The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression-The Glucocorticoid Deficit Hypothesis

Abstract

This review argues for a central role of the lateral hypothalamus in those deviant forms of aggression, which result from chronic glucocorticoid deficiency. Currently, this nucleus is considered a key region of the mechanisms that control predatory aggression. However, recent findings demonstrate that it is strongly activated by aggression in subjects with a chronically downregulated hypothalamus-pituitary-adrenocortical (HPA) axis; moreover, this activation is causally involved in the emergence of violent aggression. The review has two parts. In the first part, we review human findings demonstrating that under certain conditions, strong stressors downregulate the HPA-axis on the long run, and that the resulting glucocorticoid deficiency is associated with violent aggression including aggressive delinquency and aggression-related psychopathologies. The second part addresses neural mechanisms in animals. We show that the experimental downregulation of HPA-axis function elicits violent aggression in rodents, and the activation of the brain circuitry that originally subserves predatory aggression accompanies this change. The lateral hypothalamus is not only an integral part of this circuitry, but can elicit deviant and violent forms of aggression. Finally, we formulate a hypothesis on the pathway that connects unfavorable social conditions to violent aggression via the neural circuitry that includes the lateral hypothalamus.

Keywords: aggression; humans; hypothalamus; rodents; violence.

Figure 1

Mechanisms of glucocorticoid deficit-induced aggression are combinations of those subserving intraspecific and predatory aggressions. For explanations, see section Introduction. Dashed arrows indicate hypothetical information flow. CeA, central amygdala; LH, lateral hypothalamus; MBH, mediobasal hypothalamus (hypothalamic attack area); MeA, medial amygdala; mPFC, medial prefrontal cortex; OFC, orbitofrontal cortex; PAG, periaqueductal gray. Dashed arrows, hypothetical flow of information.

Figure 2

Hypothetical pathway from strong stressors to violent aggression through HPA-axis hypofunction. The latter is attributed to an “allostatic crash” (see section Glucocorticoid Deficits and Aggression in Humans). “Other factors” were included to indicate that hormonal conditions are likely embedded in a wider array of biological, psychological, and social factors. The time frame is based on a number of longitudinal studies performed in late childhood—early adolescence.

Figure 3

Brain mechanisms that mediate the effects of glucocorticoid deficits on aggression. Dashed arrows indicate hypothetical information flow based on earlier studies. Continuous arrows indicate the pathways discovered by Biro et al. (2018). The left hand panel is a simplified version of Figure 2. The arrows to the right and then to the left indicate the likely neural mechanism that link the hormonal to the behavioral event. The middle panel shows the “mixed” mechanism of glucocorticoid hypofunction-induced aggression complemented with two pathways that directly connect the medial prefrontal cortex to hypothalamic centers of aggression. The right hand panel shows on Paxinos and Watson slides (Paxinos and Watson, 1998) two subpopulations of medial prefrontal neurons, which project either to the lateral or mediobasal hypothalamus. The latter is an electrophysiologically defined area of the hypothalamus that covers several hypothalamic nuclei (Kruk, 1991). The optogenetic stimulation of axon terminals in the lateral hypothalamus increases the share of attacks on vulnerable targets that are poorly signaled socially. When stimulations are aimed at the mediobasal hypothalamus, the number of bites increases. Both effects are highly selective behaviorally (Biro et al., 2018). 3V, the third ventricle; AH, anterior hypothalamic nucleus; fx, fornix; IL, infralimbic cortex; OT, optic tract; PrL, prelimbic cortex. For other abbreviations, see Figure 1.