Loneliness And Depression: The Role Of Personality And BDNF Val66Met Polymorphism

Loneliness is defined as a distressing feeling that accompanies the perception that one’s social needs are not being met by the quantity or especially the quality of one’s social relationships. It is a common experience, as many as 80% of those under 18 years of age and 40% of adults over 65 years of age report being lonely at least sometimes, and it is increasingly prevalent in modern societies. Feelings of loneliness generally succeed in motivating connection or reconnection with others following geographic relocation or bereavement, for instance, thereby diminishing or abolishing feelings of social isolation. For as many as 15–30% of the general population, however, loneliness is a chronic state. Loneliness has serious consequences for cognition, emotion, behavior, and health. Previous studies have shown that loneliness was associated with changes in psychological states including increased depressive symptomatology, lower subjective wellbeing, heightened vigilance for social threats, and decreased executive functioning. loneliness is associated with a constellation of demographic and psychosocial risk factors for depressive symptoms, suggested that loneliness is a unique risk factor for depressive symptomatology.Prior work has revealed that the levels of loneliness and depressive symptoms may vary across the life span, suggest that their relationship may be moderate by other variables. In light of the strong associations between personality traits and both loneliness and depressive symptoms, personality may be a potential moderator of their relationship. Personality may influence not only the exposure to stress(e.g., the experience of loneliness) but also the responses to stress. The genetic polymorphism and brain structure may also moderate the relationship between loneliness and depression. Susceptibility to loneliness is a stable trait and is to some extent heritable. Previous studies have shown that loneliness may impact regional gray matter density and brain activation to social stimuli. Animal studies showed that both social isolation and depression were associated with reduced levels of brain-derived neurotropic factor(BDNF). Therefore, the BDNF gene might be a good candidate for transducing the effects of adverse social state, such as loneliness and depression, into brain structure and function. The BDNF is a secretory protein from the neurotrophin family which is vital for the survival, maintenance, differentiation and morphology of neurons, therefore plays an important role in brain plasticity. The BDNF met-allele has been associated with memory impairments, reduced cognitive performance and increased anxiety. It also has been related to increased susceptibility to multiple neurological and psychiatric conditions including schizophrenia, Alzheimer’s disease and depression. Previous studies have shown that the Met allele contributes to reduced cortical volume in the hippocampus, prefrontal cortex, and temporal and occipital lobar regions. In addition, it has also been suggested that the Val66 Met polymorphism modify wide range white matter microstructure.The current study investigated the moderate effect of personality and BDNF Val66 Met polymorphism on the relationship between loneliness and depression.Study 1 use questionnaire measured the subjects ’ personality traits, loneliness, depression, and anxiety. Correlation analysis revealed that loneliness was positively correlated with depression, anxiety, neuroticism, and negatively correlated with extraversion, openness, agreeableness, and conscientiousness. Moderation analysis revealed that extraversion and openness could significantly moderate the correlation between loneliness and depression.Study 2 firstly used neuroimaging method to investigate how the BDNF Val66 Met polymorphism might impact the relationship between loneliness and white matter FA. Tract-based spatial statistics(TBSS) analyses revealed that there were significant BDNF genotype × loneliness interactions on white matter fractional anisotropy(FA) across widespread major fiber tracts including bilateral superior longitudinal fasciculus(SLF), corpus callosum(CC) and right corona radiata(CR). Specifically, in all the above mentioned regions, the Met carrier was associated with negative FA-loneliness correlation, the Val/Val genotype was associated with positive FA-loneliness correlation, which mean that high loneliness Met carrier was associated with reduced FA compared with Val/Val genotype. Then the mean FA value of significant cluster was extracted. Correlation analysis show that the FA value was negatively correlated with depression only in Metcarrier but not Val/Val group. In Met carriers, mediation analysis showed that the relationship between the FA value and depression could be Mediate by loneliness.In summary, the Impact of loneliness on depression can be moderate by psychological and neurogenic factors. In behavior level, extraversion and openness could significantly moderate the correlation between loneliness and depression. In neurogenic level, BDNF Val66 Met polymorphism moderate the relationship between loneliness and white matter microstructure, and also impact the relationship between loneliness-related white matter structure and depression and anxiety.