The involvement of the overproduction of stress hormones (glucocorticoids) in the etiology of mood disorders (e.g., anxiety and depression) is well established. In contrast, the psychopathological consequences of glucocorticoid underproduction received comparatively little attention, despite the fact that disparate human studies suggest an involvement of glucocorticoid deficiency in abnormal human aggression. We have recently reported that experimentally induced glucocorticoid insufficiency induces abnormal forms of aggression in rats. Such rats target their attacks to vulnerable parts (mainly the head) of their opponents. In addition, intention signaling (threat behavior) is deficient in these rats. These data suggest that glucocorticoid deficiency is a risk factor in the etiology of aggression-related psychopathologies.
In the present work, we aimed at understanding the mechanisms of glucocorticoid insufficiency–induced aggression, with special reference to mechanisms involved in fear and anxiety. In addition, possibilities of counteracting the behavioral anomaly are surveyed.
In the experiments performed so far, we have shown that chronic but not acute glucocorticoid deficiency facilitates aberrant attacks. An acute suppression of glucocorticoid synthesis decreased aggressive behavior without affecting attack targeting. In contrast, chronic glucocorticoid deficiency did not affect the level of aggressiveness, but increased attacks aimed at vulnerable body parts of the opponents, and decreased intention signaling. Glucocorticoid deficiency did not affect anxiety levels in nonsocial settings but induced signs of anxiety in the social interaction test of anxiety. This suggests that glucocorticoid deficiency disrupts social behavior in challenging situations without affecting anxiety levels in general. Glucocorticoid deficiency also induced deviant cardiovascular responses in challenging situations. Rats with experimentally induced glucocorticoid deficiency showed decreased heart rate increases when challenged with an opponent in familiar or unfamiliar environments. The difference was not due to differences in work load, as glucocoticoid deficiency did not affect locomotion in either setting. Notably, violent criminals were shown to have decreased basal heart rates and decreased cardiovascular reactivity in challenging situations.
This suggests that glucocorticoid deficiency disrupts social behavior in challenging situations without affecting anxiety levels in general.
We have also studied the effects of glucocoticoid deficiency on the aggression-induced activation of various brain centers. We have assessed the neuronal activation patterns induced by aggressive behavior in rats. The so-called cFos technique employed provided results largely consistent with those provided earlier by lesion and stimulation techniques. We have noticed, however, that the activation of a neuronal path involving the hypothalamic attack area, mediodorsal thalamus, and frontal cortical areas is a prerequisite of attacks. We have also noticed that the activation patterns of brain centers involved in aggression control were not affected by glucocorticoid deficiency. In contrast, glucocorticoid deficiency induced a strong activation of the brain centers involved in the stress response and fear. Currently, we investigate the connections and the neurochemical nature of neurons involved in aggression control, to get more insights into the neural control of glucocorticoid deficiency–induced abnormal aggression.
The data presented above suggest that fear is an important determinant of glucocorticoid deficiency–induced aggression. Therefore, we assessed whether anxiolytics are able to suppress the abnormal behavioral pattern induced by glucocorticoid deficiency. Surprisingly, the serotonergic anxiolytic buspirone aggravated rather than ameliorated the behavioral anomaly. Studies are currently being performed with other anxiolytics and compounds used for treating aggression-related human disorders.