Replicable association between human cytomegalovirus infection and reduced white matter fractional anisotropy in major depressive disorder

Abstract

Major depressive disorder (MDD) is associated with reductions in white matter microstructural integrity as measured by fractional anisotropy (FA), an index derived from diffusion tensor imaging (DTI). The neurotropic herpesvirus, human cytomegalovirus (HCMV), is a major cause of white matter pathology in immunosuppressed populations but its relationship with FA has never been tested in MDD despite the presence of inflammation and weakened antiviral immunity in a subset of depressed patients. We tested the relationship between FA and HCMV infection in two independent samples consisting of 176 individuals with MDD and 44 healthy controls (HC) (Discovery sample) and 88 participants with MDD and 48 HCs (Replication sample). Equal numbers of HCMV positive (HCMV+) and HCMV negative (HCMV−) groups within each sample were balanced on ten different clinical/demographic variables using propensity score matching. Anti-HCMV IgG antibodies were measured using a solid-phase ELISA. In the Discovery sample, significantly lower FA was observed in the right inferior fronto-occipital fasciculus (IFOF) in HCMV+ participants with MDD compared to HCMV− participants with MDD (cluster size 1316 mm3; pFWE < 0.05, d = −0.58). This association was confirmed in the replication sample by extracting the mean FA from this exact cluster and applying the identical statistical model (p < 0.05, d = −0.45). There was no significant effect of diagnosis or interaction between diagnosis and HCMV in either sample. The effect of chronic HCMV infection on white matter integrity may—in at-risk individuals—contribute to the psychopathology of depression. These findings may provide a novel target of intervention for a subgroup of patients with MDD.

Morphological similarity of amygdala-ventral prefrontal pathways represents trait anxiety in younger and older adults

“…Prior to further processing images, quality checks on diffusion images were performed using QUAD and SQUAD, the automated quality control tool in FSL ( 79 ). Results indicated that all participants fell under the exclusion threshold from previous literature, which was average volume-to-volume head motion of <3 mm or <5% of total outliers ( 80 , 81 ). Visual inspection on the cleaned images confirmed this result, but because diffusion images are especially susceptible to head motion ( 82 ), head motion effects were further tested, as discussed in Control Analyses .…”

Brain structure and connectivity in psoriasis and associations with depression and inflammation; findings from the UK biobank

“…Fronto-occipital connections are implicated in visuospatial processing and motor function ( Makris et al, 2005 ), whilst impaired connectivity of long-distance tracts, such as the fronto-occipital and longitudinal fasciculi, which link several areas involved in pain perception and attention, has been associated with chronic pain ( Geha et al, 2008 ; Rayhan et al, 2013 ). Emerging evidence suggests that systemic inflammation leads to disruption of fronto-occipital WM tract integrity in humans ( Ho et al, 2022 ; Tagliapietra and Monaco, 2020 ; Zheng et al, 2021 ). Neutrophils and CRP did not correlate with edge strength in the current study; however, our PsA sample was small and larger studies are needed to replicate this result.…”

Cytomegalovirus antibodies are associated with mood disorders, suicide, markers of neuroinflammation, and microglia activation in postmortem brain samples

“…We recently published some of the rst work linking CMV seropositivity to neuroimaging abnormalities in the context of major depressive disorder (MDD). In up to three independent samples, we demonstrated that compared to CMV seronegative individuals with MDD, CMV positive individuals with MDD had widespread reductions in gray matter volume, decreased white matter integrity in a tract connecting the frontal and occipital lobes (inferior frontal occipital fasciculus), and reduced functional connectivity between hubs of the sensorimotor and salience networks [21][22][23] . Leboyer and colleagues had previously reported that CMV antibody levels were inversely associated with hippocampal volume in individuals with bipolar disorder (BD) and schizophrenia 24 .…”