GLAD: Genetic Links to Anxiety and Depression

The world’s largest ever scientific study into anxiety and depression is currently being undertaken at KCL. To find out more about this exciting research, The Nucleus interviewed the two lead researchers, Dr Gerome Breen and Professor Thalia Eley about the Genetic Links to Anxiety and Depression (GLAD) study.

What sets this study apart? The scale of this study is unprecedented in the field of anxiety and depression, both in terms of the number of respondents and breadth of information obtained from each one. The GLAD team hope for 40,000 people to sign up for the study, and each one will provide a saliva sample and complete a questionnaire regarding a wide range of topics, including:

• Their symptoms

• Their treatment history (both what treatments they have undergone and how successful each type of treatment was for them)

• Environmental factors, such as lifestyle.

The data obtained by these procedures will hopefully allow a wide range of questions to be answered. For example, should a future research team want to investigate how a specific panic disorder responds to a certain treatment type, the GLAD research data will be a ready-made source of information for them to draw from.

The hope is that a large portion of the respondents will consent to taking part in future data-gathering activities up to four times per year, thus creating a large, stable research community to facilitate and accelerate future research in the field.

What are the similarities and differences in causes and treatments for anxiety and depression?

About 60% of people who have one of the conditions,have both – and this percentage only increases as theseverity of the disorder increases. The genetic causes ofthe two disorders overlap by about 80%, but the environmental‘triggers’ for both are quite different fromeach other. One of the goals for this study is to understandthat relationship in more detail. The two disordersgenerally require different modes of treatment,with anxiety usually responding better to treatmentthan depression.

What is the extent to which one’s genes, as opposed to one’s environment, contribute to anxiety and depression?

Despite the name, the Genetic Links to Anxiety andDepression study is focused on both genetic and environmentalfactors. It is thought that genetic factorsplay a 30-50% role in causing anxiety and depression,though genes and the environment can and do interact:environmental triggers can ‘switch on’ certain genes.Most previous studies have focused on either genes orthe environment, but it is hoped that the GLAD study’sholistic approach can lead to increased understandingof the interrelationship between these varied factors.

A side benefit of studies such as these, that recognisethat mental illnesses often have a heritable component,is that they may help destroy the lingering stigma surroundingmental illness. Too often it is assumed that amental illness sufferer should simply be able to ‘snap outof it’, or that their condition arose as a result of some

behavioural failing on the part of the sufferer or their parents.

As it becomes more widely appreciated that there are ‘hard’, biological underpinnings to mental illness, we can surely hope to knock down some of the barriers between how society views those suffering from a mental illness, when compared to someone with a ‘physical’ injury or illness. Research programmes like KCL’s GLAD study, which take seriously the biological causes of anxiety and depression, will move us closer to this goal.

What are the goals of this study?

The currently available treatments for anxiety and depression come in several forms, but only about half of people with these disorders respond well to existing options. Pharmacological and psychological routes are available, and the latter can be delivered in many different ways: one-to-one, in group sessions or remotely via Skype. The relationship between specific conditions and appropriate modes of treatment is an area that this study hopes to make significant progress in. By analysing the data gathered on symptoms, genetic profile, environmental factors, treatments tried and their success for that individual, the GLAD team hope to glean key information about what treatments are best matched to each narrowly defined set of factors.

One angle of investigation is the “cause informing cure” hypothesis: the idea that perhaps disorders that are genetically caused respond well to pharmacological treatment, while environmentally caused disorders are better treated psychologically. It is not currently known whether this hypothesis is true, but the data obtained in this study will help us make progress. Similarly, whether someone is recommended for one-to-one, group or remote psychological sessions currently largely depends simply on the severity of their symptoms. However, other factors, such as chronicity or whether the disorder is genetically or environmentally caused, may be just as important in determining what the most effective course of action would be.

At the moment, even people who eventuallyrespond well to treatment have had to try, on average,two to three different treatment types before finding

what works for them.

The ability to better tailor the treatment to the disorder,and thus cut down on the number of treatmentsneeding to be tried, would be of special benefit to youngpeople. Suffering from these disorders while young canlead to extensive time off school and other disruption toone’s life, which can have a long-lasting impact.

If, on the other hand, one was able to simply go toone’s GP, provide a saliva sample, and then receive atreatment program that has been personally tailoredto match one’s condition, much of this distress couldbe avoided. Such a system could be ten to fifteen yearsaway, but studies such as this one can be of great use inreaching that goal.

You can help!

The GLAD researchers would like to encourageanyone with a history of anxiety or depression to signup for the study, but they are keen to emphasise thatLGBT+ and BAME people are hugely underrepresentedin psychiatric and genetic research. The KCLcommunity is incredibly diverse so, if you fall into anyof those groups, it would be even more impactful if yousign up!

by Ramana McConnon