Abstract
Major Depressive Disorder (MDD) is a disabling illness affecting more than 5% of the elderly population. Higher female prevalence and sex-specific symptomatology have been observed, suggesting that biologically-determined dimensions might affect the disease onset and outcome. Rumination and executive dysfunction characterize adult-onset MDD, but sex differences in these domains and in the related brain mechanisms are still largely unexplored. The present pilot study aimed to explore any interactions between adult-onset MDD and sex on brain morphology and brain function during a Go/No-Go paradigm. We hypothesized to detect diagnosis by sex effects on brain regions involved in self-referential processes and cognitive control. Twenty-four subjects, 12 healthy (HC) (mean age 68.7 y, 7 females and 5 males) and 12 affected by adult-onset MDD (mean age 66.5 y, 5 females and 7 males), underwent clinical evaluations and a 3T magnetic resonance imaging (MRI) session. Diagnosis and diagnosis by sex effects were assessed on regional gray matter (GM) volumes and task-related functional MRI (fMRI) activations. The GM volume analyses showed diagnosis effects in left mid frontal cortex (p < 0.01), and diagnosis by sex effects in orbitofrontal, olfactory, and calcarine regions (p < 0.05). The Go/No-Go fMRI analyses showed MDD effects on fMRI activations in left precuneus and right lingual gyrus, and diagnosis by sex effects on fMRI activations in right parahippocampal gyrus and right calcarine cortex (p < 0.001, ≥ 40 voxels). Our exploratory results suggest the presence of sex-specific brain correlates of adult-onset MDD–especially in regions involved in attention processing and in the brain default mode–potentially supporting cognitive and symptom differences between sexes.
Highlights
Major depressive disorder (MDD) is a disabling psychiatric illness affecting an increasing proportion of the global population, reaching a peak of 5.74% in late adulthood, higher among females (6.75%) compared to males (4.60%) [1, 2].The growing burden of disease in the elderly population is partly attributable to social risk factors, including stressful life events, which have been shown to facilitate Major Depressive Disorder (MDD) onset during adulthood [3,4,5,6,7]
Total Hamilton Depression Rating Scale (HDRS) scores were higher in MDD subjects compared to healthy controls (HC) and in females compared to males, but no diagnosis by sex effects emerged
In the “Go/No-Go” blocks, the percentage of correct responses to target stimuli was slightly higher in HC compared to MDD and in females compared to males, with stronger diagnosis by sex effects
Summary
Major depressive disorder (MDD) is a disabling psychiatric illness affecting an increasing proportion of the global population, reaching a peak of 5.74% in late adulthood, higher among females (6.75%) compared to males (4.60%) [1, 2].The growing burden of disease in the elderly population is partly attributable to social risk factors, including stressful life events, which have been shown to facilitate MDD onset during adulthood [3,4,5,6,7]. Major depressive disorder (MDD) is a disabling psychiatric illness affecting an increasing proportion of the global population, reaching a peak of 5.74% in late adulthood, higher among females (6.75%) compared to males (4.60%) [1, 2]. In MDD in general, sex differences are not limited to the rates of disease, and involve its clinical presentation, with females developing more somatic symptoms, comorbid anxiety disorders and atypical depression, and males having higher mortality rates, both from suicide and from somatic comorbidity or substance abuse [4, 5, 15]. Differences in the cognitive correlates of MDD between females and males have been observed, even if the results appear fragmented [16, 17]
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