Schizophrenia‐like topological changes in the structural connectome of individuals with subclinical psychotic experiences

Abstract

Schizophrenia is often regarded as a “dysconnectivity” disorder and recent work using graph theory has been used to better characterize dysconnectivity of the structural connectome in schizophrenia. However, there are still little data on the topology of connectomes in less severe forms of the condition. Such analysis will identify topological markers of less severe disease states and provide potential predictors of further disease development. Individuals with psychotic experiences (PEs) were identified from a population‐based cohort without relying on participants presenting to clinical services. Such individuals have an increased risk of developing clinically significant psychosis. 123 individuals with PEs and 125 controls were scanned with diffusion‐weighted MRI. Whole‐brain structural connectomes were derived and a range of global and local GT‐metrics were computed. Global efficiency and density were significantly reduced in individuals with PEs. Local efficiency was reduced in a number of regions, including critical network hubs. Further analysis of functional subnetworks showed differential impairment of the default mode network. An additional analysis of pair‐wise connections showed no evidence of differences in individuals with PEs. These results are consistent with previous findings in schizophrenia. Reduced efficiency in critical core hubs suggests the brains of individuals with PEs may be particularly predisposed to dysfunction. The absence of any detectable effects in pair‐wise connections illustrates that, at less severe stages of psychosis, white‐matter alterations are subtle and only manifest when examining network topology. This study indicates that topology could be a sensitive biomarker for early stages of psychotic illness. Hum Brain Mapp 36:2629–2643, 2015.© 2015 TheAuthors Human Brain Mapping Published by Wiley Periodicals, Inc.

The Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort as a resource for studying psychopathology in childhood and adolescence: a summary of findings for depression and psychosis

“…Autistic traits [84,85] and some [86,87] (but not all [86]) markers of poor social cognition are also associated with increased risk of PEs. These findings, along with evidence of brain structural differences and dysfunctional connectivity [88] lend support to the thesis that early life exposures can have subtle impacts on cerebral development, cognitive function, and onset of PEs in keeping with the neurodevelopmental hypothesis of schizophrenia.…”

Graph theory and cognition: A complementary avenue for examining neuropsychological status in epilepsy

“…Graph theory analyses of brain-related networks have led to possible investigations of whole-brain functional connectivity (fMRI), white-matter connectivity (DTI), and gray matter covariance analyses (GM) in both healthy and populations with a CNS disease or disorder [9, 24-25]. Therefore, this method has the capacity to investigate the brain at its different levels as a whole.…”

Disorganized Gyrification Network Properties During the Transition to Psychosis

“…15 Such graph-based network studies capture an important aspect of developmental maturation that is crucial for understanding the pathophysiology of psychotic disorders. 19,20 Previous studies reported reduced small-worldness of structural brain networks in patients with schizophrenia, [21][22][23] CHR individuals, 24 people at increased familial risk for schizophrenia, [25][26][27] and those with subclinical psychotic experiences, 28 characterized by increased segregation and decreased interaction of anatomical covariance (see the published reviews 18,19,[29][30][31] of network analyses in schizophrenia). Of various regional morphometric properties that can be assessed for structural covariance, gyrification is a compelling marker of early neurodevelopment.…”