# Serotonin Modulation of Neural Circuitry in bvFTD: Understanding the Neurobiology of Mood and Cognitive Symptoms

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2024 · $198,355

## Abstract

Dementia is a leading cause of disability and death worldwide, with the most significant impact on those with
young-onset dementia. Frontotemporal dementia (FTD) is the most common cause of dementia in patients
under 60, and the behavioral variant (bvFTD) is the predominant presenting syndrome. Neuropsychiatric
symptoms (NPS) are core features of bvFTD, and patients with bvFTD require family caregivers to dedicate
significant time and resources to managing NPS. In contrast to Alzheimer’s disease (AD) in which the negative
impact of NPS is well understood, prior research has not focused on the nature of NPS and its association with
functional decline in bvFTD. The applicant has identified a discrete affective symptom (AS) cluster
characterized by depression, anxiety, irritability, and agitation that occur in at least 50% of patients and
accelerate functional decline in bvFTD. The treatments developed for the major psychiatric disorders are often
ineffective in bvFTD. Given the high prevalence and disability resulting from AS in bvFTD, there is an urgent
need for more effective and safe treatments to improve both AS and cognition. The long-term goals of this
application for a Mentored Patient-Oriented Research Career Development Award (K23) from a geriatric
psychiatrist are to enhance understanding of the neurobiology of NPS in bvFTD to inform the development of
novel, precision-targeted therapies to slow functional decline, alleviate patient suffering, and ease caregiver
burden. A Positron Emission Tomography (PET) study to measure glucose metabolism is proposed to
measure changes in neural circuitry with multi-modal antidepressant (Vortioxetine) treatment that targets both
serotonin receptors and serotonin transporters in bvFTD. PET measures of cerebral glucose metabolism to
evaluate neural circuitry is a method that is sensitive to neurodegeneration and AS and cognitive impairment.
The following aims are proposed: I. To identify the neural circuitry associated with AS and cognitive deficits in
bvFTD and II. To identify the changes in neural circuitry following vortioxetine treatment in patients with bvFTD
and AS. The overarching hypothesis is that Vortioxetine will improve AS and executive functioning in bvFTD
and increase cerebral glucose metabolism in the salience network (SN) and default mode network (DMN),
respectively. The research plan is complemented by a career development plan to advance skills in 1) clinical
research methodology; 2) the design, application, image and statistical analysis, and interpretation of PET
neuroimaging studies; 3) clinical and research applications of neuropsychological assessments and 4) grant
writing and overall career development. The mentoring team, collaborators and consultants represent senior
faculty with considerable expertise in these areas. Completion of the research and training objectives will
advance the career of a junior investigator toward developing an independent research program focused on
de...

## Key facts

- **NIH application ID:** 10944923
- **Project number:** 1K23AG088248-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Christopher B. Morrow
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $198,355
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10944923

## Citation

> US National Institutes of Health, RePORTER application 10944923, Serotonin Modulation of Neural Circuitry in bvFTD: Understanding the Neurobiology of Mood and Cognitive Symptoms (1K23AG088248-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10944923. Licensed CC0.

---

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