The following is a summary of “Deterioration in cognitive control related mPFC function underlying development of treatment resistance in early psychosis,” published in the June 2024 issue of Psychiatry by Crisp et al.
About a third of people with psychosis become resistant to antipsychotic treatments, and the reasons behind it are unclear.
Researchers conducted a prospective study investigating the changes in cognitive control functions as a potential behind developing resistance to antipsychotic treatment.
They studied 50 people with early psychosis at 2 points, once at the start (mean illness duration <2 years) and again a year later. By the follow-up, 35 were treatment-responsive, and 15 became resistant. Participants did an emotion-yoked reward learning task that required cognitive control while undergoing fMRI and MR spectroscopy to measure glutamate levels from the Anterior Cingulate Cortex (ACC). Changes in cognitive control-related activity (in the prefrontal cortex and ACC) between the 2 groups were compared, and the relationship with glutamate levels was examined.
The results showed that treatment-resistant participants had less activity in the right amygdala (during the decision phase) and left pallidum (during the feedback phase) at the start, which increased over time. It also showed decreased medial Prefrontal Cortex (mPFC) activity (during the feedback phase) over time. For treatment-responsive participants, there was a negative relationship between mPFC activity and glutamate levels at follow-up, which wasn’t seen in the treatment-resistant group. Reduced activity in the right amygdala and left pallidum at the start predicted treatment resistance at follow-up (67% sensitivity, 94% specificity).
Investigators concluded that as the mPFC function declined over time, it was linked to treatment resistance in early psychosis. The disconnect between glutamate and mPFC function in cognitive control warrants further study for potential interventions.
Source: nature.com/articles/s41598-024-63474-1
