Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Abstract

60Macroscale white matter pathways form the infrastructure for large-scale communication in 61 the human brain, a prerequisite for healthy brain function. Conversely, disruptions in the 62 brain's connectivity architecture are thought to play an important role in a wide range of 63 psychiatric and neurological brain disorders. Here we show that especially connections 64 important for global communication and network integration are involved in a wide range of 65 brain disorders. We report on a meta-analytic connectome study comprising in total 895 66 patients and 1,016 controls across twelve neurological and psychiatric disorders. We 67 extracted disorder connectome fingerprints for each of these twelve disorders, which were 68 then combined into a cross-disorder disconnectivity involvement map, representing the 69 involvement of each brain pathway across brain disorders. Our findings show connections 70 central to the brain's infrastructure are disproportionally involved across a wide range of 71 disorders. Connections critical for global network communication and integration display 72 high disturbance across disorders, suggesting a general cross-disorder involvement and 73 importance of these pathways in normal function. Taken together, our cross-disorder study 74

Spatial Patterning of Tissue Volume Loss in Schizophrenia Reflects Brain Network Architecture

“…More generally, the current results are correlational: it is impossible to infer whether deformation drives structural and/ or functional dysconnectivity reported in previous literature or vice versa, or whether there is another underlying mechanism that independently potentiates both tissue loss and dysconnectivity (72)(73)(74)(75)(76). We opted to use a high-quality healthy young control dataset as a gold standard for structural and functional connectivity.…”

“…As a result, connection patterns derived from patients may misrepresent the architectural foundation for the distributed deformation patterns that we observe in chronic patients. However, this approach ignores extensive changes in structural and functional connectivity that are well documented in schizophrenia (72,76). For example, it is possible that deterioration in white matter connectivity obstructs or reroutes the spread of pathology.…”

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“…Transdiagnostic research is yielding novel insights into role of the neuronal markers 8,10,12,20,24,63 , molecular 7,64,65 , genetic 3,5,7,22,34,54,55 as well as psychosocial factors 13,66 . Pleiotropic genetic loci associated with multiple psychiatric conditions are being identified 67 .…”