptoms as distinct dimensions, rather than distinct diseases; (ii) at least three dimensions exist for describing the symptoms of schizophrenia; (Hi) the negative symptoms are not necessarily intrinsic to the schizophrenic process, and they may be due to other causes; (iv) the negative symptoms are not necessarily irreversible, and can be improved under ataractics; (v) the positive symptoms, in particular those relating to disorganization, can also be correlated with cognitive deficits.

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Combination Treatments for Schizophrenia

CNS Spectrums ◽

10.1017/s1092852900004363 ◽

2004 ◽

Vol 9 (S9) ◽

pp. 19-23 ◽

Cited By ~ 9

Author(s):

Alexander L. Miller

Keyword(s):

Electroconvulsive Therapy ◽

Cognitive Deficits ◽

Negative Symptoms ◽

Current Evidence ◽

Positive Symptoms ◽

Combination Therapies ◽

Safety And Efficacy ◽

Combination Treatments ◽

Improved Outcomes ◽

Expert Recommendations

ABSTRACTCombination treatments, especially combinations of antipsychotics, are used frequently for schizophrenia, despite a paucity of evidence regarding their safety and efficacy. Because the literature basis is weak and expert recommendations are largely lacking, providers should be vigilant in documenting improved outcomes for patients thought to benefit from combination treatments. Target symptoms that have been studied include psychosis, cognitive deficits, and negative symptoms. The strongest evidence is for augmentation of clozapine with another antipsychotic or with electroconvulsive therapy for persistent positive symptoms. Combination treatments for cognitive deficits and negative symptoms are being actively investigated, but current evidence is insufficient to recommend available agents for these components of schizophrenia. It is important that appropriate monotherapies be given adequate trials before resorting to combination therapies.

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