The genetics of neuroticism slowly unpicked

Neuroticism is a personality trait that predisposes people to other mental and physical health issues. For the first time, it has been linked to multiple genetic components. The study, published in Molecular Psychology, may eventually open doors to new forms of treatment for an array of mental health conditions.
[Gene markers laboratory]
The origins of neuroticism might slowly be giving up their secrets.

Neuroticism is a human trait found across all cultures, making it a subject of interest since personalities were first studied.

In a nutshell, neuroticism is the tendency to respond to threat, loss or frustration with negative emotions; it is considered to be one of five fundamental personality traits that we all display to some degree.

Although in itself, it is not necessarily a health issue, it is known to be associated with other, more serious conditions.

Among others, neuroticism is associated with obesity, anxiety disorders, substance misuse and schizophrenia. There is also evidence that our level of neuroticism predicts our quality and longevity of life.

As with any psychological trait, the environment plays a part, but twin studies have shown that around 40% of trait variance for neuroticism is heritable.

Untangling the neurotic genome

Because neuroticism is so widespread and linked to other, more troublesome conditions, discovering its origins and the mechanisms behind it could be hugely beneficial for society at large.

Previous research has uncovered a single genetic location on chromosome 3 that appears to be involved in the trait; Prof. Daniel Smith from the University of Glasgow’s Institute of Health and Wellbeing set out to unearth more genetic markers for neuroticism.

Prof. Smith’s team, including researchers from the Universities of Edinburgh and Cardiff, UK, and Queensland, Australia, conducted a genome-wide association study, hunting for the genetic fingerprints of neuroticism.

Involving more than 10,000 individuals, the study is the largest genetic study of a particular personality trait ever undertaken. The data was retrieved from the UK Biobank cohort, the Generation Scotland sample and the Queensland Institute of Medical Research sample.

In total, the team found no less than nine neuroticism-associated loci. Prof. Smith says:

“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 well-being.”

The function of neurotic genes

Now that loci have been identified, the next challenge is to understand exactly how these specific portions of the genome make an individual more susceptible to neurotic thoughts and behaviors.

One of the DNA locations that the team pinpointed, known as CRHR1, is thought to be involved in managing the body’s stress response through the hypothalamic-pituitary-adrenal pathway; this pathway is known to go awry in depression.

CRHR1 appears to play a part in the release of cortisol, also known as the “stress hormone,” and is involved in anxiety-related behaviors in mice. Interestingly, the gene is also known to code for a protein that plays a part in reproduction, the immune response and obesity.

At least two of the genetic locations are thought to influence pathways involving glutamate, an excitatory neurotransmitter. Glutamate is known to play a role in a number of psychiatric disorders including depression, suicide and schizophrenia.

One of the glutamate-related sections – GRIK3 – has previously been shown to be a strong predictor of suicide, and another sequence – PTPRD – is known to be associated with restless leg syndrome.

The results from the study are sure to ripple across the field of psychiatry and beyond; one of the study team members, Prof. Ian Deary, from the University of Edinburgh, says:

“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.”

The findings are fascinating and tantalizing, but at this stage, they are just a glimpse of the discoveries that they may lead to in the future. As the fledgling field of molecular psychiatry reaches full stride, discoveries like these are sure to come thick and fast.

Medical News Today recently covered research linking anxiety to bad decision-making.

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