Aggression in Boys May Start Before Birth (McGill University)

This new(ish) study from McGill University looked at the epigenetic genesis of some behavioral issues in boys and discovered that the cause can often be traced back to the pregnancy.

Their study revealed that men who displayed chronic aggressive behavior between the ages of 6 and 15 had lower blood levels of four biomarkers of inflammation (cytokines) than in men who displayed "normal" levels of aggressive behavior in their youth (from the original paper).

Compared to the control group, males on a chronic physical aggression trajectory from childhood to adolescence had consistently lower plasma levels of five cytokines: lower pro-inflammatory interleukins IL-1α (T(28.7) = 3.48, P = 0.002) and IL-6 (T(26.9) = 3.76, P = 0.001), lower anti-inflammatory interleukin IL-4 (T(27.1) = 4.91, P = 0.00004) and IL-10 (T(29.8) = 2.84, P = 0.008) and lower chemokine IL-8 (T(26) = 3.69, P = 0.001).

This allowed researchers to distinguish between men with physically aggressive histories from men without such histories simply on the basis of four cytokines (IL-1α, IL-4, IL-6, and IL-8).

In a follow-up study with the same men with aggressive pasts, "the DNA encoding the cytokines showed methylation patterns different from those of the comparison group."

Methylation is an epigenetic modification of DNA in relation to imprinting by parents or caregivers. Methylation also plays a role in regulating gene expression (turning a gene on or off). 

According to the researchers, the prenatal and early postnatal environment may trigger these epigenetic shifts that cause reduced levels of the four specific cytokines associated with youthful aggression.

The authors speculate in the discussion on the connection between specific cytokines and various brain chemicals, specifically serotonin and cortisol (from the original paper):

First, high cortisol levels were found to be associated with high levels of aggression in adolescent males from the same sample [41]. Cortisol levels are known to regulate immune and inflammatory responses [42]. Second, Vasopressin, a mediator of the HPA axis activity released in the brain enhances arousal and aggression [43]. Brain vasopressin is also involved in stress-induced suppression of immune functions in rats [44], [45]. Third, serotonin, a key player in aggressive behavior, is induced by cytokines, such as IL-6 and IL-1β, in brain and in blood [46]–[48]. Serotonin is also known to be involved in regulating IL-4, IL-8, IL-6, TNF-α and IL-1 expression and secretion through the CREB signaling pathway [49], [50]. Together, these studies suggest a link between known mediators previously shown to be involved in aggression and cytokines.

More importantly, the researchers suggest:

There is good evidence that the parents of children on a high trajectory of physical aggression had similar behavior problems and created early childhood family environments which did not support learning to regulate physically aggressive reactions [4], [10]–[14].

As is often the case, aggression is a family issue and is usually intergenerational. The fundamental question, as always, is causality: "Does chronic aggression during childhood result in lowered cytokine activity or does lowered cytokine activity result in more aggression?"

This is an excellent study and worth the time to read. Below is a summary of the research from Futurity, followed by the abstract of the original study.

Aggression in boys may start before birth

Posted by Cynthia Lee-McGill on September 23, 2013


"If our results show that behavioral problems originate from as far back as pregnancy, it means that we can reduce violence through preventive intervention from as early as pregnancy," says Richard Tremblay. (Credit: Peter Dutton/Flickr)

McGill University -- Original Study (PLoS ONE)

Chronic aggressive behavior exhibited by some boys from disadvantaged families may be due to epigenetic changes during pregnancy and early childhood.

A new study shows that men who displayed chronic aggressive behavior during childhood and adolescence have lower blood levels of four biomarkers of inflammation than in men who exhibited average levels of aggressive behavior in their youth, from 6 to 15 years of age.

“This means that using four specific biomarkers of inflammation, called cytokines, we were able to distinguish men with chronic physical aggression histories from those without,” says Richard Tremblay, professor emeritus at the University of Montreal.

In a second study, in the same men with aggressive pasts, the DNA encoding the cytokines showed methylation patterns different from those of the comparison group.

