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A gene involved in ADHD could be related to addictive substance use

February 25, 2019

Some variations in the gene LPHN3 -associated with the attention deficit / hyperactivity disorder (ADHD) in kids and adults- could favour likelihood to smoke, consume alcohol, cannabis and other addictive substances, according to an article published in the journal Translational Psychiatry, from the Nature Publishing Group.

The findings are based on the study of around 2,700 patients -children, adolescents and adults- from the United States, Colombia and Spain, and it will contribute to provide new genetic tools to improve prevention of addictive behaviours in people with ADHD.

The new study is led by the experts Mauricio Arcos Burgos and Maximilian Muenke, from the National Institutes of Health in Bethesda (United States). Other participants in the study are the experts Bru Cormand and Noelia Fernàndez, from the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), Institut de Recerca de Sant Joan de Déu (IRSJD) and the Rare Diseases Networking Biomedical Research Centre (CIBERER), Josep Antoni Ramos Quiroga and Marta Ribasés, from Vall d'Hebron Research Institute (VHIR) and the Mental Health Networking Biomedical Research Centre (CIBERSAM), and experts from the University of Antioquia and the University Simón Bolivar in Colombia, among other institutions.

ADHD: a complex disorder affecting children, adolescents and adults

ADHD is one of the most commons disorders in childhood and adolescence -it can linger until adulthood- and its traits are hyperactivity, impulsiveness, and attention deficit. One of the genes related to ADHD susceptibility is LPHN3, which codes the protein latrophilin 3, "a molecule related to the formation of synaptic connections between certain types of neurons, and therefore, a good candidate to set a relation with any psychiatric disorder", notes the lecturer Bru Cormand, head of the Research Group on Neurogenetics of the Faculty of Biology of the UB.

The connection between LPHN3 and ADHD is one of the most studied regarding the etiology of the disorder. This gene, in addition, has an impact on the patients' response to the medication, the degree of severity of the disease and disruptive behaviour. However, so far, the depth of the relation between the gene LPHN3 and substance addiction had not been explored.

In the new study, the experts applied an innovative statistical method (Recursive-partitioning Frameworks) which integrates clinical, demographic and genetic information on a specific disorder -in this case, ADHD- to predict another co-morbid disorder (which appears concurringly), such as addiction to tobacco, alcohol, cocaine, cannabis and marijuana, among others.

Conclusions note that, within the group of Spanish patients with ADHD, a specific variation of the LPHN3 gene increases by 40 % the risk of nicotine dependence. According to the experts, results are similar in the cases for alcohol and illegal drugs, which have been studied together in the research.

Why some patients use addictive substances and others do not?

Not all those affected by ADHD show behaviours with an addictive profile over their lives. "We now know genetics play an important role in these behaviours. This helps us to prevent future risks in kids and adults with ADHD and to improve prevention strategies. However, ADHD genetics are diverse, there are many involved genes and these vary among the patients with the disorder", notes Cormand.

75 % of ADHD has a genetic base and the remaining 25 % is related to environmental factors which can vary, according to the experts. Therefore, external factors can be relevant in the appearance of addictive behaviours in people with ADHD. For example, certain lifestyles or social interactions can play an important role.

"Also, cocaine and other addictive substances -warns Cormand- have a psychostimulant action similar to the one in the main pharmacological treatment for ADHD. This would explain why, in some cases, these are used by the affected people as self-medication for its apparently 'beneficial' effects".

Addictive behaviours: clinical studies to improve prevention measures

Psychological and pharmacological treatment and psychopedagogical intervention are the combined strategies that are most efficient in ADHD treatment. In the future, we will need new clinical studies to analyse the importance of genetics in ADHD susceptibility and addictive behaviours which can affect the patient's health.

"It is difficult to access patients with an ADHD diagnosis and records of drug use who authorize participation in these research studies. Also, in genetic studies, population samples have to be homogeneous. Other added problems are the difficulty to get data from all individuals, or even from those who can lie about their use of addictive substances", concludes the researcher Noèlia Fernàndez, from the Department of Genetics, Microbiology and Statistics of the UB, and member of IBUB, CIBERER and IRSJD.
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University of Barcelona

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