A group of researchers from Spain, The Netherlands, Germany, Estonia, Denmark and USA have joined efforts to gain insight into the genetics of ADHD and its comorbidities. This ambitious objective was addressed by the Work Package 2 of a big project called CoCA: “Comorbid Conditions of Attention deficit/hyperactivity disorder (ADHD)”, funded by the European Union for the period 2016-2021.

In psychiatry, the co-occurrence of different conditions in the same individual (or comorbidity) is the rule rather than the exception. This is particularly true for ADHD, where conditions like major depressive disorder or substance use disorders frequently add to the primary diagnosis and lead to a worse trajectory across the lifespan.

There are different reasons that may explain the advent of the comorbidities: Sometimes the two conditions have independent origins but coincide in a single patient. Comorbidity can also appear as a consequence of a feature of a primary disorder that leads to a secondary disorder. For example, impulsivity, a trait that is common in ADHD, can be an entry point to substance use. Comorbidity can also be the result of shared genetic causes. The latter has been the focus of our investigations and it involves certain risk genes that act on different pathologies, a phenomenon called pleiotropy.

Our project started with an approach based on the exploration of candidate genes, particularly those involved in neurotransmission (i.e. the connectivity between neurons) and also in the regulation of the circadian rhythm. We used genetic data of more than 160,000 patients with any of eight psychiatric disorders, including ADHD, and identified a set of neurotransmission genes that are involved at the same time in ADHD and in autism spectrum disorder [1]. In another study we identified the same gene set as involved in obesity measures [2].

Then we opened our analyses to genome-wide approaches, i.e. to the interrogation of every single gene in the genome. To do that we used different statistical methods, including the estimation of the overall shared genetics between pairs of disorders (genetic correlation, rg), the prediction of a condition based on the genetic risk factors for another condition (polygenic risk score analysis, PRS) and the establishment of the causal relationships between disorders (mendelian randomization). As a result, we encountered genetic connections between ADHD and several psychiatric disorders, like cannabis or cocaine use disorders [3, 4, 5], alcohol or smoking-related phenotypes [6, 7, 8], bipolar disorder [9], depression [6], disruptive behavior disorder [10], but also with personality or cognition traits, like neuroticism, risk taking, emotional lability, aggressive behavior or educational attainment [6 , 11, 12, 13], or with somatic conditions, such as obesity [11, 12].

All these results and others, reported in more than 40 (!) scientific publications, support our initial hypothesis that certain genetic factors cut across psychiatric disorders and explain, at least in part, the comorbidity that we observe between ADHD and many other conditions. This information can be very useful to anticipate possible clinical trajectories in ADHD patients, and hence prevent potential negative outcomes.

Dr. Bru Cormand is full professor of genetics and head of the department of Genetics, Microbiology & Statistics at the University of Barcelona. He leads workpackage 2 of the CoCA project ( on the genetics of ADHD comorbidity.


  1. Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders | medRxiv
  2. Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures – PubMed (
  3. Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality – PubMed (
  4. Genome-wide association study implicates CHRNA2 in cannabis use disorder – PubMed (
  5. Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions – PubMed (
  6. Association of Polygenic Risk for Attention-Deficit/Hyperactivity Disorder With Co-occurring Traits and Disorders – PubMed (
  7. Investigating causality between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization – PubMed (
  8. Genetic liability to ADHD and substance use disorders in individuals with ADHD – PubMed (
  9. Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis – PubMed (
  10. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder – PubMed (
  11. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder – PubMed (
  12. Shared genetic background between children and adults with attention deficit/hyperactivity disorder – PubMed (
  13. RBFOX1, encoding a splicing regulator, is a candidate gene for aggressive behavior – PubMed (

Towards a diagnosis of autism based on biochemical markers?

An interesting piece of work on the diagnosis of autism has recently been published in the scientific journal PLOS Computational Biology. The authors work at the Rensselaer Polytechnic Institute in New York.

Autistic patients have limited social interaction skills and show restricted repetitive behaviors. Although important progress has been made in recent years to understand the underlying pathophysiology of this disorder, its causes remain largely unknown. This lack of biological knowledge restricts diagnoses to be made based on behavioral observations and psychometric tools.

This study tackles a new approach that uses biochemical measures taken from blood samples in the diagnosis of the disorder. The idea behind this method is that certain metabolic pathways are frequently altered in autism. The authors have developed an algorithm that combines data from a number of blood metabolites and is able to predict the outcome of the disorder with high accuracy at least in a subset of the cases. The authors, who are system biologists, have used big data analytical tools. According to one of them, Juergen Hahn, “instead of looking at individual metabolites, we investigated patterns of several metabolites and found significant differences between metabolites of children with ASD and those that are neurotypical“. And he added that “by measuring 24 metabolites from a blood sample, this algorithm can tell whether or not an individual is on the Autism spectrum, and even to some degree where on the spectrum they land.”

The model developed by this team seem to have much stronger predictability than any existing approaches from the scientific literature and paves the way towards a diagnosis based on biomarkers for the first time.

More information can be found at

Women in science

Dear colleagues, I am transmitting a message from Noèlia Fernàndez-Castillo and Bàrbara Torrico, postdocs in my research group:

“Last 5th of July, both the Aggressotype and the CoCA projects were mentioned in the ‘Women in Neuroscience’ workshop at the 10th FENS Forum in Copenhagen, which we had the pleasure to attend. Different researchers from the field presented their personal experiences, either working to bring to light gender differences in science, promoting gender equality programs or as young researchers trying to reconcile work and family life. After their nice and encouraging talks, all the assistants had the opportunity to formulate their questions and/or comments, generating very productive debates.

A lot of effort is still needed in science to reach gender equality, an issue that does not only affect women, and that involves much more than simply fighting against the gender bias in obtaining senior positions. This is a problem that affects all of us in the way we work on science and treat our partners. Several issues were addressed in the workshop that we were not aware of and that we think should be important to disseminate and discuss with our colleagues.

For that purpose, we would like to propose a short talk and a mini-debate on gender equality in the next general assembly meetings of our EU projects that may contribute a bit to deal with this issues. Given the international character of our projects, we could address differences regarding gender policies among countries in research institutions. We consider that people working on the same project should share equal perspectives regardless of their sex, but also of their place of work. We thank the organization of the FENS meeting for this enriching and encouraging workshop.”