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Brain Sciences
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Exploring Negative Symptoms of Schizophrenia: Where Do We Stand?
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Exploring Negative Symptoms of Schizophrenia: Where Do We Stand?

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropsychiatry".

Deadline for manuscript submissions: closed (25 November 2024) | Viewed by 4756

Special Issue Editors

Prof. Dr. Sonia Dollfus

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Guest Editor
Psychiatry Department, University of Caen Normandy, 14000 Caen, France
Interests: schizophrenia; negative symptoms; physical activity; antipsychotics; brain imaging; neurostimulation
Prof. Dr. Ingrid Melle

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Guest Editor
Department of Adult Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Interests: first episode psychosis; negative symptoms; treatment response; treatment resistance; suicidal behaviors; illness trajectories; prediction
Dr. Ann Faerden

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Guest Editor
Department of Acute Psychiatry, Oslo University Hospital, Oslo, Norway
Interests: psychosis; negative symptoms; understanding reduced motivation in psychotic disorders; clinical trials, user involvement; global mental health

Special Issue Information

Dear Colleagues,

Negative symptoms are prevalent among many individuals diagnosed with schizophrenia, and these significantly impact their social functioning and overall quality of life. Despite their significant impact, negative symptoms have often been overshadowed in diagnostic criteria, treatment approaches, and research pertaining to schizophrenia, especially when compared to positive symptoms. Additionally, there remains a lack of clarity in clinical practice regarding the definition and differentiation between primary and secondary negative symptoms. Nevertheless, recognizing secondary negative symptoms is crucial, as this can enable tailored treatment interventions, especially considering the fact that these symptoms can stem from various factors such as positive symptoms, substance abuse, medication side effects, or depressive episodes.

The objective of this Special Issue, therefore, is to offer fresh insights into negative symptoms by presenting clinical tools, brain imaging studies, physiological data, and innovative treatment modalities.

Controlled trials involving medications targeting neurotransmitter systems other than dopamine, or exploring adjunctive therapies alongside antipsychotics, such as neurostimulation, cognitive remediation, physical activity, or social rehabilitation, are anticipated. Furthermore, research aimed at enhancing our understanding of the pathophysiology underlying negative symptoms is encouraged, and original research, meta-analyses, and reviews may be accepted.

Prof. Dr. Sonia Dollfus
Prof. Dr. Ingrid Melle
Dr. Ann Faerden
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • schizophrenia
  • negative symptoms
  • brain imaging
  • pathophysiology
  • scales
  • cognitive remediation
  • physical activity
  • neurostimulation
  • social rehabilitation
  • neurotransmitter
  • drugs
  • quality of life
  • treatment
  • antipsychotics

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Published Papers (4 papers)

