This study conducted a meta-analysis of structural neuroimaging studies across multiple psychiatric diagnoses, followed by parallel analyses of three large-scale healthy participant data sets to interpret the structural findings. The meta-analysis included 193 studies with a total of 15,892 individuals across six diagnostic groups (schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety). The results showed that gray matter loss converged across diagnoses in three regions: the dorsal anterior cingulate, right insula, and left insula. In contrast, diagnosis-specific effects were found only for schizophrenia and depression. Follow-up analyses in healthy participants revealed that the common gray matter loss regions formed a tightly interconnected network during tasks and at rest, and lower gray matter in this network was associated with poor executive functioning. The findings suggest a transdiagnostic neural substrate for mental illness, emphasizing the importance of shared neural mechanisms across psychopathology.This study conducted a meta-analysis of structural neuroimaging studies across multiple psychiatric diagnoses, followed by parallel analyses of three large-scale healthy participant data sets to interpret the structural findings. The meta-analysis included 193 studies with a total of 15,892 individuals across six diagnostic groups (schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety). The results showed that gray matter loss converged across diagnoses in three regions: the dorsal anterior cingulate, right insula, and left insula. In contrast, diagnosis-specific effects were found only for schizophrenia and depression. Follow-up analyses in healthy participants revealed that the common gray matter loss regions formed a tightly interconnected network during tasks and at rest, and lower gray matter in this network was associated with poor executive functioning. The findings suggest a transdiagnostic neural substrate for mental illness, emphasizing the importance of shared neural mechanisms across psychopathology.