comorbidity – Mind the Gap Blog

Genetics of dopamine and serotonin explain overlap in psychiatric disorders

Posted on January 20, 2022 by jcabanadominguez

Psychiatric disorders such as attention deficit / hyperactivity disorder (ADHD), autism, major depression or bipolar disorder, often overlap and occur together. For example, individuals with ADHD on average experience twice as many depressive symptoms as the general population without ADHD [1,2]. In addition to the distress and impairment that is brought on by a single psychiatric condition, having multiple conditions can hugely increase the severity of symptoms and hinder treatment. To better understand why these disorders overlap, we investigated the genetic risk factors that are shared among psychiatric disorders, and found several genes that play important roles in regulating two signaling-mechanisms of the brain: dopamine and serotonin [3].

Dopamine and serotonin are two important neurotransmitters (messengers molecules that transmit messages between brain cells) that control a wide range of essential functions in your brain (e.g. controlling your movements, cognition, motivation, regulation of emotions, and responding to reinforcement and reward). For that reason, alterations in these two systems have been related with the physiopathology of several psychiatric disorders, and also have been pointed as possible therapeutic targets for them.

We systematically explored the contribution of common variants in genes involved in dopaminergic and serotonergic neurotransmission in eight psychiatric disorders (ADHD, anorexia nervosa, autism spectrum disorder , bipolar disorder, depression, obsessive-compulsive disorder, schizophrenia and Tourette’s syndrome) studied individually and in combination. To do so, we used data from the Psychiatric Genomics Consortium (PGC, https://www.med.unc.edu/pgc/) to explore the entire genome in thousands of patients with different psychiatric conditions, which were compared with controls (individuals without any psychiatric condition).

In this way, we could identify variations in genes (and in groups of related genes) that confer susceptibility to a given disorder. For example, a gene named CACNA1C that is involved in the connectivity between brain cells, was found to contribute to both bipolar disorder and schizophrenia. Using this approach, we found 67 dopaminergic and/or serotonergic genes associated with at least one of the eight studied disorders, and twelve of them were associated with two conditions. Interestingly, five out of these twelve genes, including CACNA1C, belong to both the dopaminergic and serotonergic neurotransmitter systems, highlighting the importance of those genes that participate in both systems and their high interconnectivity. Next, we analyzed groups of genes that work together, and found that the dopaminergic genes have an important role in ADHD, autism, depression, and in the combination of all of the eight disorders that we studied. We also found that the group of serotonergic genes are relevant for the overlap between depression and bipolar disorder.

These results support the existence of a set of dopaminergic and serotonergic genes that increase the risk of having multiple psychiatric conditions. Having identified these genes, the next step is to investigate if any of these could be targeted by new drugs that directly influence specific parts of the dopaminergic or serotonergic system, compared to the more unspecific drugs that currently exist. That would be an important step for treating psychiatric comorbidity.

If you want to know more about this research, you can read our publication here.

This blog was written by dr. Judit Cabana-Domínguez. She is a postdoctoral researcher of psychiatric genomics at the Vall d’Hebron Research Institute (VHIR). The work described here is part of the CoCA project on comorbid conditions of ADHD.

References

McIntosch et al. (2009). Adult ADHD and comorbid depression: A consensus-derived diagnostic algorithm for ADHD (nih.gov) Neuropsychiatric Disease and Treatment, 5: 137-150. doi: 10.2147/ndt.s4720
Di Trani et al. (2014). Comorbid Depressive Disorders in ADHD: The Role of ADHD Severity, Subtypes and Familial Psychiatric Disorders (nih.gov) Psychiatry Investigation, 11(2): 137-142. doi: 10.4306/pi.2014.11.2.137
Cabana-Domínguez et al. (2022). Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders. Translational Psyciatry, 12(1): 11. doi: 10.1038/s41398-021-01771-3

What have we learned about ADHD comorbidities?

