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.”

The NIMH-MATRICS Consensus Statement on Negative Symptoms

Quality of life (QoL) has been recognized as an important outcome of schizophrenia treatment, yet the determinants of QoL for individuals with schizophrenia are not well known. Research has consistently found psychiatric symptoms to be negatively related to QoL, however, findings concerning the strength of these relationships have been mixed, making it difficult to determine the degree to which such symptoms are related to poor QoL. This research presents a systematic meta-analysis of studies examining the relationship between psychiatric symptoms and QoL in schizophrenia, in an effort to elucidate the determinants of QoL for this population. A total of 56 studies were extracted from literature searches of relevant databases for empirical reports published between 1966 and 2005 examining the relationship between positive, negative, and/or general psychiatric symptoms and QoL. Weighted effect size analyses revealed small relationships between psychiatric symptoms and QoL, with general psychopathology showing the strongest negative associations across all QoL indicators. Moderator analyses indicated that variation in effect sizes could be accounted for by differing operationalizations of QoL, study design, sample, and participant treatment setting. In particular, positive and negative symptoms were more strongly related to poor QoL among studies of schizophrenia outpatients, whereas general psychopathology showed a consistent negative relationship with QoL across all study samples and treatment settings. Implications for future research and treatment development are discussed.

/pdf/psychiatric-symptoms-and-quality-of-life-in-schizophrenia-a-58t4qcucbt.pdf

Psychiatric Symptoms and Quality of Life in Schizophrenia: A Meta-Analysis

The burgeoning interest in investigating the first episode of schizophrenia and related disorders provides an opportunity to examine how this approach has assisted our understanding of the heterogeneity of psychopathology of this disorder and the trajectories of its outcome. We present a review of relevant literature on categorical versus dimensional perspectives on psychopathology, with special reference to early signs, its relationship with other patient- and system-related characteristics, and the status and determinants of functional outcome and quality of life. The findings from longitudinal studies of the dimensional psychopathology of first-episode psychosis suggest continuity of some psychopathological dimensions from premorbid through prodromal to post-onset phases of psychosis and some aspects of longer-term course. Short-term functional outcome improves after treatment of the first episode, but longer-term outcome remains relatively poor for a substantial proportion of patients and is associated with preadolescent onset, poor premorbid adjustment, poor cognitive functioning, cerebral asymmetry, and negative symptoms during prodromal and post-onset phases. Poor quality of life is related to residual psychopathology, long delays in treatment, and poor premorbid adjustment. The potential effects of improved treatment and/or early intervention on functional outcome and quality of life have not been adequately examined, nor have the interrelationships between predictors and the underlying processes involved in determining variations in outcome. Studies of functional outcome still lack the rigor of operational definitions, choice of specific instruments for measurement, and use of large enough samples to generate meaningful results.

/pdf/first-episode-psychosis-psychopathology-quality-of-life-and-1q3gk2q25g.pdf

First-Episode Psychosis: Psychopathology, Quality of Life, and Functional Outcome

Subjective and objective quality of life in schizophrenia.

Medication Adherence and Psychoeducation Despite the effectiveness of psychopharmocological interventions in producing improved outcomes in schizophrenia, medication nonadherence occurs frequently (in up to 50% or more of cases) and for various reasons (123). A recent comprehensive review identified that the lack of awareness of illness was a key factor in medication nonadherence (124). Such lack of insight has been hypothesized by some to be a cognit ive impairment associated with schizophrenia itself (125,126). Other issues contributing to nonadherence include concurrent alcohol or drug abuse, problems with the therapeutic alliance (127), medication side effects (128) and complicated dosage schedules, problems with access to treatment, and financial obstacles to obtaining medication (129). The impact of nonadherence is costly, not only for the person and his or her family but also more generally for the health care system (130).

/pdf/clinical-practice-guidelines-treatment-of-schizophrenia-56binrflaj.pdf

CLINICAL PRACTICE GUIDELINES Treatment of Schizophrenia

Objective: Reports suggesting that quality of life in schizophrenia is more highly related to negative rather than positive symptoms are largely based on use of the Quality of Life Scale which was devised to assess deficit symptoms and does not include an assessment of subjective general wellbeing In the current paper we examined symptoms, level of community functioning as well as living circumstances as correlates of Quality of Life Scale scores and scores on the General Well-Being Scale



Method: One hundred and twenty-eight patients completed the General Well-Being Scale and were rated on the Quality of Life Scale as well as scales assessing positive and negative symptoms



Results: While negative symptoms, level of functioning and positive symptoms all were related to the scores on the Quality of Life Scale, General Well-Being Scale scores were primarily related to positive symptoms, particularly reality distortion



Conclusion: The results highlight the importance of recognizing the complex nature of the concept of quality of life They demonstrate that varying indices of quality of life are likely to have different predictors

Leonard Cortese

Papers

The relationship of symptoms and level of functioning in schizophrenia to general wellbeing and the Quality of Life Scale.