Abstract
BackgroundRecent neuroimaging studies revealed dysregulated neurodevelopmental, or/and neurodegenerative trajectories of both structural and functional connections in schizophrenia. However, how the alterations in the brain’s structural connectivity lead to dynamic function changes in schizophrenia with age remains poorly understood.MethodsCombining structural magnetic resonance imaging and a network control theory approach, the white matter network controllability metric (average controllability) was mapped from age 16 to 60 years in 175 drug-naïve schizophrenia patients and 155 matched healthy controls.ResultsCompared with controls, the schizophrenia patients demonstrated the lack of age-related decrease on average controllability of default mode network (DMN), as well as the right precuneus (a hub region of DMN), suggesting abnormal maturational development process in schizophrenia. Interestingly, the schizophrenia patients demonstrated an accelerated age-related decline of average controllability in the subcortical network, supporting the neurodegenerative model. In addition, compared with controls, the lack of age-related increase on average controllability of the left inferior parietal gyrus in schizophrenia patients also suggested a different pathway of brain development.ConclusionsBy applying the control theory approach, the present study revealed age-related changes in the ability of white matter pathways to control functional activity states in schizophrenia. The findings supported both the developmental and degenerative hypotheses of schizophrenia, and suggested a particularly high vulnerability of the DMN and subcortical network possibly reflecting an illness-related early marker for the disorder.
Highlights
Recent neuroimaging studies revealed dysregulated neurodevelopmental, or/and neurodegenerative trajectories of both structural and functional connections in schizophrenia
Further analysis revealed that the patients with schizophrenia had lower average controllability than healthy controls, but showed no significant age-related change on average controllability of default mode network (DMN) network (r = 0.11, p = 0.148), while healthy controls showed significant age-related decline on average controllability of DMN (r = −0.17, p = 0.036) (Fig. 1)
Further analysis revealed that the patients with schizophrenia showed significant age-related decline on average controllability of subcortical network (r = −0.19, p = 0.011), while healthy controls showed no significant age-related change (r = 0.11, p = 0.195) (Fig. 1)
Summary
Recent neuroimaging studies revealed dysregulated neurodevelopmental, or/and neurodegenerative trajectories of both structural and functional connections in schizophrenia. The prior findings of accelerated aging in gray matter [9, 10], white matter [11, 12] and largescale functional brain networks in schizophrenia [13] provided evidence supporting the neurodegenerative model underlying schizophrenia. In this context, schizophrenia might be a disorder that incorporates both neurodevelopmental and neurodegenerative processes, but which brain regions/networks are specific to each of them remains to be established
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