Posted on July 2, 2021July 2, 2021 by Jeanette Mostert

After 5.5 years, the CoCA project has come to an end. In this large-scale European research project, an interdisciplinary group of researchers investigated comorbid conditions of ADHD. They particularly focussed on depression, anxiety, substance use disorder and obesity, as these conditions frequently co-occur with ADHD in adulthood.

What has this extensive study brought us? Experts dr. Catharina Hartman (University Medical Center Groningen, The Netherlands) and prof. dr. Andreas Reif (University Hospital Frankfurt, Germany) were invited by Jonathan Marx for an interview on the online radio program Go To Health Media. In this program they talk about several aspects of the CoCA project: How often do comorbid conditions co-occur with ADHD? What do the genetics of ADHD comorbidities tell us? What should clinicians do to prevent or reduce these comorbidities in ADHD?

As professor Andreas Reif summarizes at the end of the interview, the main things that we learned from the CoCA project are:

Comorbidity in ADHD is a very big problem. Adults with ADHD frequently have co-occuring conditions such as depression, anxiety, obesity and to a bit lesser extent substance use disorder.
The type and prevalence of comorbidities differ between men and women.
There is considerable genetic overlap between ADHD and comorbid conditions. We think that at least part of the overlap between comorbidities is caused by genetic effects (next to environmental effects that also play a role).
The dopamine system plays an important role in comorbidity, through influencing brain processes.
Disturbances in the circadian system (i.e. sleep cycle) are unlikely to play a causal role in these comorbidities, but they might be a consequence.
Clinicans should look out for comorbidities when they treat ADHD patients, and inform their patients about their increased risk to develop comorbidities so that they can take preventive measures (i.e. be careful with alcohol to avoid substance use disorder). Secondly, clinicians should actively look out for ADHD symptoms when treating conditions such as depression, anxiety, substance use disorder or obesity.

Watch the full interview with both experts by clicking on the image below:

More information about the CoCA project: www.coca-project.eu

Just-in-time-adaptive-interventions

Posted on June 8, 2021 by elenakochkit

Aid for ADHD individuals personal needs, right when it is needed

You might know the tenet of “just in time” from economics. It means bringing goods to a recipient at the right time, exactly when it is needed. But what if we could apply this also to treatments or interventions for mental health problems? Can we provide small interventions at exactly the time when a person needs it? And can this provide us with more insights into what triggers ADHD symptoms?

Just in time economics is possible and required because of dynamic processes in economical markets. Dynamic processes are also present in mental disorders. Attention-deficit/hyperactivity disorder (ADHD) is a condition that is dynamic by nature. Core symptoms of ADHD are hyperactivity, inattention and impulsivity, and many individuals also experience emotion dysregulation. In the past, research focused mainly on how patients with ADHD differ from healthy individuals or other disorders. But what about ADHD individuals’ context or other dynamics, that may trigger symptoms? For this we need to look much more closely at the dynamics of an individual’s life.

Ambulatory Assessment: collecting data in real time and in real life

The Ambulatory Assessment method makes use of smartphones, accelerometers, GPS-tracking and geolocation approaches to track how you feel, what you do, where you go, who you meet, what you eat, and how you’re body is doing (i.e. your heartrate) (1). This method has improved a lot over years and technical progress makes it more and more feasible to investigate associations between variables over time and how these variables interact in everyday life. This provides researchers with new insights into many different factors that can influence a person’s symptoms and mental health.

The importance of context

The Ambulatory Assessment method also enables to better differentiate between real and deceptive associations. Imagine, a person is asked for hyperactivity in the morning at 9:00 am, noon and evening and it turns out that the person is very hyperactive in the morning. Your conclusion may be that this individual is more hyperactive in the morning, but you don’t know why. If you know more about this person’s context, it may turn out that every day at 08:30 am the person drinks two cups of coffee which causes the measured hyperactivity at 9:00 am. This gives you much more insight into what triggers his or her symptoms.

