Aggression and violence are correlated with disturbed impulse control, fear regulation, and threat processing, which supports the potential role of the amygdala in SCZ with violent behaviors, as evidenced by previous studies (Bacq et al., 2018; Hoptman et al., 2010; Tesli et al., 2020a).
However, considering the heterogeneity of the amygdala's structure, it is rational to explore the subfields of the amygdala rather than take the amygdala as a whole. In accordance with previous studies, the present study revealed that the volumes of amygdala subnuclei were decreased in patients with SCZ compared to healthy control. Specifically, the volume of the left basal nucleus was significantly smaller in the SCZ group compared to HC. Amygdala basal nucleus is a hub for relaying information from the lateral amygdala to the central amygdala nucleus, which elicits fear-potentiated reactions (Amano et al., 2011). Accumulating evidence has proven that the amygdala basal nucleus is involved in the process of contextual fear conditioning (Onishi and Xavier, 2010). Impaired contextual fear-conditioning was associated with SCZ, as evidenced by animal and human research (Gill et al., 2018; Tani et al., 2019). Decreased volume of the basal nucleus may be related to impaired fear conditioning. We speculate that schizophrenia patients(including patients with violent behavior)might have a weak ability to associate the cues of violent acts with moral shames and social punishment. In the present study, the volume of the left basal nucleus was smaller in the SCZ group. However, basal nucleus volume was not significantly different for VS and NVS groups. We propose that decreased volume of the left basal nucleus may be a biomarker for SCZ rather than SCZ with violent behaviors. To our knowledge, only one research has reported the volume alteration of amygdala subregions in SCZ with a history of violent behaviors (Tesli et al., 2020b). In line with that study, our study found the volumetric reduction of the left amygdala basal nucleus in the SCZ group. However, no differences in amygdala nuclei volumes were found between VS and NVS groups in that study.
In addition, the volume of the central nucleus was smaller in VS group compared to the NVS group, adjusted for age, duration of illness, and total intracranial volume. Amygdala central nucleus is the primary region for sending neural signals from the amygdala to the cerebral cortex and brainstem and is responsible for the emotion-induced elevated sympathetic nervous reaction. In accordance with our hypothesis, animal study reveals that aggressive behaviors are related to the damage of the amygdala central nucleus (Zagrodzka et al., 1998). In addition, oxytocin can modulate anxiety behaviors via oxytocin receptors within the amygdala central nucleus (Laszlo et al., 2016). Elevated anxiety behaviors in rats are proven to be associated with high aggressions (Patki et al., 2015). We speculate that reduced volume of the amygdala central nucleus might correlate with decreased number of the oxytocin receptor, which may reduce the modulation function of oxytocin and thus increase aggression behaviors.
However, our study has several limitations. Firstly, the sample size was relatively small. Secondly, our study was cross-sectional in nature, which limited the power to predict future violence. Thirdly, the duration of illness in VS group was significantly longer than that in the NVS group, which might influence the result. This issue was addressed by considering the duration of illness as covariates. Fourthly, we haven't collected fMRI and structural MRI data, so it was hard to do multimodal MRI analysis, which might be more powerful. In future research, we will collect multimodal MRI data and predict violence in a prospective study.
In summary, our study suggests that a smaller volume of left amygdala subnuclei might be relevant to violence risk in patients with schizophrenia.