Don’t forget to focus on the negative

Negative symptoms in psychosis are under-researched and often receive less attention than positive symptoms. However, they are critically important to functional recovery, and should not be forgotten by early intervention services.

What are negative symptoms?

Negative symptoms are an oft-neglected but core feature of schizophrenia and other psychotic illnesses. Broadly speaking, negative symptoms refer to the loss or diminution of normal functions related to motivation and emotional expression. This includes symptoms such as reduced social interaction, loss of motivation, reduced speech and loss of enjoyment in previous interests.

Negative symptoms are a discrete symptom dimension, separate from positive symptoms (i.e., hallucinations and delusions), disorganisation, mood symptoms and cognitive impairment. However, there has been limited progress in understanding the neurobiological mechanisms that underlie negative symptoms and therefore in developing effective treatment. Interest in studying negative symptoms is increasing, and a consensus was recently achieved on conceptualising negative symptoms as consisting of five domains.  These five domains are avolitionavolition:Reduced initiation and persistence of goal-directed activity due to decreased motivation, asocialityasociality:Reduced social interactions and initiative due to decreased interest in and motivation for forming and maintaining relationships with others, anhedoniaanhedonia:Reduced experience of pleasure, blunted affectblunted affect:Decrease in non-verbal emotional expression and reactivity, as manifested in reduction in facial expression, vocal intonation and expressive gestures. and alogiaalogia:Reduction in verbal output and spontaneous elaboration.¹

Despite receiving less attention historically than positive symptoms, negative symptoms are in fact prevalent in the early course of psychotic disorders, and they are among the most frequently observed symptoms in the prodromal phase (ie, symptoms experienced in the lead-up to a first episode of psychosis). Importantly, negative symptoms are critically associated with poor psychosocial functioning, increased likelihood of unemployment and greater burden for carers in people with early psychosis.

Two main approaches have been adopted to classifying negative symptoms in clinical research and management. These are, (1) distinguishing between primary and secondary negative symptoms² and (2) dividing the five symptom domains into two subdomains: reduced motivation and interest (‘amotivation’), comprising avolitionavolition:Reduced initiation and persistence of goal-directed activity due to decreased motivation, asocialityasociality:Reduced social interactions and initiative due to decreased interest in and motivation for forming and maintaining relationships with others and anhedoniaanhedonia:Reduced experience of pleasure; and diminished emotional expressivity (‘diminished expression’), comprising blunted affectblunted affect:Decrease in non-verbal emotional expression and reactivity, as manifested in reduction in facial expression, vocal intonation and expressive gestures. and alogiaalogia:Reduction in verbal output and spontaneous elaboration.¹

Why are they important?
Primary negative symptoms (PNS) are regarded as intrinsic to the illness process of psychotic disorders, while secondary negative symptoms stem from co-occurring conditions, such as depression, paranoid suspiciousness, antipsychotic-induced motor effectsmotor effects:Stiffness and shakiness, uncomfortable restlessness, movement of the jaw, tongue or mouth and environmental deprivation. Persistent PNS robustly predicts concurrent and longitudinal functional impairment in people with early psychosis.

Amotivation has been found to be more prevalent in the early stage of illness, and is a much stronger predictor of functional disability than diminished expression. Amotivation may be a key determinant of functional outcome in early psychosis, having a greater effect than cognitive deficits and other symptom dimensions.³ Of note, it is well recognised that a significant proportion of people with first-episode psychosis (FEP) still experience persistent functional impairment even after achieving remission from acute psychosis. This indicates that negative symptoms, especially amotivation, might be a pivotal therapeutic target in promoting early functional recovery in first-episode populations.

How do we manage them?
Although negative symptoms don’t respond well to medication, early detection and intensive phase-specific intervention for FEP can be effective in reducing negative symptom severity. Recent reviews have revealed that shortening delays in treatment for an initial psychotic episode (i.e., reducing duration of untreated psychosis) is associated with fewer negative symptoms at first presentation and better negative symptom outcome at follow-up.