Another example: imagine that a symptom always occurs in a special situation, at a special place or with a special person (e.g., after trying to catch the connecting train every morning at the same time). If you always ask for symptoms at the same time of day, you may miss this special occasion because it always occurs at another time. This way, you may miss out on important associations between symptoms and situations, places or persons. It is therefore very important to measure symptoms at random time points, or when they are triggered by certain events. This gives you much more informative data.

Cause or consequence?

However, the Ambulatory Assessment method is not yet perfect. The main limitation is that it’s difficult to determine what causes what (2). For example, do fluctuations in mood in patients with ADHD lead to impulsivity or hyperactivity? Or does mood change as a consequence of impulsivity? Another example: Do I feel better after exercising or do I move more because I feel good? Researchers recently found evidence for both directions (3,4).

Towards developing just in time treatment

Let’s think about the next step. A better understanding of causes and consequences and associations between symptoms and environmental triggers in an individual’s real world, creates the basis for just-in-time interventions (6). The idea is to react on dynamics in how symptoms are experienced or triggered, by timing the interventions exactly when it is needed. This could be realized by smartphones or wearables, which are already implemented in Ambulatory Assessment research. These devices are then not only used to collect data in real-time, but also to give feedback and provide interventions to reduce or prevent symptoms.

Exercise intervention through a smartphone app

The antecedent of just-in-time-adaptive-interventions are ecological momentary interventions (EMIs). One example of such an EMI or electronic diary intervention with a smartphone and an accelerometer for individuals with ADHD is the PROUD trial of the European funded project CoCA (5). In this trial, individuals with ADHD received a smartphone and a kind of sports watch (that measures your movement) that together measured their behavior, activity, daylight exposure, mood and symptoms during the day. The smartphone also provided an intervention, either in the form of sports exercises or in the form of bright light therapy. During the exercise intervention, participants are given instructions to perform exercises via a smartphone app by which they are guided through their training by weekly goals, motivational reminders, and training videos. Every evening, they get feedback on performed intervention parameters from that day in real time. This system was not yet so developed that it also changed the type or timing of the intervention to the data that was collected during the day, but that would be the next step to create a just-in-time intervention.

In conclusion, it is important to investigate the associations between ADHD individuals’ symptoms and their personal everyday lives. This helps researchers to understand the dynamic processes behind ADHD and to create tailor-made interventions that can easily be integrated in the everyday life of these individuals. A physician cannot support a patient throughout every step he/she takes, but there are already devices that can be supportive around the clock and technical innovations will surely pave the way to improve personal just-in-time interventions in the near future.

This blog was written by Elena Koch. She is a PhD student at Karlsruhe Institute for Technology in Germany.

References

1. Reichert M, Giurgiu M, Koch ED, Wieland LM, Lautenbach S, Neubauer AB, Haaren-Mack B v., Schilling R, Timm I, Notthoff N, Marzi I, Hill H, Brüßler S, Eckert T, Fiedler J, Burchartz A, Anedda B, Wunsch K, Gerber M, Jekauc D, Woll A, Dunton GF, Kanning M, Nigg CR, Ebner-Priemer U, Liao Y. Ambulatory assessment for physical activity research: State of the science, best practices and future directions. Psychology of Sport and Exercise. 2020;50101742. doi:10.1016/j.psychsport.2020.101742

2. Reichert M, Schlegel S, Jagau F, Timm I, Wieland L, Ebner-Priemer UW, Hartmann A, Zeeck A. Mood and Dysfunctional Cognitions Constitute Within-Subject Antecedents and Consequences of Exercise in Eating Disorders. Psychother Psychosom. 2020;89(2):119–21. doi:10.1159/000504061

3. Koch ED, Tost H, Braun U, Gan G, Giurgiu M, Reinhard I, Zipf A, Meyer-Lindenberg A, Ebner-Priemer UW, Reichert M. Relationships between incidental physical activity, exercise, and sports with subsequent mood in adolescents. Scand J Med Sci Sports. 2020;30(11):2234–50.

