Do genes explain the overlap between ADHD and other conditions, such as cognitive functioning, obesity, mood disorders and substance use?

ADHD is a heritable disorder, which means that genes contribute to the risk for getting the disorder. There are hundreds or even thousands of genes that contribute to ADHD, and while each single gene itself will not cause ADHD, together they contribute to the risk. But it is important to note that genes are not everything – environmental influences, such as preterm birth or exposures during pregnancy, may also contribute to the risk for ADHD.


Individuals with ADHD sometimes have other co-occurring conditions, such as mood disorders, obesity and substance abuse. This has led to the important research question of why do these conditions often co-occur with ADHD. Are there shared risk factors?


We know that people with ADHD not only tend to have a family history of ADHD, but they also are more likely to have siblings or parents with certain other co-occurring traits and disorders. This suggests that there are overlapping familial risk factors – which could be genes – between ADHD and other conditions.


A very large and recent genetic study that examined thousands of common genetic markers across our DNA, identified for the first time several genes that underlie risk for ADHD2. This information allowed us to investigate the genetic overlap between ADHD and other disorders using actual genetic data. In our new paper published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging3, we selected a bunch of genetic markers that most strongly underlie risk for ADHD, identified in the previous genetic study, and tested if they showed an overlap with other traits and disorders that often co-occur with ADHD. We tested this on a very large sample of 135,000 people in the UK. We found that some of the genetic risk factors were shared between ADHD and co-occurring conditions in the general population, specifically – atypical cognitive functioning, higher body mass index, neurotic behaviour, anxiety, depression, risk-taking behaviour, smoking and alcohol use.


Our study findings suggest that genes do, at least to some extent, explain the overlap between ADHD and co-occurring conditions. These genetic factors contribute to cognitive functioning, body mass index, mood symptoms and substance use in the general population.


The aim of this research is to further our understanding of ADHD and co-occurring traits and disorders. A better understanding of why ADHD often co-occurs with other conditions may help in the development of new treatments. Also, if we know how to predict which individuals with ADHD are at risk for other co-occurring disorders, we will be in a better position to offer early interventions that could prevent such further problems from developing.


Ebba Du Rietz and Jonna Kuntsi



  1. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005; 57:1313–1323. doi: 10.1016/j.biopsych.2004.11.024.
  2. Demontis D, Walters RK, Martin J, et al. Discovery of the first genome-wide significant risk loci for ADHD. bioRxiv 145581. 2017. doi:
  3. Du Rietz E, Coleman J, Glanville K, Wan Choi S, O’Reilly PF, Kuntsi J. Association of polygenic risk for attention-deficit/hyperactivity disorder with co-occurring traits and disorders. Biol Psychiatry: CNNI. In press. doi:


ADHD and school failure

Patient involvement is essential in health care, as well as in medical research.

For this purpose, our research group at the University of Bergen is collaborating with a board of ADHD patient representatives. The panel is committed to provide suggestions for future research topics and feedback on our work. During a recent meeting, panel members were asked what they considered the most urgent (research) needs in this field.

Much to our surprise, all four panel members expressed almost univocal messages: “You must fix the school system”. “There is too little knowledge about ADHD among teachers”. “Schools either ignore our problems, or offer too little assistance, too late “.

Perhaps these complaints shouldn’t be that surprising? After all, ADHD symptoms typically appear in school settings. Whether an ADHD condition is formally diagnosed during childhood, or the diagnosis is made retrospectively in adults, most people with an ADHD diagnosis will tell that they had negative experiences during school and many also suffered from academic failure.

The connection between learning difficulties, ADHD symptoms and dropping out of school are obvious also in genetic studies. In fact, this connection inspired us to perform a molecular genetic study, where large scale data collected about the genetics of educational attainment (EA) was coupled to a genome wide association (GWA) studies on ADHD genetics. Taking advantage of this connection, this design was able to boost the statistical power of the ADHD GWA study.

Until recently, genome wide studies on ADHD have been small and failed to provide reliable genome wide significant association signals. When a conditional false discovery rate method was applied to GWA data on ADHD educational data, to identify ADHD-associated loci and loci overlapping between ADHD and EA, we identified five ADHD-associated loci, three of these being shared between ADHD and EA. These five novel loci associated with ADHD confirm that there is a shared genetic basis between ADHD and EA and may increase our understanding of the genetic risk architecture of ADHD .

From this study, we have learned: (1) the importance of patients and society being engaged our work, (2) that there is a strong connection between ADHD and failed educational attainment and (3) that this connection can be used to find ADHD susceptibility genes.

