# Biobehavioral Basis and Outcomes of Cognitive Dysfunction in Childhood-Systemic Lupus Erythematosus

> **NIH NIH R21** · BOSTON CHILDREN'S HOSPITAL · 2024 · $194,700

## Abstract

ABSTRACT
 Cognitive dysfunction (CD) is a common neuropsychiatric manifestation of childhood-onset systemic
lupus erythematosus (cSLE) that remains poorly diagnosed and undertreated. CD and other neuropsychiatric
symptoms of cSLE can negatively impact school function, self-management, and psychosocial health, as well
as lifelong health-related quality of life and occupational opportunity during adulthood. While prior studies in
patients with cSLE point to the association of CD with volumetric reductions of gray and white matter, the
functional neurobiological aberrancies underlying CD and their relationship to negative health-related behaviors
remain largely understudied. Furthermore, in a heightened inflammatory state, the homeostasis of the CNS is
likely compromised, implicating neuroimmune systems such as the choroid plexus, which serve as blood-
cerebral spinal fluid or immunological barriers. Disruptions localized to the choroid plexus may initiate a range of
outcomes, including neuroinflammation, alterations in gray and white matter structural properties, or
neuropsychiatric manifestations including CD. The goal of this R21 is to characterize the biobehavioral basis of
CD in cSLE by cross-sectional interrogation of (i) prefrontal and parietal cortices with fNIRS and fMRI, (ii)
microstructural white matter properties using diffusion tensor imaging (DTI), (iii) volumetric properties of the
choroid plexus using high-resolution structural MRI, (iv) neurometabolite (e.g., choline (Cho) and myo-inositol
(mIns)) concentrations using single-voxel MRS, (iv) cognitive function using the Pediatric Automated
Neuropsychological Assessment Metrics (PedANAM) and supplementary cognitive tests (e.g., Digit span task)40,
41, and (v) psychiatric symptom (brief psychiatric rating scale [BPRS]42) and disease (SLE Disease Activity Index-
2K [SLEDAI-2K]43) severities. We will prospectively enroll 20 cSLE patients (12-18 years old, male or female)
and 20 age-sex matched healthy controls (HCs). To better understand the role of comorbid mood symptoms in
cSLE, we will also enroll 20 children with depressive or anxiety disorders. We will leverage existing structural
MRI datasets (30 cSLE patients + 30 matched HCs). Our hypothesis is that CD in cSLE is underpinned by a
combination of dysfunction of the prefrontal cortex, altered white matter microstructure, and compromised
choroid plexus barrier function marked by morphological change. Understanding the biological basis and
behavioral outcomes of CD can improve recognition of neuropsychiatric cSLE and realign therapeutic strategies
with neurobiological phenotypes. We propose the following Specific Aims: Aim 1: Investigate functional CNS
properties associated with CD in cSLE. Aim 2: Determine the associations among white matter microstructure
with severity of CD in cSLE. Aim 3: Quantify the choroid plexus volume in cSLE and its relationship with CD,
glial activity, and disease activity. To carry out this work, we assemb...

## Key facts

- **NIH application ID:** 10987200
- **Project number:** 1R21AR083599-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Joyce Chun-Ling Chang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,700
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987200

## Citation

> US National Institutes of Health, RePORTER application 10987200, Biobehavioral Basis and Outcomes of Cognitive Dysfunction in Childhood-Systemic Lupus Erythematosus (1R21AR083599-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10987200. Licensed CC0.

---

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