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Research

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15 pages, 282 KiB  
Article
Dutch Validation of the Self-Evaluation of Negative Symptoms Scale (SNS)
by Tim van Brouwershaven, Anika Poppe, Gerdina Hendrika Maria Pijnenborg, André Aleman, Nynke Boonstra, Shiral Gangadin, Sonia Dollfus, Wim Veling, Stynke Castelein, Jan Alexander de Vos, Edith Liemburg, PHAMOUS-researchers and Lisette van der Meer
Brain Sci. 2025, 15(1), 15; https://doi.org/10.3390/brainsci15010015 - 27 Dec 2024
Viewed by 924
Abstract
Background/objectives: Negative symptoms in schizophrenia spectrum disorders are related to impaired social functioning and lower quality of life, making accurate assessment important. To date, most tools for assessing negative symptoms are observational, which can be influenced by the raters’ experience and opinion. Self-rating [...] Read more.
Background/objectives: Negative symptoms in schizophrenia spectrum disorders are related to impaired social functioning and lower quality of life, making accurate assessment important. To date, most tools for assessing negative symptoms are observational, which can be influenced by the raters’ experience and opinion. Self-rating scales, like the Self-Evaluation of Negative Symptoms (SNS), could complement observer ratings by adding information from the patient’s perspective. Here, we aim to evaluate the psychometric properties of the Dutch translation of the SNS and the relationship between the SNS and functional outcomes. Methods: The SNS was added to the Pharmacotherapy Monitoring Outcome Survey (PHAMOUS)-protocol for adults with a DSM-5 classification of a disorder in the psychosis spectrum. Internal consistency was assessed by Cronbach’s alpha. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of the five subscales of the SNS. Correlational analyses were performed between the SNS and the Positive and Negative Syndrome Scale (PANSS), the Health of Nation Outcomes Scales (HoNOS), the Global Assessment of Functioning (GAF), Functional Remission tool (FR) and the Manchester Short Assessment of Quality of Life (ManSA). Results: A total of 247 patients participated in this study. Internal consistency was good (α = 0.87). CFA confirmed the five-factor structure of the SNS. The SNS was significantly correlated (all p < 0.001) with the PANSS positive (r = 0.31), PANSS negative (r = 0.33), HoNOS (r = 0.37), FR (r = 0.27) and the ManSA (r = −0.40). Conclusions: The Dutch SNS shows good psychometric properties and is related to functional outcomes and quality of life. The SNS can be valuable in complementing current observational-based instruments, and future research may investigate whether the SNS can be used as a standalone measurement tool for the assessment of negative symptoms. Full article
(This article belongs to the Special Issue Exploring Negative Symptoms of Schizophrenia: Where Do We Stand?)
16 pages, 2104 KiB  
Article
A New Three-Hit Mouse Model of Neurodevelopmental Disorder with Cognitive Impairments and Persistent Sociability Deficits
by Imane Mouffok, Caroline Lahogue, Thomas Cailly, Thomas Freret, Valentine Bouet and Michel Boulouard
Brain Sci. 2024, 14(12), 1281; https://doi.org/10.3390/brainsci14121281 - 20 Dec 2024
Viewed by 1038
Abstract
Background/Objectives: Cognitive deficits and negative symptoms associated with schizophrenia are poorly managed by current antipsychotics. In order to develop effective treatments, refining animal models of neurodevelopmental disorders is essential. Methods: To address their multifactorial etiology, we developed a new three-hit mouse model based [...] Read more.
Background/Objectives: Cognitive deficits and negative symptoms associated with schizophrenia are poorly managed by current antipsychotics. In order to develop effective treatments, refining animal models of neurodevelopmental disorders is essential. Methods: To address their multifactorial etiology, we developed a new three-hit mouse model based on the hypoglutamatergic hypothesis of the pathology combined with early stress, offering strong construct validity. Thus, a genetic susceptibility (serine racemase deletion) was associated with an early environmental stress (24 h maternal separation at 9 days of age) and a further pharmacological treatment with phencyclidine (PCP, a glutamate receptor antagonist treatment, 10 mg/kg/day, from 8 to 10 weeks of age). The face validity of this model was assessed in female mice 1 and 6 weeks after the end of PCP treatment by a set of behavioral experiments investigating positive- and negative-like symptoms and cognitive deficits. Results: Our results showed that the three-hit mice displayed persistent hyperlocomotion (positive-like symptoms) and social behavior impairment deficits (negative-like symptoms) but non-persistent spatial working memory deficits (cognitive symptoms). Conclusions: Our work confirms the usefulness of a three-hit combination to model, particularly for negative-like symptoms associated with schizophrenia and other psychiatric disorders. The model therefore gathers powerful construct and face validities and supports an involvement of glutamate dysfunction in behavioral symptoms. Full article
(This article belongs to the Special Issue Exploring Negative Symptoms of Schizophrenia: Where Do We Stand?)
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12 pages, 1109 KiB  
Article
Contrasting Effects of Oxytocin on MK801-Induced Social and Non-Social Behavior Impairment and Hyperactivity in a Genetic Rat Model of Schizophrenia-Linked Features
by Daniel Sampedro-Viana, Toni Cañete, Paula Ancil-Gascón, Sonia Cisci, Adolf Tobeña and Alberto Fernández-Teruel
Brain Sci. 2024, 14(9), 920; https://doi.org/10.3390/brainsci14090920 - 13 Sep 2024
Cited by 1 | Viewed by 1084
Abstract
Social withdrawal in rodents is a measure of asociality, an important negative symptom of schizophrenia. The Roman high- (RHA) and low-avoidance (RLA) rat strains have been reported to exhibit differential profiles in schizophrenia-relevant behavioral phenotypes. This investigation was focused on the study of [...] Read more.
Social withdrawal in rodents is a measure of asociality, an important negative symptom of schizophrenia. The Roman high- (RHA) and low-avoidance (RLA) rat strains have been reported to exhibit differential profiles in schizophrenia-relevant behavioral phenotypes. This investigation was focused on the study of social and non-social behavior of these two rat strains following acute administration of dizocilpine (MK801, an NMDA receptor antagonist), a pharmacological model of schizophrenia-like features used to produce asociality and hyperactivity. Also, since oxytocin (OXT) has been proposed as a natural antipsychotic and a potential adjunctive therapy for social deficits in schizophrenia, we have evaluated the effects of OXT administration and its ability to reverse the MK801-impairing effects on social and non-social behavior and MK801-induced hyperactivity. MK801 administration produced hyperlocomotion and a decrease in social and non-social behavior in both rat strains, but these drug effects were clearly more marked in RHA rats. OXT (0.04 mg/kg and 0.2 mg/kg) attenuated MK801-induced hyperlocomotion in both rat strains, although this effect was more marked in RHA rats. The MK801-decreasing effect on exploration of the “social hole” was moderately but significantly attenuated only in RLA rats. This study is the first to demonstrate the differential effects of OXT on MK801-induced impairments in the two Roman rat strains, providing some support for the potential therapeutic effects of OXT against schizophrenia-like symptoms, including both a positive-like symptom (i.e., MK801-induced hyperlocomotion) and a negative-like symptom (i.e., MK801 decrease in social behavior), while highlighting the importance of the genetic background (i.e., the rat strain) in influencing the effects of both MK801 and oxytocin. Full article
(This article belongs to the Special Issue Exploring Negative Symptoms of Schizophrenia: Where Do We Stand?)
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Review

