Elsevier

Biological Psychiatry

Volume 51, Issue 1, 1 January 2002, Pages 11-17
Biological Psychiatry

Social anxiety: from laboratory studies to clinical practice
The primate amygdala and the neurobiology of social behavior: implications for understanding social anxiety

https://doi.org/10.1016/S0006-3223(01)01307-5Get rights and content

Abstract

The amygdala has long been implicated in the mediation of emotional and social behaviors. Because there are very few human subjects with selective bilateral damage of the amygdala, much of the evidence for these functional associations has come from studies employing animal subjects. Macaque monkeys live in complex, highly organized social groups that are characterized by stable and hierarchical relationships among individuals who engage in complex forms of social communication, such as facial expressions. Understanding the role of the amygdala in animals that display a level of social sophistication approaching that of humans will help in understanding the amygdala’s role in human social behavior and in psychopathology such as social anxiety. Selective bilateral lesions of the amygdala in mature macaque monkeys result in a lack of fear responses to inanimate objects and a “socially uninhibited” pattern of behavior. These results imply that the amygdala functions as a protective “brake” on engagement of objects or organisms while an evaluation of potential threat is carried out. They also suggest that social anxiety may be a dysregulation or hyperactivity of the amygdala’s evaluative process. Finally, recent data from developmental studies raise the possibility that, at least at some developmental stages, fear in social contexts may be subserved by different brain regions than fear of inanimate objects.

Section snippets

Historical overview

The amygdala is a complex of nuclei that resides in the anterior temporal lobe of the human and nonhuman primate brains (Amaral et al 1992). In recent years, work carried out primarily in the rat has implicated the amygdala in the mediation of emotional behavior, particularly fear (Ledoux 1995); however, the amygdala has also been implicated in the organization of social behaviors in a number of mammalian species (rats: Jonason and Enloe 1971, cats: Schreiner and Kling 1953, dogs: Fuller et al

A brief summary of amygdala neuroanatomy

Before describing some of the changes that take place in social behavior following bilateral lesions of the amygdala in macaque monkeys, it is perhaps worthwhile to briefly reiterate some of the main features of the connectional organization of the nonhuman primate amygdala. A detailed description of the cytoarchitectonic organization, chemical neuroanatomy, and connections of the monkey amygdala can be found in Amaral et al (1992). The monkey amygdala has at least 13 distinct nuclei and

The function of the amygdala—a working hypothesis

A working hypothesis of our laboratory, which has been supported by our recent lesion studies, is that the amygdala is a protection device; it is designed to detect and avoid danger. A primary function of the amygdala is to evaluate objects or organisms in the environment prior to interacting with them (or deciding not to interact with them). Based on the outcome of the evaluation, an appropriate species-typical response is coordinated by the amygdala. If, for example, a monkey were to

Effects of bilateral lesions of the amygdala in macaque monkeys

Mature, male monkeys with discrete ibotenic acid lesions of the amygdala demonstrate many of the same attributes of the Kluver-Bucy syndrome that results from much larger lesions of the temporal lobe Emery et al 2001, Kluver and Bucy 1938. For example, they demonstrate a distinct hyperorality. While exploring outdoor cages, they pick up any object that they can find and place it into their mouths. They also excessively mouth the chain link fence and any other objects that are within their grasp.

Lack of social stress is indicated by analysis of cortisol levels

During the course of behavioral analyses, we were also in the position to evaluate the response of the hypothalamic-pituitary-adrenal (HPA) axis to various stressors (Ruys et al, unpublished data). In each of these experiments, baseline cortisol levels were compared with cortisol levels following either a social or physical stressor. As one example, the cortisol response to first interactions with novel animals was evaluated. Typically, the first meeting of novel animals is a highly stressful

The effects of neonatal amygdala lesions

One premise of the research program that we are undertaking is that the amygdala may be essential for gaining some facets of social knowledge but may not be the final repository of this information. By analogy with the hippocampal memory system, it is well known that the hippocampal formation and related medial temporal lobe structures are essential for the encoding of long-term episodic memories (Milner 1972); however, long-term storage appears to be in structures outside of the hippocampal

Conclusions

The overarching hypothesis governing, and thus far supported by, our program of studies is that the amygdala is a “protection device.” Among its various functions, it appears to play a role in inhibiting an organism’s approach to novel objects or other organisms. During the period of inhibited behavior, the amygdala participates in an evaluation of the environmental stimuli to ascertain whether there is something that is potentially dangerous. If so, the amygdala participates in the

Acknowledgements

This work was supported, in part, by National Institute of Mental Health grants 41479 and 57502 and National Institutes of Health grant RR00169.

Aspects of this work were presented at the conference, “Social Anxiety: From Laboratory Studies to Clinical Practice,” held March 22, 2001 in Atlanta, Georgia. The conference was supported by an unrestricted educational grant to the Anxiety Disorders Association of America (ADAA) from Wyeth-Ayerst Pharmaceuticals, and jointly sponsored by the ADAA, the

References (32)

  • J.P. Capitanio et al.

    Social stress results in altered glucocorticoid regulation and shorter survival in simian acquired immune deficiency syndrome

    Proc Natl Acad Sci USA

    (1998)
  • E.C. Crosby et al.

    Studies of the vertebrate telencephalon. II. The nuclear pattern of the anterior olfactory nucleus, tuberculum olfactorium and the amygdaloid complex in adult man

    J Comp Neurol

    (1941)
  • E.C. Crosby et al.

    Studies of the vertebrate telencephalon. III. The amygdaloid complex in the shrew (Blarina brevicauda)

    J Comp Neurol

    (1944)
  • M. Davis et al.

    The amygdalavigilance and emotion

    Mol Psychiatry

    (2001)
  • D. Dicks et al.

    Uncus and amygdala lesionsEffects on social behavior in the free-ranging rhesus monkey

    Science

    (1968)
  • N.J. Emery et al.

    The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta)

    Behav Neurosci

    (2001)
  • Cited by (303)

    • FTY720 decreases ceramides levels in the brain and prevents memory impairments in a mouse model of familial Alzheimer's disease expressing APOE4

      2022, Biomedicine and Pharmacotherapy
      Citation Excerpt :

      As previously reported, APOE4 transgenic mice were less active in the OF task [57] and displayed increased anxiety in the EZM [58]. The abnormalities in anxious behavior are thought to be caused by reduced ApoE expression in the amygdala, the brain center important for fear and anxiety processing [58]. In the memory test WM, the E4FAD was the only genotype showing memory impairments at 28 weeks of age.

    View all citing articles on Scopus
    View full text