Finally , as our patients have explained; this is not only about persons with ADHD failing at school, but also about a school system failing to adapt their teaching to persons with ADHD-related problems. This is obviously also a field in need of future research and interventions.

Adult ADHD and gender differences in psychiatric comorbidity

Interestingly, ADHD symptoms are usually different in girls and boys during childhood. Girls show less hyperactivity and this may lead to later identification and later treatment. Could this affect the development of other psychiatric disorders in adulthood? This was the big question behind a study examining differences in mental health among men and women with ADHD.

Previous studies have tried to figure out differences among men and women with ADHD in the risk of psychiatric comorbidities. Our study is the first to actually show such differences.

In our study, we linked information from four large national registries in Norway, and identified 40,000 adults with ADHD, which is 2.4% of the adult population. We compared them with the remaining population of 1.6 million Norwegian adult inhabitants without ADHD. The psychiatric disorders we studied were anxiety, bipolar, depression, personality disorder, schizophrenia spectrum (schizophrenia) and substance use disorders (SUD).

Both men and women with ADHD were 4-9 more likely to be diagnosed with these psychiatric disorders compared with the remaining population. We also found that there were significant differences in risk of a psychiatric diagnosis between men and women with ADHD.


Women with ADHD were significantly more often diagnosed with anxiety, depression, bipolar and personality disorder than men, while men with ADHD had more schizophrenia and SUD.

We also found that a considerable proportion of anxiety, bipolar disorder, depression, schizophrenia, SUD and personality disorders in the population could be explained by an underlying ADHD. About 6 percent of depression and 13 percent of bipolar disorders in women could be related to ADHD.

What clinicians need to know is that when treating adults with ADHD, they should be aware of these gender-specific psychiatric comorbidities, in order to both detect the conditions and offer early treatment if diagnosed. Importantly, clinicians should also be aware of a possible underlying ADHD when adults present with symptoms of other psychiatric disorders.

It is also important to identify children and adolescents with ADHD at earlier stages in order to reduce the risk of future psychiatric comorbidity. This may be particularly important in girls and women with ADHD, who often have a lower degree of hyperactivity and are therefore at an increased risk of being undiagnosed in childhood. This could result in a higher risk of developing other psychiatric disorders as a possible consequence as they grow older.

This study was done at Stiftelsen Kristian Gerhard Jebsen Center for research on Neuropsychiatric disorders, University of Bergen, Norway, and published OnlineOpen in Acta Psychiatrica Scandinavica, December 2017, with the title: “Gender Differences in Psychiatric Comorbidity: A Population-based Study of 40,000 Adults with Attention-Deficit Hyperactivity Disorder”;jsessionid=9377E31A46561F6810527AC39EC90981.f02t04

A call for better mental health: How modern technology may improve access to ADHD services

Masai mobile

Kenya, Kajiado district. Isaac Mkalia (20), a Maasai and a teacher by profession, checks his mobile phone while guarding a flock of cattle. © Sven Torfinn

According to a UN report more people now have mobile phones than toilets: Of the world’s 7.5 billion people, only around 3 billion have safely managed sanitation, but there are 3.7 billion Internet users and over 5 billion unique mobile phone users in the world in 2017. One day this week, whilst bemoaning the apparent global sanitation crisis, I started to ponder what promises the widespread use of mobile and Internet technology nonetheless might hold, particularly with regards to mental health and more specifically ADHD.

Access to mental health services and evidence-based treatment can be poor in rural areas, with lower availability of services and greater distances to specialist care. In addition, psychosocial factors (e.g. stigma), financial constraints and a lack of human resources (i.e. clinicians and practitioners) may create barriers to treatment, and long waiting times, in both rural and urban areas. E-mental health could be key to tackling these problems.

E–mental health can be defined as the “use of digital technologies and new media for the delivery of screening, health promotion, prevention, early intervention, treatment, or relapse prevention, as well as for improvement of health care delivery (e.g. electronic patient files), professional education (E-learning), and online research in the field of mental health” (Riper et al., 2010). This means that e-mental health has the capacity to aid with anything from prevention and early diagnosis to behaviour management and high-quality treatment.

Online therapies have emerged as a valuable and effective approach to delivering evidenced-based care via the Internet. These types of therapies can comprise electronic modules patients can work through in their own time, (recorded or real-time) videoconferencing to conduct mental health visits within the patient’s home, or a combination of the two. One example of an evidenced-based self-administered programme is the Triple P (Positive Parenting Program) Online (Sanders, Kirby, Tellegen & Day, 2014), which provides support for parents of children with disruptive behaviour in eight self-paced modules.