“Methylation is an epigenetic modification—hence reversible—of DNA, in relation to parental imprinting. It plays a role in regulating gene expression,”says Moshe Szyf, a professor at McGill University.

“The pre- and postnatal environment could cause these differences in biomarkers associated with chronic aggression,” Szyf says.

Various studies conducted with animals show that hostile environments during pregnancy and early childhood have an impact on gene methylation and gene programming leading to problems with brain development, particularly in regard to the control of aggressive behavior.

Begins with mom?

Previous work suggests that men with aggressive pasts have one thing in common: the characteristics of their mothers.

“They are usually young mothers at the birth of their first child, with low education, often suffering from mental health problems, and with substance use problems,” Tremblay says.

The significant difficulties these mothers experienced during pregnancy and the early childhood of their child may have an impact on the expression of genes related to brain development, the immune system, and many other biological systems critical for the development of their child.

For the two studies, published in PLOS ONE, researchers collected blood from 32 participants who took part in either of two longitudinal studies that began nearly 30 years ago. The first study followed young Quebecers from disadvantaged backgrounds, while the second involved a representative sample of children who were in kindergarten in Quebec in 1986-87.

It is important to note that in disadvantaged families, the rate of boys with chronic aggressive behavior represents about 4 percent of the population. This greatly restricts the selection of potential participants.

Disorganized lifestyles

“Once they are adults, they are difficult to find because they have disorganized lifestyles,” Tremblay says. “We are studying the impact of the socioeconomic environment on the third generation, now that these children are grown up and have children.”

While no study has yet been published on the subject, he anticipates “significant intergenerational ties, since we observed an association between parental criminality of the first generation and the behavior of their children.”

Nevertheless, Tremblay, who has conducted his work for decades with a prevention perspective, is optimistic.

“If our results show that behavioral problems originate from as far back as pregnancy, it means that we can reduce violence through preventive intervention from as early as pregnancy. We have already shown that support given to families of aggressive boys in kindergarten prevents school dropout and crime in adulthood.”

* * * * *

Here is the abstract of the original article from PLoS ONE, available as an open access publication and downloadable as a PDF.

Childhood Chronic Physical Aggression Associates with Adult Cytokine Levels in Plasma

Nadine Provençal, Matthew J. Suderman, Frank Vitaro, Moshe Szyf, Richard E. Tremblay 

Abstract

Background

An increasing number of animal and human studies are indicating that inflammation is associated with behavioral disorders including aggression. This study investigates the association between chronic physical aggression during childhood and plasma cytokine levels in early adulthood.

Methodology/Principal Findings

Two longitudinal studies were used to select males on a chronic physical aggression trajectory from childhood to adolescence (n = 7) and a control group from the same background (n = 25). Physical aggression was assessed yearly by teachers from childhood to adolescence and plasma levels of 10 inflammatory cytokines were assessed at age 26 and 28 years. Compared to the control group, males on a chronic physical aggression trajectory from childhood to adolescence had consistently lower plasma levels of five cytokines: lower pro-inflammatory interleukins IL-1α (T(28.7) = 3.48, P = 0.002) and IL-6 (T(26.9) = 3.76, P = 0.001), lower anti-inflammatory interleukin IL-4 (T(27.1) = 4.91, P = 0.00004) and IL-10 (T(29.8) = 2.84, P = 0.008) and lower chemokine IL-8 (T(26) = 3.69, P = 0.001). The plasma levels of four cytokines accurately predicted aggressive and control group membership for all subjects.

Conclusions/Significance

Physical aggression of boys during childhood is a strong predictor of reduced plasma levels of cytokines in early adulthood. The causal and physiological relations underlying this association should be further investigated since animal data suggest that some cytokines such as IL-6 and IL-1β play a causal role in aggression.

Full Citation: 
Provençal N, Suderman MJ, Vitaro F, Szyf M, Tremblay RE. (2013, Jul 26), Childhood Chronic Physical Aggression Associates with Adult Cytokine Levels in Plasma. PLoS ONE 8(7): e69481. doi:10.1371/journal.pone.0069481