Cognitive impairment, as a key symptom of schizophrenia

In this symposium presented at the 35th ECNP Congress in Vienna, Austria (15th−18th Oct), titled ‘Piecing together the cognitive impairment puzzle: cognitive domains and schizophrenia in clinical practice,’ Prof Philip D. Harvey (University of Miami Miller School of Medicine, USA) discussed how cognitive functioning arises from a number of circuits in the brain and that cognitive deficits in patients with schizophrenia may be similar to those in other neurological conditions and worsen as the person ages. Prof Silvana Galderisi (University of Campania Luigi Vanvitelli, Italy) discussed how cognitive impairments can impact everyday functioning and social cognition in patients with schizophrenia and how it is important to assess patients on an individual basis so as to provide them with the required level of help. Prof Alice Medalia (Columbia University Irving Medical Center, USA) expanded on this and discussed how patients with schizophrenia rank memory and attention problems high on their list of needs to be addressed. Ways to address these can best be accomplished through a shared decision making process. Finally, Prof Peter Falkai (University of Munich, Germany) discussed how tools, such as the Brief Assessment of Cognition in Schizophrenia and the Screen for Cognitive Impairment in Psychiatry, can be used to help ascertain a patient’s deficits and needs in terms of cognition.

Cognitive dysfunction in schizophrenia

Cognition encompasses several domains of functioning, including memory, attention/vigilance, processing speed, executive functions, perception and sensation.1 These arise due to networks including the cortical circuit (hippocampal-medial temporal involvement) and the frontal-striatal circuit (thalamic-limbic-cortical involvement). This indicates that while someone may have a deficit in one part of the brain, it may manifest in a way more associated with another area of the brain in that network.2-4

Fronto-striatal impairments are demonstrated in patients with Parkinson’s disease and Huntington’s disease. In cortical dementias, such as Alzheimer’s disease, impairments are shown across all cognitive functions. In fronto-striatal conditions, recognition memory and the ability to name objects is spared.5,6 Cognitive changes shown in these diseases, according to Prof Harvey, are akin to those shown in patients with schizophrenia.

Cognitive functioning arises from a number of networks in the brain

In schizophrenia, the most important domains of cognitive dysfunction are attention/vigilance, working and episodic memory, executive functions and processing speed.7 This occurs prior to treatment and is similar in first-episode patients and those who have been treated for a number of years.8 Individual tests of processing speed may be very useful to quickly ascertain overall cognitive impairment in a patient with schizophrenia.9

Comparing results of neuropsychological tests in older patients with schizophrenia reveals deficits in verbal learning and delayed recall far below those of matched healthy controls, more similar to, especially for verbal learning, patients with Alzheimer’s disease.10 However, in schizophrenia, recognition memory is intact even if recall memory is dysfunctional. This, explained Prof Harvey, means that if a patient cannot remember something you know they learnt, they may be able to recall it if given cues.11


The impact of cognitive impairment on functioning for patients with schizophrenia

Although it is known that cognitive scores in patients with schizophrenia are below that of healthy controls,12 cognitive impairments are not included in the diagnostic criteria for schizophrenia.13 Cognitive impairment is typically observed from childhood in patients with schizophrenia, many years prior to the emergence of mood symptoms and psychosis.14 Cognitive performance can be impacted with longer durations of first episode psychosis.15 Decline is also shown in cognitive performance as a patient with schizophrenia ages, earlier than shown in a healthy population.16 This can impact community functioning and social/interpersonal skills for patients with schizophrenia.17

Cognitive impairments typically manifest from childhood in patients with schizophrenia

In an Italian study in 921 community-dwelling participants with schizophrenia (age 40.2 ±10.7; 70% male),18 cognitive functioning in a number of domains, as well as social cognition, were found to be around 1.5 standard deviations (SDs) below a healthy control population. The heterogeneity of schizophrenia was revealed when further examination of the data showed that while 44% had SDs 1.0−1.5 below the healthy controls, around 20% had an SD of 0.0−0.50 and 12% had SDs 2.5−3.0 below the healthy controls. Similar findings were shown for social cognition, with some being highly impaired and some having little impairment. This is important, highlighted Prof Galderisi, as not all patients with schizophrenia may require, for instance, cognitive impairment training.18

This study also showed that neurocognition predominantly impacted real-life functioning via impacts on domains, such as social cognition, functional capacity, engagement with mental health services and internalised stigma.18 Network analysis showed that valuables relative to social cognition from a broad range of tests clustered together, as did those related to neurocognition. These were found to have a strong relationship with everyday life skills.19 Longitudinal analysis of 618 of the community-dwelling participants in the above study revealed that over 4 years, improvements in work skills and interpersonal functioning were predicted by higher baseline social cognition scores and that improvements in functional capacity, everyday life/work skills and social cognition were predicted by higher baseline neurocognitive functioning.20


Improving quality of life by tackling cognitive difficulties

Poor cognitive impairment can impact how well a patient can function in the community and how they manage their medication and it can contribute to social isolation.21 As such, treatments being developed for patients with schizophrenia include cognitive remediation therapies, where patients complete exercises and discuss ways to help improve cognition. These can have low-moderate outcomes in terms of effects on global cognition, functioning, verbal and working memory and attention.22,23 Positive moderators of effectiveness include having active components that link cognition to everyday functioning and having strategy coaching.22 Pharmacological treatments are also being developed for cognitive impairment associated with schizophrenia.24

When asked, patients with schizophrenia rate memory and attention problems among the top needs to be addressed.25 Prof Medalia discussed how successful implementation of cognitive impairment-focused treatments means first those barriers need to be identified and addressed with regards to how treatment is provided, including staff training, service user acceptability, costs and access to, for instance, cognitive assessment tools.26,27 According to Prof Medalia, there are also ‘mindset barriers’, such as believing that cognitive impairments are a consequence/subset of negative or positive symptoms of schizophrenia, an adverse event of an antipsychotic treatment or are linked to developmental disorders. While this may hold true in some cases, cognitive impairment can still occur when all of these are addressed.

