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.

The high prevalence of mild cognitive impairment (MCI) in Hong Kong, as previously reported, requires verification. Furthermore, the relationship between loneliness, depression, and cognitive impairment with regards to MCI are unclear. The present study aims to establish the prevalence of MCI in a community sample in Hong Kong and determine if participants with MCI feel significantly lonelier, even after depression has been taken into consideration.

Participants from a community sample (N = 376) were assessed with subjective and objective measures of cognitive impairments to determine whether the criteria had been met for MCI. The MCI cases are then compared with age, sex, and education-matched controls on subjective measures of loneliness and depression.

A total of 66 (17.6%) participants were diagnosed with MCI. These participants reported significantly higher levels of perceived loneliness and depression compared to the matched controls. Differences between groups in loneliness remained significant, even after depression levels have been controlled.

Loneliness is implicated in MCI. The relationship between loneliness and MCI is, at least, partially independent of depression. The implications of these finding are discussed.