ENIGMA‐DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross‐diagnostic psychiatric research

Abstract

The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessivecompulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.

Age‐related white matter changes revealed by a whole‐brain fiber‐tracking method in bipolar disorder compared to major depressive disorder and healthy controls

“…We also found significant main effects of the group in the white matter tracts of the corpus callosum and the fornix. The large‐scale ENIGMA‐DTI workgroup's research showed significant deficits in the fornix tract in BD but not in MDD, which was consistent with our findings 15 . These two tracts are commissural fibers that connect the left and right cerebral hemispheres, which generally show earlier maturation than association fibers and projection fibers.…”

“…The ENIGMA‐DTI workgroup has reported a large meta‐analysis comparing white matter deficit patterns among schizophrenia, BD, MDD, obsessive–compulsive disorder, post‐traumatic stress disorder, and traumatic brain injury patients. The patients with BD and MDD showed similar negative effect size on average FA values, and disease‐specific, significant regional reduction patterns in FA values 15 …”

A White Matter Connection of Schizophrenia and Alzheimer’s Disease

“…The RVI is a simple measure of the similarity between an individual and the expected deficit pattern derived from a representative disease sample. 31 , 32 In this study, it is calculated as a correlation between an individual’s pattern of FA in the 22 white matter regions and the expected pattern of a disease condition. Regional FA for each tract was z -normalized by calculating the residual values after the regression of age and sex effects, and then subtracting the average value for a region and dividing it by the standard deviation calculated from the sample’s healthy controls.…”

“… 19–30 A large and inclusive meta-analytic SZ study performed by the Enhancing Neuro Imaging Genetics Meta-Analysis (ENIGMA) consortium showed that patients have reproducible and stable patterns of white matter deficits. 31 Here, we aimed to evaluate the similarity of the white matter deficit patterns between AD and SZ as a potential explanation for the higher risk of developing AD in SZ patients.…”

Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment‑resistant schizophrenia using miRNA sequencing and integrated bioinformatics

“…Several studies have made outstanding contributions to the development of precise psychiatric medical treatments. The eniGMa-diffusion Tensor imaging working group confirmed that the normal variation of human white matter is genetically associated with mental, neurological and developmental disorders (44,45). The eniGMa consortium performed a meta-analysis of 760 patients with ScZ and 957 healthy participants and revealed that the cognitive function of patients with ScZ is associated with the connectivity of the overall brain structure (46).…”