Neurodevelopmental and neuropsychiatric disorders represent an interconnected molecular system

A. S. Cristino, S. M. Williams, Z. Hawi, J. Y. An, M. A. Bellgrove, C. E. Schwartz, L. Da F. Costa, C. Claudianos

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)


Many putative genetic factors that confer risk to neurodevelopmental disorders such as autism spectrum disorders (ASDs) and X-linked intellectual disability (XLID), and to neuropsychiatric disorders including attention deficit hyperactivity disorder (ADHD) and schizophrenia (SZ) have been identified in individuals from diverse human populations. Although there is significant aetiological heterogeneity within and between these conditions, recent data show that genetic factors contribute to their comorbidity. Many studies have identified candidate gene associations for these mental health disorders, albeit this is often done in a piecemeal fashion with little regard to the inherent molecular complexity. Here, we sought to abstract relationships from our knowledge of systems level biology to help understand the unique and common genetic drivers of these conditions. We undertook a global and systematic approach to build and integrate available data in gene networks associated with ASDs, XLID, ADHD and SZ. Complex network concepts and computational methods were used to investigate whether candidate genes associated with these conditions were related through mechanisms of gene regulation, functional protein-protein interactions, transcription factor (TF) and microRNA (miRNA) binding sites. Although our analyses show that genetic variations associated with the four disorders can occur in the same molecular pathways and functional domains, including synaptic transmission, there are patterns of variation that define significant differences between disorders. Of particular interest is DNA variations located in intergenic regions that comprise regulatory sites for TFs or miRNA. Our approach provides a hypothetical framework, which will help discovery and analysis of candidate genes associated with neurodevelopmental and neuropsychiatric disorders.

Original languageEnglish
Pages (from-to)294-301
Number of pages8
JournalMolecular Psychiatry
Issue number3
Publication statusPublished - 2014 Mar
Externally publishedYes

Bibliographical note

Funding Information:
AS Cristino was supported by a University of Queensland Post-doctoral Fellowship. C Claudianos received funding support from the ARC (110100292) and NHMRC of Australia (1008125), MA Bellgrove from the NHMRC (569636; 569533; 1002458) and L da F Costa from FAPESP (2011/50761-2) and CNPq (304351/2009-1) Brazil.


  • Gene networks
  • Mental health disorder
  • Neurodevelopmental disorder
  • Neuropsychiatric disorder
  • Systems biology

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Molecular Biology


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