4. Koch ED, Tost H, Braun U, Gan G, Giurgiu M, Reinhard I, Zipf A, Meyer-Lindenberg A, Ebner-Priemer UW, Reichert M. Mood Dimensions Show Distinct Within-Subject Associations With Non-exercise Activity in Adolescents: An Ambulatory Assessment Study. Front Psychol. 2018;9268. doi:10.3389/fpsyg.2018.00268

5. Mayer JS, Hees K, Medda J, Grimm O, Asherson P, Bellina M, Colla M, Ibáñez P, Koch E, Martinez-Nicolas A, Muntaner-Mas A, Rommel A, Rommelse N, Ruiter S de, Ebner-Priemer UW, Kieser M, Ortega FB, Thome J, Buitelaar JK, Kuntsi J, Ramos-Quiroga JA, Reif A, Freitag CM. Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit / hyperactivity disorder: study protocol for a randomized controlled trial. Trials. 2018;19(1):140. doi:10.1186/s13063-017-2426-1

6. Koch, ED, Moukhtarian, TR, Skirrow, C, Bozhilova, N, Ashersn, P, Ebner-Priemer, UW. Using e-diaries to investigate ADHD – State-of-the-art and the promising feature of just-in-time-adaptive interventions. Neuroscience & Biobehavioral Reviews. 2021. https://doi.org/10.1016/j.neubiorev.2021.06.002

IS GENETICS BEHIND THE CO-OCCURRENCE OF ADHD AND OTHER DISORDERS?

Posted on May 10, 2021May 12, 2021 by Bru Cormand

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, r_g), 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 (www.coca-project.eu) on the genetics of ADHD comorbidity.

References

Common mental health symptoms in ADHD

Posted on August 13, 2020August 13, 2020 by Jeanette Mostert

Image by Anastasia Gepp from Pixabay — Excessive, uncontrolled mind-wandering is common to ADHD, but also to other mental health conditions. Mobile apps that prompt questions during the day can give more insight into the nature of these symptoms and how they differ between (often comorbid) conditions.

The majority of individuals with ADHD have one or more comorbid disorders. Comorbidity is a technical (and admittedly, not very cheerful) word for ‘co-occuring’, meaning that multiple disorders or conditions are present at the same time. Anxiety and depression are the most prevalent conditions that co-occur with ADHD.

Researchers and clinicians want to better understand this comorbidity in ADHD. Does having ADHD increase your risk of developing other conditions? Is there a biolgical mechanism that underlies both ADHD and other conditions? Or are symptoms of ADHD actually broader than the attentional, hyperactivity and impulsivity problems defined by the DSM/ICD, and therefore also linked to other conditions? Or all of the above?

Going with the third option (which by no means excludes the alternatives), clinicians have noticed that many individuals with ADHD experience symptoms that are not specific to ADHD, but are also often seen in other psychiatric conditions. You could call these symptoms ‘mainstream’, or ‘common’ mental health problems. Some examples that are often experienced by those with ADHD are emotional instability, sleep problems, low self-esteem, distractibility and concentration problems, and mental restlesnesss or excessive mind wandering.

Understanding these comorbidities better is important, because often one condition can hide the ‘true’ underlying condition. For instance, a person with ADHD who experiences many symptoms that are also characteristic of anxiety (i.e. low self-esteem, excessive mind-wandering, sleep problems, avoiding difficult situations). In such a case, the person could receive treatment for anxiety problems, while he or she is actually needing treatment for ADHD.

To distinguish between these conditions better, we need to find out more about these common symptoms. Being distracted can have many different causes and can happen in many different situations. For instance: are you distracted due to pervasive negative thoughts, because the task you’re doing is boring, or because you’re thinking of many related things and drift off to new ideas?

