Takeaways on Cognitive Impairment in Schizophrenia from ACNP 2023 Annual Meeting


Check out these brief summaries on cognitive impairment in schizophrenia from an excellent session at the ACNP 2023 Annual Meeting!



Presenters Kathryn Lewandowski, PhD; Mark Weiser, MD; Sophia Frangou, FRCPsych; and Abraham Reichenberg, PhD, tackled the topic of cognitive impairment in schizophrenia at the American College of Neuropsychopharmacology 2023 Annual Meeting. As this is a major aspect of schizophrenia that can have significant long-term effects, Psychiatric Times listened in to provide you a few top takeaways.

Kathryn Lewandowski, PhD, associate professor and director of clinical programming at Harvard Medical School and McLean Hospital, characterized cognitive heterogeneity in psychosis.

“We know that people, even in the first episode of psychosis, also experience at the group level, cognitive impairments,” said Lewandowski.

She and colleagues have attempted to identify meaningful cognitive subgroups within populations via cluster analysis.1

“We can try is to see if approaches like cluster analysis can help us leverage that variability to identify distinct subgroups within that variable of interest that might tell us something meaningful about that particular presentation and that particular person,” said Lewandowski.

In order to understand what neuroprogression look like across the early course of illness and psychosis, they studied 89 participants, assessed at baseline then 8 and 16 months, using the NIH toolbox to measure cognition and number of different measures of mood, psychosis, and functioning. The 3-cluster solution was the best fit for the data. Cluster 1 was the impaired cluster with 36 participants. Cluster 2 were high performers. Cluster 3 were average.

She identified that:

-Cognitive clusters can be identified early in course of psychosis transdiagnostically

-Clusters are predictive of symptoms and functioning over time, despite few differences at baseline

-Little evidence of deterioration of cognition or symptoms over the course of follow up

-Social and occupational functioning worsened for those in the impaired cluster

-There are implications for neurobiological differences and potential for personalized interventions

Mark Weiser, MD, professor of psychiatry at Tel Aviv University, the associate director for treatment trials at the Stanley Medical Research Center, and chairman of the department of psychiatry at Sheba Medical Center, prerecorded his session from Tel Aviv on the timing of cognitive impairments in psychotic disorders.

Many patients with psychotic disorders have impaired premorbid cognitive functioning, shared Weiser. He wanted to interrogate when cognitive impairment in psychotic disorders occur, and to characterize the pattern of cognitive decline in patients with psychotic disorders.

“The problem is that the vast majority of patients who will later have schizophrenia function in the average or above average level of cognitively, hence making it impossible to use a cognition to predict to later,” said Weiser.

In this ongoing study, he examines adolescent Israeli males who were assessed by the Israeli Military Draft Board at age 17, before the onset of psychosis. To date, the study group includes 32 participants, and the control group includes 26 participants. Participants are assessed at baseline (pre-diagnosis), then 1 to 12 years after the first test and more than 6 months after their first psychotic break. The test results are then compared to controls.

The standardized draft board cognitive assessment has 4 subtests:

-Instruction comprehension

-Raven, or differentiating figures


-Verbal analogies

Results shows that 50% of patients with schizophrenia have decline in cognitive ability while the majority (55%) of controls have increases in cognitive ability. In terms of ability to understand instruction, the controls did not change much, but patients with schizophrenia declined over the course of study. On the Raven subtest, the controls performed better, and those with schizophrenia performed worse. In arithmetic, controls performed better, and those with schizophrenia again performed worse. Interestingly, in the verbal analogies subtest, the controls improved but those with schizophrenia did not show much change over study course.

The overall results relative to controls showed a mean decrease of 0.5 SD (p=0.003).

Weiser suggested that future studies should perform structural and functional MRI in order to characterize patients who decline cognitively.

Brain organization changes with age, but these investigators looked further.

“Patients with schizophrenia have older appearing brains,” shared Sophia Frangou, PhD,

professor of psychiatry at Icahn School of Medicine. Frangou shared with ACNP attendees more on the topic of BrainAGE, or the difference between neuroimaging predicted brain age and actual chronological age.

Higher BrainAGE is associated with adverse physical, cognitive, and mental health phenotypes.

How do you calculate BrainAGE?

-Machine learning algorithms

-Sample size

-Same age range

-Density of data points within any age bin

-Number of neuroimaging features used as input into machine learning models

-Handling of site effects

-Age bias confirmation

Brain aging in schizophrenia shows significant spatial variation and tracks cognitive dysfunction, Frangou shared.

Are you interested in discussing schizophrenia? Email us at PTEditor@MMHGroup.com!


1. Lewandowski KE, Baker JT, McCarthy JM, et al. Reproducibility of cognitive profiles in psychosis using cluster analysis. J Int Neuropsychol Soc. 2018;24(4):382-390.

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