Exogenous cortisol enhances aggressive behavior in females, but not in males.
Psychoneuroendocrinology. 2010 Feb 1;
Böhnke R, Bertsch K, Kruk MR, Richter S, Naumann E
The hypothalamic-pituitary-adrenal (HPA) axis plays a major role in the development, elicitation, and enhancement of aggressive behavior in animals.
Increasing evidence suggests that this is also true for humans.
Here, we report on a study of the role of basal and acute HPA axis activity in a sample of 48 healthy male and female adults.
We pharmacologically enhanced cortisol levels and used the Taylor Aggression Paradigm (TAP) to induce and measure aggression (divided into three blocks). Participants either received an oral dose of 20mg hydrocortisone (cortisol group) or a placebo (placebo group).
Half of each group received high or low levels of provocation with the TAP, respectively. Before, we assessed the cortisol awakening response as a trait measure of basal HPA axis activity.
Participants in the cortisol group reacted more aggressively in the third block of the TAP compared to the placebo group. Furthermore, gender interacted with treatment: only females, but not males showed enhanced aggressive behavior after cortisol administration. There was no significant difference in males between the placebo and cortisol group.
Basal HPA axis activity was negatively related to aggressive behavior, but again only in females and most strongly within the placebo group.
This study provides the first evidence for a causal involvement of acute HPA axis activation in aggressive behavior in humans.
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The problem I have with this article is the interpretation. It is prone to misinterpretation – particularly given the title (cortisol increases aggressive behavior).
The authors want to see if increased HPA Axis activity affects aggression in women and men. This is an interesting topic in psychiatry.
They found that adding 20 mg of hydrocortisone to a healthy subjects increases aggressive behavior in women but not men.
They measured basal HPA Axis Activity using Cortisol Awakening Response as a measure. Cortisol Awakening Response is the amount of cortisol increase about 20-30 minutes after awakening in the morning. They found that women with lower HPA Axis Activity are more aggressive than women with higher HPA Axis Activity. And they find no difference in men.
The problem is the juxtaposition of the title (cortisol increases aggressive behavior) and the actual results of the study.
Adding 20 mg of exogenous Hydrocortisone suppresses HPA Axis activity, not increases it – particularly in women. This is NOT explained in the title nor the abstract. To those who don’t know any better, a casual reading of the article would make it seem as if cortisol is the cause of aggressive behavior. It is not.
Let us look more deeply:
The adrenal gland consists of an inner medulla, which is essentially a sympathetic nervous system ganglion, which produces norepinephrine and epinephrine. And it has an outer cortex, which in response to ACTH from the pituitary and other signals (such as norepinephrine produced by the medulla), produces a group of hormones in shot-gun fashion: cortisol (hydrocortisone), DHEA, progesterone, testosterone, estradiol, and multiple others. These signals/hormones, each have important effects on one’s ability to respond to stress.
If I wanted to stimulate the HPA Axis, I would have injected a sympathomimetic – such as norepinephrine. This would have stimulated all of the HPA Axis – the medulla and cortex.
Adding cortisol instead suppresses the HPA Axis. Adding cortisol would suppress the nervous system norepinephrine-CRH positive feedback circuit – which would then reduce sympathetic nervous system activation of the adrenal gland via innervation to the medulla and ACTH to the cortex. The exogenous cortisol may make up for the loss of cortisol production in the cortex. But the rest of the cortex production (DHEA, progesterone, testosterone, etc.) would have been suppressed.
It is the loss of these adrenocortical hormones that can primarily determine the outcome of the study. For example, DHEA, Progesterone, and Testosterone have a calming effect on behavior. Progesterone, in particular, has significant sedative effects through its metabolites. Estradiol, unbalanced by these other hormones can produce aggressive behavior. In women, most of progesterone is made by the adrenal glands in the non-luteal phase of the menstrual cycle, half of testosterone is produced in the adrenal glands. Suppressing DHEA, Progesterone and Testosterone would leave a woman open to the aggressive effects of estrogen on behavior. For men, only 5% of testosterone is produced by the adrenal glands. The loss of DHEA, Progesterone and Testosterone. Suppressing adrenal cortex hormone production in men to the level done in this study (which uses a subphysiologic dose of hydrocortisone – given 60 % first pass metabolism in the liver) would not be expected to increase aggression as in women because so much testosterone is produce in the testes that the loss of adrenal testosterone production would not have been significant. In addition, the male subjects would have lost significant estradiol adrenal production, making it much easier to suppress aggressive behavior. If the men were hypogonadal, perhaps aggression may be seen.
There are numerous other complex interactions between the nervous system, endocrine system, and immune system which can be influence the outcome, but the the basic set of adrenal hormones discussed above should give a clue as why the result occurred in the study.
Interestingly, this is born out by the second finding of the study: lower baseline HPA Axis activity is associated with aggressive behavior in women, not men.
Thus, I would be happier if the title of the study was changed to: “Suppressing HPA Axis activity by adding exogenous cortisol enhances aggressive behavior in females but not in males.” The original title is misleading – though unfortunately mythologically correct.