Microstructural and diffusion tensor imaging of clozapine for treatment-resistant schizophrenia

Area of Science:

• Neuroimaging
• Schizophrenia Research
• Pharmacology

Background:

• Clozapine (CLZ) is highly effective for treatment-resistant schizophrenia (TRS).
• The underlying mechanisms of CLZ's efficacy remain unclear.
• Cortical-basal ganglia (BG) pathway dysfunction is implicated in schizophrenia and CLZ's action.

Purpose of the Study:

• To investigate the microstructural changes associated with CLZ treatment in TRS using diffusion-weighted imaging (DWI).
• To examine changes within cortical and BG gray matter and white matter tracts.

Main Methods:

• Diffusion-weighted imaging (DWI) was used in 26 participants with TRS starting CLZ.
• 19 participants were rescanned after 12 weeks of treatment.
• Microstructural and white matter measures were analyzed in relation to symptom changes.

Main Results:

• Increased mean kurtosis (MK) in left putamen, caudate, and globus pallidus correlated with CLZ response.
• Changes in corticostriatal white matter tracts (increased MK, decreased axial diffusivity, decreased fractional anisotropy) were linked to treatment response.
• Exploratory analyses connected BG microstructural changes with corticostriatal connectivity.

Conclusions:

• Microstructural changes in BG gray matter and white matter alterations in the striatum are implicated in CLZ's mechanism of action.
• These findings enhance understanding of how CLZ works in TRS.
• Further research into pharmacologic effects at the microstructural level is warranted.