Gender-specific structural abnormalities in major depressive disorder revealed by fixel-based analysis

Abstract

BackgroundMajor depressive disorder (MDD) is a chronic disease with a large global impact. There are currently no clinically useful predictors of treatment outcome, and the development of biomarkers to inform clinical treatment decisions is highly desirable.MethodsIn this exploratory study we performed fixel-based analysis of diffusion MRI data from the International Study to Predict Optimized Treatment in Depression with the aim of identifying novel biomarkers at baseline that may relate to diagnosis and outcome to treatment with antidepressant medications. Analyses used MR data from individuals with MDD (n = 221) and healthy controls (n = 67).ResultsWe show focal, gender-specific differences in the anterior limb of the internal capsule (males) and bilaterally in the genu of the corpus callosum (females) associated with diagnosis. Lower fibre cross-section in the tapetum, the conduit between the right and left hippocampi, were also associated with a decreased probability of remission. Analysis of conventional fractional anisotropy showed scattered abnormalities in the corona radiata, cerebral peduncles and mid-brain which were much lower in total volume compared to fixel-based analysis.ConclusionsFixel-based analysis appeared to identify different underlying abnormalities than conventional tensor-based metrics, with almost no overlap between significant regions. We show that MDD is associated with gender specific abnormalities in the genu of the corpus callosum (females) and in the anterior limb of the internal capsule (males), as well as gender-independent differences in the tapetum that predict remission. Diffusion MRI may play a key role in future guidance of clinical decision-making for MDD.

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

“…Across both sexes, lower fiber cross-section, an approximation of the fiber bundle area perpendicular to fiber length, in the tapetum predicted decreased likelihood for remission after antidepressant treatment [Lyon et al, 2019]. As the tapetum is the major connector between the left and right hippocampus, these findings align with existing studies by our group and others implicating the hippocampus as a common site for brain disruption in MDD.…”

Prevalence of depression and its association with quality of life in clinically stable patients with COVID-19

“…Higher prevalence of depression in women was associated with hormonal changes (Marrocco and McEwen, 2016) and sex chromosome aneuploidies (Green et al, 2019). Neuroimaging studies of structural changes of the genu of the corpus callosum may implicate different risk of depression between genders (Lyon et al, 2019). Moreover, gut microbiota-immune-brain axis function may also contribute to gender differences in depression (Audet, 2019).…”

Fixel-based analysis reveals fiber-specific alterations during the progression of Parkinson’s disease

“…FBA facilitates fiber tract-specific comparisons, in contrast to analyses of voxel-averaged metrics. This method has been used to detect white matter alterations in several diseases, including Alzheimer’s disease ( Mito et al, 2018 ), Major Depression Disorder ( Lyon et al, 2019 ), and Multiple Sclerosis ( Gajamange et al, 2018 ), and has been shown to demonstrate good sensitivity and reliability.…”