To learn more about the nature of these symptoms, researchers have given mobile apps or smartwatches to participants with ADHD. Several times a day, the watch buzzes and the app prompts a question that the person has to give answer to immediately. Questions can for instance be: How are you feeling right now? Have good/bad things happend to you in the last hour? How much has this affectd you? Were you concentrating on a task or where you distracted? Where you tinking about something (un)pleasant? etc. This method called ‘experience sampling’ can give very valuable information about someone’s symptoms. When combining the information from a lot of individuals, this can also identify differences between different disorders, that were not really known before.

If you want to learn more about this topic, you can watch this webinar by professor Philip Asherson from King’s College London. He explains the common mental health symptoms of ADHD in more detail, and gives examples from his research, also using experience sampling.

This blog is based on the webinar by Philip Asherson “ADHD in the mainstream” that was created as part of the CoCA project. The CoCA project investigates comorbid conditons of ADHD: .

How psychiatric genetics can help to guide diagnostic practice and therapy

Posted on June 4, 2020 by Jeanette Mostert

Recently, professor Stephen Faraone from SUNY Upstate University in the USA gave a webinar about genetic research in psychiatry (especially ADHD) and how this can help to better understand diagnosis and provide better treatment. In this blog I will share with you some highlights from this webinar.

ADHD is a continuous trait in the population

ADHD is not something that you either have or don’t have. Rather, symptoms or characteristics of ADHD are present in the entire population, in varying severity. The system for psychiatric diagnoses is however based on categorical definitions that determine when a certain combination of symptoms and severity can be classified as a particular disorder. Although these categories can be of great help to provide public health data or determine insurance coverage, they often don’t really match individual cases. Hence there arise problems with heterogeneity, subtypes, subthreshold cases and comorbidity.

Genetic research has shown that psychiatric conditions such as ADHD are not caused by a few single genes, but rather by thousands or tens of thousands genetic variants that each contribute slightly to the ADHD risk. These so-called polygenic risk scores form a normal distribution across the entire population, with the majority of people having low polygenic risk scores (so a low to average risk of ADHD), while a small portion of individuals have a very low or very high risk. This adds to our understanding that ADHD is a continuous trait in the population.

*Image from the webinar by prof. Stephen Faraone*. *The higher the number on the x-axis, the higher the genetic risk of having ADHD. Negative numbers mean reduced genetic risk of ADHD.*

2. Comorbidity in psychiatry is the norm, rather than the exception

In the webinar, Stephen Faraone explains that in 90’s it was thought impossible that an individual can have both ADHD and depression. Now, we know better than that. There are substantial genetic correlations between different psychiatric disorders, meaning that the genes that increase the risk of for instance ADHD, also increase the risk of schizophrenia, depression, bipolar disorder, autism and tic disorder. This is further evidence that psychiatric conditions are not separate, categorial entities but rather arise from similar biological mechanisms.

3. Personalised medicine and pharmacogenetics are not yet sufficiently established to adopt widely and replace current medication on a broad scale

The second part of the webinar was about pharmacogenetic testing. This means that an individual’s genetic profile is used to determine whether a drug will be effective, and in what dose. Although this sounds promising, there is still a lot of discussion about the validity of such tests. This is due to varying results, differing protocols and large heterogeneity between studies. In some cases, pharmacogenetic testing can help to find the right treatment for an individual, for instance when this person is not responding well to regular treatment, but it is definitely not a fool-proof method yet. Better randomized controlled clinical trials are needed to improve reliability of these tests.

You can watch the full webinar here: https://www.youtube.com/watch?v=DLgqdJWZKIo

The genetics of having multiple mental health conditions

Posted on May 26, 2020May 26, 2020 by Jeanette Mostert

We know that psychiatric conditions have a strong genetic component. This means that genes play an important role in determining an individual’s risk or vulnerability to develop a psychiatric condition. However, there is evidence that there are genetic variants that increase the risk for multiple psychiatric disorders. This is called pleiotropy. Researchers of the “Cross-Disorder Group of the Psychiatric Genomics Consortium” have searched the entire genome of 727,000 individuals (of whom 233,000 were diagnosed with a psychiatric disorder) to identify genetic variants with such pleiotropy.

