A meta-analysis of structural neuroimaging studies across multiple psychiatric diagnoses identified common neurobiological substrates in mental illness. The study found that gray matter loss converged in three regions: the dorsal anterior cingulate, right insula, and left insula, across diagnoses such as schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety. These regions formed a tightly interconnected network during tasks and at rest, with lower gray matter in this network associated with poor executive functioning. The findings suggest a shared neural substrate across psychiatric diagnoses, despite likely diverse etiologies. This shared substrate may relate to executive function deficits observed across diagnoses. The study also found that diagnosis-specific effects were limited to schizophrenia and depression. The results highlight the importance of shared neural substrates in psychopathology, which is not currently an explicit component of psychiatric nosology. The study used voxel-based morphometry (VBM) and activation likelihood estimation (ALE) to analyze structural neuroimaging data. The findings suggest that anterior insula and dACC gray matter loss represent a transdiagnostic neural abnormality evident across a wide variety of mental illnesses, most pronounced in psychosis. The study also found that these regions are functionally interconnected and that decreased gray matter in these regions is associated with worse executive functioning. The results suggest that common gray matter loss in the anterior insula and dACC may account for dysfunction in psychiatric disorders, but less so for diagnosis-specific symptoms. The study also found that these regions are involved in emotional processing and that decreased gray matter in these regions may reflect the illness itself rather than a risk state. The study highlights the importance of shared neural substrates in psychopathology and suggests that interventions targeting the anterior insula and dACC may prove of broad use across psychopathology.A meta-analysis of structural neuroimaging studies across multiple psychiatric diagnoses identified common neurobiological substrates in mental illness. The study found that gray matter loss converged in three regions: the dorsal anterior cingulate, right insula, and left insula, across diagnoses such as schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety. These regions formed a tightly interconnected network during tasks and at rest, with lower gray matter in this network associated with poor executive functioning. The findings suggest a shared neural substrate across psychiatric diagnoses, despite likely diverse etiologies. This shared substrate may relate to executive function deficits observed across diagnoses. The study also found that diagnosis-specific effects were limited to schizophrenia and depression. The results highlight the importance of shared neural substrates in psychopathology, which is not currently an explicit component of psychiatric nosology. The study used voxel-based morphometry (VBM) and activation likelihood estimation (ALE) to analyze structural neuroimaging data. The findings suggest that anterior insula and dACC gray matter loss represent a transdiagnostic neural abnormality evident across a wide variety of mental illnesses, most pronounced in psychosis. The study also found that these regions are functionally interconnected and that decreased gray matter in these regions is associated with worse executive functioning. The results suggest that common gray matter loss in the anterior insula and dACC may account for dysfunction in psychiatric disorders, but less so for diagnosis-specific symptoms. The study also found that these regions are involved in emotional processing and that decreased gray matter in these regions may reflect the illness itself rather than a risk state. The study highlights the importance of shared neural substrates in psychopathology and suggests that interventions targeting the anterior insula and dACC may prove of broad use across psychopathology.