Researchers identify genetic associations of neuroticism
An international research team led by the University of Glasgow has discovered nine new genetic associations linked to neuroticism — a personality dimension strongly connected to depression, anxiety and a range of physical health conditions including cardiovascular disease. The findings, published in Molecular Psychiatry, improve our understanding of the biological contributions to personality and to vulnerability to mental illness.
The study was co-led by Professor Daniel Smith at the Institute of Health and Wellbeing and included collaborators from the Universities of Edinburgh and Cardiff and the Queensland Institute of Medical Research in Australia. Researchers analysed genetic and questionnaire data from more than 100,000 individuals drawn from the UK Biobank, the Generation Scotland sample and the Queensland cohort.
Neuroticism is one of the five major personality traits and is characterized by a tendency to experience negative emotions such as anxiety, worry and low mood. High neuroticism is a well-established risk factor for common psychiatric disorders, particularly clinical depression and anxiety disorders, and it is also associated with poorer physical health outcomes such as obesity and heart disease.
This investigation represents the largest genetic study focused on a single personality trait to date. By combining multiple large samples, the research team identified nine distinct regions of the genome where variation is associated with individual differences in neuroticism. These gene associations point toward biological pathways that may underlie why some people are more likely to experience persistent negative emotion and why they are at greater risk of developing mood and anxiety disorders.
Professor Daniel Smith said: “As a psychiatrist, this is an exciting discovery because we have identified for the first time genetic risk factors for a personality trait which is of fundamental importance for psychological wellbeing.
“This work could open new avenues for future research and for the identification of new treatment approaches for depression and anxiety. It is a first step to understanding the biology and genetic basis of a person’s vulnerability to depression and anxiety.”
Although further work is required to determine the precise DNA changes that are driving these associations, the results highlight candidate molecules that may link neuroticism to mental illness. Among the implicated pathways are systems that help the body respond to stress and mechanisms that influence glutamate function, a key neurotransmitter involved in a range of psychiatric conditions.
Glutamate is critical for normal brain signalling and plasticity; alterations in glutamatergic function have been implicated in depression, schizophrenia and suicidal behaviour. The involvement of stress-response pathways also fits with extensive evidence that stress sensitivity is crucial in the development and course of mood and anxiety disorders.
Professor Ian Deary of the University of Edinburgh, who has researched human personality for decades, commented: “I have been researching on human personality for almost 30 years. These new results are, at last, a start for our understanding the biological mechanisms that predispose some people to generally feel more anxious and low in mood than others.”
Professor Michael O’Donovan of Cardiff University added perspective on the broader implications: “This research confirms at a molecular level what epidemiological research has clearly shown to those who are not blinded by prejudice; to understand the origins of psychological traits, the most human of all our characteristics, we have to understand both our genetic inheritance and our environment.”
Dr Raliza Stoyanova, Neuroscience & Mental Health Senior Portfolio Developer at the Wellcome Trust, noted the value of pooling large datasets: “By combining a number of very large studies, including UK Biobank, the researchers have identified new genetic associations for neuroticism – one of the five fundamental personality traits present in all of us.
“It will be important for future work to uncover how these genetic links affect brain function, and to pin down whether they increase someone’s chance of developing clinical depression.”
Source: Ali Howard – University of Glasgow
Image Credit: Image is in the public domain.
Original Research: The study appears in Molecular Psychiatry.