# Specificity of Hippocampal Subregion Cerebral Blood Volume Abnormalities in Psychiatric Disorders

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $154,762

## Abstract

Project Summary
Severe mental illnesses (SMI) are the leading cause of global disability and responsible for the largest cost burden among
all the non-communicable diseases. One of the major challenges for clinical neuroscience is achieving a mechanistic
understanding of the brain circuitry involved in SMI. Such understanding is critical to developing treatments aimed at
ameliorating the underlying biological causes of these disorders. Among the psychiatric syndromes, important similarities
and differences exist between schizophrenia and bipolar disorder. For instance, mood and psychotic symptoms occur in
both disorders and they show significant genetic overlap, yet schizophrenia does not commonly present with the manic
and depressive illness phases that are the hallmark of bipolar disorder. These findings suggest that common and disease-
specific neural circuitry alterations are associated with schizophrenia and bipolar disorder, which we will examine from a
dimensional in addition to a categorical perspective. One of the brain regions implicated in most neuropsychiatric
disorders, including schizophrenia and bipolar disorder, is the hippocampal formation (HF). The HF is involved in
emotion, stress regulation, and memory formation. This proposal puts forward a model of hippocampal circuitry
dysfunction in bipolar disorder to enable systematic hypothesis driven research. The aim of this proposal is to tests this
hippocampal circuitry dysfunction model of bipolar disorder by identifying common and disease-specific HF circuitry
abnormalities between schizophrenia and bipolar disorder in comparison to healthy volunteers. To achieve this aim, the
proposed study will utilize state-of-the-art high-resolution hippocampal cerebral blood volume (CBV) and connectivity
mapping. In addition to categorical group comparisons, this study will also examine relationships between these brain
imaging measures and dimensional neurocognitive, symptom, and functional outcome profiles. The study builds upon the
discovery of the promising novel neuroimaging biomarker for schizophrenia, namely high anterior hippocampal CA1
cerebral blood volume (CBV), assessed using high-resolution CBV mapping; a finding recently replicated. Findings from
this line of research are driving new treatment strategies for schizophrenia that use high anterior hippocampal CBV as an
imaging based biomarker to assess treatment target engagement. This proposal aims to follow a similar research strategy
for bipolar disorder. To our knowledge, the proposed study is first to utilize high-resolution CBV mapping of
hippocampal circuitry in bipolar disorder, and first to utilize high-resolution resting state connectivity analyses of
hippocampal circuitry in both schizophrenia and bipolar disorder. The proposed research is in line with NIH/NIMH's
strategic goal to “advance novel assays and tools to develop biomarkers of disease and for therapeutic discovery”, and will
provide new treatment targets, enabl...

## Key facts

- **NIH application ID:** 9924650
- **Project number:** 5R21MH118674-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Theodorus G.M. van Erp
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $154,762
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924650

## Citation

> US National Institutes of Health, RePORTER application 9924650, Specificity of Hippocampal Subregion Cerebral Blood Volume Abnormalities in Psychiatric Disorders (5R21MH118674-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9924650. Licensed CC0.

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