# Laminar dissection of cortical human brain gene expression in neuropsychiatric disorders

> **NIH NIH R01** · LIEBER INSTITUTE, INC. · 2022 · $802,692

## Abstract

Project Summary/Abstract
The DLPFC is a true six layered neocortex, and neurons in different cortical layers show distinct expression
patterns, morphology, physiology and patterns of connectivity. Converging evidence suggests that impairments
in the formation or maintenance of synapses may be involved in schizophrenia and other neuropsychiatric
disorders. Studies in the postmortem brains of subjects have pointed to specific cell types and revealed
differences in neuronal and synaptic structure that are localized to specific layers, suggesting that genetic risk
for schizophrenia may manifest with laminar specificity. Given the close relationship between brain structure
and function, precisely assigning gene expression to the spatial coordinates of individual cell populations within
this cortical cytoarchitecture would significantly advance our understanding of how dysregulation in these areas
contributes to debilitating neuropsychiatric disorders. In this application, we propose to generate detailed
spatial transcriptomics maps of the human DLPFC in patients with schizophrenia (SCZD), bipolar (BPD), major
depressive (MDD) and autism spectrum (ASD) disorders, and contrast these laminar expression patterns to
those derived from matched neurotypical controls (CONT). We will use the 10x Genomics Visium platform,
which combines transcriptome-wide RNA sequencing with detailed high-resolution histology and
immunofluorescence imaging, to generate these spatial transcriptomics profiles. We will combine these
topographic and cell type-specific maps to implicate layer- and cell type-specific populations in psychiatric
disorder genetic risk and illness state that will be validated using complementary quantitative in situ
hybridization techniques. These layer-specific and cell type-specific expression profiles can refine the
molecular causes and consequences of debilitating neuropsychiatric disorders that can be targeted for
prevention and treatment.

## Key facts

- **NIH application ID:** 10436944
- **Project number:** 5R01MH126393-02
- **Recipient organization:** LIEBER INSTITUTE, INC.
- **Principal Investigator:** Keri Martinowich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $802,692
- **Award type:** 5
- **Project period:** 2021-06-23 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436944

## Citation

> US National Institutes of Health, RePORTER application 10436944, Laminar dissection of cortical human brain gene expression in neuropsychiatric disorders (5R01MH126393-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436944. Licensed CC0.

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