Shared subcortical–default mode morphological dysconnectivity in adolescent bipolar disorder, major depressive disorder and schizophrenia

Adolescence is a critical window of vulnerability to psychiatric disorders, yet transdiagnostic network abnormalities remain poorly characterized at this stage. Here, we compare single-subject morphological brain networks in 61 adolescents with bipolar disorder (BD), 73 with major depressive disorder (MDD), 55 with schizophrenia (SCH), and 181 healthy controls. All three disorders show altered morphological connectivity (MC), predominantly linking subcortical structures with multiple cortical subsystems, particularly the default mode network. Shared nodal efficiency alterations include increases in the left superior frontal gyrus and decreases in the left cingulate gyrus, left basal ganglia, and right thalamus. Cortical MC increases in BD and SCH spatially correspond to serotonergic, dopaminergic, GABAergic, cholinergic, and glutamatergic maps. Subcortical nodal efficiency alterations in BD align with serotonin, GABA, cerebral blood flow, and cell type-enriched gene expression, whereas those in MDD align with dopamine. These findings suggest convergent adolescent morphological network alterations with disorder-specific neurobiological signatures.