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Effects of Early-Life Stress on Brain Dysfunction in HIV+ Adults: An fMRI Study

Award Number: K23MH096628
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/23/2012
PERIOD OF PERFORMANCE END DATE: 04/30/2018

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Effects of Early-Life Stress on Brain Dysfunction in HIV+ Adults: An fMRI Study - DESCRIPTION (provided by applicant): Nearly half of all HIV patients eventually develop neuropsychiatric difficulties, despite advances in combined antiretroviral therapy (cART) permitting greater control of viral migration into the brain post-infection. Increased importance has thus been placed on understanding the role that comorbid conditions play in the etiology of HIV-related neurocognitive and psychological disorders in the cART era. This K23 proposal takes the novel approach of investigating early-life stress (ELS), as a comorbid risk factor for increased neuropsychiatric impairments in HIV patients. Such an investigation is critical given that high ELS, which is known to cause significant brain abnormalities, is common among HIV+ individuals. Preliminary structural MRI findings indicate that HIV and high ELS have combined effects on brain volume, specifically in the amygdala, which correlate with cognitive impairments in HIV patients. The proposed K23 study will investigate the independent and combined effects of HIV and high ELS on amygdala function using functional magnetic resonance imaging (fMRI), which offers a more direct method of examining brain dysfunction than structural MRI. The study employs a cross sectional 2x2 design that will include 50 HIV+ and 50 HIV-seronegative control participants, with and without high ELS (4 groups of 25 participants). The primary dependent variables will be measures of fMRI blood oxygen level dependent (BOLD) response during cognitive and emotional tasks, and performances on cognitive and psychological measures assessed outside of the MRI scanner. The study will test whether HIV and high-ELS interact to: 1) increase abnormalities in amygdala fMRI BOLD response, and 2) reduce the functional connectivity between amygdala and frontal lobe regions. It will also test whether these two fMRI measures are associated with cognitive and psychological dysfunction in HIV patients. Exploratory analyses will test the relation of fMRI measures to plasma biomarkers of inflammation (e.g., cytokines). It is hypothesized that HIV+ high-ELS patients will display increased amygdala BOLD response and reduced amygdala-frontal lobe connectivity, which will correlate with cognitive and psychological dysfunction and biomarker abnormalities. The long-term objective of this research program is to better understand the mechanisms through which high ELS increases neural dysfunction in HIV patients, in order to improve our ability to prevent, assess, and treat HIV-related neuropsychiatric disorders. This 5-year award aims to foster the PI's transition into becoming an independent fMRI investigator whose research examines the etiology of neuropsychiatric disorders in HIV patients. The PI is trained in clinical neuropsychology and structural MRI investigations of HIV-related neural abnormalities. The proposed training plan will provide coursework and mentorship at Brown University to build the PI's expertise in 3 vital areas: fMRI methodology, the cognitive sequelae of neuroAIDS, and the biological correlates of ELS. This K23 addresses key issues in the etiology of neuroAIDS, and will fully prepare the PI to conduct independent patient-oriented research in this field.


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: 2018 ( Subtotal = $0 )
2018	2017	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	6	9/27/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $169,442 )
2017	2017	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	6	4/21/2017	NON-COMPETING CONTINUATION	$169,442
														Subtotal = $169,442

Issue Date FY: 2016 ( Subtotal = $175,974 )
2016	2016	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Mental Health Research Grants	000	5	4/21/2016	EXTENSION WITH OR WITHOUT FUNDS	$175,974
														Subtotal = $175,974

Issue Date FY: 2015 ( Subtotal = $176,916 )
2015	2015	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Mental Health Research Grants	000	4	4/28/2015	NON-COMPETING CONTINUATION	$176,916
														Subtotal = $176,916

Issue Date FY: 2014 ( Subtotal = $176,460 )
2014	2014	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Mental Health Research Grants	000	3	4/30/2014	NON-COMPETING CONTINUATION	$176,460
														Subtotal = $176,460

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Mental Health Research Grants	001	2	6/26/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$175,856
2013	2012	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Mental Health Research Career/Scientist Development Awards	000	1	6/26/2013	NEW	-$175,856
2013	2012	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Mental Health Research Grants	003	2	7/11/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$175,856
2013	2012	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Mental Health Research Grants	002	2	6/27/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$175,856
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $175,856 )
2012	2012	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Mental Health Research Career/Scientist Development Awards	000	1	5/23/2012	NEW	$175,856
														Subtotal = $175,856

Grand Total All Awards = $874,648

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Effects of Early-Life Stress on Brain Dysfunction in HIV+ Adults: An fMRI Study

Award Number: K23MH096628

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/23/2012

PERIOD OF PERFORMANCE END DATE: 04/30/2018

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