Characteristics of White Matter Structural Networks in Chronic Schizophrenia Treated With Clozapine or Risperidone and Those Never Treated

Abstract

Background Despite its benefits, a major concern regarding antipsychotic treatment is its possible impact on the brain’s structure and function. This study sought to explore the characteristics of white matter structural networks in chronic never treated schizophrenia and those treated with clozapine or risperidone, and its potential association with cognitive function. Methods Diffusion tensor imaging was performed on a unique sample of 34 schizophrenia patients treated with antipsychotic monotherapy for over five years (17 treated with clozapine and 17 treated with risperidone), 17 never-treated schizophrenia patients with illness duration over five years, and 27 healthy control subjects. Graph theory and network-based statistic (NBS) approaches were employed. Results We observed a disrupted organization of white matter structural networks as well as decreased nodal and connectivity characteristics across the schizophrenia groups, mainly involving thalamus, prefrontal and occipital regions. Alterations in nodal and connectivity characteristics were relatively milder in risperidone-treated patients than clozapine-treated patients and never-treated patients. Altered global network measures were significantly associated with cognitive performance levels. Structural connectivity as reflected by NBS mediated the difference in cognitive performance levels between clozapine-treated and risperidone-treated patients. Limitations Those results are constrained by the lack of random assignment to different types of antipsychotic treatment. Conclusion These findings provide insight into the white matter structural network deficits in patients with chronic schizophrenia, either being treated or untreated, and suggest white matter structural networks supporting cognitive function may benefit from antipsychotic treatment, especially in those treated with risperidone.

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

“…The current findings, together with findings from previous studies, suggest that chronic exposure to antipsychotics may have an impact on anatomical organization of the CC in schizophrenia [ 11 , 12 ]. In this study, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region in comparison with NT-SCZ.…”

“…In contrast, clozapine has a low affinity to dopamine D2 receptors [ 10 ]. In addition, our previous study on chronic schizophrenia showed less alterations in white matter structural networks in risperidone-treated patients compared with clozapine-treated or never-treated patients [ 11 ]. However, few studies have explored the effects of long-term monotherapy with clozapine or risperidone on callosal structure in chronic schizophrenia.…”

“…In the present study, we combined structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to examine the impacts of long-term clozapine and risperidone therapies on the micro- and macrostructures [fractional anisotropy (FA) & volume respectively] of the CC. According to our previous findings [ 11 , 12 ], we hypothesized that antipsychotic-treated schizophrenia patients would show larger volumes and/or increased FA values of the CC compared with never-treated patients, especially in those with long-term risperidone monotherapy.…”

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

“…In contrast, clozapine has a low a nity to dopamine D2 receptors [10]. In addition, our previous study on chronic schizophrenia showed less alterations in white matter structural networks in risperidone-treated patients compared with clozapine-treated or never-treated patients [11]. However, few studies have explored the effects of long-term monotherapy with clozapine or risperidone on callosal structure in chronic schizophrenia.…”

“…In groups of never-treated and mono-antipsychotic treated chronic schizophrenia patients, FreeSurfer was used to automatically identify and segment CC for each participant to reduce random errors, rater errors and inter-participant variability of manual editing [12]. According to our previous ndings [11,[13][14][15], we hypothesized that long-term clozapine-treated (CT-SCZ) and risperidone-treated schizophrenia patients (RT-SCZ) would show different alterations in the volume and/or FA values of the CC.…”