Widespread asymmetries of amygdala nuclei predict auditory verbal hallucinations in schizophrenia

Background: Auditory verbal hallucinations, which frequently involve negative emotions, are reliable symptoms of schizophrenia. Brain asymmetries have also been linked to the condition, but the relevance of asymmetries within the amygdala, which coordinates all emotional signals, to the content of and response to auditory verbal hallucinations has not been explored.

Methods: We evaluated the performance of two asymmetry biomarkers that were recently introduced in literature: the distance index, which captures global asymmetries, and a revised version of the laterality index, which captures left-right local asymmetries. We deployed random forest regression models over values computed with the distance index and with the laterality index over amygdala nuclei volumes (lateral, basal, accessory-basal, anterior amygdaloid area, central, medial, cortical, cortico-amygdaloid area, and paralaminar) for 71 patients and 71 age-matched controls.

Results: Both biomarkers made successful predictions for the 35 items of the revised version of the Belief About Voices Questionnaire, such that hallucination severity increased with increasing local asymmetries and with decreasing global asymmetries of the amygdala.

Conclusions: Our findings highlight a global reorganization of the amygdala, where left and right nuclei volumes differ pairwise but become proportionally more similar as hallucinations increase in severity. Identifying asymmetries in particular brain structures relevant to specific symptoms could help monitor the evolution and outcome of psychopathological conditions.