The researchers found one particular gene – called DCC – that increases vulnerability for all eight disorders that were investigated: ADHD, autism spectrum disorder, anorexia nervosa, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia and Tourette syndrome.

They also found more than 100 genetic variants that predispose to at least two psychiatric disorders, and around 20 variants that are associated with four or more. This means that the genes that contain these variants can be interesting to further understand why certain individuals are more vulnerable to develop psychiatric illnesses than others.

One of the researchers, professor Bru Cormand, explains more about this research in this blog.

Further reading: Cross-Disorder Group of the Psychiatric Genomics Consortium (2019): Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell, 179(7): 1469-1482.e11.

Professor Cormand is involved in the CoCA research consortium where he investigates the genetic overlap between ADHD, major depression, anxiety disorder, substance use disorder and obesity. To read more about this, see for instance this other blog by him and dr. Judit Cabana Dominguez.

Cocaine dependence is in part genetic, and it shares genetic risk factors with other psychiatric conditions and personality traits.

Posted on July 4, 2019 by jcabanadominguez

Cocaine is one of the most used illicit drugs worldwide and its abuse produces serious health problems. In Europe, around 5.2% of adults (from 15 to 64 years old) have tried cocaine, but only 20% will develop addiction. Why? Genetics is part of the answer. Cocaine dependence is a complex psychiatric disorder that results from the interaction of both environmental and genetic risk factors. Twin and adoption studies indicate that genetic alterations contribute substantially to cocaine dependence susceptibility, which has an estimated genetic load (heritability) as high as 65-79%. Although many studies with focus on candidate genes have been performed, only a few risk variants for cocaine dependence have been identified and replicated so far.

https://www.
flickr.com/photos/30478819@N08/24042216187

In this study we performed a meta-analysis of genome-wide association studies (GWAS) of cocaine dependence using more than 6,000 European ancestry individuals. This approach allowed us to inspect a huge number of genetic variants distributed all along the genome that are common in the general population. We identified a gene (HIST1H2BD) associated with cocaine dependence that is located in a region on chromosome 6 enriched in genes that encode histones, proteins that combine with DNA, protecting it and contributing to the activation (or inhibition) of genes. Some of these genes have previously been associated with schizophrenia.

Several studies have shown that substance use disorders (SUD), and especially cocaine dependence, co-occur in patients with other psychiatric disorders and personality traits. Such comorbidity is associated with increased severity for all disorders, although it is unclear whether this relationship is causal or the result of shared genetic and/or environmental risk factors. We calculated the shared genetics (genetic correlation) between cocaine dependence and six comorbid conditions. For the first time we found significant genetic correlation with attention deficit/hyperactivity disorder (ADHD), schizophrenia, major depression and risk- taking behavior. We also used another approach (polygenic risk score analysis, PRS) to prove that all tested comorbid conditions are associated with cocaine dependence status, suggesting that cocaine dependence is more likely in individuals that carry genetic risk factors for the tested conditions than in those that do not.

To our knowledge, this is the largest reported GWAS meta-analysis in European-ancestry individuals with cocaine dependence. We identified suggestive risk factors for the disorder in several genomic regions and found evidence for shared genetic risk factors between cocaine dependence and several co-occurring psychiatric traits. However, the size of the sample is still limited and further studies are needed to confirm our results.

ADHD and autism – similar or different disorders?

Posted on May 9, 2019June 27, 2019 by beritskrettingsolberg

Have you ever thought that ADHD and autism could perhaps be the same disorder? – Or have you thought that they are way too different, two different planets in the psychiatric universe? Researchers do not agree on this. We know that both ADHD and autism are neurodevelopmental conditions with onset in childhood and that they share some common genetic factors, however, they appear with quite different phenotypical characteristics. We also know that people with ADHD or autism have an increased risk of getting other psychiatric disorders, so-called comorbidities, and smaller studies have shown that individuals with ADHD or autism get different psychiatric disorders, and at a different degree.

