The NIMH-MATRICS Consensus Statement on Negative Symptoms

TLDR: A consensus development conference was held to review the data relating to the existence of separate domains within negative symptoms, as a prerequisite for choosing appropriate measures of these domains in clinical trials and to examine issues that may interfere with treatment development.

Abstract: The impairments now called negative symptoms have long been noted as common features of schizophrenia, and the concept of negative symptoms itself has a long history.1,2 Patients who exhibit significant negative symptoms have particularly poor function and quality of life,3–8 and this aspect of schizophrenia has been proposed as a separate domain with distinctive pathophysiological and therapeutic implications since at least 1974.9 Despite the attention these problems receive, no drug has received Food and Drug Administration (FDA) approval for an indication of negative symptoms, and available data indicate that second-generation antipsychotic medications have not met early hopes for a highly effective treatment for alleviation of negative symptoms.10 Because of limited progress in the development of effective treatments for negative symptoms, under the auspices of the National Institute of Mental Health (NIMH), Drs. Steve Marder, Wayne Fenton, William T. Carpenter, Jr, and Brian Kirkpatrick initiated a process to examine issues that may interfere with treatment development. The NIMH had previously focused attention on impaired cognition as a therapeutic target with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project. The success of the MATRICS process suggested similar progress could be made in the area of negative symptoms and provided a possible model for proceeding in the area of negative symptoms. Marder, Fenton, Carpenter, and Kirkpatrick organized a consensus development conference, which was held at the NIMH Neuroscience Center in Rockville, Maryland, on January 26–27, 2005. Those attending are listed in the appendix. The mission statement of the meeting was: To review the data relating to the existence of separate domains within negative symptoms, as a prerequisite for choosing appropriate measures of these domains in clinical trials. To initiate a process for developing or identifying widely acceptable, evidence-based measures and methodologies needed to establish the efficacy of treatments that target negative symptoms. Prior to the meeting, the organizers asked experts to address a series of questions: What are the separate components of negative symptoms? Are they independent, or components of the same latent construct? Which aspect of each domain belongs to the negative symptom construct? Does this area need a separate assessment? What is the best assessment method for clinical trials? Since research has suggested that both negative symptoms and cognitive impairments were significant determinants of poor outcome in schizophrenia, an additional set of questions related to the relationship between these domains of psychopathology was also addressed at the conference: Which aspects of cognition are part of the negative symptom construct? Which are independent? Which are uncertain? Articles that more fully address the topics of these presentations can be found in this issue of Schizophrenia Bulletin. Those articles address regulatory issues and negative symptoms,11 negative symptoms as a therapeutic target,12 the factor structure of negative symptoms,13 restricted affect,14 anhedonia,15 and the relationship between negative symptoms and cognitive impairment.16 At the conference other presentations were also made: Wayne Fenton spoke on “Meeting Goals and Objectives: The NIMH Perspective,” Robert Buchanan on “Summary of the MATRICS Process,” William Carpenter, Jr, on “Study Design and the “Pseudospecificity' Problem,” Michael Green on “Social Cognition,” Nancy Andreasen on “Alogia,” and Jeffrey Cummings on “Apathy.”