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Aggression

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Neuroscience in the 21st Century

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Abstract

Aggression is a normal and necessary component of social behavior that evolved to promote the protection of self, resources, progeny, and territory. However, excessive aggressiveness and disruptive violent outbursts are common problematic symptoms of multiple psychiatric disorders and represent a significant global burden. Current therapeutic strategies are limited due to a lack of understanding about the neural and molecular mechanisms underlying the “vicious” shift of normal adaptive aggression into violence. However, increasingly sophisticated neuroimaging tools for measuring human brain structure and function, together with the rapidly emerging preclinical tools for detailed mapping, measuring, and manipulating neuronal activity in the animal brain, have provided significant understanding of the precise neural microcircuitry and its dynamic molecular functioning underlying aggressive behavior. The core neuronal aggression network includes discrete clusters of neurons in the medial nucleus of the amygdala, bed nucleus of the stria terminalis, ventrolateral part of the ventromedial hypothalamus, and ventral part of the ventromedial premammillary nucleus. This core aggression circuit drives the various motor and autonomic aspects of aggression via its prominent projection to the midbrain periaqueductal gray area that in turn orchestrate the brainstem/spinal cord structures involved in executing motor output. Cognitive “top-down” forebrain control of this aggression circuit is mainly mediated through hippocampus-lateral septal and (prefrontal) cortical input supported by ascending midbrain monoaminergic nuclei like the dorsal/medial raphe nucleus (serotonin) and ventral tegmental area (dopamine).

This central circuit is evolutionary well conserved in all vertebrate species. The same holds for serotonin, dopamine, vasopressin, oxytocin, and adrenal/gonadal steroids as the major neurochemical modulators of offensive aggression and its underlying neuronal network. Obviously, the current emerging circuit-level knowledge of the neuronal and molecular underpinnings of aggression in both its normal and excessive forms have great potential to guide the rational development of effective therapeutic interventions for pathological aggressive behavior.

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Abbreviations

5-HIAA:

5-hydoxyindoleacetic acid

5-HT:

Serotonin

5-HTT:

Serotonin transporter

AAS:

Anabolic androgen steroids

ACC:

Anterior cingulate cortex

AMYG:

Amygdala

Aob:

Accessory olfactory bulb

AVP:

Arginine vasopressin

AVPV:

Anteroventral periventricular nucleus

BNST:

Bed nucleus of the stria terminalis

CeA:

Central amygdala

Cp:

Caudate putamen

CSF:

Cerebrospinal fluid

DRN:

Dorsal raphé nucleus

ER:

Estrogen receptor

GABA:

Gamma amino butyric acid

Glu:

Glutamate

HIP:

Hippocampus

HYP:

Hypothalamus

LHB:

Lateral habenula

LS:

Lateral septum

MeA:

Medial amygdala

MPOA:

Medial preoptic nucleus

MRN:

Medial raphé nucleus

NAc:

Nucleus accumbens

NO:

Nitric oxide

Ob:

Olfactory bulb

OXT:

Oxytocin

PAG:

Periaqueductal gray

PET:

Positron emission topography

PFC:

Prefrontal cortex

Pit:

Pituitary

PMV:

Ventral premammillary nucleus

SBN:

Social behavioral network

SDMN:

Social decision-making network

SNR:

Substantia nigra

SPECT:

Single photon emission computer tomography

SPZ:

Subparaventricular zone

Thal:

Thalamus

Vp:

Ventral pallidum

VTA:

Ventral tegmental area

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Authors and Affiliations

  1. Department of Behavioral Neuroscience, GELIFES, University of Groningen, Groningen, The Netherlands

    Sietse F. de Boer & Jaap Koolhaas

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  1. Sietse F. de Boer
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  2. Jaap Koolhaas
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Correspondence to Sietse F. de Boer .

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Editors and Affiliations

  1. Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA

    Donald W. Pfaff

  2. National Institute on Drug Abuse, Rockville, MD, USA

    Nora D. Volkow

  3. Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA

    John L. Rubenstein

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de Boer, S.F., Koolhaas, J. (2022). Aggression. In: Pfaff, D.W., Volkow, N.D., Rubenstein, J.L. (eds) Neuroscience in the 21st Century. Springer, Cham. https://doi.org/10.1007/978-3-030-88832-9_74

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