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Collaborative Studies of Neurodevelopmental Trajectories in Children at Familial Risk for Schizophrenia or Bipolar Disorder

NAMHC Concept Clearance


Shelli Avenevoli, Ph.D.
Chief, Developmental Trajectories of Mental Disorders Branch
Division of Developmental Translational Research (DDTR)


This initiative solicits collaborative research applications to conduct a coordinated, multi-site, multi-modal longitudinal study charting middle-childhood (ages 6–12 years) trajectories of brain, cognitive, and affective development among those at high and low familial risk for schizophrenia or bipolar disorder, before the onset of prodromal symptoms. 


Existing evidence suggests that serious mental illness is rooted in early development.  In spite of this knowledge, significant gaps remain in our understanding of brain and behavioral trajectories before the onset of prodromal symptoms.  Specifically, there are few prospective studies that (a) commence sufficiently early to identify developmental aberrations that precede syndrome onset; (b) assess more than two time points to define and track trajectories from healthy development to illness; or, (c) collectively evaluate brain changes in structure, function, and connectivity across development.  Mapping the trajectories of brain and behavioral development during middle childhood (ages 6–12 years) will fill a critical gap in our knowledge of the course of illness across development  and may identify sensitive periods that are amenable to early intervention (addressing Objective 2 of the NIMH Strategic Plan). 

This initiative focuses on neurodevelopmental trajectories among those at high and low familial risk for schizophrenia or bipolar disorder.  Although schizophrenia and bipolar disorder share many clinical symptoms and genetic risk factors, there is evidence supporting distinct neural circuitry.  Longitudinal study of the neurodevelopmental trajectories of these disorders may enable the detection of unique biosignatures, points of divergence in development, and opportunities for intervention.

It is expected that responsive applications will include the following:

  • A sample comprising individuals at high and low risk for schizophrenia and/or bipolar disorder;
  • Participants, ages 6–12 years, who are largely asymptomatic for schizophrenia or bipolar disorder at the time of study enrollment;
  • Longitudinal/prospective assessments with three or more time points;
  • Multimodal imaging;
  • Assessments focused on components of mental illness that reflect underlying neural circuitry;
  • Standardized measures that bridge to ongoing studies;
  • Assessments of prenatal, infant, and early childhood factors;
  • Collection and banking of genetic material; and,
  • An effective data coordination, integration, and sharing plan.

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