How can we utilize this knowledge about different psychiatric comorbidities between ADHD and autism? How can we get closer to an answer to this question; are ADHD and autism similar or different conditions? By using large datasets; unique population-based registries in Norway, we wanted to compare the pattern of psychiatric comorbidities in adults diagnosed with ADHD, autism or both disorders. In addition, we wanted to compare the pattern of genetic correlations between ADHD and autism for the same psychiatric traits, and for this, we exploited summary statistics from relevant genome-wide association studies.

In the registries, we identified 39,000 adults with ADHD, 7,500 adults with autism and 1,500 with both ADHD and autism. We compared these three groups with the remaining population of 1.6 million Norwegian adult inhabitants without either ADHD or autism. The psychiatric disorders we studied were anxiety, bipolar, depression, personality disorder, schizophrenia spectrum (schizophrenia) and substance use disorders (SUD).

Interestingly, we found different patterns of psychiatric comorbidities between ADHD and autism, overall and when stratified by sex (Fig.1). These patterns were also reflected in the genetic correlations, however, only two of the six traits showed a significant difference between ADHD and autism (Fig.2).

Figure 1 - Solberg et al. 2019 — Figure 1. Prevalence ratios of psychiatric disorders in adults with ADHD, autism or both ADHD and autism, relative to the remaining population, by sex. As can be seen in the figure, schizophrenia is more frequent in autism or ADHD+autism than ADHD alone, while the reverse is true for substance use disorder. There are also significant differences in prevalence between men and women. Figure from Solberg et al. 2019, CC-BY-NC-ND.

Figure 2A: The pattern of prevalence ratios of psychiatric comorbidity in adults with ADHD or autism observed in this study (ADHD; n=38,636, autism; n=7,528). Psychiatric conditions are highly prevalent in both ADHD and ASD, with schizophrenia being most prevalent in ASD and antisocial personality disorders in ADHD. Figure from Solberg et al. 2019, CC-BY-NC-ND.

Figure 2B: Genetic correlations (rg) calculated from genome wide association studies. Genetic correlations are also high with both disorders, with especially high correlations between ADHD and alcohol dependence, smoking behavior and anti-social behavoiur. Major depressive disorder has high genetic correlations with both ADHD and autism. Figure from Solberg et al. 2019, CC-BY-NC-ND.

Figure 2. Left: The pattern of prevalence ratios of psychiatric comorbidity in adults with ADHD or autism observed in this study (ADHD; n=38,636, autism; n=7,528). Right: genetic correlations (rg) calculated from genome wide association studies. Psychiatric conditions are highly prevalent in both ADHD and ASD, with schizophrenia being most prevalent in ASD and antisocial personality disorders in ADHD. Genetic correlations are also high with both disorders, with especially high correlations between ADHD and alcohol dependence, smoking behavior and anti-social behavoiur. Major depressive disorder has high genetic correlations with both ADHD and autism. Figure from Solberg et al. 2019, CC-BY-NC-ND.

The most marked differences were found for schizophrenia and SUD. Schizophrenia was more common in adults with autism, and SUD more common in adults with ADHD. Associations with anxiety, bipolar and personality disorders were strongest in adults with both ADHD and autism, indicating that this group of adults suffers from more severe impairments than those with ADHD or autism only. The sex differences in risk of psychiatric comorbidities were also different among adults with ADHD and ASD.

In conclusion, our study provides robust and representative estimates of differences in psychiatric comorbidities between adults diagnosed with ADHD, autism or both ADHD and autism. With the results from analyses of genetic correlations, this finding contributes to our understanding of these disorders as being distinct neurodevelopmental disorders with partly shared common genetic factors.

Clinicians should be aware of the overall high level of comorbidity in adults with ADHD, autism or both ADHD and autism, and the distinct patterns of psychiatric comorbidities to detect these conditions and offer early treatment. It is also important to take into account the observed sex differences. The distinct comorbidity patterns may further provide information to etiologic research on biological mechanisms underlying the pathophysiology of these neurodevelopmental disorders.

