Schizophrenia Bulletin Advance Access originally published online on February 15, 2006
Schizophrenia Bulletin 2006 32(2):212-213; doi:10.1093/schbul/sbj061
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Editor's Introduction: Theme Issue on Negative Symptoms
2 Department of Psychiatry and Health Behavior, Medical College of Georgia
Keywords: schizophrenia / methodology / clinical trials / drug development
Although negative symptoms are such an important problem in schizophrenia that no special justification is needed, this theme issue was a response to an initiative by the National Institute of Mental Health (NIMH) to facilitate drug discovery and drug development in the area of negative symptoms. Although there is controversy over the efficacy for negative symptoms of available antipsychotic medications, few would argue that these drugs are satisfactory treatments. NIMH had previously recognized impaired cognition as an unmet treatment need in schizophrenia and had initiated the MATRICS project to clarify assessment problems and facilitate drug trials in that area. The MATRICS consensus statement on clinical trial design was published in the January 2005 issue of Schizophrenia Bulletin.
The good progress of the ongoing MATRICS project encouraged NIMH to begin a similar effort for negative symptoms. The outcome and some of the details of the first major milestone step in the negative symptoms project, the Consensus Development Conference on Negative Symptoms, are described in the Consensus Statement in this issue. The articles by Horan et al., Harvey et al., and Kirkpatrick and Fischer are expanded versions of presentations from the conference.
The workshop and consensus report published in this theme issue have some limitations that merit comment. First, because the workshop was organized as an extension of the NIMH initiative to facilitate discovery of drugs with efficacy for cognition (ie, the MATRICS process), participation of the Food and Drug Administration (FDA) in the conference was considered crucial. As a consequence, the focus of the conference was clearly on issues related to drug development and testing. Laughren and Levin of the FDA, who participated in the conference, provide an important commentary. However, a focus on drug development omits the critical area of interpersonal and cognitive approaches to the treatment of negative symptoms. We asked Nicolas Tarrier to provide a commentary from the perspective of psychosocial treatment.
The second issue relates to the NIMH, FDA, and academic affiliations of the workshop participants. Problems in drug development may appear quite differently from within the pharmaceutical industry. Larry Alphs was invited to provide a critique of the consensus statement from that perspective, and members of the pharmaceutical industry are now participating in the ongoing negative symptom process begun by NIMH. Another limitation came from the decision made by the conference organizers not to focus on the neurobiology of negative symptoms, despite the obvious importance of this issue for drug discovery and development. It was thought that this was too complex an issue to add to the agenda of a 2-day meeting and that any attempt to do so would make it more difficult to move forward in other areas. The Consensus Statement suggests how to deal with neurobiology as the NIMH process moves forward.
Some interesting themes recur in the articles in this issue. One is that the boundaries of negative symptoms are not certain. A decrease in emotionality—the subjective experience of emotion, as opposed to the objective "signs" of blunted affect—may be an important omission from the domains addressed in the Consensus Statement. However, as should be clear from the Consensus Statement, the conference participants did not intend to present their list of the subdomains of negative symptoms as the final word. A related uncertainty is whether negative symptoms represent a single entity or whether more than 1 factor exists within the construct of negative symptoms. The papers by Blanchard and Cohen, Kimhy et al., and Gur et al. provide intriguing information on this issue.
Important controversies are also addressed in these articles. Disagreement can be found with regard to study design and interpretation, especially for a so-called broad spectrum agent. This issue of the degree of independence of negative symptoms from other impairments in schizophrenia is an important problem for treatment development, and the Consensus Statement and the articles by Harvey and coauthors, Laughren and Levin, Kane, and Alphs all address it.
These controversies and uncertainties reflect a useful rethinking of the concept of negative symptoms. NIMH has provided very helpful leadership in the MATRICS process and in the area of negative symptoms. Both of these projects seem likely to facilitate the development of treatments that will benefit those who suffer from schizophrenia.
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1To whom correspondence should be addressed; e-mail: bkirkpatrick2{at}aol.com.
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  P. D. Shepard Editorial--Modeling Negative Symptoms: What's Missing? Schizophr Bull, July 1, 2006; 32(3): 403 - 404. [Full Text] [PDF]
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