Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone

Neuroimage Clin. 2015 Nov 22:10:146-58. doi: 10.1016/j.nicl.2015.11.015. eCollection 2016.

Abstract

Objective: To describe abnormalities in large scale functional networks in unmedicated patients with schizophrenia and to examine effects of risperidone on networks.

Material and methods: 34 unmedicated patients with schizophrenia and 34 matched healthy controls were enrolled in this longitudinal study. We collected resting state functional MRI data with a 3T scanner at baseline and six weeks after they were started on risperidone. In addition, a group of 19 healthy controls were scanned twice six weeks apart. Four large scale networks, the dorsal attention network, executive control network, salience network, and default mode network were identified with seed based functional connectivity analyses. Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps.

Results: In unmedicated patients with schizophrenia we found resting state connectivity to be increased in the dorsal attention network, executive control network, and salience network relative to control participants, but not the default mode network. Dysconnectivity was attenuated after six weeks of treatment only in the dorsal attention network. Baseline connectivity in this network was also related to clinical response at six weeks of treatment with risperidone.

Conclusions: Our results demonstrate abnormalities in large scale functional networks in patients with schizophrenia that are modulated by risperidone only to a certain extent, underscoring the dire need for development of novel antipsychotic medications that have the ability to alleviate symptoms through attenuation of dysconnectivity.

Keywords: ALFF, amplitude of low frequency fluctuations; Antipsychotic medication; BOLD, blood oxygen level dependent signal; BPRS, Brief Psychiatric Rating Scale; DAN, dorsal attention network; DARTEL, diffeomorphic anatomical registration using exponentiated lie algebra algorithm; DMN, default mode network; Default mode network; Dorsal attention network; ECN, executive control network; Executive control network; FD, framewise displacement; FDR, false discovery rate; HC, healthy control; KE, cluster extent; MNI, Montreal Neurological Institute; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; SZ, patient with schizophrenia; Salience network.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention / physiology
  • Brain / drug effects*
  • Brain / physiopathology*
  • Brain Mapping
  • Executive Function / physiology
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Risperidone / pharmacology*
  • Risperidone / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology*

Substances

  • Risperidone