Biological Clocks and Rhythms of Anger and Aggression

Abstract

The body's internal timekeeping system is an under-recognized but highly influential force in behaviors and emotions including anger and reactive aggression. Predictable cycles or rhythms in behavior are expressed on several different time scales such as circadian (circa diem, or approximately 24-h rhythms) and infradian (exceeding 24 h, such as monthly or seasonal cycles). The circadian timekeeping system underlying rhythmic behaviors in mammals is constituted by a network of clocks distributed throughout the brain and body, the activity of which synchronizes to a central pacemaker, or master clock. Our daily experiences with the external environment including social activity strongly influence the exact timing of this network. In the present review, we examine evidence from a number of species and propose that anger and reactive aggression interact in multiple ways with circadian clocks. Specifically, we argue that: (i) there are predictable rhythms in the expression of aggression and anger; (ii) disruptions of the normal functioning of the circadian system increase the likelihood of aggressive behaviors; and (iii) conversely, chronic expression of anger can disrupt normal rhythmic cycles of physiological activities and create conditions for pathologies such as cardiovascular disease to develop. Taken together, these observations suggest that a comprehensive perspective on anger and reactive aggression must incorporate an understanding of the role of the circadian timing system in these intense affective states.

Keywords: aggression; anger; circadian rhythm; clock genes; infradian rhythm.

Figure 1

In mammals, the circadian molecular clock comprises a group of genes (“clock genes”) that regulate their own transcription and translation in a cycle that takes approximately 24 h to complete. This regulation is carried out through a series of interlocking negative feedback loops: the transcription factors BMAL1 and CLOCK heterodimerize and promote the expression of the Period (Per1/Per2) and Cryptochrome (Cry1/Cry2) genes, the nuclear receptors retinoid-related orphan receptor (RORα) and REV-ERBα, and a number of downstream genes referred to as clock-controlled genes (CCGs) including monoamine oxidase A (mao-a), excitatory amino acid transporter (eaat) and estrogen receptor beta (ERβ). In turn, the protein products of the Per and Cry genes dimerize and inhibit the transcriptional activity of CLOCK-BMAL1. The precise timing of this process is regulated by several kinases, such as casein kinase 1 epsilon/delta (CK1ε/δ), which regulate the post-transcriptional activity of PER-CRY dimers. RORα and REV-ERBα also regulate the transcription of BMAL1, whereby RORα promotes its expression, whereas REV-ERBα inhibits it (Huang et al., ; Mohawk et al., 2012). Sirtuin-1 (sirt1) is believed to regulate this feedback loop at several levels including through promoting RORα-mediated amplification of bmal expression (Asher et al., 2008) and acetylation of bmal (Nakahata et al., 2008). Figure adapted from Hood and Amir (2017) under a Creative Commons license.

Figure 2

Overview of aggressive behaviors that have been observed to exhibit either seasonal (infradian) or daily (circadian) rhythmicity in humans or non-human species. In terms of infradian rhythms, seasonal changes in daylight length may trigger a variety of hormonal changes that alter the activity of brain structures implicated in aggression such as the ventromedial hypothalamus (VMH). For circadian rhythms, the genetic clockwork that underlies daily cycles of behavior regulates a variety of genes (CCGs, e.g., mao-a; eaat; serotonin receptors including 5htb). In turn, these genes influence the activity of neurotransmitter systems within brain networks involving structures such as the amygdala and striatum. These changes in activation patterns may increase the probability of expressing anger and hostility.