A Dissociation in Effects of Risperidone Monotherapy on Functional and Anatomical Connectivity Within the Default Mode Network

Abstract

Respective changes in functional and anatomical connectivities of default mode network (DMN) after antipsychotic treatment have been reported. However, alterations in structure–function coupling after treatment remain unknown. We performed diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging in 42 drug-naive first-episode schizophrenia patients (FESP) both at baseline and after 8-weeks risperidone monotherapy, and in 38 healthy volunteers. Independent component analysis was used to assess voxel-wise DMN synchrony. A 3-step procedure was used to trace fiber paths between DMN components. Structure–function couplings were assessed by Pearson’s correlations between mean fractional anisotropy and temporal correlation coefficients in major tracts of DMN. Pretreatment, FESP showed impaired functional connectivity in posterior cingulate cortex/precuneus (PCC/PCUN) and medial prefrontal cortex (mPFC), but no abnormalities in fibers connecting DMN components. After treatment, there were significant increases in functional connectivities of PCC/PCUN. Increases in functional connectivity between PCC/PCUN and mPFC correlated with improvement in positive symptoms. The structure–function coupling in tracts connecting PCC/PCUN and bilateral medial temporal lobes decreased after treatment. No alterations in DMN fiber integrity were detected. This combination of functional and anatomical findings in FESP contributes novel evidence related to neurobehavioral treatment effects. Increased functional connectivities between PCC/PCUN and mPFC may be treatment response biomarkers for positive symptoms. Increases in functional connectivities, no alterations in fiber integrity, combined with decreases in structural–functional coupling, suggest that DMN connectivities may be dissociated by modality after 8-week treatment. Major limitations of this study, however, include lack of repeat scans in healthy volunteers and control group of patients taking placebo or comparator antipsychotics.

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

“…Several studies have reported differential effects of typical and atypical antipsychotics on the brain’s structure ( Bartzokis et al, 2007 , 2009 ; Vita et al, 2015 ; Leroux et al, 2018 ). Our present finding that patients on long-term risperidone monotherapy showed fewer deficits within their white matter structural networks than never-treated patients is consistent with the hypothesis that risperidone has the capacity to restore dysconnectivity and normalize topological parameters after short-term treatment ( Hu et al, 2016 ; Kraguljac et al, 2016 ; Nelson et al, 2018 ; Zong et al, 2019 ). Risperidone may thus have neuroprotective effects on white matter structural networks when administered as a long-term treatment.…”

Adjunct ketamine treatment effects on treatment-resistant depressive symptoms in chronic treatment-resistant schizophrenia patients are short-term and disassociated from regional homogeneity changes in key brain regions – a pilot study

“…Previous studies reporting that a single ketamine treatment may alleviate treatment resistant depression by normalizing aberrant activity in DMN components and the frontal cortex [66][67][68]. Although it is well established that ketamine can decrease functional activity in the DMN and other brain regions [47][48][49][50][51][52][53][54][55][56][57][58][59][60], we found increased ReHo in the DMN in CTRS patients with TRD symptoms in this pilot study. We postulated that this seemingly contradictory finding may be related to neuropathological features of schizophrenia.…”

“…Notably, neural activities in the DMN and OFC have been reported to be markedly decreased in depressive patients [51][52][53][54][55][56]. Furthermore, structural and functional deficits in the DMN and OFC have been related to affective and memory processing disturbances in patients with schizophrenia [57][58][59][60][61][62][63][64].…”

Mapping Theme Trends and Knowledge Structure of Magnetic Resonance Imaging Studies of Schizophrenia: A Bibliometric Analysis From 2004 to 2018

“…While results in this area are inconsistent, most studies have shown increased DMN functional connectivity in schizophrenia, as well as weaken functional connections in the prefrontal cortex (57,58). Nevertheless, taking antipsychotics and changes in psychiatric symptoms can influence resting brain networks, and the intrinsic relationship between genes and DMN have gradually become noteworthy academic issues in recent years (59,60).…”