Healthcare professionals may have internal barriers regarding cognitive impairments that need to be overcome

Cognitive health interventions, advised Prof Medalia, must adhere to both scientific and recovery principles. Healthcare providers need to ask about and listen out for evidences of cognitive problems that are impacting functionality and, if possible, assess their patients regarding these. Other factors that can impact cognition also need to be taken into account, such as diet, stress, sleep, medical factors and substance use. Talking to patients about cognitive interventions is best approached using shared decision-making making where individual values and preferences are taken into account alongside best scientific evidence during discussions between a healthcare provider and the patient.28 Questions Prof Medalia suggested including were “What is it you want to accomplish in the next month?” and “Would better cognitive health help you meet that goal?”


Assessing cognitive impairment

Cognitive impairment associated with schizophrenia is, said Prof Falkai, somewhat neglected in clinical practice.29 This is despite the fact that there are several tools to assess such difficulties. The Brief Assessment of Cognition in Schizophrenia takes around 30 minutes and assesses a number of cognitive domains, including motor speed, working and verbal learning memory, problem solving, speed of processing and attention.30 The Screen for Cognitive Impairment in Psychiatry takes around 15 minutes and evaluates verbal fluency, processing speed and working and verbal learning memory.31

Cognitive impairments in schizophrenia can be assessed using quick screening tools

Assessing cognitive abilities in patients with schizophrenia is important, said Prof Falkai, as it can help guide treatment selection and modification. While traditionally, the dopamine hypothesis of schizophrenia helps explain positive, negative and cognitive symptoms, glutamate is being more recognised for its role as well.32 Normal functioning of the glutamatergic N-methyl-D-aspartate (NMDA) receptor requires both glutamate and glycine.33 Selective inhibition of glycine receptors has been shown to lead to improvements in cognitive symptoms in patients with schizophrenia.34


Educational financial support for this Satellite symposium was provided by Boehringer Ingelheim.

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. Harvey PD. Dialogues Clin Neurosci. 2019; 21: 227-237.
  2. Adcock RA, et al. Proc Natl Acad Sci U S A. 2000; 97: 3567-3572.
  3. Callicott JH, et al. Cereb Cortex. 1999; 9: 20-26.
  4. Gotham AM, et al. Brain. 1988; 111 ( Pt 2): 299-321.
  5. Paulsen JS, et al. Neurology. 1995; 45: 951-956.
  6. Paulsen JS, et al. J Clin Psychol. 1995; 51: 48-58.
  7. Nuechterlein KH, et al. Schizophr Res. 2004; 72: 29-39.
  8. Saykin AJ, Shtasel DL, Gur RE, et al. Arch Gen Psychiatry. 1994; 51: 124-131.
  9. Harvey PD, et al. Neuropsychology. 2016; 30: 28-39.
  10. Davidson M, et al. Am J Psychiatry. 1996; 153: 1274-1279.
  11. Harvey PD, et al. J Clin Exp Neuropsychol. 2002; 24: 55-66.
  12. Keefe RS, et al. Biol Psychiatry. 2005; 57: 688-691.
  13. American Pscyhiatric Association. Diagnostic and statistical manual of mental disorders. Fifth edition. United States of America: American Psychiatric Association; 2013.
  14. Howes OD, Murray RM. Lancet. 2014; 383: 1677-1687.
  15. Bora E, et al. Schizophr Res. 2018; 193: 3-10.
  16. Fett AJ, et al. JAMA Psychiatry. 2020; 77: 387-396.
  17. Halverson TF, et al. Neurosci Biobehav Rev. 2019; 105: 212-219.
  18. Galderisi S, et al. World Psychiatry. 2014; 13: 275-287.
  19. Galderisi S, et al. JAMA Psychiatry. 2018; 75: 396-404.
  20. Mucci A, et al. JAMA Psychiatry. 2021; 78: 550-559.
  21. Nuechterlein KH, et al. Schizophr Bull. 2011; 37 Suppl 2(Suppl 2): S33-40.
  22. Lejeune JA, et al. Schizophr Bull. 2021; 47: 997-1006.
  23. Vita A, et al. JAMA Psychiatry. 2021; 78: 848-858.
  24. Horan WP, et al. Curr Top Behav Neurosci. 2022; Aug 2: online ahead of print.
  25. Moritz S, et al. Eur Arch Psychiatry Clin Neurosci. 2017; 267: 335-339.
  26. Medalia A. CNS Spectr. 2019; 24: 163-173.
  27. Arlia C, et al. Schizophr Res. 2022; 243: 456-457.
  28. Deegan PE, Drake RE. Psychiatr Serv. 2006; 57: 1636-1639.
  29. Østergaard SD, et al. Innov Clin Neurosci. 2017; 14: 68-72.
  30. Keefe RS, et al. Am J Psychiatry. 2006; 163: 426-432.
  31. Purdon SE, Psych R. The Screen for Cognitive Impairment in Psychiatry. Administration and psychometric properties Edmonton, Alberta, Canada: PNL. 2005.
  32. Stahl SM. Stahl's Essential Psychopharmacology. 4th ed. Cambridge, UK: Cambridge University Press; 2013
  33. Yu A, Lau AY. Structure. 2018; 26: 1035-1043.e1032.
  34. Fleischhacker WW, et al. Lancet Psychiatry. 2021; 8: 191-201.