Neurodevelopmental insights into circuit dysconnectivity in schizophrenia

Nath, Moushumi; Wong, Tak Pan; Srivastava, Lalit K.

doi:10.1016/j.pnpbp.2020.110047

Cited by 14 publications

(10 citation statements)

References 116 publications

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“…The PS follows a continuous distribution of severity, with absence of these symptoms at one end and disorders such as schizophrenia, which greatly impact daily functioning (2), at the other (3). Transition along the PS towards schizophrenia occurs predominantly during adolescence and young adulthood (2,4), and is thought to be underpinned by widespread structural dysconnectivity that emerges during this time (5–7). In this context, regional (dys)connectivity is typically characterized by examining the direct connections between a given region and the rest of the brain.…”

Section: Introductionmentioning

confidence: 99%

Network controllability in transmodal cortex predicts psychosis spectrum symptoms

Parkes

Moore

Calkins

et al. 2020

Preprint

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Background: The psychosis spectrum is associated with structural dysconnectivity concentrated in transmodal association cortex. However, understanding of this pathophysiology has been limited by an exclusive focus on the direct connections to a region. Using Network Control Theory, we measured variation in both direct and indirect structural connections to a region to gain new insights into the pathophysiology of the psychosis spectrum. Methods: We used psychosis symptom data and structural connectivity in 1,068 youths aged 8 to 22 years from the Philadelphia Neurodevelopmental Cohort. Applying a Network Control Theory metric called average controllability, we estimated each brain region's capacity to leverage its direct and indirect structural connections to control linear brain dynamics. Next, using non-linear regression, we determined the accuracy with which average controllability could predict negative and positive psychosis spectrum symptoms in out-of-sample testing. We also compared prediction performance for average controllability versus strength, which indexes only direct connections to a region. Finally, we assessed how the prediction performance for psychosis spectrum symptoms varied over the functional hierarchy spanning unimodal to transmodal cortex. Results: Average controllability outperformed strength at predicting positive psychosis spectrum symptoms, demonstrating that indexing indirect structural connections to a region improved prediction performance. Critically, improved prediction was concentrated in association cortex for average controllability, whereas prediction performance for strength was uniform across the cortex, suggesting that indexing indirect connections is crucial in association cortex. Conclusions: Examining inter-individual variation in direct and indirect structural connections to association cortex is crucial for accurate prediction of positive psychosis spectrum symptoms.

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Section: Introductionmentioning

confidence: 99%

Network controllability in transmodal cortex predicts psychosis spectrum symptoms

Parkes

Moore

Calkins

et al. 2020

Preprint

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“…Importantly this disruption in white matter integrity occurs before the onset of frank schizophrenia and worsens as symptoms progress (194)(195)(196). Additionally, diffusor tensor imaging (DTI) has revealed widespread decreases in white matter tracts across a number of long-range pathways within schizophrenia, such as frontaltemporal-limbic, and cortico-cerebellar pathways (197,198).…”

Section: The Dysconnectivity Hypothesismentioning

confidence: 99%

Oxidative Stress and the Pathophysiology and Symptom Profile of Schizophrenia Spectrum Disorders

et al. 2021

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Schizophrenia is associated with increased levels of oxidative stress, as reflected by an increase in the concentrations of damaging reactive species and a reduction in anti-oxidant defences to combat them. Evidence has suggested that whilst not the likely primary cause of schizophrenia, increased oxidative stress may contribute to declining course and poor outcomes associated with schizophrenia. Here we discuss how oxidative stress may be implicated in the aetiology of schizophrenia and examine how current understanding relates associations with symptoms, potentially via lipid peroxidation induced neuronal damage. We argue that oxidative stress may be a good target for future pharmacotherapy in schizophrenia and suggest a multi-step model of illness progression with oxidative stress involved at each stage.

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“…The PS follows a continuous distribution of severity, with absence of these symptoms at one end and disorders such as schizophrenia at the other (2,3). Transition along the PS towards schizophrenia occurs predominantly during adolescence and young adulthood (2,4), and is thought to be underpinned by widespread structural dysconnectivity that emerges during this time (5)(6)(7). In this context, regional (dys)connectivity is typically characterized by examining the direct connections between regions.…”

Section: Introduction Introduction Introduction Introductionmentioning

confidence: 99%

Network Controllability in Transmodal Cortex Predicts Positive Psychosis Spectrum Symptoms

Parkes

Moore

Calkins

et al. 2021

Biological Psychiatry

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Neurodevelopmental insights into circuit dysconnectivity in schizophrenia

Cited by 14 publications

References 116 publications

Network controllability in transmodal cortex predicts psychosis spectrum symptoms

Network controllability in transmodal cortex predicts psychosis spectrum symptoms

Oxidative Stress and the Pathophysiology and Symptom Profile of Schizophrenia Spectrum Disorders

Network Controllability in Transmodal Cortex Predicts Positive Psychosis Spectrum Symptoms

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