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Supported by (1) medical research grants CMRPG3C0041/42 from Chang Gung Memorial Hospital and NRRPG2H0031 from Ministry of Science and Technology, Taiwan to Chemin Lin (2) NMRPG3G6031/32 from Ministry of Science and Technology, Taiwan to Shwu-Hua, Lee (3) the KKHo International Charitable Foundation to Tatia Lee.
Suicide rate tends to peak in old age, and major depression is the most salient risk factor for late-life suicide. However, few studies have focused on the neuroscientific facet of suicide in the context of late-life depression (LLD).
We recruited 114 participants of LLD (28 with history of suicide attempt and 86 without) and 47 elderly controls. They received MRI scanning and behavioral assessment. White matter hyperintensity (WMH) was quantified by an automated segmentation algorithm and graph theoretical analysis was applied to resting-state fMRI. We used ANCOVA to compare group difference in WMH loading and multivariate generalized linear model to compare global and local topological parameters in fMRI signals, controlling for demographics. Partial correlation was conducted between imaging parameters and behavioral data in group of suicide attempters.
We found significant higher WMH in suicide attempters than those of LLD without suicide attempts and elderly controls (F =7.091; p = 0.001). Suicide attempters also had increased betweenness centrality (BC) in right superior occipital gyrus (SOG) (Bonferroni corrected), right precuneus (False positive corrected) and right superior temporal gyrus (uncorrected) and decreased BC in left hippocampus (uncorrected). In suicide attempters, higher BC in right SOG correlated with higher WMH, higher depression severity, higher illness awareness and insight, and lower cognitive function (digit backward), while higher BC in right precuneus correlated with higher decrease awareness and insight and higher cognitive function (digit backward).
Resonating with the vascular hypothesis in LLD, higher WMH was found in those having history of suicide attempts. However, the re-organized brain topology changes are related with divergent cognitive function and convergent heightened disease insight.
Perceived loneliness, an increasingly prevalent social issue, is closely associated with major depressive disorder (MDD). However, the neural mechanisms previously implicated in key cognitive and affective processes in loneliness and MDD still remain unclear. Such understanding is critical for delineating the psychobiological basis of the relationship between loneliness and MDD.
We isolated the unique and interactive cognitive and neural substrates of loneliness and MDD among 27 MDD patients (mean age = 51.85 years, 20 females), and 25 matched healthy controls (HCs; mean age = 48.72 years, 19 females). We assessed participants' behavioral performance and neural regional and network functions on a Stroop color-word task, and their resting-state neural connectivity.
Behaviorally, we found greater incongruence-related accuracy cost in MDD patients, but reduced incongruence effect on reaction time in lonelier individuals. When performing the Stroop task, loneliness positively predicted prefrontal-anterior cingulate-parietal connectivity across all participants, whereas MDD patients showed a decrease in connectivity compared to controls. Furthermore, loneliness negatively predicted parietal and cerebellar activities in MDD patients, but positively predicted the same activities in HCs. During resting state, MDD patients showed reduced parietal-anterior cingulate connectivity, which again positively correlated with loneliness in this group.
We speculate the distinct neurocognitive profile of loneliness might indicate increase in both bottom-up attention and top-down executive control functions. However, the upregulated cognitive control processes in lonely individuals may eventually become exhausted, which may in turn predispose to MDD onset.
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