Elsevier

Schizophrenia Research

Volume 186, August 2017, Pages 19-28
Schizophrenia Research

Primary and persistent negative symptoms: Concepts, assessments and neurobiological bases

https://doi.org/10.1016/j.schres.2016.05.014Get rights and content

Abstract

Primary and persistent negative symptoms (PPNS) represent an unmet need in the care of people with schizophrenia. They have an unfavourable impact on real-life functioning and do not respond to available treatments. Underlying etiopathogenetic mechanisms of PPNS are still unknown. The presence of primary and enduring negative symptoms characterizes deficit schizophrenia (DS), proposed as a separate disease entity with respect to non-deficit schizophrenia (NDS). More recently, to reduce the heterogeneity of negative symptoms by using criteria easily applicable in the context of clinical trials, the concept of persistent negative symptoms (PNS) was developed.

Both PNS and DS constructs include enduring negative symptoms (at least 6months for PNS and 12months for DS) that do not respond to available treatments. PNS exclude secondary negative symptoms based on a cross-sectional evaluation of severity thresholds on commonly used rating scales for positive symptoms, depression and extrapyramidal side effects; the DS diagnosis, instead, excludes all potential sources of secondary negative symptoms based on a clinical longitudinal assessment.

In this paper we review the evolution of concepts and assessment modalities relevant to PPNS, data on prevalence of DS and PNS, as well as studies on clinical, neuropsychological, brain imaging electrophysiological and psychosocial functioning aspects of DS and PNS.

Section snippets

Primary and persistent negative symptoms: evolution of concepts and assessment

Negative symptoms of schizophrenia represent a heterogeneous clinical construct and different strategies have been proposed to reduce their heterogeneity in the context of clinical trials and neurobiological research. The distinction between primary negative symptoms, a core aspect of the illness (Carpenter et al., 1988) and negative symptoms secondary to other factors (e.g. positive symptoms, extrapyramidal side effects, depression or isolation) bears important therapeutic implications. In

Definition

DS is defined by the diagnostic criteria outlined in the Box 1. The categorization of patients into DS and NDS by means of the Schedule for the Deficit Syndrome (SDS, Kirkpatrick et al., 1989) has been shown to have good inter-rater reliability (Kirkpatrick et al., 1989, Fenton and McGlashan, 1994, Amador et al., 1999, Galderisi et al., 2002, Peralta and Cuesta, 2004) and a high degree of stability with good test-retest reliability (Kirkpatrick et al., 1993, Fenton and McGlashan, 1994, Amador

Definition

The concept of PNS is broader than that of DS (Buchanan, 2007) and, according to the NIMH-MATRICS consensus report, includes symptoms that have not responded to the usual treatments, interfere with patient’s ability to perform normal role functions, persist during periods of clinical stability, and represent an unmet therapeutic need (Kirkpatrick et al., 2006). PNS criteria according to Buchanan (2007) are listed in Box 2.

Conclusions

In the last decades, the attempt to reduce heterogeneity of negative symptoms of schizophrenia led to the identification of two psychopathological constructs: DS and PNS.

Since the introduction of the criteria for diagnosing DS a large body of research has been carried out, trying to distinguish DS from NDS. An important research question is whether DS represents a more severe form of the same illness with respects to NDS or a separate disease entity. Brain imaging (Gonul et al., 2003, Heckers

Authors' contributions

All authors were involved in the manuscript development and review and have approved the final draft of the manuscript for publication.

Conflicts of interest

Armida Mucci has received a partial coverage of the expenses to participate in the 2015 EPA congress from Janssen-Cilag (unrelated to this paper).

Alp Üçok has received honoraria from Abdi Ibrahim, Otsuka, AstraZeneca and Janssen-Cilag (unrelated to this paper).

Silvana Galderisi participated in advisory boards for Hoffmann-La Roche, Janssen-Cilag, Lundbeck, Angelini-Acraf, Amgen and Pierre Fabre (unrelated to this paper).

André Aleman was supported by an ERC consolidator grant (project no.

Acknowledgments

The authors wish to thank the European negative symptoms research network (EuroNES) group and the ECNP Schizophrenia Network for the fruitful discussion of the reviewed topics.

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