Loneliness is related to smaller gray matter volumes in ACC and right VLPFC in people with major depression: a UK biobank study

The anterior cingulate cortex (ACC) and right ventrolateral prefrontal cortex (VLPFC) are thought to have important roles in loneliness (feeling of social isolation/exclusion) experience or regulation and in the pathophysiology of their disturbance in major depressive disorder (MDD). However, the structural abnormalities of these regions and the correlates with loneliness in MDD across the healthy population have not fully been clarified. The study analyzed the link between loneliness and gray matter volumes (GMVs) in the ACC and right VLPFC among 1,005 patients with MDD and 7,247 healthy controls (HCs) using UK Biobank data. Significant reductions in GMV in the right VLPFC were found in MDD males compared to HCs. MDD males also showed a higher association between loneliness and reduced GMVs in the right VLPFC and bilateral ACC than HCs. No such associations were found in MDD females. The findings suggest that loneliness may influence brain structures crucial for emotion experience and regulation, particularly in middle-older aged men with MDD. This highlights the potential adverse effects of loneliness on brain structure in MDD and suggests that social engagement could have a positive impact.