Seven new genes linked to anxiety disorders

Researchers have linked seven new genes to anxiety disorders such as obsessive compulsive disorder, panic disorder and social anxiety disorder.

These gene links mean that new drug treatments could be created to target these gene products specifically in the treatment of anxiety disorders. It gives hope to thousands of people who currently have no treatment plan.

Treatments for anxiety disorders involve both drug-free and drug-based therapies. The most effective treatment strategies are a combination of the two, differing in application from patient to patient.

To treat these conditions using drug-based therapies, drugs have been designed to target specific genes which produce proteins associated with the progression of disorders. Because these disorders are so complex, gene discovery is difficult.

Currently, there are only two core pathways that are associated with drug-based therapies: the dopaminergic and the serotonergic pathways. Dopamine changes have been linked to movement, motivation, reward-response and addiction. Serotonin in the brain has been linked to mood, social behaviour, memory and cognitive function.

Drug-based therapies work on roughly half of those affected and treated, leaving a large number of people without tangible assistance. The current treatments for anxiety disorders are not as effective as hoped. A better understanding of why and how these disorders exist is essential for better treatment strategies.

Looking at novel gene targets

Our research uncovered several new genes that could potentially play roles in how anxiety disorders develop and progress. We used an interdisciplinary approach on both animals and people to uncover these genes.

To help us identify the candidate genes, we focused on the striatum section of the brain in which the synaptic plasticity pathway was chosen. In neuroscience, synaptic plasticity refers to the ability of synapses (connections in the brain) to strengthen or weaken over time in response to a stimulus. The striatum helps co-ordinate motivation with body movement. It can be as simple as fine-motor function or as complex as behavioural inhibition depending on social interaction.

The result was that we identified seven new genes as possible candidates for further study. Six of these genes have never been implicated in anxiety disorders before.

To date, global research has identified a number of risk factors for anxiety disorders. These can be grouped into two categories: genetic factors and environmental factors. Genetic factors relate to differences in one’s genetic code that either protect or put you at risk for developing anxiety disorders. Environmental factors include childhood trauma and substance abuse.

To further complicate things, these categories tend to interact with one another. Scientists believe the interaction is what results in a plethora of differences among patients even when they have the same disorder. For example, two people may have severe obsessive compulsive disorder and be on the same treatment schedule. Due to the differences in their genetic make-up and lifestyles, they could respond differently to treatment.

Drug-based therapies only work for half of the people suffering from anxiety disorders.shutterstock

Some of these candidates also appear to interact with environmental stressors. Trauma experienced during early developmental years has been thought to be a risk factor for anxiety disorders for a number of years now. It is believed to be a key factor in the variation seen among different patients.

Although this theory is difficult to investigate and depict, it was possible using the strict and specific conditions that we did. The finding provides a precedent for future work to try and better understand how the environment interacts with genetics to manifest in disease.

Anxiety disorders such as obsessive compulsive disorder, panic disorder and social anxiety disorder are among the most severe and debilitating conditions. They currently affect up to 350 million people worldwide.

Despite this disease burden, they have not achieved the visibility, attention or funding they comparatively deserve. For example, the US allocated (in millions) $3920 to cover all brain disorders research for the 2015 financial year. HIV, with an incidence rate well below anxiety disorder – let alone brain disorders in general – received $3000 (in millions).

Myths, fear and stigma are the persistent barriers in the understanding of mental illness. It also hampers public awareness. As a result, as history has shown, those who suffer from mental health illnesses have been ostracised in communities, treated with prejudice and considered second-class citizens.

The way forward

By uncovering these new candidates genes – involved not only in risk, but environmental interplay – there is new hope for better and improved treatment strategies.

But whether it is by realising new drug targets, a better understanding at a molecular level or how one’s environment influences disease, a small – yet promising – arsenal of candidates could shed a little more light on a rather dimly lit road.

Nathaniel McGregor receives funding from the National Research Foundation (NRF). He is affiliated with the MRC Unit on Anxiety and Stress Disorders.