Research into videoconferencing for ADHD is still in its infancy. A preliminary study recently found that, despite minor technological glitches, ADHD symptoms decreased in 20 children with ADHD at a similar rate to face-to-face sessions (Sibley, Comer & Gonzalez, 2017). Given the scarcity of mental health providers, the distance to services and problems with transportation access, especially in remote areas, as well as scheduling conflicts and long waiting times, online therapies may prove to be a useful tool to improve cost-effectiveness and access to evidenced-based treatment in underserved areas. Online therapies may also be more attractive to patients who are reluctant to seek face-to-face care due to stigma or other concerns (Christensen & Hickie, 2010).

An even more comprehensive way of employing the Internet for medical practice is the use of web portals, which can address several key aspects of healthcare, including screening, symptom tracking, patient registries and online communication between patients and their clinicians. One example of an ADHD web portal is, developed by Cincinnati Children’s Hospital Medical Center (Epstein, Langberg, Lichtenstein, Kolb, Altaye & Simon, 2011). The web portal consists of online training for community-based practitioners, ADHD assessment as well as treatment for children with ADHD. Parents and teachers can complete ADHD rating scales about patients online and rating scales are automatically scored and summarized to aid the clinician in diagnosis and treatment monitoring. The ADHD web portal also allows parents, teachers, and clinicians to communicate with each other and with other mental health professionals during assessment and treatment via an online emailing system. Although ADHD web portals can have high clinical utility, their implementation may be burdensome for healthcare professionals because these portals usually exist outside of official electronic health records and information has to be transferred between the two.

Smartphones provide considerable healthcare-related opportunities. Since their inception, the development of smartphone applications, so-called apps, has skyrocketed. In 2016, an estimated 150 billion apps were downloaded worldwide. As smartphones and apps become ever more integral to the lives of many people around the world, these technologies offer great possibilities for improving the provision of mental health services and encouraging healthy behaviours. Apps can, for instance, help with behavioural change, goal setting and education by providing both training (repeated exposure to a task to improve ability) and support (facilitation of a skill while the technology is in use). Available apps related to ADHD may improve organizational skills by employing push notifications, reminders and timers. They can also help to reduce stress and track behaviour, as well as making use of positive reinforcement through the ‘gamification’ (using badges or phrases to reward participants for meeting their goals) of arduous tasks. The CoCA-PROUD project is currently piloting an app, which monitors physical activity and light exposure, analyses the behaviour in real-time and provides encouraging feedback to the user to improve motivation in order to provide new insights into the potential of smartphones to improve ADHD symptomatology and comorbidities such as obesity and depression. Moreover, this list includes some useful examples of apps that may be beneficial to individuals with ADHD. However, some users may rightly raise concerns about digital privacy and security. Few apps to-date are supported by an evidence base, and there is currently no governing body responsible for quality control. The American Psychiatric Association has therefore developed a hierarchical model to assess health apps to guide clinicians and service users in their decision-making.

While overall more evidence for the efficacy of E-mental health services is still required, the widespread use of smartphone and Internet technology holds immense promise for the future with the lauded benefits including cost-effectiveness, geographic and temporal flexibility, the reduction in therapist time, stigma and waiting time for treatment, as well as the increase in help-seeking behaviours and treatment satisfaction (Musiat & Tarrier, 2014).

The up-goer five of ADHD

Launch of the Saturn V space shuttle (Wikimedia commons / by NASA)

Can you explain your research using only the thousand most common words in the English language? This challenge has been going around since Randall Munroe (famous for the xkcd comics) published a comic in which he explains how the Saturn V space shuttle works using only sketches and the thousand most common words. Hence the name up-goer five, as both the words shuttle and rocket are not in that list. The fun thing about this challenge is that it makes you think about what your research is really about, and formulate this using normal, everyday language.

As dissemination manager of CoCA (i.e. the person who tells other people what we find in our studies), I took it upon me to describe the CoCA project using only these thousand most common words. Luckily, someone was kind enough to create an online tool that tells you when you’re using a word that’s not in the list (so now I know that project and research are not allowed, but studies is. Yay!).

