Cognitive functioning and lifetime major depressive disorder in UK Biobank

Abstract

Background. Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD. Methods. Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use. Results. Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5). Conclusions. Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

‘Inflammaging’ in Major Depressive Disorder: Associations between markers of inflammation and brain ageing in depression across two large community-based cohorts

“…This is consistent with a large body of previous evidence demonstrating that MDD, in particular late-life depression, is associated with increased WMHs, thought to be ischemic/ cerebrovascular in origin (Firbank et al 2005;Herrmann, Le Masurier, and Ebmeier 2008;Taylor et al 2005). The frontal lobe is also important for cognition and emotional regulation and pathology in this area may explain the emotional dysregulation and cognitive dysfunction seen in MDD (de Nooij et al, 2020). These findings were however not replicated in the LBC1936 sample.…”

Neuroinflammation in the amygdala is associated with recent depressive symptoms

“…This signal in the amygdala retained its association with depression even after adjusting for effects of demographics, lifestyles, and CRP concentration that also all showed significant associations with depressive symptoms. In light of recent investigations on the UKB dataset suggesting that the more strictly defined lifetime MDD phenotype (i.e., based on CIDI-SF;(47)) may have higher genomic and behavioral relevance specific major depression (57,58), our results highlight a direct link between neuroinflammation index (i.e., inflammationrelated cellularity) in the amygdala and elevated depressive symptoms. Our findings are also consistent with a growing body of evidence showing that inflammation can contribute to depression via the stress-induced remodeling of amygdalar structure and function (59).…”

Characterizing Heterogeneity in Neuroimaging, Cognition, Clinical Symptoms, and Genetics Among Patients With Late-Life Depression

“…WM tracts connecting frontosubcortical and frontolimbic regions are most frequently affected, including the uncinate fasciculus, anterior thalamic radiation, superior longitudinal fasciculus, and posterior cingulate cortex . Dimension 2 demonstrated clinical features of patients with LLD that are frequently associated with more severe cognitive deterioration . Interestingly, previous studies using depressive symptom and cognitive scores, or metabolic-inflammatory profile, derived 1 subtype that was a healthy group and other subgroups that demonstrated higher depressive symptom scores or a more specific immune-inflammatory dysregulation profile.…”