Stanford Psychiatry receives grant to research synaptic protein composition and localization in individuals with schizophrenia

June 2024

Agnieszka Kalinowski, MD, PhD

We are pleased to announce that the National Institute of Mental Health has awarded a grant to Agnieszka Kalinowski, clinical assistant professor of psychiatry and behavioral sciences.

This grant funds Dr. Kalinowski’s project, “Synaptic protein composition and localization in individuals with schizophrenia (SZ),” which aims to map the detailed ways in which brains of people with schizophrenia differ, using a new imaging method to test whether there is an abnormality in the number of specific types of connection points between neurons.

Converging evidence in the field points to abnormalities in synapses, and perhaps a reduction in specific synaptic subtypes in distinct cortical layers due to ongoing synapse elimination, that may result in abnormal neuronal signaling that interfere with cognition. However, methodological limitations have impeded progress in testing the neuroanatomical basis of this hypothesis. In this project, a novel multiplex imaging method, Array Tomography, will be applied to a large cohort of dorsolateral prefrontal cortex (DLPFC) sections of postmortem brain samples from individuals with schizophrenia and controls in combination with transcriptomic data to test whether individuals with SZ a have a lower synaptic density of excitatory and inhibitory synapses in layer 3 (L3) of the DLPFC that correlate with high C4A gene expression.

“Demonstrating a strong correlation between high C4A gene expression and low synaptic density would provide supporting evidence for the excessive synaptic pruning hypothesis and C4A gene expression as a primary mediator of synaptic density,” says Dr. Kalinowski. “Work on this project will provide empirical data for leading hypotheses in the field.”

This career development funding will support Dr. Kalinowski in gaining experience using novel imaging methods, performing bioinformatic analyses, deepening knowledge of synaptic biology, and building a publication record and preliminary data on this body of work. She will work closely with her research mentors, Alexander Urban, associate professor of psychiatry and behavioral sciences, Philippe Mourrain, associate professor of psychiatry and behavioral sciences, and a research mentoring team in the department.

Recent publications co-authored by Dr. Kalinowski on topics related to this work include “Synaptic pruning in schizophrenia is not classical” to be published in the journal Brain Behavior and Immunity, and “Reductions in synaptic marker SV2A in early-course Schizophrenia” in the Journal of Psychiatric Research.

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