An Honest Reckoning With the Amygdala and Mental Illness

Anxiety disorders are a leading source of human misery, morbidity, and premature mortality. Existing treatments are far from curative for many, underscoring the need to clarify the underlying neural mechanisms. Although many brain regions contribute, the amygdala has received the most intense scientific attention. Over the past several decades, this scrutiny has yielded a detailed understanding of amygdala function, but it has failed to produce new clinical assays, biomarkers, or cures. Rising to this urgent public health challenge demands an honest reckoning with the functional-neuroanatomical complexity of the amygdala and a shift from theories anchored on “the amygdala” to models centered on specific amygdala nuclei and cell types. This review begins by examining evidence from studies of rodents, monkeys, and humans for the “canonical model,” the idea that the amygdala plays a central role in fear- and anxiety-related states, traits, and disorders. Next, the authors selectively highlight work indicating that the canonical model, while true, is overly simplistic and fails to adequately capture the actual state of the evidentiary record, the breadth of amygdala-associated functions and illnesses, or the complexity of the amygdala’s functional architecture. The authors describe the implications of these facts for basic and clinical neuroimaging research. The review concludes with some general recommendations for grappling with the complexity of the amygdala and accelerating efforts to understand and more effectively treat amygdala-related psychopathology.