Integrated early intervention services are effective for improving negative symptoms among people with FEP. There is also growing evidence that specific psychosocial interventions such as cognitive-behavioral therapy (CBT), cognitive remediation and social skills training can effectively alleviate negative symptoms.⁴ In particular, CBT that specifically tries to rectify unhelpful attitudes, including defeatist beliefs and low self-efficacy, has recently been shown to significantly improve amotivation and functional outcome in people with psychotic disorders.

As negative symptoms constitute a major barrier to functional recovery in the early phase of illness, it is crucial to incorporate regular, comprehensive assessment of negative symptoms within the early intervention framework. This will aid evaluation and enhancement of functional outcome in people experiencing a first episode. Specifically, to accurately capture the nature and magnitude of symptom severity, the use of second-generation negative symptom rating scales (i.e., Brief Negative Symptom Scale, BNSS; Clinical Assessment Interview for Negative Symptoms, CAINS), which are were developed according to the current conceptualisations of negative symptoms and cover the five consensus domains, is recommended. This will in turn facilitate early symptom identification and provision of prompt, targeted interventions to prevent progression towards persistent negative symptoms and subsequent deterioration in functioning.⁵

Careful assessment should also be conducted to differentiate between primary and secondary negative symptoms, as the latter can be treated by managing the underlying cause.^2,5 For instance, antidepressant treatment for depression or antipsychotic dose reduction for motor effectsmotor effects:Stiffness and shakiness, uncomfortable restlessness, movement of the jaw, tongue or mouth.

Optimising treatment of negative symptoms is critical to attaining functional recovery in patients with early psychosis. Further research is warranted to clarify how early intervention services should be modified or which treatment elements should be strengthened so that the benefits of treatment are sustained after a person leaves early psychosis care.

Dr. Wing-Chung CHANG is a psychiatrist (FRCPsych, FHKCPsych), a clinical associate professor at the Department of Psychiatry and a principal investigator of the State Key Laboratory of Brain & Cognitive Sciences, University of Hong Kong (HKU). He has been working in early intervention service for psychosis, namely the EASY programme for 15 years. His research interests include early intervention and outcome of first-episode psychosis, negative symptoms and amotivation, at-risk mental state and psychosis prediction, and physical health in severe mental illness. He has published 145 articles in international peer-reviewed journals and 4 book chapters. He has received several research awards including International Early Psychosis Association Young Investigator Award, and NARSAD Young Investigator Award by Brain & Behaviour Research Foundation.

Glossary:

Anhendonia: Reduced experience of pleasure

Blunted affect: Decrease in non-verbal emotional expression and reactivity, as manifested in reduction in facial expression, vocal intonation and expressive gestures.

Alogia: Reduction in verbal output and spontaneous elaboration

Motor Effects: Stiffness and shakiness, uncomfortable restlessness, movement of the jaw, tongue or mouth

References

1. Galderisi S, Mucci A, Buchanan RW, Arango C. Negative symptoms of schizophrenia: new developments and unanswered questions. Lancet Psychiatry 2018; 5:664-677.

2. Kirschner M, Aleman A, Kaiser S. Secondary negative symptoms: a review of mechanisms, assessment and treatment. Schizophrenia Research 2017; 186:29-38.

3. Chang WC, Wong CSM, Or PCF, et al. Inter-relationships among psychopathology, premorbid adjustment, cognition and psychosocial functioning in first-episode psychosis: a network analysis approach. Psychological Medicine 2020; 50:2019-2027

4. Lutgens D, Gariepy G, Malla A. Psychological and psychosocial interventions for negative symptoms in psychosis: systematic review and meta-analysis. British Journal of Psychiatry 2017; 210:324-332.

5. Correll CU, Schooler NR. Negative symptoms in schizophrenia: a review and clinical guide for recognition, assessment, and treatment. Neuropsychiatric Disease and Treatment 2020; 16:519-534.

Declaration of Interests: None

Acknowledgements:

This project was made possible thanks to a sponsorship from H/Lundbeck A/S. The opinions expressed in these materials do not necessarily reflect those of H.Lundbeck.