Cognitive flexibility potential new target in treatment resistant schizophrenia

Researchers at King’s College London have found that an important brain mechanism that allows us to switch between thinking about two or more ideas may help treat patients with schizophrenia who do not respond well to current treatments. 

Schizophrenia effects approximately 1% of the population and roughly one third of patients do not get better with treatment at a high cost to the patient and their family as well as healthcare services. 

Researchers used sophisticated brain imaging techniques to look at cognitive flexibility, which is a person’s ability to flexibly update their thinking depending on new information, in 34 control, 21 treatment-responsive and 20 treatment-resistant participants recruited from the South London and Maudsley NHS Foundation Trust. Brain connectivity and levels of glutamate, a key neurotransmitter in the brain, were compared and related to the participant’s behaviour and clinical symptoms, such as hallucinations.

A new subtype of schizophrenia

During a task set by the researchers while undergoing fMRI scanning, patients with treatment resistance showed an absence of the cognitive flexibility mechanism compared to treatment-responsive patients. This suggests an alternative mechanism impacting learning and decision making that is uniquely impaired in treatment resistance.

This significantly altered cognitive flexibility suggests treatment resistance represents a subtype of schizophrenia with a distinct underlying neurobiological mechanism.

Researchers suggest that a personalised antipsychotic treatment that targets the cognitive flexibility brain mechanism may offer a new long-term treatment target. Dr Charlotte Horne, lead author and Postdoctoral research associate at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London said:

“For the first time, we show a fundamental problem in cognitive flexibility in patients with schizophrenia that fail to respond to treatment. While this is a small study, the findings are important as they present a clear target for long-term treatment in these patients. Our research also helps us move towards treatment strategies that work for each person, meaning that in future, each patient with schizophrenia has the best chance of recovery.”

Author Sukhwinder Shergill, Professor of Psychiatry & Systems Neuroscience at IoPPN and Consultant Psychiatrist at South London and Maudsley NHS Foundation Trust said:

“We propose a core non-dopaminergic impairment that impacts cognitive control networks in treatment-resistant schizophrenia. This impairment disrupted learning and could be underpinned by abnormal glutamate function. These findings inform the focus of future treatment strategies (e.g. glutamatergic targets and giving clozapine earlier) in resistant patients.”

Cognitive control network connectivity differentially disrupted in treatment resistant schizophrenia was published today (30 March 2021) in Neuroimage: Clinical and was funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre, the European Research Council and the Wellcome/EPSRC Centre for Medical Engineering.

Tags: Clinical disorders and health behaviours - Publications - Precision psychiatry - Neuroimaging -

By NIHR Maudsley BRC at 1 Apr 2021, 12:00 PM

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