A scientific analysis of the UK Biobank data revealed an association between loneliness and reduced gray matter volume in the anterior cingulate cortex and right ventrolateral prefrontal cortex regions of the brain. This correlation appears particularly strong in males diagnosed with depression, whereas it was not observed in females. The paper was published in Cerebral Cortex.
Depression or major depressive disorder is a leading cause of disability globally. It represents a profound burden both on the individual and on family, health, and social care systems. Individuals suffering from this disorder experience persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in previously enjoyable activities, Major depressive disorder can also lead to changes in appetite or weight, sleep disturbances, fatigue, feelings of worthlessness or excessive guilt, difficulty thinking or concentrating, and recurrent thoughts of death or suicide.
Research suggests that emotional difficulties in major depressive disorder may be linked to the neural circuitry responsible for emotion processing and regulation, located in the frontal-subcortical region of the brain. Numerous studies have reported structural brain abnormalities in individuals with this disorder, including reduced brain mass volume, particularly in the anterior cingulate cortex and prefrontal cortex regions.
Study author Zhenhong He and his colleagues wanted to examine whether there are abnormalities in the volume of the gray mass of the anterior cingulate cortex and the right ventrolateral prefrontal cortex regions of the brain in individuals suffering from major depressive disorder compared to brains of healthy individuals. Gray mass is mainly composed of neuronal cell bodies, dendrites, and unmyelinated axons. It is crucial for processing and interpreting information in the brain.
The researchers also sought to explore whether loneliness correlates with structural changes in these brain regions. They focused on these areas based on previous studies suggesting their connection to feelings of loneliness.
In this study, brain data from males and females were analyzed and compared separately. The data was sourced from the September 17, 2019, version of the UK Biobank database, comprising 21,402 individuals who underwent structural brain magnetic resonance imaging. The researchers excluded data from participants with extremely low or high gray matter volumes in these regions and from those who reported diagnoses of neurological or neurodevelopmental disorders.
Participants with major depressive disorder were categorized into three severity categories based on the number of depressive episodes they had. Participants with no depressive episodes were considered healthy controls. Loneliness was assessed based on answers to two questions: “Do you often feel lonely?” and “How often are you able to confide in someone close to you?” Both questions were yes/no, resulting in a loneliness score ranging from 0 to 2.
After eliminating all participants with incomplete data and those who fulfilled the criteria for exclusion, the final sample for analysis consisted of data from 339 males with major depressive disorder and 3,781 healthy male participants. The female sample included data from 666 individuals with major depressive disorder and 3,466 healthy women.
Results showed that males with major depressive disorder had lower gray mass volume in the right ventrolateral prefrontal cortex. This difference was not found in females. In males with major depressive disorder, lonelier individuals tended to have lower gray mass volumes in the left and right anterior cingulate cortex areas and in the right ventrolateral prefrontal cortex. In healthy males, lonelier individuals tended to have lower gray mass volumes in the right anterior cingulate cortex. These associations were absent in females.
“Findings indicate the adverse effect of loneliness on brain health in MDD [major depressive disorder], and the possibility that social engagement may have a direct and measurable effect on brain volume in middle-older aged men vulnerable to depression,” the study authors concluded.
The study sheds light on the links between structural brain characteristics and mental health. However, it’s important to note that it employed a cross-sectional design. Consequently, the long-term relationship between brain structure and loneliness remains unclear. The data does not clarify whether loneliness and major depressive disorder are the cause of the observed structural brain changes in males, or if these brain changes lead to the psychological symptoms of loneliness and major depression. Other possibilities remain open for exploration.
The paper, “Loneliness is related to smaller gray matter volumes in ACC and right VLPFC in people with major depression: a UK biobank study”, was authored by Zhenhong He, Youcun Zheng, Jingxuan Ni, Jin Huang, Qingqing Pang, Tongtong Chen, Nils Muhlert, and Rebecca Elliott.
