Decoupling of amygdala–salience circuit associated with negative symptoms in adolescents with early‐onset schizophrenia

AIM: Early-onset schizophrenia (EOS) is characterized by prominent negative symptoms, particularly socio-emotional deficits. This study examined functional connectivity within the large-scale socio-emotional circuits, including negative affect, positive affect, and salience circuits, and their associations with negative symptoms in EOS adolescents. METHOD: A total of 106 adolescents with EOS and 67 healthy controls (HCs) underwent resting-state fMRI and clinical assessment using the Positive and Negative Syndrome Scale (PANSS). Seed-based functional connectivity analyses were performed focusing on key nodes within affect circuits and the salience network, including the amygdala, caudate, medial frontal cortex, orbitofrontal cortex, anterior cingulate cortex, insular cortex, pallidum, putamen, and nucleus accumbens. Associations between altered connectivity and negative symptom dimensions were further examined. RESULTS: Compared with HCs, EOS patients demonstrated significantly decreased functional connectivity between the amygdala and core salience network regions, reflecting a decoupling of this circuit, including the bilateral insula, anterior cingulate cortex, and putamen. Reduced amygdala-salience connectivity was significantly associated with poor rapport. Similar patterns of amygdala-salience decoupling were observed in both drug-naïve and medicated patients, although medicated patients showed more spatially restricted decoupling involving the right amygdala-right putamen connection. CONCLUSIONS: These findings indicate disrupted coupling between the amygdala and the salience circuit in adolescents with EOS, which may contribute to socio-emotional dysfunction and negative symptoms. The persistence of amygdala-salience decoupling across both drug-naïve and medicated EOS patients suggests that this circuit abnormality is not fully normalized by current antipsychotic treatment and may represent a candidate target for future mechanistic and longitudinal studies.