Nav: Home

Genetic variation linked to response to anxiety could inform personalised therapies

July 02, 2019

A new study in marmoset monkeys suggests that individual variation in genes alters our ability to regulate emotions, providing new insights that could help in the development of personalised therapies to tackle anxiety and depression.

Some individuals are at greater risk of developing anxiety and depression than others and this depends in part upon the interaction between our genes and our environment, such as stressful or adverse events in our lives. Moreover, some of those who develop anxiety or depression may respond better to treatment while others struggle to benefit.

Although much research has been dedicated to finding effective treatments, we still have a poor understanding of how mental health disorders such as these develop and of the underlying brain mechanisms.

A study published today in PNAS has identified specific brain mechanisms that may underlie how genetic variation in the serotonin transporter gene, a key gene that regulates mood and stress responses, can influence the way we respond to perceived threat.

In a previous study working with marmoset monkeys, Dr Andrea Santangelo in the laboratory of Professor Angela Roberts at the University of Cambridge showed that the particular variant of the gene carried by a monkey will influence whether it perceives an ambiguous stimulus as being high or low threat. This characteristic of an individual's personality is called 'trait anxiety'.

High trait anxiety is a risk factor in humans for developing anxiety and mood disorders, and genetic variation in the serotonin transporter gene has been linked with an increased likelihood of developing these disorders.

In this earlier study, the researchers showed that variants of the gene also affected how a monkey responds to certain medicines. Specifically, individuals carrying the variant of the gene associated with high anxiety actually increased their anxiety towards a threat immediately after treatment with a commonly-used antidepressant known as a 'selective serotonin re-uptake inhibitor', or SSRI. This so called 'anxiogenic' effect is often seen in patients in the early stages of treatment and is thought to be part of the reason why these patients do not respond favourably to SSRIs.

In this new study, Dr Santangelo and Professor Roberts, along with colleagues including those at the Wolfson Brain Imaging Centre and Translational Neuroimaging Laboratory, have revealed how variation in the serotonin transporter gene has an impact on the number of a specific type of serotonin receptor, known as the type 2A receptor, in a specific brain area. Receptors are proteins in the brain that enable particular molecules - in this case serotonin - to affect the function of nerve cells. Monkeys carrying the variant of the gene associated with high anxiety had lower numbers of this receptor, hence changing the way in which serotonin-based drugs act upon them.

Medicines targeting these receptors have recently been used in the treatment of anxiety and mood disorders, so these findings suggest that it could be important in the future to know what variant of the serotonin transporter gene an individual is carrying when deciding on a treatment strategy.

The specific brain area where the number of receptors was reduced was the insula cortex, an important site for integrating information about sensations coming from the body with cognitive information processed in other areas to generate feelings and self-awareness, and to help guide decision-making.

This new finding suggests that those cognitive behavioural therapies (CBT) that focus on controlling sensations from the body could help patients in whom SSRI drugs are not effective.

"As many as one in three people affected by anxiety and depression does not respond to anti-depressants, so we need to find better treatments to help improve their quality of life," says Dr Santangelo from the Department of the Physiology, Development and Neuroscience at the University of Cambridge.

"Our research suggests that differences in our DNA may help predict which of us will respond well to these medicines and which of us require a different approach. This could be assessed using genetic testing."
-end-
The research was carried out using marmoset monkeys because this type of genetic variation in the serotonin transporter gene is only present in humans, apes and monkeys, and not rodents. Moreover, the marmoset's brain shares many similarities with the human brain, so using monkeys in research allows us to identify exactly which mechanisms are behind conditions such as anxiety and depression, helping inform the development of much needed new treatments.

The research was funded by the Medical Research Council.

Reference

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates. PNAS; 1 July 2019; DOI: 10.1073/pnas.1902087116

University of Cambridge

Related Depression Articles:

Tackling depression by changing the way you think
A thought is a thought. It does not reflect reality.
How depression can muddle thinking
Depression is associated with sadness, fatigue and a lack of motivation.
Neuroimaging categorizes 4 depression subtypes
Patients with depression can be categorized into four unique subtypes defined by distinct patterns of abnormal connectivity in the brain, according to new research from Weill Cornell Medicine.
Studies suggest inflammatory cytokines are associated with depression and psychosis, and that anti-cytokine treatment can reduce depression symptoms
Studies presented at this year's International Early Psychosis Association meeting in Milan, Italy, (Oct.
Is depression in parents, grandparents linked to grandchildren's depression?
Having both parents and grandparents with major depressive disorder was associated with higher risk of MDD for grandchildren, which could help identify those who may benefit from early intervention, according to a study published online by JAMA Psychiatry.
Postpartum depression least severe form of depression in mothers
Postpartum depression -- a household term since actress Brooke Shields went public in 2005 about her struggle with it -- is indeed serious.
Tropical Depression 1E dissipates
Tropical Depression 1E or TD1E didn't get far from the time it was born to the time it weakened to a remnant low pressure area along the southwestern coast of Mexico.
Diagnosing depression before it starts
MIT researchers have found that brain scans may identify children who are vulnerable to depression, before symptoms appear.
Men actually recommend getting help for depression
Participants in a national survey read a scenario describing someone who had depressed symptoms.
Depression too often reduced to a checklist of symptoms
How can you tell if someone is depressed? The Diagnostic and Statistical Manual of Mental Disorders (DSM) -- the 'bible' of psychiatry -- diagnoses depression when patients tick off a certain number of symptoms on the DSM checklist.

Related Depression Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...