Now before I show to you the result of my effort, let me first write a disclaimer. One of the nice things about the richness of language is that you can use it for nuances. And nuance is something that scientists love. By specifically choosing your words, you can make clear what you mean exactly. Jargon helps us even more in this, because everyone else who knows this jargon knows exactly what you mean. Anyway, the disclaimer here is that if you use only the most common thousand words, you lose nuance. So  I know that ‘a person who cannot sit still and pay attention’ is a very poor description of a person with ADHD. But I challenge you to do better!

So here it goes, the CoCA project described in common English:

We study why people who can’t sit still and pay attention also often feel sad, or eat too much, or use too much of things that are not good for them and can’t stop with it. They have these problems more often than people who are better at sitting still and paying attention, and the problems get worse when they become older. We think that this is because their brain works a bit different. We try to help them by making them jump and run every day, and by giving them more light. And we give them a phone to show them what they should do, and how good they are doing each day. The jumping and running and more light each day should make them more happy. We also look in their brains for things that cause both not sitting still and eating too much, or not paying attention and feeling sad. When we understand better how these things in our brains can cause these problems, we can help the people who have these problems to get better.

What do you think? Does this help you to understand what the project is about? Or does it remain very vague (what problems? Which things in brains?).

I’m very curious to see if other CoCA researchers can do a better job at this. Or maybe they can describe their parts in the project using this online tool. And researchers from the other projects, Aggressotype, MiND, can use the tool to describe their projects. Challenge accepted?

Try it out yourself: (or use the Norwegian or Spanish version!)

And in case you are now very curious about what the CoCA project is really about, you can read more about it here.


Fitter bodies, fitter brains?

Is the brain of fitter individuals different from that of less fit individuals? Yes, several investigations support that there are indeed important structural differences in the brain in people with different physical fitness levels.

As an example, a recent study conducted by our group in 100 overweight-obese children explored the whole brain and observed that the children with higher aerobic fitness (capacity of a person to do exercise for a long time and efficiently, also known as cardiorespiratory fitness) have higher volume in 9 cortical and subcortical brain regions relevant for cognition, executive function, and academic achievement [1]. In addition, we observed in a different study and group of children that aerobic fitness level was associated with the shapes of subcortical brain regions, showing therefore a link between physical fitness and brain morphology [2]. Similarly, other researchers have observed that hippocampus and dorsal striatum, key brain structures responsible for memory and other high cognitive functions, are markedly larger in fitter kids compared with less fit kids [3,4].


cerebro entrenando FINAL

Image taken from:


But differences in brain volumes according to physical fitness are not only observed in the growing brains of children, but also in adults and in older adults in which brain volume is known to shrink as a person ages. Several investigations have consistently shown that hippocampus volume is larger in fitter older adults than in their less fit peers [5]. However, even more important are the results of another study which demonstrated that 1 year of aerobic training in older adults did not only attenuate the natural decline in hippocampus volume observed in the control group that did not train, but did even successfully reverse the natural trend, increasing hippocampal volume by 2% and leading to improvements in memory function [6].


Collectively, existent evidence concisely supports that individuals with a better aerobic fitness level, have more developed certain regions of the brain, which in turn has shown to positively influence cognition. Therefore, there is emerging evidence suggesting that to exercise and be in a good fitness level is healthy not only for the body, but also for the brain and cognition. Thus, as stated in the title of a landmark review article in this topic [7]… “Be smart, exercise your heart”.



Francisco B. Ortega, Adrià Muntaner-Mas, Antonio Martínez-Nicolás and Irene Esteban-Cornejo

The PROFITH research group:

University of Granada, Spain.




[1]       Esteban-Cornejo I, Cadenas-Sanchez C, Contreras-Rodriguez O, et al. A whole brain volumetric approach in overweight/obese children: Examining the association with different physical fitness components and academic performance. The ActiveBrains project. Neuroimage 2017;159:346-354.

[2]       Ortega FB, Campos D, Cadenas-Sanchez C, et al. Physical fitness and shapes of subcortical brain structures in children. Br J Nutr 2017:1-10.

[3]       Chaddock L, Erickson KI, Prakash RS, et al. A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children. Brain Res 2010;1358:172-183.

[4]       Chaddock L, Erickson KI, Prakash RS, et al. Basal ganglia volume is associated with aerobic fitness in preadolescent children. Dev Neurosci 2010;32:249-256.

[5]       Erickson KI, Prakash RS, Voss MW, et al. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus 2009;19:1030-1039.

[6]       Erickson KI, Voss MW, Prakash RS, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 2011;108:3017-3022.

[7]       Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 2008;9:58-65.