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15 pages, 249 KiB  
Review
Assessment of Negative Symptoms in Schizophrenia: From the Consensus Conference-Derived Scales to Remote Digital Phenotyping
by Armida Mucci, Stefan Leucht, Giulia M. Giordano, Luigi Giuliani, Sophia Wehr, Lucia Weigel and Silvana Galderisi
Brain Sci. 2025, 15(1), 83; https://doi.org/10.3390/brainsci15010083 - 17 Jan 2025
Viewed by 1101
Abstract
The assessment of negative symptoms in schizophrenia has advanced since the 2006 NIMH-MATRICS Consensus Statement, leading to the development of second-generation rating scales like the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms. These scales address the limitations of [...] Read more.
The assessment of negative symptoms in schizophrenia has advanced since the 2006 NIMH-MATRICS Consensus Statement, leading to the development of second-generation rating scales like the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms. These scales address the limitations of first-generation tools, such as the inclusion of aspects that are not negative symptoms and the lack of assessment of the subject’s internal experience. However, psychometric validation of these scales is still in progress, and they are not yet recommended by regulatory agencies, thus limiting their use in clinical trials and settings. Complementing these traditional methods, remote digital phenotyping offers a novel approach by leveraging smartphones and wearable technology to capture real-time, high-resolution clinical data. Despite the potential to overcome traditional assessment barriers, challenges remain in aligning these digital measures with clinical ratings and ensuring data security. Equally important is patient acceptance, as the success of remote digital phenotyping relies on the willingness of patients to use these technologies. This review provides a critical overview of both second-generation scales and remote digital phenotyping for assessing negative symptoms, highlighting future research needs. Full article
(This article belongs to the Special Issue Exploring Negative Symptoms of Schizophrenia: Where Do We Stand?)
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