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Updated: Dec 29, 2025

Animal Models of Depression - Chronic Despair Model CDM
Published on: September 23, 2021
The neuroscience of sadness: A multidisciplinary synthesis and collaborative review
Juan A Arias1, Claire Williams2, Rashmi Raghvani2
1Department of Psychology, Swansea University, United Kingdom; Department of Statistics, Mathematical Analysis, and Operational Research, Universidade de Santiago de Compostela, Spain.
Abstract:
Sadness is typically characterized by raised inner eyebrows, lowered corners of the mouth, reduced walking speed, and slumped posture. Ancient subcortical circuitry provides a neuroanatomical foundation, extending from dorsal periaqueductal grey to subgenual anterior cingulate, the latter of which is now a treatment target in disorders of sadness. Electrophysiological studies further emphasize a role for reduced left relative to right frontal asymmetry in sadness, underpinning interest in the transcranial stimulation of left dorsolateral prefrontal cortex as an antidepressant target. Neuroimaging studies - including meta-analyses - indicate that sadness is associated with reduced cortical activation, which may contribute to reduced parasympathetic inhibitory control over medullary cardioacceleratory circuits. Reduced cardiac control may - in part - contribute to epidemiological reports of reduced life expectancy in affective disorders, effects equivalent to heavy smoking. We suggest that the field may be moving toward a theoretical consensus, in which different models relating to basic emotion theory and psychological constructionism may be considered as complementary, working at different levels of the phylogenetic hierarchy.
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