Exploring the genetic and neurobiological bases for mental disorders
Psychiatric disorders are a major, though often "hidden", health problem. It is estimated that mental disorders affect more than 160 million Europeans - 38% of the population each year. According to the World Health Organisation (WHO), one in four of us will suffer from at least one mental disorder during our lifetime. In addition to the direct impact this has on patients and their families, the impact on national healthcare systems is significant. In Europe, the annual cost is estimated to be more than €200 billion.
IMAGEN, a ground-breaking European Union (EU)-funded research project, was established in 2007 to identify how variations in genetic make-up and brain activity patterns in different individuals can determine their behaviour - and from this to establish what relevance these genetic and neurobiological factors might have for the development of mental disorders. This understanding would then help to guide the development of future prevention and treatment strategies.
The central focus of the five-and-a-half-year project was the way in which the brain is activated during the processes of reward anticipation, impulse inhibition or response to emotional cues. Variations and abnormalities in these behavioural “reinforcers”, in response to individual characteristics such as degree of impulsivity, sensitivity to the likely risk/reward outcomes, or attitudes to risk-taking, are at the core of many mental disorders.
In the words of IMAGEN’S project co-ordinator, Professor Gunter Schumann, Professor of Biological Psychiatry at King’s College, London: “These constructs – reward, punishment, impulsivity, emotional recognition – are very pervasive ones that are relevant for normal behaviour. But in extreme or abnormal cases, or in some sort of unlucky combination, they can significantly contribute to, or form the basis of, psychiatric disorders.”
The analysis of genetic factors in mental disorders has been hampered in the past by a limited ability to classify different types of mental disorder, which have consequently tended to be grouped into single broad categories. Advances in brain imaging methods such as Magnetic Resonance Imaging (MRI) have now made it possible to understand the brain mechanisms that underlie the various disorders. At the same time, advances in genomics have made it possible to identify the particular genes involved and how they are linked to the observed brain mechanisms and behavioural changes.
The IMAGEN consortium focused on teenagers because this is the age at which the mind is in transition. Developmental processes in adolescence are critical for the establishment of normal adult brain function. For the same reason, mental disorders frequently have their roots in this phase of life, so understanding the teenage brain and its workings is vital.
The first ever study on this topic, IMAGEN worked with a group of 2,000 14-year-olds from around Europe. In addition to neuro-imaging of the brain and genetic analyses, the researchers also gathered information by means of questionnaires, interviews, and behavioural assessments of the participants. As a result of this research, IMAGEN was able to identify clear links between genetic and neural variations and a range of disorders such as addiction, depression, impulsive behaviours and anxiety. For example, it demonstrated that variations in neural network activity and in a specific hormone-transporter gene are associated with the symptoms of drug addiction and attention-deficit hyperactivity disorder (ADHD).
In addition, by studying the same group of teenagers at the age of 18 as well as at 14, the IMAGEN project was able to gain a picture of the way in which disorders develop and manifest themselves over time, in the hope that patterns could be picked up and addressed earlier than might otherwise be possible.
“The idea,” explains Professor Schumann, “would be to identify early, ideally in a pre-symptomatic stage, people that are at risk for particular mental disorders, because early interventions are known to be the most effective. These interventions would be informed by neuro-imaging and genetic studies, but the tools you would use would be more behavioural and psychotherapeutic interventions, as opposed to pharmacological ones.”
The international response to IMAGEN has been notable, says Professor Schumann, with numerous invitations to speak at important international conferences and requests for collaboration. It is a response which underlines the truly ground-breaking nature of this research, with its new hope for treating and preventing mental disorders.
Project acronym: IMAGEN
Participants: United Kingdom (Coordinator), France, Germany, Norway, Ireland, Canada