The stress with high stress-reactivity and 5-HTTLPR

One of the most intriguing scientific research on human infant development is Jermone Kagan’s study of highly reactive babies. About 20% of babies are highly reactive and they typically display an inhibited (shy) temperament as toddlers. My wife and I have first-hand experience, what it means to have a highly reactive (i.e. “difficult) baby: they cry a lot (often referred to as “colicky” for a lack of a better explanation), are hard to put to sleep and wake up frequently, they startle easily and it often takes a long time to soothe them when they are stressed. In brief, highly stress reactive babies are highly stressful for their parents.

This temperament is partially inherited and the children have some typical life-trajectories: as toddlers, they might throw frequent tantrums and are consistently shy with strangers and avoidant of unfamiliar situations. As teenagers, they are prone to worry (neuroticism) and overthinking and many (though by far not all) suffer from social anxiety. Neuroticism and anxiety are often also predictive of mental disorder (depression, bi-polar, etc.) in late adolescence/early adulthood. Kagan notes that many of the highly reactive babies choose carriers such as scientists, artists or writers as adults.

What is highly interesting to note is the percentage. 20% of people are also highly sensitive (HSPs), orchid children (Thomas Boyce) and intuitives in the Myers-Briggs system (correlates with high openness in the Big 5 inventory). Genetically this phenotype corresponds somewhat to the short allele of the serotonin transporter gene (5-HTTLPR), which has been associated with a variety of phenomena, including, higher stress (amygdala) reactivity, poor sleep, anxiety, alcohol dependence, mental disorders and suicide.

The short 5-HTTLPR polymorphism is associated with various proclivities that, taken together, might be called emotional sensitivity, including increased negative emotion, harm avoidance, attentional biases to negative information, sensitivity to cues of rejection, and augmented risk for depression when exposed to environmental stressors. ( Winegard et al. )

In Ruth Karpinski’s model of the “hyper brain — hyper body” model high IQ people (gifted children are frequently hyperreactive) are at a higher risk of a variety of illnesses:

This is not where it ends, however. High stress leves are associated with other unfavourable outcomes: obesity, cardiovascular diseases, insomnia, irritable bowel syndrome, burnout and many more.

While a single gene is not very predictive, it is still surprising why evolution would have kept such a vulnerable phenotype. What’s more, we can be pretty sure that at 20% of the population we are dealing with an ancient adaptation here. I have argued before that our personality/temperament are adaptations to our ancestral modes of subsistence and life-history strategy:

Hunter-gatherers would have had longer lives than early farmers, who in turn would have had longer life-spans than pastoralists. Shorter life-spans would have increased risk-taking (dopamine) and reduced stress-reactivity (cautiousness) according to life-history theory.

Returning to highly reactive babies: if these are considered “hunter-gatherer” type babies, it makes sense that they are more easily stressed. Children in agricultural societies would have been more protected (e.g. from predators) than hunter-gatherer children. It was therefore highly adaptive for them to wake up/startle more easily or to cry more often to keep their caregiver close-by. Also, high social sensitivity is highly important in egalitarian hunter-gatherer societies, in which social ostracism is one of the worst outcomes imaginable.

Kagan’s research also showed that about 30–40% of babies were the exact opposite of highly reactive, i.e. low reactive. They often develop into outgoing, spontaneous, fearless children — uninhibited. If my model of evolution and temperament is correct, these children should approximately correspond to the “pastoralist” type. In fact, this is very close to the distribution of personality types in the Myers-Briggs system:

It would be advantageous for parents as well as teachers to have an idea of a child’s temperament. Observant parents and caregivers might easily find patterns in a child’s behaviour to give them clues. Pastoralist type children are at risk of early puberty and getting into trouble with teachers and the law. Hunter-gatherer type children are averse to authority and might develop ODD (oppositional defiant disorder) or anxiety and depression early on. Farmer type children are usually not very problematic: they are adapted to a “farmer society”, like we live in, they tend to stick to the rules, work hard at school and show little risk-taking or deviant behaviour.

Originally published at on June 6, 2020.