Identification of a common neurobiological substrate for mental Illness

Madeleine Goodkind, Simon B. Eickhoff, Desmond J. Oathes, Ying Jiang, Andrew Chang, Laura B. Jones-Hagata, Brissa N. Ortega, Yevgeniya V. Zaiko, Erika L. Roach, Mayuresh S. Korgaonkar, Stuart M. Grieve, Isaac Galatzer-Levy, Peter T. Fox, Amit Etkin

Research output: Contribution to journalArticlepeer-review

755 Scopus citations


Importance: Psychiatric diagnoses are currently distinguished based on sets of specific symptoms. However, genetic and clinical analyses find similarities across a wide variety of diagnoses, suggesting that a common neurobiological substrate may exist across mental illness. Objective: To conduct ameta-analysis of structural neuroimaging studies across multiple psychiatric diagnoses, followed by parallel analyses of 3 large-scale healthy participant data sets to help interpret structural findings in the meta-analysis.Data Sources: PubMed was searched to identify voxel-based morphometry studies through July 2012 comparing psychiatric patients to healthy control individuals for the meta-analysis. The 3 parallel healthy participant data sets included resting-state functional magnetic resonance imaging, a database of activation foci across thousands of neuroimaging experiments, and a data set with structural imaging and cognitive task performance data.Data Extraction And Synthesis: Studieswere included in the meta-analysis if they reported voxel-based morphometry differences between patients with an Axis I diagnosis and control individuals in stereotactic coordinates across the whole brain, did not present predominantly in childhood, and had at least 10 studies contributing to that diagnosis (or across closely related diagnoses). Themeta-analysis was conducted on peak voxel coordinates using an activation likelihood estimation approach.Main Outcomes And Measures: We tested for areas of common gray matter volume increase or decrease across Axis I diagnoses, as well as areas differing between diagnoses. Follow-up analyses on other healthy participant data sets tested connectivity related to regions arising from the meta-analysis and the relationship of gray matter volume to cognition.CONCLUSIONS AND REVELANCE We identified a concordance across psychiatric diagnoses in terms of integrity of an anterior insula/dorsal anterior cingulate-based network, which may relate to executive function deficits observed across diagnoses. This concordance provides an organizing model that emphasizes the importance of shared neural substrates across psychopathology, despite likely diverse etiologies, which is currently not an explicit component of psychiatric nosology.

Original languageEnglish (US)
Pages (from-to)305-315
Number of pages11
JournalJAMA Psychiatry
Issue number4
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Psychiatry and Mental health


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