White Matter Abnormalities in Major Depression Biotypes Identified by Diffusion Tensor Imaging

Abstract

Identifying data-driven biotypes of major depressive disorder (MDD) has promise for the clarification of diagnostic heterogeneity. However, few studies have focused on white-matter abnormalities for MDD subtyping. This study included 116 patients with MDD and 118 demographically-matched healthy controls assessed by diffusion tensor imaging and neurocognitive evaluation. Hierarchical clustering was applied to the major fiber tracts, in conjunction with tract-based spatial statistics, to reveal white-matter alterations associated with MDD. Clinical and neurocognitive differences were compared between identified subgroups and healthy controls. With fractional anisotropy extracted from 20 fiber tracts, cluster analysis revealed 3 subgroups based on the patterns of abnormalities. Patients in each subgroup versus healthy controls showed a stepwise pattern of white-matter alterations as follows: subgroup 1 (25.9% of patient sample), widespread white-matter disruption; subgroup 2 (43.1% of patient sample), intermediate and more localized abnormalities in aspects of the corpus callosum and left cingulate; and subgroup 3 (31.0% of patient sample), possible mild alterations, but no statistically significant tract disruption after controlling for family-wise error. The neurocognitive impairment in each subgroup accompanied the white-matter alterations: subgroup 1, deficits in sustained attention and delayed memory; subgroup 2, dysfunction in delayed memory; and subgroup 3, no significant deficits. Three subtypes of white-matter abnormality exist in individuals with major depression, those having widespread abnormalities suffering more neurocognitive impairments, which may provide evidence for parsing the heterogeneity of the disorder and help optimize typespecific treatment approaches.

Biotypes of major depressive disorder: Neuroimaging evidence from resting-state default mode network patterns

“…Results of the present study also suggest that patients with MDD mainly exhibit two subtypes with dysfunctional connectivity of the DMN, which are identified in a large multi-site sample and replicated in an independent single-site dataset. Our prior study also reported that subtype of MDD with widespread white-matter abnormalities had more neurocognitive deficit ( Liang et al, 2019 ). Findings of subtypes with distinct profiles of brain abnormalities may reveal the potential neurobiological substrates of key sources of heterogeneity in depression ( Price et al, 2017a , Williams, 2016 ).…”

Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice

“…The acute effects of psychedelics resemble some of the positive symptoms (i.e., hallucinations and delusions) in patients with schizophrenia ( Vollenweider et al, 1998 ; Schmid et al, 2015 ), and chronic LSD administration alters rat frontal cortex expression of a group of genes relevant to schizophrenia ( Martin et al, 2014 ). Markers linked to white matter structural changes, which have been associated with depression ( Liang et al, 2019 ), were also significantly altered upon DOI administration.…”

Prolonged epigenetic and synaptic plasticity alterations following single exposure to a psychedelic in mice

“…The acute effects of psychedelics resemble some of the positive symptoms ( i.e ., hallucinations and delusions) in patients with schizophrenia ( 50, 51 ), and chronic LSD administration alters rat frontal cortex expression of a group of genes relevant to schizophrenia ( 59 ). Markers linked to white matter structural changes, which have been associated with depression ( 60 ), were also significantly altered upon DOI administration. We identified genetic substrates associated with depression in the epigenomic landscapes of DOI exposure, but the concurrence of genetic markers for schizophrenia may serve as a molecular warning on the risks associated to the use of psychedelics in psychotic-prone individuals.…”