Reassessing Asymmetry Reduction in Psychosis: Cingulate Folding and Gyrification Covariance in Patients with Auditory Hallucinations.

Background and hypothesis: Prior research links a shorter paracingulate sulcus (PCS) to hallucinations in schizophrenia, but its symmetry hemispheric specificity and relevance to bipolar disorders remain unclear. We hypothesized that reduced PCS asymmetry and interhemispheric gyrification covariance in salience and auditory networks are associated with lifetime auditory hallucinations (AH) in psychotic spectrum disorders.

Study design: We compared patients with and without AH, and healthy controls, focusing on PCS asymmetry in five ordinal classes, sulcal length and depth, and interhemispheric gyrification covariance.

Study results: Among 351 patients with schizophrenia or bipolar spectrum disorders (SSD/BSD), 194 (55.3%) had AH, compared to 157 without and 278 healthy controls. We found no significant PCS class asymmetry between hemispheres (V = 6648.5, P = .097) and decreased leftward asymmetry in PCS length (F(2,621) = 3.19, P = .013) in patients with AH, compared with those without and healthy controls. Compared to patients without AH, those with AH showed increased gyrification covariance in the auditory network (F(2,625) = 42.5, P < .001). In the salience network, patients with SSD and AH had increased covariance (F(2,625) = 299, P < .001), while patients with BSD and AH displayed decreased covariance (F(2,625) = 102, P < .001).

Conclusions: This study, featuring the largest cohort to date, links the AH trait to replicable reduced leftward PCS asymmetry and altered interhemispheric covariance in psychotic spectrum disorders, supporting theories of reduced asymmetry and altered brain network coordination as part of the mechanistic pathway to psychosis.