Negative symptoms of schizophrenia: Clinical features, relevance to real world functioning and specificity versus other CNS disorders
Introduction
Recognition of negative symptoms in schizophrenia extends back over a century, with the early descriptions of dementia praecox by Kraepelin, and subsequently schizophrenia by Bleuler, highlighting the central role seen for volitional and affective disturbances, in the course and progression of this illness (Bleuler, 1950, Kraepelin, 1919). The assimilation of these symptoms into the construct of “negative symptoms” has its origins in the work of John Russell Reynolds in epilepsy, who initially proposed this terminology to reflect a cluster of symptoms characterized by the loss of “vital properties”, in contrast to “positive symptoms” which he posited were a reflection of an excess of “vital properties”, with these two symptom constructs being independent of each other (Berrios, 1985, Messinger et al., 2011, Pearce, 2004). It was John Hughlings Jackson who brought this concept forward in psychiatry, building on Reynolds, as well as Spencer's work on dissolution and evolution of the nervous system, and proposed that negative symptoms reflected a loss of normal function and dissolution of “neural arrangements”, while positive (i.e., psychotic) symptoms represented excess activity that resulted from the loss of higher inhibitory controls and consequent release of lower systems (Berrios, 1985, Jackson, 1958). In contrast to Reynolds, Jackson viewed these symptoms as closely interrelated, with the negative symptoms reflecting the core lesion of the disease and positive symptoms being a secondary consequence due to loss of top-down inhibitory activity (Berrios, 1985).
The introduction of modern psychopharmacology for schizophrenia, with the discovery of chlorpromazine in the 1950s and its efficacy in treating the positive symptoms, drove the field's focus on this domain as the primary outcome measure over the next decades. However, there continued to be a recognition of the importance of these negative symptoms, driven in large part by the work of John Wing and colleagues throughout the 1960s and 1970s (Wing, 1989). In the mid-1970s and early 1980s formal definitions of positive and negative symptoms emerged, along with subtypes of schizophrenia, and poor-outcome trajectories (Andreasen and Olsen, 1982, Crow, 1980, Strauss et al., 1974). There also emerged a broader understanding of the negative symptom construct, with definitions including symptoms of affective flattening, alogia, avolition and apathy, anhedonia, and asociality (Andreasen, 1982). In addition, a distinction between primary, or idiopathic, and secondary negative symptoms was highlighted, the latter including iatrogenic, environmental, and disease-related phenomena (e.g., antipsychotic treatment, extrapyramidal symptoms, chronic institutionalization, depression, suspicious withdrawal, etc.). A subgroup of individuals with schizophrenia that exhibited primary enduring negative symptoms, even during times of clinical stability, was identified and classified as the “deficit syndrome” (Carpenter et al., 1988). This classification was found to be stable over many years (Amador et al., 1999, Strauss et al., 2010), and prevalent in both first-episode and chronic populations (15% and 25–30%, respectively) (Kirkpatrick et al., 2001).
In the following article we explore advances in our understanding of the phenomenology of negative symptoms in schizophrenia, including an exploration of the discrete symptoms that comprise the negative symptom subdomain. We then proceed to examine some of the interrelationships between negative symptoms and other domains of psychopathology in schizophrenia, and the relevance of negative symptoms to functional outcomes in schizophrenia. Finally, we move beyond schizophrenia to explore the nature and functional correlates of negative symptoms across schizophrenia-spectrum disorders, as well as in other neuropsychiatric disorders.
Section snippets
The negative symptoms in schizophrenia
The emergence of the National Institute of Mental Health (NIMH) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative on negative symptoms underscores the importance of these symptoms, their impact on outcomes in schizophrenia, and the unmet need that continues to exist for effective treatments of these symptoms (Kirkpatrick et al., 2006, Marder et al., 2011). While definitions of the symptoms that comprise this symptom domain have varied over the past
Functional consequences of negative symptoms
Schizophrenia is generally considered to be a disorder marked by poor functional outcomes (Jobe and Harrow, 2005, McGlashan, 1988), and the search for more effective therapeutic options for this disorder has led to countless investigations of the predictors of these poor outcomes. Through these efforts, negative symptom severity has been consistently linked to worse functional outcomes in schizophrenia, including specific relationships with impaired occupational functioning, household
Negative symptoms across the schizophrenia spectrum
While most studies have focused on the evaluation of negative symptoms in individuals with schizophrenia, at times with a mixed sample including individuals with schizoaffective disorder, there have also been efforts specifically comparing the nature of negative symptoms between these two diagnostic groups. Through this work, cross-sectional and longitudinal studies have found negative symptoms overall to be more severe in schizophrenia than schizoaffective disorder (Averill et al., 2004, Bora
Negative symptoms beyond schizophrenia
While negative symptoms have traditionally been described in the context of schizophrenia and related psychoses, it has become increasingly apparent that these same negative symptoms are present in a host of other neuropsychiatric illnesses (Table 1). Major depressive disorder (MDD) represents the most commonly considered disorder in which negative symptoms have been described, with findings around the distinction between depression and negative symptoms in schizophrenia described above. In
Conclusions
Historical descriptions of the phenomenology of schizophrenia highlighted disturbances in drive and affective expression in these patients, now subsumed under the construct of negative symptoms, and posited that these symptoms represented the hallmarks of this illness. Over the ensuing century, advances in our understanding and measurement of negative symptoms have led to important clarifications and reconceptualizations. While the SANS has represented the most comprehensive instrument for the
Role of funding source
This work has been supported by a Canadian Institutes of Health Research (CIHR) Clinician-Scientist Training Award to Dr. Foussias. This organization had no further role in the development of the manuscript or the decision to submit for publication.
Contributors
Dr. Foussias developed and wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest
Dr. Foussias has served as an investigator on research sponsored by Medicure Inc., Neurocrine Bioscience, and Hoffman-La Roche. He has served on advisory boards for Hoffman-La Roche, and received speaker's fees from Hoffman-La Roche and Novartis. Dr. Agid has received research support from Pfizer and Janssen-Ortho, consultant fees from Janssen-Ortho and Eli Lilly, and speaker's fees from Janssen-Ortho, Eli Lilly, Novartis, Sepracor and Sunovion. Mr. Fervaha has no relationships with industry to
Acknowledgments
None.
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