# Negative Valence Systems in Schizophrenia

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $737,053

## Abstract

Schizophrenia is a severe and heterogeneous mental disorder that impacts most domains of function including
behavior, cognition, and emotion. Recent models have highlighted important alterations of the emotion brain
networks in schizophrenia that contribute to schizophrenia symptoms, like paranoia and delusions. To date, the
studies of emotion in schizophrenia have primarily focused on fear processing and have shown heightened
amygdala responses to neutral stimuli and altered amygdala-prefrontal cortex connectivity. However, recent
research suggests that another brain region—the bed nucleus of the stria terminalis (BNST)—may play a
critical role in anxiety and that BNST-mediated anxiety is distinct from amygdala-mediated fear. The RDoC’s
Negative Valence System recognizes this fear-anxiety distinction and has separate constructs for Response to
Acute Threat (amygdala) and Response to Potential Harm (BNST). To our knowledge, the BNST has yet to be
examined in individuals with schizophrenia. Using methods pioneered by our lab to study the human BNST, we
have collected preliminary data in schizophrenia. Our pilot data provides initial evidence for BNST connectivity
differences in both response to unpredictable threat, a measure of the response to potential harm construct,
and during a resting state in individuals with schizophrenia compared to healthy controls. Further, we found
evidence that BNST alterations in schizophrenia differ for those who do or do not have comorbid anxiety.
Individuals with schizophrenia and anxiety disorders demonstrated stronger connectivity between BNST and
multiple brain regions involved in threat detection, uncertainty, and anxiety relative to those with schizophrenia
and no anxiety disorder. The current study will investigate BNST connectivity in three groups: individuals with
schizophrenia with a comorbid anxiety disorder (SZ+ANX), individuals with schizophrenia without a comorbid
anxiety disorder (SZ-ANX), and healthy controls (HC). We hypothesize that individuals with schizophrenia will
have altered BNST connectivity in response to unpredictable threat and altered BNST intrinsic connectivity
relative to HC. In addition we predict that SZ+ANX group will show BNST hyperconnectivity relative to SZ-
ANX. We will test these hypotheses with three specific aims. (1) Investigate BNST connectivity in response to
unpredictable threat in individuals with schizophrenia; (2) Determine whether there are differences in BNST
intrinsic connectivity in individuals with schizophrenia; (3) Test for relationships among BNST connectivity,
stress responses (skin conductance and cortisol), and clinical symptoms in schizophrenia. Given the
prevalence of anxiety in schizophrenia, BNST alterations within schizophrenia are likely and may shed new
light on the neurobiological mechanisms underlying emotion alterations in schizophrenia. The results from the
proposed study can provide a foundation for future studies of emotion in schizophrenia, de...

## Key facts

- **NIH application ID:** 10275869
- **Project number:** 1R01MH127018-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jennifer Urbano Blackford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $737,053
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275869

## Citation

> US National Institutes of Health, RePORTER application 10275869, Negative Valence Systems in Schizophrenia (1R01MH127018-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10275869. Licensed CC0.

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