What’s missing matters: Negative symptoms of schizophrenia

Negative symptoms in schizophrenia – faculties apparently lacking or somehow diminished – have long been a cause for concern both for clinicians and for patients with schizophrenia.1 Often times, it’s the negative rather than positive symptoms of schizophrenia that are most clinically relevant with up to 60% of patients experiencing them.2 But what underlies such symptoms? And what is being done to try to ameliorate them?

First and foremost, in order to promote comprehensive research on negative symptoms in schizophrenia it’s important to assess them using validated assessment instruments.1


BNSS validated

The European College of Neuropsychopharmacology (ECNP) Schizophrenia Network conducted a multinational (10 countries) validation study of the Brief Negative Symptom Scale (BNSS).1 A total of 249 subjects with schizophrenia were assessed using both BNSS and the Positive and Negative Syndrome Scale (PANSS), as well as other instruments for depression, extrapyramidal symptoms and psychosocial functioning.


BNSS highlights avolition

Across countries, BNSS demonstrated an excellent internal consistency. Furthermore, BNSS offered advantages compared to PANSS in the identification of the avolition domain - unlike PANSS, BNSS-avolition explained 23.9% of psychosocial functioning - and more patients with negative symptoms were identified using BNSS than with PANSS.

BNSS offered advantages compared to PANSS in the identification of the avolition domain



The Italian Network for Research on Psychoses (INRP) has recently reported findings from two interesting studies, the first of which involved the use of MATRICS Consensus Cognitive Battery (MCCB).

Because the disorganization dimension is a strong predictor of real-life functioning in patients with schizophrenia, INRP undertook an investigation of the electrophysiological and neurocognitive MCCB, which correlates of the components of disorganization - ‘conceptual disorganization’, ‘difficulty in abstract thinking’, ‘poor attention’ - and cognitive deficits.3

They found only a partial overlap between disorganization and cognitive deficits, suggesting that impairment of neurobiological functions may not be being fully assessed using MCCB.

MCCB may not fully assess impairment of neurobiological functions in patients with schizophrenia

However, alternatives to MCCB also need to be carefully evaluated. For instance, a longitudinal comparison of CANTAB (Cambridge Neuropsychological Test Automated Battery) and MCCB in 39 subjects with schizophrenia and 10 healthy controls, showed that – unlike use of MCCB – a significant effect of time was noted with CANTAB. This is suggestive of practice effects in the use of the latter.4


Networking differs in recovered and non-recovered patients

A 4-year follow-up study of the INRP’s large network analysis, which explored the relationship between illness-related variables, personal resources, context-related factors and real-life functioning in patients with schizophrenia, revealed that the network structure and connectivity of recovered and non-recovered patients was very different.5

This suggests that tightly coupled symptoms/dysfunctions self-reinforce, contributing to poor outcome in schizophrenia.5 Emergence of these debilitating networks could be prevented through use of early and integrated treatment plans.

Tightly coupled symptoms/dysfunctions self-reinforce, contributing to poor outcome in schizophrenia


Psychoeducational intervention reduces ER visits

Improvement in negative symptoms and reduction in the number of visits to emergency room (ER) was reported in those recruited to a psychoeducational (PE) group compared to a non-structured (NS) intervention for adolescents with psychosis.6 Could executive function (EF) – a cognitive domain for problem solving – be behind this difference in response?

EF was, therefore, assessed in 22 individuals randomized to undergo PE or NS interventions. Improvements in EF correlated both with reduction in negative symptoms and reduction in ER visits. Investigators believe that these findings could influence the development of new clinical interventions.

Improvements in executive function correlated both with reduction in negative symptoms and reduction in ER visits

Although not identified as a negative symptom per se, the negative effects of cognitive impairment are noted early in the course of schizophrenia, often well before positive symptoms present.7

Currently, opinions are mixed as to whether cognitive impairment should be included as a separate diagnostic criterion for schizophrenia.7 Nevertheless, it is clear that both negative symptoms and cognitive impairment constitute unmet medical needs in the management of schizophrenia.


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Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


  1. Mucci A, et al. Eur Neuropsychopharmacol 2019;29:947-959
  2. Correll C & Schooler N. Neuropsychiatr Dis Treat 2020;16;519-534
  3. Vignapiano A, et al. Int J Psychophysiol 2019;145:98-108
  4. Rodriguez-Toscano E, et al. Schizophr Res 2019; Dec 5 E pub ahead of print
  5. Galderisi S, et al. World Psychiatry 2020;19:81-91
  6. Rapado-Castro M, et al. J Clin Med 2019;8(12)
  7. Davidson M, World Psychiatry 2019;18:171-172