TY - JOUR
T1 - Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia
AU - Li, T
AU - Wang, Q
AU - Zhang, J
AU - Rolls, ET
AU - Yang, W
AU - Palaniyappan, L
AU - Zhang, L
AU - Cheng, W
AU - Yao, Y
AU - Liu, Z
AU - Gong, X
AU - Luo, Q
AU - Tang, Y
AU - Crow, TJ
AU - Broome, MR
AU - Xu, K
AU - Li, C
AU - Wang, J
AU - Liu, Z
AU - Lu, G
AU - Wang, F
AU - Feng, J
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.
AB - Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.
KW - whole brain functional-connectivity analysis
KW - thalamus
KW - resting-state fMRI
KW - clinical staging model
KW - Broca’s area
U2 - 10.1093/schbul/sbw099
DO - 10.1093/schbul/sbw099
M3 - Article
SN - 0586-7614
VL - 43
SP - 436
EP - 448
JO - Schizophrenia bulletin
JF - Schizophrenia bulletin
IS - 2
ER -