How psychiatric genetics can help to guide diagnostic practice and therapy

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.

  1. 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

These are the world’s most high ranking experts on ADHD

Who are the most knowledgeable people about ADHD in the world? According to the website expertscape.com, these are professors Stephen Faraone (SUNY upstate University), Samuel Cortese (University of Southampton) and Jan Buitelaar (Radboud University Nijmegen).

What’s more, several scientists who are involved in our research consortia that investigate ADHD (i.e. Aggressotype, CoCA, IMpACT, Eat2beNICE) are top-ranked in this list of more than 30.000 possible experts in the field. These include Stephen Faraone, Jan Buitelaar, Philip Asherson, Barbara Franke, Joseph Antoni Ramos-Quiroga, Henrik Larsson, Catharina Hartman and Pieter Hoekstra. What this means is that the ADHD research that we do, and that is often reported on in this blog, is lead by the world’s top ADHD experts.

adhdexperts_pic
‘Our’ top-ranked ADHD experts. From left-to-right: Stephen Faraone, Jan Buitelaar, Philip Asheron, Barbara Franke, Joseph Antoni Ramos-Quiroga, Henrik Larsson, Catharina Hartman, Pieter Hoekstra.

How is an expert defined?

The website expertscape was started by John Sotos when he was looking for an expert on Parkinson’s disease to treat his uncle. This turned out to be more difficult than he thought. As John Sotos was a doctor himself, he luckily had a large network of doctors that he could contact about this. But this made him realise that people who don’t have such a network, would not be able to find out who the most knowledgeable persons are on a particular topic. He therefore created this website expertscape.com

The way the website works is quite simple: it searches for academic, peer-reviewed publications by a certain person on a certain topic. The more someone has published on a topic, the higher this person is ranked. Thus,  “[a]n expert is not just someone who knows a lot about a particular topic. We additionally require that the expert write about the topic, and be involved at the leading edge of investigation of the topic.”

This means that the site is actually not a very good tool to find a good doctor. As the website acknowledges “a great doctor has many important qualities beyond expert knowledge of your very specific medical condition.” However, it does mean that the website is pretty good at providing a simple overview of who has a lot of scientific knowledge about a specific topic.

So are they really experts?

In the past years I have met with most people in the top of this list, and I dare say that they are very knowledgeable indeed. Each of them has been working in the ADHD field for a considerable amount of time and has added important new insights into ADHD through research and publications. What I find most striking from this list however, is that most of these experts work together in consortia and international networks. And that is how the field really moves forward: by combining the knowledge of all these experts.

Several of these experts have also written for this blog:

 

Source: http://expertscape.com/ex/attention+deficit+disorder+with+hyperactivity

 

This blog was written by Jeanette Mostert. Jeanette studied brain connectivity in adult ADHD during her PhD. She is now dissemination manager of the international consortia CoCA and Eat2beNICE. 

 

Pay Attention to ADHD – Podcast with prof. Stephen Faraone

Professor Stephen Faraone – professor in Psychiatry at SUNY Upstate University and expert on ADHD – was interviewed by dr. Therese Markow for the podcast series ‘Critically Speaking’. In this podcast they discuss myths about ADHD and the scientific evidence that debunks these myths. Stephen Faraone explains why it is so important to diagnose and treat ADHD early. He also explains why ADHD is often undiagnosed in girls, and why sometimes adults are diagnosed with ADHD who have not sought treatment earlier in their life.

Critically Speaking is a podcasts series hosted by dr. Therese Markow who interviews experts to discuss in plain language complex issues that concern our health, society and planet.

You can listen to the podcast here: http://criticallyspeaking.libsyn.com/002-pay-attention-adhd-with-dr-stephen-faraone

 

ADHD Is A Risk Factor For Type Two Diabetes And High Blood Pressure, As Well As Other Psychiatric Disorders

All Swedish residents have their health records tracked through unique personal identity numbers. That makes it possible to identify psychiatric and medical disorders with great accuracy across an entire population, in this case encompassing more than five and a half million adults aged 18 to 64. A subgroup of more than 1.6 million persons between the ages of 50 and 64 enabled a separate examination of disorders in older adults.

Slightly over one percent of the entire population (about 61,000) were diagnosed with ADHD at some point as an adult. Individuals with ADHD were nine times as likely to suffer from depression as were adults not diagnosed with ADHD. They were also more than nine times as likely to suffer from anxiety or a substance use disorder, and twenty times as likely to be diagnosed with bipolar disorder.  These findings are very consistent with reports from clinical samples in the USA and Europe.

Adults with ADHD also had elevated levels of metabolic disorders, being almost twice as likely to have high blood pressure, and more than twice as likely to have type 2 diabetes. Persons with ADHD but without psychiatric comorbidities were also almost twice as likely to have high blood pressure, and more than twice as likely to have type 2 diabetes.

Similar patterns were found in men and women with ADHD, although comorbid depression, bipolar disorder, and anxiety were moderately more prevalent in females than in males, whereas substance use disorder, type 2 diabetes, and hypertension were more prevalent in males than in females.

ADHD was less than a third as prevalent in the over-50 population as in the general adult population. Nevertheless, individuals in this older group with ADHD were twelve times as likely to suffer from depression, anxiety, or substance use disorders, and more than 23 times as likely to be diagnosed with bipolar disorder as their non-ADHD peers. They were also 63% more likely to have high blood pressure, and 72% more likely to have type 2 diabetes.

The authors noted, “Although the mechanisms underlying these associations are not well understood, we know from both epidemiologic and molecular genetic studies that a shared genetic predisposition might account for the co­existence of two or more psychiatric conditions. In addition, individuals with ADHD may experience increased difficulties as the demands of life increase, which may contribute to the development of depression and anxiety.” As for associations with hypertension and type 2 diabetes, these “might reflect health ­risk behaviors among adult patients with comorbid ADHD in addition to a shared biological substrate. As others have noted, inattention, disinhibition, and disorganization associated with ADHD could make it difficult for patients to adhere to treatment regimens for metabolic disorders.” They concluded that “Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes.”

Stephen Faraone is distinguished Professor of Psychiatry and of Neuroscience and Physiology at SUNY Upstate Medical University and is working on the H2020-funded project CoCA. 

REFERENCES

Qi Chen, Catharina A. Hartman, Jan Haavik, Jaanus Harro, Kari Klungsøyr, Tor­Arne Hegvik, Rob Wanders, Cæcilie Ottosen, Søren Dalsgaard, Stephen V. Faraone, Henrik Larsson, “Common psychiatric and metabolic comorbidity of adult attention-deficit/hyperactivity disorder: A population-based cross-sectional study,” PLoS ONE (2018), 13(9): e0204516. https://doi.org/10.1371/journal.pone.0204516.