Resting-state functional MRI in treatment-resistant schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Radiology

Background:

• Schizophrenia (SCZ) pathophysiology involves brain region abnormalities.
• Functional connectivity irregularities may serve as biomarkers for treatment response or resistance.
• Resting-state functional magnetic resonance imaging (rs-fMRI) can detect connectivity changes before structural alterations.

Purpose of the Study:

• To review rs-fMRI findings on brain functional connectivity in treatment-resistant schizophrenia (TRS) and ultra-treatment-resistant schizophrenia (UTRS).
• To associate connectivity abnormalities with symptoms in TRS and UTRS.
• To evaluate support for the dysconnectivity hypothesis in schizophrenia.

Main Methods:

• A systematic review of rs-fMRI studies published in the last 10 years.
• Search focused on TRS patients unresponsive to at least two adequate antipsychotic treatments.
• Inclusion of 18 articles with 648 participants (TRS and control groups).

Main Results:

• Frontal hypoconnectivity was observed before treatment initiation (CLZ or riluzole).
• Riluzole treatment increased frontal connectivity; fronto-temporal hypoconnectivity may indicate non-response.
• Widespread abnormal connectivity noted during mixed treatments; ECT affected the limbic system.

Conclusions:

• Heterogeneity in patient cohorts and treatments limits definitive conclusions.
• Frontal brain region irregularities, particularly in the prefrontal cortex, align with the dysconnectivity hypothesis.
• Improved definitions of TRS and UTRS are crucial for future longitudinal studies to identify functional biomarkers for treatment resistance.