# Dysregulation of dopamine receptors in the basal ganglia in OCD and tic disorders: Positron Emission Tomography with [11C]-PHNO

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $30,326

## Abstract

NIMH Diversity Supplement
Parent grant: 5R01MH130609-02
Principal Investigator: Christopher Pittenger MD PhD
Trainee: Enock B. Teefe MD
PROJECT SUMMARY:
Obsessive-Compulsive Disorder (OCD) and tic disorders, including Tourette Syndrome (TS) are severe
neuropsychiatric conditions thought to involve disrupted dopamine signaling within cortico-basal ganglia neural
circuits. Despite this association, existing neuroimaging research on D2 and D3 dopamine receptor binding has
yielded inconsistent results, possibly owing to poorly understood genetic variations that affect dopamine
function. This proposed supplement aims to fill this knowledge gap by augmenting an existing parent grant
(5R01MH130609), which utilizes positron emission tomography (PET) with 11C-PHNO to study D2/D3 receptor
binding in adults with OCD and tics (15 OCD, 15 OCD+tics, 15 tics, 15 controls). In Aim 1, the supplement
proposes whole-genome sequencing for all study participants, enabling the calculation of polygenic risk scores
specifically for OCD and TS. This will allow for investigations into the association between common genetic risk
factors and D2/D3 receptor binding potential. Aim 2 involves generating dopamine receptor polygenic co-
expression indices based on post-mortem human brain gene expression data. This will enable us to test
whether co-expression modules involving dopamine receptor genes (DRD2 and DRD3) affect dopamine
binding within basal ganglia regions. Aim 3 will focus on understanding the distinct impact of genetic variants
within canonical dopamine-related genes on D2/D3 receptor binding. Additionally, exploratory analyses will be
conducted to examine the contributions of rare genetic variants to D2/D3 receptor binding. Overall, this
supplemental study employs an innovative imaging-genetics integration approach, leveraging whole-genome
sequencing to understand the complex genetic factors that influence dopamine receptor alterations pertinent to
OCD and tic pathophysiology. The findings are expected to inform the development of much needed novel,
targeted therapeutic interventions. Concurrently, the study will offer specialized mentoring and training in
statistical genetics and multi-omic data integration, providing the trainee with valuable skills essential for a
productive career in translational neurogenetics research.

## Key facts

- **NIH application ID:** 10938454
- **Project number:** 3R01MH130609-02S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Christopher John Pittenger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $30,326
- **Award type:** 3
- **Project period:** 2022-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938454

## Citation

> US National Institutes of Health, RePORTER application 10938454, Dysregulation of dopamine receptors in the basal ganglia in OCD and tic disorders: Positron Emission Tomography with [11C]-PHNO (3R01MH130609-02S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10938454. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*