Attention deficit hyperactivity disorder (ADHD) plays a prominent role in genetics. In addition, environmental risk factors, which modify the expression of certain genes, increase the risk of developing the disorder. The Psychiatry, Mental Health and Addictions group of the Vall d'Hebron Research Institute (VHIR) and group 27 of the CIBER of Mental Health (CIBERSAM) has demonstrated that the analysis of genetic variants together with gene expression in blood samples helps to predict the risk of ADHD. These results suggest that gene expression in blood could help to confirm the diagnosis of the disorder. The study, published in Molecular Psychiatry, was carried out in collaboration with the University of Aarhus in Denmark and received funding from the Instituto de Salud Carlos III.

Until now, ADHD research has focused mainly on the study of genetic variants that are associated with an increased risk of having ADHD. "This is the first time that we calculate the risk, not only based on the genetic variants that a person presents, but also on the actual expression of certain genes. These are complementary calculations that allow us to take into account the effect that the environment has on the development of the disease", explain Drs. Marta Ribasés and Judit Cabana, researchers of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM. Environmental factors, such as psychological or physical stress, the consumption of toxic substances by the mother during gestation or complications during pregnancy or childbirth, can alter the expression of genes.

In a first phase of the study, available gene expression data in different brain regions were used together with genetic information from 38,691 people with ADHD and 186,843 healthy people and 56 genes were selected that could play a role in the development of the pathology. Among these are some genes involved in brain function, such as genes involved in synapses or the differentiation of neurons.

In the second phase of the study, selected genes were analyzed in blood samples from 222 people with ADHD and 269 healthy people, with the aim of calculating a risk score for the disorder that could be useful as a biomarker to differentiate, based on the expression pattern of certain genes, whether a person is at greater or lesser risk of developing the disease.

The results of this work allow us to classify high-risk population groups, but do not allow us to make individual predictions or establish a diagnosis. Studies with larger samples will make it possible to improve the tool with the aim of, in the future, assessing its application in clinical practice to identify people at risk of having the disease. "This analysis in blood samples is a non-invasive tool that would allow predicting a child's risk of suffering from ADHD before he or she manifests the most severe symptoms. The early detection of people at higher risk will allow defining preventive strategies aimed at particularly vulnerable groups", says Dr. Josep Antoni Ramos Quiroga, head of the Psychiatry Department at Vall d'Hebron University Hospital and of the Psychiatry, Mental Health and Addictions group at VHIR and CIBERSAM researcher.

In addition to being a risk prediction tool, gene expression analysis could help in the future to confirm the diagnosis of ADHD if it is accompanied by ADHD symptoms, such as difficulties in concentration or organization, excessive activity or impulsivity.