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Theories and models of negative symptoms in schizophrenia and clinical implications

Abstract

Negative symptoms in schizophrenia include avolition, anhedonia, asociality, alogia and affective blunting. These symptoms correlate strongly with clinical and functional outcomes, but respond poorly to conventional treatments. Research on the origins and mechanisms of negative symptoms can potentially advance the development of interventions. In this Review, we outline important points of convergence for phenomenological and neurobiological evidence. First, we summarize how negative symptoms are conceptualized and how these psychopathologies manifest in clinical and subclinical populations. Next, we critically review theoretical and empirical models of negative symptoms. We propose that the ‘trait with state-elevation’ properties of negative symptoms make them particularly useful for identifying individuals who may be at risk of developing psychosis and for predicting the onset of psychosis. Finally, we suggest that future research should use sophisticated technology and longitudinal designs to capture both inter-individual and intra-individual variability in negative symptoms and to improve diagnosis and treatments.

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Fig. 1: An integrated perspective on theoretical frameworks for negative symptoms.
Fig. 2: Roadmap and future research on negative symptoms.

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Acknowledgements

The preparation of this paper was supported by the CAS Key Laboratory of Mental Health, Institute of Psychology and Philip K. H. Wong Foundation (to R.C.K.C.).

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R.C.K.C. conceived the general framework for the review. R.C.K.C., L.l.W. and S.S.Y.L. researched data for the article. R.C.K.C. and S.S.Y.L. wrote the first draft of this article. All authors contributed substantially to discussion of content and reviewed and/or edited the manuscript before submission.

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Glossary

At-risk mental state

The clinical presentation of those considered at risk of developing psychosis or schizophrenia but who do not currently meet diagnostic criteria.

Ultra-high-risk cases

Individuals at high and imminent risk of developing a first episode of psychosis.

Attenuated psychosis syndrome

A subthreshold psychosis-like psychiatric condition characterized by mild hallucinations, delusions or disorganized speech with relatively intact reality testing.

Antipsychotic-induced Parkinsonism

The effects of dopamine-blocking agents (commonly antipsychotic medications) on mesolimbic and mesocortical brain pathways, resulting in movement-disorder-like symptoms.

Endophenotype

A type of biological marker that is simpler to detect than genetic sequences and that may be useful in researching vulnerability to a wide range of psychological, psychiatric and neurological disorders.

Transcranial direct-current stimulation

(tDCS). A non-invasive brain stimulation technique that applies direct low-dose electrical currents via scalp electrodes to modulate neuronal activities of cortical areas of the brain.

Transcranial magnetic stimulation

(TMS). A non-invasive brain stimulation technique in which regional magnetic pulses are applied close to the scalp surface to modulate cortical excitability.

Neurofeedback

A type of biofeedback in which real-time feedback from brain activation is provided to participants.

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Chan, R.C.K., Wang, Ll. & Lui, S.S.Y. Theories and models of negative symptoms in schizophrenia and clinical implications. Nat Rev Psychol 1, 454–467 (2022). https://doi.org/10.1038/s44159-022-00065-9

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