White Matter Microstructure and Its Relation to Longitudinal Measures of Depressive Symptoms in Mid- and Late Life

Abstract

BackgroundStudies of white matter microstructure in depression typically show alterations in individuals with depression, but they are frequently limited by small sample sizes and the absence of longitudinal measures of depressive symptoms. Depressive symptoms are dynamic, however, and understanding the neurobiology of different trajectories could have important clinical implications.MethodsWe examined associations between current and longitudinal measures of depressive symptoms and white matter microstructure (fractional anisotropy and mean diffusivity [MD]) in the UK Biobank Imaging Study. Depressive symptoms were assessed on two to four occasions over 5.9 to 10.7 years (n = 18,959 individuals on at least two occasions, n = 4444 on four occasions), from which we derived four measures of depressive symptomatology: cross-sectional measure at the time of scan and three longitudinal measures, namely trajectory and mean and intrasubject variance over time.ResultsDecreased white matter microstructure in the anterior thalamic radiation demonstrated significant associations across all four measures of depressive symptoms (MD: βs = .020–.029, pcorr < .030). The greatest effect sizes were seen between white matter microstructure and longitudinal progression (MD: βs = .030–.040, pcorr < .049). Cross-sectional symptom severity was particularly associated with decreased white matter integrity in association fibers and thalamic radiations (MD: βs = .015–.039, pcorr < .041). Greater mean and within-subject variance were mainly associated with decreased white matter microstructure within projection fibers (MD: βs = .019–.029, pcorr < .044).ConclusionsThese findings indicate shared and differential neurobiological associations with severity, course, and intrasubject variability of depressive symptoms. This enriches our understanding of the neurobiology underlying dynamic features of the disorder.

Brain structural associations with depression in a large early adolescent sample (the ABCD study®)

“…For example, DS from both reports was significantly associated with global cortical volume (caregiver: β = −0⋅037; child: β = −0⋅027) and surface area (caregiver: β = −0⋅034; child: β = −0⋅020), while MDD status was associated with decreased whole brain FA (caregiver: β = −0⋅030; child: Cohen's d = −0⋅021). The effect sizes were similar to those found in adults [6] . However, the current study also revealed that reports of depression by caregivers on adolescents demonstrated stronger and more numerous associations with brain structural measures than by adolescent self-report.…”

“…Adolescent depression is notably associated with a more severe illness course and can lead to the propagation of difficulties across the lifespan [4] . MDD is associated with disruptions in brain structure [5] , [6] , [7] , [8] . However, due to a lack of large-scale neuroimaging samples for adolescents, the origin and development of depression-related imaging features remains largely unknown.…”

“…Large population-based neuroimaging studies in adults have allowed unparalleled insight into the neurobiological underpinnings of depression [ 5 , 6 ]. For example, recent evidence from the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium demonstrated widespread structural abnormalities in MDD from large adult samples, including reduced hippocampal volume, decreased frontal cortical thickness [8] ( N = 10,105) and altered fronto-limbic and fronto-thalamic tract microstructure [9] ( N = 2907).…”

White matter abnormalities in adults with bipolar disorder type-II and unipolar depression

“…Our results are consistent with previous research showing that participants with BD II/NOS, compared to HC, had significant reductions in FA in the major white matter tracts 31 , and that white matter microstructure in the anterior thalamic radiation connecting thalamus to the frontal cortex 64 and arcuate fasciculus connecting temporal and parietal cortices to the frontal cortex 65 was associated with depressive symptoms. The frontal aslant tract connects the posterior part of the inferior frontal gyrus with supplementary and pre-supplementary motor areas 66 and is frequently associated with speech, language, and verbal fluency 67 , 68 .…”

Age-Related Changes of Peak Width Skeletonized Mean Diffusivity (PSMD) Across the Adult Lifespan: A Multi-Cohort Study

“…Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD) are well-established markers of normal brain maturation (1)(2)(3)(4)(5) and ageing (6)(7)(8)(9)(10)(11)(12) and have been proposed as potential tools for the investigation of various brain disorders (13)(14)(15)(16)(17)(18)(19).…”