An international research team has linked genes and brain anatomy with the human propensity for risky behaviors, such as smoking, alcohol and drug use, speeding, or frequently changing sexual partners, which collectively result in enormous health and economic consequences. The team says the study, reported in nature human behaviour, “ … constitutes one step towards understanding how the complex development of human risky behavior may be constrained by genetic factors,” and identifies what the authors call “distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.” Headed by University of Zurich neuro-economists Goekhan Aydogan, Todd Hare, and Christian Ruff, the researchers reported on their findings in a paper titled, “Genetic underpinnings of risky behaviour relate to altered neuroanatomy.”

Taking risks, which the authors state represents “an essential element of many human experiences,” is based on balancing positive and negative outcomes. Exploration, innovation, and entrepreneurship, for example, can have great benefits, but can also all too often fail. Common risky behaviors can also have serious consequences, they continued. “Similarly, common behaviors such as smoking, drinking, sexual promiscuity, or speeding are considered rewarding by many but might expose individuals and those around them to deleterious health, social, and financial consequences.” In fact, the investigators pointed out, in the United States, such common risky behaviors resulted in an estimated economic burden of nearly $600 billion in 2010. But in order to define measures that could reduce these costs, scientists first need a better understanding of the basis and mechanisms of risk-taking. And while prior studies have indicated that risk tolerance and risky behaviors are partially heritable, there is little known about how brain features translate genetic dispositions into actual risky behavior.

For their newly reported study, Aydogan and colleagues looked at the genetic characteristics that correlate with risk-taking behavior. They started with data from 25,000 participants in the UK Biobank, and examined the relationship between individual differences in brain anatomy—including grey matter volume (GMV)—and the propensity to engage in risky behavior, principally self-reported drinking, smoking, speeding on motorways, and sexual promiscuity. The results highlighted localized inverse associations between risky behavior and GMV in distinct regions of the brain, “… only some of which were expected on the basis of previous small-scale studies,” the researchers noted. As Aydogan pointed out, “We found both functional and anatomical differences.”

Negative associations between grey matter volume and risky behavior were particularly evident in both cortical and subcortical areas of the brain, including the hypothalamus, where the release of hormones such as orexin, oxytocin, and dopamine controls the vegetative functions of the body, and in the hippocampus, which is essential for storing memories. The studies also pointed to the dorsolateral prefrontal cortex (dlPFC), which plays an important role in self-control and cognitive deliberation, along with the amygdala, which controls, among other things, the emotional reaction to danger, and the ventral striatum, which is activated when processing rewards. “We identify localized inverse associations between risky behavior and GMV in distinct regions, only some of which were expected on the basis of previous small-scale studies,” they wrote.

“In subcortical areas, we identify associations bilaterally in expected areas such as the amygdala and ventral striatum, as well as in less expected areas such as the posterior hippocampus, putamen, thalamus, hypothalamus, and cerebellum. We also identify bilateral associations between risky behavior and GMV in cortical regions that include the ventral medial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), ventro-anterior insula (aINS), and the precentral gyrus. The researchers subsequently confirmed their findings in an additional, independent UK Biobank cohort.

They were particularly surprised by the measurable anatomical differences found in the cerebellum, an area of the brain that is not usually included in studies of risk behaviors, due to the assumption that it is mainly involved in fine motor functions. In recent years, however, significant doubts have been raised about this assumption. These doubts have now been backed by the newly reported study. “… our finding that risky behavior is linked to the structure of several cerebellar areas confirms the under-appreciated importance of the cerebellum for human cognition and decision-making, and highlights the need for further research on the specific behavioral contributions of this brain area,” the scientists wrote. “It appears that the cerebellum does, after all, play an important role in decision-making processes such as risk-taking behavior,” confirmed Aydogan. “In the brains of more risk-tolerant individuals, we found less gray matter in these areas. How this gray matter affects behavior, however, still needs to be studied further.”

The team also carried out a genome-wide association study (GWAS) in an independent sample of nearly 300,000 UK biobank participants, to construct polygenic risk scores (PRS) that effectively linked genetic variation with risky behavior, and explore whether the genetic disposition for risky behavior was associated with neuroanatomical features. Their results confirmed that the polygenic risk scores for risky behavior derived from the GWAS were inversely associated with grey-matter volume in the dlPFC, putamen, and hypothalamus. “This relation mediates roughly 2.2% of the association between genes and behavior,” they wrote.

Reporting their findings, the researchers concluded, “Our results extend previous findings by showing that the neural foundation of risky behavior is complex. Our analyses identify additional negative associations between risky behavior and GMV in several areas, including the cerebellum, posterior hippocampus, hypothalamus, and putamen.”

The results suggest that risk-taking draws on many different neuroal processes, including areas involved in memory, emotion processing, neuroendocrine processing, reward processing, and executive functions. “Thus, it appears that risky behavior taps into multiple elements of human cognition, ranging from inhibitory control to emotion regulation and the integration of outcomes and risks,” they stated. “Additionally, our results underscore the long-suspected role of the hypothalamic–pituitary–adrenal axis in regulating risk-related behaviors, in line with hormonal studies that link risky behavior and sensation-seeking to stress responsivity.”

The study breaks new ground in several regards, the investigators suggest. It is the first time that the foundations of risk-taking behavior have been investigated with such a large and representative sample. It is also the first study to examine possible influencing factors—genetic predisposition and differences in anatomy and function of brain areas—in combination rather than in isolation. At present, it is still unclear to what extent the connection between genetic disposition and neurobiological expression is causal, stresses Aydogan: “How exactly the interplay of environment and genes determines risk-taking requires further research.”


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