The presence of metabolic syndrome is significantly associated with cognitive dysfunction in individuals with schizophrenia, according to a meta-analysis and systematic review published online in JAMA Psychiatry. In this Q&A, corresponding author Christoph U. Correll, MD, Zucker Hillside Hospital, Glen Oaks, New York, explains the study's purpose, surprising findings, and how it could help guide clinicians in choosing between antipsychotic treatments.

Q: What led you and your colleagues to investigate the association between cardiovascular risk factors and cognitive impairment in people with schizophrenia?

A: The aim of this study was to assess whether in people with schizophrenia who have cognitive dysfunction at a degree of 1 to 2 standard deviations below the population norm and who have much poorer cardiometabolic health than the general population, metabolic syndrome and its elements would be related to poorer cognition. If this were true, like in the general population, then clinicians would need to focus on physical health monitoring and improvement not only to target improved physical but also psychiatric health outcomes.

Q: Please briefly describe the study method and participants.

A: To study the association between cognitive dysfunction and cardiovascular risk factors and cognitive impairment in individuals with schizophrenia, we conducted a systematic literature search and quantitative meta-analysis.

Studies were included that (1) examined cognitive functioning in patients with schizophrenia or schizoaffective disorder; (2) investigated the association of cardiovascular disease risk factors, including metabolic syndrome, diabetes, obesity, overweight, obesity or overweight, hypertension, dyslipidemia, and insulin resistance with outcomes; and (3) compared cognitive performance of patients with schizophrenia/schizoaffective disorder between those with vs without cardiovascular disease risk factors.

The primary outcome was global cognition, defined as a test score using clinically validated measures of overall cognitive functioning; secondary outcomes included specific cognitive domains.

Altogether, 27 studies involving 10 174 individuals with schizophrenia were included in this meta-analysis.

Q: Please briefly describe the most significant finding(s).

A: We found that significantly greater global cognitive deficits were present in patients with schizophrenia who had several cardiometabolic risk factor constellations, with effect sizes that were small to medium. This included metabolic syndrome (13 studies; n = 2800; effect size = 0.31, P = 0.001), diabetes (8 studies; n = 2976; effect size = 0.32; P < 0.001), or hypertension (5 studies; n = 1899; effect size = 0.21; P < 0.001).

Nonsignificantly greater global cognitive deficits were present in patients with obesity (8 studies; n = 2779; P = 0.20), overweight (8 studies; n = 2825; P = 0.41), and insulin resistance (1 study; n = 193; P = 0.18). Worse performance in specific cognitive domains was associated with cardiovascular risk factors regarding 5 cognitive domains in patients with diabetes (effect size range, 0.23 to 0.40) as well as 4 domains with metabolic syndrome (effect size range, 0.15 to 0.40) and hypertension (effect size range, 0.15 to 0.27).

Q: Were any outcomes different than you expected?

A: We expected to also see a significant association between overweight or obesity and cognitive dysfunction. However, this association was only a numerical and not statistically significant finding. This result suggests that overweight and obesity, per se, may not exert a sufficiently large effect that results in reduced cognition. Rather downstream effects of overweight and obesity, such as metabolic syndrome, diabetes, and hypertension, may be required for cognition to be impaired in people with schizophrenia who already have reduced cognition due to the underlying psychiatric illness.

Q: Are there any practical applications of your findings for clinicians treating patients with schizophrenia?

A: The significant association of metabolic syndrome, diabetes, and hypertension with cognitive dysfunction in individuals with schizophrenia indicates that clinicians need to keep the body in mind to improve physical outcomes and not worsen already challenged cognitive functioning in this population.

Clinicians should prefer antipsychotics with low cardiometabolic risk, educate about and endorse healthy lifestyle behaviors, and proactively monitor weight and glucose and lipid parameters as well as adherence to healthy lifestyle in all individuals with schizophrenia in order to enhance not only physical health and well-being but also psychiatric outcomes via improving or, at least, not worsening cognitive dysfunction that has been associated with poor functional outcomes.

Q: Are you conducting any more research in this area, and are there any other studies you feel are needed?

A: Prospective randomized trials are needed to investigate to what degree and in which patient populations targeted interventions aimed at restoring or maintaining healthy body weight and improved cardiometabolic status can significantly improve cognition and functional outcomes in individuals with schizophrenia.

Reference:

Hagi K, Nosaka T, Dickinson D, et al. Association between cardiovascular risk factors and cognitive impairment in people with schizophrenia: a systematic review and meta-analysis. JAMA Psychiatry. 2021;78(5):510-518. doi:10.1001/jamapsychiatry.2021.0015

Christoph Correll, MD, is Professor of Psychiatry at the Zucker School of Medicine at Hofstra/Northwell, New York, New York and a professor and department chair at Charité University Medicine, Berlin, Germany. He completed his medical studies at the Free University Berlin, Germany, and Dundee University Medical School, Scotland.

Dr Correll’s research and clinical work focus on the identification, characterization, and treatment of people with severe mental illness. He further focuses on psychopharmacology, epidemiology, clinical trials, comparative effectiveness, meta-analyses, and the interface between physical health and mental health.

Declaration of interest:

Dr Correll has been a consultant and/or advisor to or has received honoraria from: Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.