Federal Grant Award Summary

The National Institute of Mental Health (NIMH) awarded The Children's Hospital of Philadelphia Research Institute a $721,440 Project Grant under the Mental Health Research Grants program (CFDA 93.242) beginning July 15, 2026, and concluding July 14, 2030. This award supports research investigating the role of mitochondrial dysfunction in variable schizophrenia penetrance within 22q11.2 deletion syndrome (22QDS), with emphasis on presynaptic glutamate release mechanisms. The research employs induced neurons (iNeurons) derived from patient stem cells to circumvent traditional limitations in studying human brain development and psychiatric disease mechanisms.

The grant funds two primary research objectives: (1) testing whether mitochondrial dysfunction in presynaptic compartments results in diminished glutamate release through optical imaging of glutamate and synaptic vesicle cycling in iNeurons from 22QDS individuals with and without schizophrenia under varying neuronal stimulation frequencies; and (2) applying computational modeling to assess how alterations in presynaptic mitochondrial function contribute to circuit connectivity and entropy in affected neural populations. The research is expected to generate insights into mitochondrial influence on glutamatergic neurotransmission and the emergence of schizophrenia symptoms in 22QDS while establishing a robust human cellular model, directly supporting NIMH's strategic objective to define brain mechanisms underlying mental illness.