Behavior results from the complex interplay between genes and environment. Our genes predispose us to how we act and feel, by influencing how our brain develops and functions. This way, certain genetic variants in our genome increase the risk of developing mental health problems (while others may decrease this risk). Whether someone actually develops a mental health disorder or not, depends on many other factors in our environment, such as stressors and experiences. Nonetheless, studying these genetic risk factors for mental health conditions is an important aspect of understanding these disorders.

As an example of such research, we have now identified several genetic risk factors that contribute to cocaine dependence. For this we combined genetic data from a lot of studies, including more than 6000 individuals. What’s even more interesting is that we found that the genetic variants that are related to cocaine dependence are correlated with the genetic risk factors for other conditions such as ADHD, schizophrenia and major depression. What this means is that certain small variations in DNA increase the risk for not just cocaine dependence, but actually several psychiatric conditions. Probably, there is a common biological mechanism that underlies all these conditions. Thanks to our genetic research, we are now only a small step closer towards unraveling these mechanisms.

We also wrote a blog post explaining our research findings. You can read it here: https://mind-the-gap.live/2019/07/04/cocaine-dependence-is-in-part-genetic-and-it-shares-genetic-risk-factors-with-other-psychiatric-conditions-and-personality-traits/

The original publication can be found here: https://www.sciencedirect.com/science/article/pii/S0278584619301101?via%3Dihub

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Increasing evidence is showing that the gut microbiota can alter the brain and behavior, and thus may play a role in the development of psychiatric and neurodevelopmental disorders, such as autism and schizophrenia.

Animal models are a useful tool to study this mechanism. For example, germ-free (GF) mice, which have never been exposed to microorganisms, are compared with mice exposed to microorganisms, known as conventional colonized mice (CC). Recent studies have schizophrenia and autismreported that GF animals show increased response to stress, as well as reduced anxiety and memory. In most cases, these alterations are restricted to males, in which there are higher incidence rates of neurodevelopmental disorders compared with females.

Mice, like humans, are a social species and are used to study social behavior. A recent study compared GF and CC mice using different sociability tests. GF mice showed impairments in social behavior compared with CC mice, particularly in males. Interestingly, they demonstrate that social deficits can be reversed by bacterial colonization of  the GF gut (GFC), achieving normal social behavior.

Microbiota seem to be crucial for social behaviors, including social motivation and preference for social novelty. Microbiota also regulate repetitive behaviors, characteristic of several disorders such as autism and schizophrenia.

Bacterial colonization can change brain function and behavior, suggesting that microbial-based interventions in later life could improve social impairments and be a useful tool to effect the symptoms of these disorders.

This blog was co-authored by Noèlia Fernàndez and Judit Cabana

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What makes some of us more likely to drive over the speed limit, participate in extreme sports or make decisions that can impact health over time? Risk-taking behavior has distinct subtypes (for example disinhibition, sensation seeking, calculated risks, impulsivity) that develop due to the complex interplay of different factors: our lifestyle and environment, our personal susceptibility (genetic and biological variants) and a wide range of psychological effects.

In the study of Strawbridge and colleagues (2018) the goal was to identify genetic determinants of this trait. This approach has the potential to improve our understanding of impulsive behavior across different psychiatric disorders. It can also help later on to explore the possible overlap between mental illnesses and physical health.

„Would you consider yourself a risk taker?” This was the question posed to 116,255 participants, aged 40 to 69, from the UK Biobank project, a large population cohort containing a wide range of sociodemographic and medical information. Roughly one-quarter answered yes, they were the ’risk takers’ group.

A subset of participants took part in a prolonged follow-up occasion as well, where the same question was asked enabling an assessment of response consistency. Reproducibility was quite good, 81% of all participants responded consistently, 13% inconsistently, while in 6% the data was missing.

Genetic loci associated with risk-taking behavior were explored using the genome-wide association study approach. The authors identified one potential locus on chromosome 3 (CADM2) consistently, which was previously implicated in cognitive and executive functions.

Considering the entire genome using the polygenic risk score approach, the authors found, that the genetic variants that make us risk-prone also make us more likely to develop mental illnesses, such as bipolar disorder, schizophrenia, attention-deficit hyperactivity disorder, and post-traumatic stress disorder.

This trait has not only significant positive genetic correlations with a range of mental health disorders, but also with smoking, lifetime cannabis use and body mass index (BMI). The latter implies the possibility that this finding could be followed up in a study exploring the nutritional aspects of impulsivity as well.

Overall, using dimensional approach for traits (from “normal” to pathological) rather than discrete diagnostic categories could be helpful for finding the common ground in the neurobiological underpinnings across psychiatric disorders. From this point of view, risk-taking behavior is also a complex and important phenotype for investigations.

You can find the full research article here.

Strawbridge, R. J., Ward, J., Cullen, B., Tunbridge, E. M., Hartz, S., Bierut, L., Horton, A., Bailey, M. E. S., Graham, N., Ferguson, A., Lyall, D. M., Mackay, D., Pidgeon, L. M., Cavanagh, J., Pell, J. P., O’Donovan, M., Escott-Price, V., Harrison, P. J., & Smith, D. J. (2018). Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort. Translational Psychiatry, 8. https://doi.org/10.1038/s41398-017-0079-1

This was co-authored by  Tünde Kilencz, a psychologist and research assistant at Semmelweis University, Department of Psychiatry and Psychotherapy in Budapest, Hungary.

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