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Negative Valence Systems in Schizophrenia

Award Number: R01MH127018
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Negative Valence Systems in Schizophrenia - 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, determine whether there are neurobiological differences in anxiety subgroups, and guide the development of novel neuroscientifically-informed treatments.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	5	11/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $617,385 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	5	5/6/2025	NON-COMPETING CONTINUATION	$617,385
														Subtotal = $617,385

Issue Date FY: 2024 ( Subtotal = $701,423 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	001	4	5/15/2024	NON-COMPETING CONTINUATION	$701,423
2024	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	3	4/30/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $701,423

Issue Date FY: 2023 ( Subtotal = $631,281 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	3	5/24/2023	NON-COMPETING CONTINUATION	$631,281
														Subtotal = $631,281

Issue Date FY: 2022 ( Subtotal = $661,423 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	2	6/6/2022	NON-COMPETING CONTINUATION	$661,423
														Subtotal = $661,423

Issue Date FY: 2021 ( Subtotal = $737,053 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	001	1	8/4/2021	NEW	$0
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	1	6/30/2021	NEW	$737,053
														Subtotal = $737,053

Grand Total All Awards = $3,348,565

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Negative Valence Systems in Schizophrenia

Award Number: R01MH127018

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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