Left amygdala alterations mediate the effects of negative symptoms on social dysfunction in schizophrenia

Abstract

Social dysfunction remains a core feature of schizophrenia (SCZ), particularly in individuals exhibiting prominent negative symptoms. The amygdala (AMYG), a key structure in emotional and social processing, may contribute to this dysfunction. This study investigated whether structural and functional alterations in the AMYG mediate the effects of negative symptoms on social functioning in SCZ. A total of 205 male participants were included: 53 with deficit schizophrenia (DS), 76 with non-deficit schizophrenia (NDS), and 76 matched healthy controls (HCs). Negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms, and social functioning was evaluated with the Scale of Social Function in Psychosis Inpatients. Structural and resting-state functional MRI data were acquired. Amygdala volumes and region-of-interest-based functional connectivity (FC) were analyzed, and path analysis was used to test mediation effects. Patients with SCZ showed significantly reduced bilateral AMYG volumes compared to HCs. Within the SCZ group, the left amygdala (AMYG.L) was smaller than the right, with further reduction observed in DS compared to NDS. FC between the AMYG.L and the left superior temporal gyrus (STG.L) was also decreased in DS. Mediation analysis revealed that both AMYG.L volume and its FC with STG.L partially mediated the association between negative symptoms and poor social function. These findings suggest that AMYG.L abnormalities may involve social dysfunction in DS, offering potential targets for early intervention aimed at improving social outcomes in male patients with schizophrenia.

Fig. 1. Differences in whole-brain FC among the DS, NDS, and HC groups using the left amygdala as the seed point.

FC functional connectivity, DS deficit schizophrenia, NDS non-deficit schizophrenia, HC healthy controls. Z represents the location of the transect. ORBsupmed.R right superior frontal gyrus, medial orbital, INS.R right insula, CAL.R right calcarine fissure and surrounding cortex, SOG.R right superior occipital gyrus, STG.L left superior temporal gyrus, STG.R right superior temporal gyrus, SMA.L left supplementary motor area, MTG.R right middle temporal gyrus, INS.L left insula, LING.L left lingual gyrus. A Significant differences in FC between the DS and HC groups. Red and blue, respectively, indicate regions where the DS group had higher or lower FC than the HC group. B Significant differences in FC between the DS and NDS groups. Red and blue, respectively, represent regions where the DS group had higher and lower FC compared to the NDS group. C Significant differences in FC between the NDS and HC groups. Red and blue, respectively, represent regions where the NDS group had higher and lower FC compared to the HC group.

Fig. 2. Path analysis: estimated standardized direct effects for the final model.

Squares represent measured variables (scale or scale dimension scores). Arrows connecting circles and rectangles in one direction show a hypothesized direct relationship between two variables. The numbers next to the paths are standardized regression coefficients. The bold black line represents that the effect between the variables is statistically significant (p < 0.05). The letter “e” represents the associated error. SANS Scale for Assessment of Negative Symptoms, AMYG.L left amygdala, STG.L left superior temporal gyrus, GMV volume of gray matter, FC functional connectivity.