Study On The Influential Factors And The Underlying Neurogenetic Mechanism Of Neuroticism

Neuroticism is an important dimension of the trait personality theory,which refers to the stability of individual emotions.It not only has a specific innate genetic basis,but also is affected by the environment,especially the family environment in which the individual grows up.Neurotic personality can affect individuals' perception of things.Individuals with high neuroticism are more likely to experience negative emotional stimuli and are more sensitive to stressful events.As an important personality trait,neuroticism is also an important risk factor for many common mental illnesses,such as depression and anxiety disorders.Therefore,comprehensively investigate the causes of neuroticism and explore the potential genetic and brain mechanism of neurotic personality,which has important theoretical values for the cultivation of sound personality and the prevention and intervention of neurotic mood disorders in the future.All the time,neuroticism is the focus of personality research,scholars try to understand the individual differences on neuroticism from various aspects.In terms of psychological cognition,some researchers found that individuals with high neuroticism were more likely to experience negative emotions even when faced with the same stimuli,and they were more sensitive to stress events;some researchers found a significant negative correlation between neuroticism and individual well-being;others found that individuals with high neuroticism were more likely to have physical or mental health problems.In terms of genetic factors,the twin studies found that genetic factors could account for 41% to 61% of the total variation of individual neuroticism,the whole genome association study revealed a close relationship between neuroticism and some of the genetic variants,and the research of candidate genes also confirmed that individuals with different genotypes had significant differences in neuroticism.In terms of the environmental factors,the family environment of individual growth also plays a vital role in shaping neurotic personality.Previous studies found that negative parenting styles,like severe and lack of warm care,physical abuse or emotional neglect in childhood,and low family socioeconomic status were closely linked to high neuroticism.In terms of neural basis,structural imaging studies found that there were significant differences in total brain volume,frontal cortical thickness,and regional gray matter volume among different levels of neurotic individuals;resting state imaging studies found that the strength of functional connectivity between brain regions was associated with neuroticism;and a large number of task imaging studies also found significant differences in the intensity of activation of brain regions in different neurotic individuals when viewing different types of stimuli.Although there are many unilateral findings about neuroticism,few studies have combined genetic,environmental,and imaging data to research the effects of the complex interactions among these factors on neuroticism.Therefore,this study aims to explore how genetic factors,family environmental factors,and the interaction between them affect the formation of neurotic personality,to explore the relationship between genetic factors,brain structure and neuroticism,and to reveal the underlying biological mechanism behind this complex relationship.Study 1 attempts to investigate how the genetic factors and their interactions with family environment affect neurotic personality.Considering that neuroticism is a complex polygenic personality trait,this study calculated the neurotic polygenic risk score for each subject based on the results of a large sample genome-wide association study of neuroticism to predict individual neurotic personality.After that,the relationship between family environment and neurotic personality was explored,and how the interaction between each sub-dimension of family environment and genetic factors affected neuroticism was also studied.The results showed that polygenic risk score of neuroticism significantly predicted individuals' neurotic personality at some different thresholds;cohesion,conflict,intellectual cultural orientation,active recreational orientation,and organization in the family environment were significantly related to neurotic personality;and cohesion and expressiveness significantly regulated the relationship between gene and neurotic personality.In a high cohesion or high expressiveness environment,genetic factors had a great influence on neurotic personality.But in a low cohesion or low expressiveness environment,genetic factors did not significantly affect neurotic personality.Study 2 aims to explore the relationship between genetic factors,brain structure and neuroticism based on the gene-brain-behavior model.Whereas the previous studies have found that cortical thickness and surface area are the two brain indicators that can most effectively reveal the connection between genetic factors and neural basis,and cortical thickness is stable and reliable under different scanners,scanning sequences and magnetic field intensity,this study selects cortical thickness for subsequent analysis.First,the subjects' intracranial volume was regressed to re-calculate the polygenic risk score,and the new polygenic risk score was used to predict neuroticism.Secondly,whole brain regression analysis was used to examine the association between the cortical thickness of some brain regions and neurotic polygenic risk scores.The mean cortical thickness value of each significantly region was then extracted.Finally,mediation analysis was performed to explore the relationship among the polygenic risk score,cortical thickness of the significant regions,and neurotic personality.The results showed that the polygenic risk scores of neuroticism still significantly predicted neuroticism,and it was also negatively associated with the cortical thickness of the left rostral middle frontal gyrus.The mean value of this region significantly mediated the prediction of neuroticism related genetic factors on neuroticism.The goal of study 3 is to explore the link between the genetic risk factors of neuroticism and the cortical thickness of significant region and its changes after one year by using the longitudinal brain imaging data,and to reveal the underlying biological mechanisms by which genetic factors influence brain structure.Firstly,the cortical thickness in the left rostral middle frontal gyrus was extracted,and its changes was calculated.Next,paired sample t test was used to investigate whether the cortical thickness of this region was changed.The genetic risk of neuroticism was then used to predict the cortical thickness value and its changes in this region.Finally,the existing biological information databases were used to annotate the function of neuroticism-related genes.Results showed that there was significant difference in cortical thickness between the two measurements,the neurotic polygenic risk score significantly predicted individual's cortical thickness in the left rostral middle frontal gyrus,but there was no significant relationship between the changes and the neurotic polygenic risk scores.In addition,the results also found that neuroticism related genes were primarily involved in cell or biological adhesion,neuronal projection guidance,axonal guidance,and neuronal or synaptic components,and these genes were also significantly overexpressed in some common psychiatric disorders,such as depression and substance abuse.In short,this study found that genetic factors,family environment and the interaction between them were related to neuroticism;genetic risk factors for neuroticism could influence individuals' neuroticism by affecting the cortical thickness of the left rostral middle frontal gyrus,and this effect on brain are sustained;genes related to neuroticism mainly affect the underlying biological mechanisms about neurons,axons,and the formation of brain network,and these genes were also associated with many common mental disorders,like depression.In summary,through a cross-scale approach,this study revealed the complex interaction between gene and family environment in the formation of neurotic personality,and revealed the complex relationships between gene,brain structure and neuroticism,which helps to comprehensively understand the formation mechanism of individual neuroticism,provides reference value for preventing the development of high neuroticism and cultivating sound personality.