DMN hyperconnectivity and structure in the clinical high-risk stage of schizophrenia
Poster No:
672
Submission Type:
Abstract Submission
Authors:
Chelsea Ajunwa1, Jiahe Zhang2, Guusje Collin3,4,5, William Stone6, Jijun Wang7, Yingying Tang7, Tianhong Zhang8, Martha Shenton9,10,11, Margaret Niznikiewicz12, Susan Whitfield Gabrieli13,14
Institutions:
1Northeastern University, Cambridge, MA, 2Northeastern University, Boston, MA, 3Radboudumc Department of Psychiatry, Nijmegen, Netherlands, 4Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands, 5McGovern Institute for Brain Research, Cambridge, MA, 6Beth Israel Deaconess Medical Center, Boston, MA, 7Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, Shanghai, 8Shanghai Mental Health Center, Shanghai, China, 9Brigham and Women's Hospital, Boston, MA, 10Research and Development, VA Boston Healthcare System, Brockton, MA, 11Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 12Department of Psychiatry, VA Boston Healthcare System, Brockton, MA, 13Department of Psychology, Northeastern University and Department of Psychiatry, MGH, Boston, MA, 14McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA
First Author:
Co-Author(s):
Guusje Collin, MD, PhD
Radboudumc Department of Psychiatry|Donders Institute for Brain, Cognition and Behaviour|McGovern Institute for Brain Research
Nijmegen, Netherlands|Nijmegen, Netherlands|Cambridge, MA
Radboudumc Department of Psychiatry|Donders Institute for Brain, Cognition and Behaviour|McGovern Institute for Brain Research
Nijmegen, Netherlands|Nijmegen, Netherlands|Cambridge, MA
Jijun Wang
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai
Yingying Tang
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai
Martha Shenton, PhD
Brigham and Women's Hospital|Research and Development, VA Boston Healthcare System|Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School
Boston, MA|Brockton, MA|Boston, MA
Brigham and Women's Hospital|Research and Development, VA Boston Healthcare System|Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School
Boston, MA|Brockton, MA|Boston, MA
Susan Whitfield Gabrieli
Department of Psychology, Northeastern University and Department of Psychiatry, MGH|McGovern Institute for Brain Research, Massachusetts Institute of Technology
Boston, MA|Cambridge, MA
Department of Psychology, Northeastern University and Department of Psychiatry, MGH|McGovern Institute for Brain Research, Massachusetts Institute of Technology
Boston, MA|Cambridge, MA
Introduction:
Schizophrenia is characterized by a diverse set of symptoms including hallucinations, delusions, social withdrawal, and impaired cognition (Tandon et al., 2009). Some of these deficits begin prior to the onset of illness, in the prodromal, or Clinical High Risk (CHR) stage, which typically occurs in adolescence or young adulthood (Cannon, 2015; Cornblatt et al., 1999; Yung & McGorry, 1996).
Both hyperactivity and hyperconnectivity of the default-mode network (DMN) have been observed in early schizophrenia (Buckner, 2013; Whitfield-Gabrieli et al., 2009). Structural abnormalities have also been observed in the disorder, especially in temporal regions, and are associated with auditory hallucinations (Shenton et al., 2001). However, the extent to which abnormal connectivity and structure are present in the CHR stage, prior to illness onset, is unknown.
Both hyperactivity and hyperconnectivity of the default-mode network (DMN) have been observed in early schizophrenia (Buckner, 2013; Whitfield-Gabrieli et al., 2009). Structural abnormalities have also been observed in the disorder, especially in temporal regions, and are associated with auditory hallucinations (Shenton et al., 2001). However, the extent to which abnormal connectivity and structure are present in the CHR stage, prior to illness onset, is unknown.
Methods:
As part of the Shanghai At-Risk for Psychosis (SHARP) program, resting-state fMRI data were collected from 251 young adults (158 CHR and 93 healthy controls, M = 18.72, SD = 4.68, 129 male). Preprocessing and analysis were performed using the CONN toolbox. We examined functional connectivity of the DMN by performing a whole-brain seed-to-voxel analysis. A 10mm sphere centered at MNI coordinates (-3, 44, -2), in the medial prefrontal cortex (MPFC), was used as the seed. We examined cortical thickness across the whole brain using FreeSurfer. For each parcel, a t-test was performed to compare the average cortical thickness between CHR and healthy controls (HC). Parcels were defined by the Destrieux cortical atlas.
Clinical and behavioral measures were also collected. A validated Chinese version of the Structural Interview for Prodromal Symptoms (SIPS) was administered, along with the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D).
Clinical and behavioral measures were also collected. A validated Chinese version of the Structural Interview for Prodromal Symptoms (SIPS) was administered, along with the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D).
Results:
Compared to controls, CHRs exhibited significantly greater functional connectivity between the MPFC and 1) the PCC, another key DMN node, and 2) the auditory cortex (middle temporal gyrus and superior temporal gyrus). Furthermore, these two patterns of hyperconnectivity were associated with distinct symptom clusters. MPFC-PCC connectivity was significantly correlated with measures of anxiety and depression (r=0.19, p=0.01), while MPFC-auditory connectivity was significantly correlated with SIPS, a measure of prodromal symptom severity (r=0.26, p=0.0006).
After FDR correction for multiple comparisons and correction for mean cortical thickness, CHRs exhibited decreased cortical thickness in a number of areas including the anterior cingulate cortex (p=0.02) and the dorsal PCC (p=0.02). They also exhibited decreased cortical thickness in the middle temporal gyrus (p=0.003) and superior temporal sulcus (p=0.006), two auditory regions.
After FDR correction for multiple comparisons and correction for mean cortical thickness, CHRs exhibited decreased cortical thickness in a number of areas including the anterior cingulate cortex (p=0.02) and the dorsal PCC (p=0.02). They also exhibited decreased cortical thickness in the middle temporal gyrus (p=0.003) and superior temporal sulcus (p=0.006), two auditory regions.
Conclusions:
These results demonstrate that two dissociable patterns of DMN hyperconnectivity precede the onset of schizophrenia and may play a mechanistic role in the pathophysiology of the disease. Furthermore, cortical thickness is decreased in regions hyperconnected to the DMN, which suggests that there is a relationship between hyperconnectivity and structure in the CHR stage of schizophrenia. These findings also provide evidence for the resting-state hypothesis of auditory hallucinations, which states that auditory hallucinations are the result of an abnormal relationship between anterior DMN regions like the MPFC and auditory regions like the superior temporal gyrus and medial temporal gyrus (Northoff & Qin, 2011).
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
ADULTS
Data analysis
FUNCTIONAL MRI
Psychiatric Disorders
Schizophrenia
STRUCTURAL MRI
1|2Indicates the priority used for review
Provide references using author date format
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