Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

Abstract

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

Coordinated Cortical Thickness Alterations across Psychiatric Conditions: A Transdiagnostic ENIGMA Study

“…Our study reports coordinated effects of six major mental disorders (SCZ, BD, OCD, ASD, ADHD, and MDD) on cortical thickness and their association with functionally relevant neurobiological patterns across multiple scales of analysis. Thus, we extended previous investigations of shared regional effects (19–22) towards a network-based approach that embeds regional alterations within cortical hierarchies of transdiagnostic covariance of illness effects.…”

“…These studies consistently report cortical thickness alterations in mental illness (10–15), which serves as a proxy measure for neuronal density, cytoarchitecture, and intracortical myelination (16–18). Crucially, previous ENIGMA findings suggest that regional morphological alterations are not only shared between disorders (19–22), but also in part associated with shared genetic etiology (20), regional pyramidal-cell gene expression (21), microstructure and neurotransmitter system organization (22). While these findings highlight regional overlaps as shared effects between disorders, the current study aims to address inter-regional dependencies capturing coordinated transdiagnostic patterns of illness effects.…”

“…Such gradients (or 'axes') compactly summarize covariance patterns via connectome decomposition techniques (35,39), and place brain regions with similar covariance profiles closer together in a common coordinate-frame, regardless of their position on the cortex. These axes offer insights into the global arrangements of cortical features and appear to be distorted in several neuropsychiatric conditions (22,(40)(41)(42). While the convergence of hierarchical neurobiological profiles thus appears to be a central feature of healthy brain organization, it is currently unknown whether the global arrangement of regional vulnerability to mental illness follows a hierarchical organization as well.…”

Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders

“…These studies consistently report cortical thickness alterations in neurodevelopmental and psychiatric disorders [10][11][12][13][14][15] , which serves as a proxy measure for neuronal density, cytoarchitecture, and intracortical myelination [16][17][18] . Crucially, previous ENIGMA findings suggest that regional morphological alterations are not only shared between disorders [19][20][21][22] , but also in part associated with shared genetic etiology 20 , regional pyramidal-cell gene expression 21 , microstructure, and neurotransmitter system organization 22 . While these findings highlight regional overlaps as shared effects between disorders, the current study aims to address inter-regional dependencies capturing coordinated transdiagnostic patterns of illness effects.…”

A phylogenetically-conserved axis of thalamocortical connectivity in the human brain

“…In contrast to delineating discrete brain regions, recent efforts in neuroimaging have focused on the definition of continuous axes of spatial variation based on measures of brain microstructure, anatomy, and/or function [25][26][27] . This approach has proven insightful, identifying continuous and overlapping patterns of anatomical variation that converge with patterns of gene expression and ontogenetic timing in the developing brain [43][44][45] ; align with hierarchies of cortical function 29,46 , and are disrupted in neurodevelopmental disorders and psychopathology 29,30,47,48 . As such, smooth transitions in anatomy, cytoarchitecture and function supported by spatially-varying gradients of gene expression may be considered a hallmark organisational motif of the mammalian brain 25,28,32,49 .…”