This study was done at Stiftelsen Kristian Gerhard Jebsen Centre for Neuropsychiatric disorders, University of Bergen, Norway, and published OnlineOpen in Biological Psychiatry, April 2019, with the title:

“Patterns of psychiatric comorbidity and genetic correlations provide new insights into differences between attention-deficit/hyperactivity disorder and autism spectrum disorder”. https://doi.org/10.1016/j.biopsych.2019.04.021

Figure 1 and 2 are re-printed by permission https://creativecommons.org/licenses/by-nc-nd/4.0/

Berit Skretting Solberg is a PhD-candidate at the Department of Biomedicine/Department of Global Health and Primary Care, University of Bergen, Norway. She is also a child- and adolescent psychiatrist/adult psychiatrist. She is affiliated with the CoCa-project, studying psychiatric comorbidities in adults with ADHD or autism, using unique population-based registries in Norway.

ADHD and cannabis use

Posted on April 2, 2019June 27, 2019 by María Soler Artigas

It is not uncommon for individuals to suffer from two or more psychiatric disorders at the same time. The appearance of these disorders frequently follows a specific order, and one disorder may predispose to others, all of which in combination contribute to the worsening of the quality of life of the individuals who suffer them. This is usually associated with more severe symptoms and worse prognosis. In addition, making a diagnosis and applying personalized treatments becomes more challenging in this context. By investigating the genetic overlap between disorders, we gain better understanding of why the disorders frequently co-occur.

In mental health, substance use disorders often appear when there is another mental condition. This is the case for attention-deficit/hyperactivity disorder (ADHD) and substance use disorder, where individuals with ADHD are more likely to use drugs during their lifetime than individuals who do not have ADHD. In particular, cannabis is the most commonly used substance among individuals with ADHD, which can also lead to the use of other drugs and to the worsening of their symptoms. ADHD is one of the most common neurodevelopmental disorders, affecting around 5% of children and 2.5% of adults, and is characterized by attention deficit, hyperactivity and impulsivity. Both ADHD and cannabis use are conditions determined partly by environmental factors but where genetic factors also play an important role.

We recently investigated the genetic overlap between ADHD and cannabis use, and found that the increased probability of using cannabis in individuals with ADHD, can be, in part, due to a common genetic background between the two conditions. We identified four genetic regions involved in increasing the risk of both ADHD and cannabis use, which could point to potential druggable targets and help to develop new treatments. In addition, we confirmed a causal link between ADHD and cannabis use, and estimated that individuals with ADHD are almost 8 times more likely to consume cannabis than those who do not have ADHD. This evidence goes in line with a temporal relationship, where the ADHD appears in childhood and the use of cannabis during adolescent or adulthood. This suggests that having ADHD increases the risk of using cannabis, and not vice versa.

This research has only been possible thanks to large international collaborations by the Psychiatric Genomics Consortium (PGC), iPSYCH, and the International Cannabis Consortium (ICC), where the genomes of around 85 000 individuals were analysed.

Overall, these results support the idea that psychiatric disorders are not independent, but have a common genetic background, and share biological pathways, which put some individuals at higher risk than others. This will help to overcome the stigma of addiction and mental disorders. In addition, the potential of using genetic information to identify individuals at higher risk will have a strong impact on prevention, early detection and treatment.

Further reading

María Soler Artigas et al. Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality, Molecular Psychiatry (2019) – https://www.nature.com/articles/s41380-018-0339-3

About the author

María Soler Artigas is postdoctoral researcher at the Psychiatry, Mental Health and Addictions group at Vall d’Hebron Institut de Recerca (VHIR), also part of the Biomedical Research Networking Center in Mental Health (CIBERSAM). Her research is part of the CoCA consortium that investigates comorbid conditions of ADHD.