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"7/9" Predictors and Mechanisms of Conversion to Psychosis

Award Number: U01MH081984
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2008
PERIOD OF PERFORMANCE END DATE: 01/31/2021

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"7/9" Predictors and Mechanisms of Conversion to Psychosis - DESCRIPTION (provided by applicant): Schizophrenia and other psychotic disorders are serious and debilitating mental illnesses that incur substantial suffering for patients and major challenges to our health care system. The clinical high-risk (CHR) prodromal phase is the period prior to the onset of psychosis when clinical symptoms gradually emerge and function declines. The presence of a CHR syndrome in young adults is associated with heightened risk (~30%) for the later development of psychosis. The North American Prodrome Longitudinal Study (NAPLS) and other CHR studies have made substantial progress towards predicting psychosis, and in showing an accelerated reduction in prefrontal cortex (PFC) gray matter (GM) density in CHR converters from pre- to post-psychosis onset, but the mechanisms driving conversion remain elusive, partly because no studies include repeated measures prior to the onset of psychosis. In NAPLS2, we found that disrupted resting-state (rs) thalamo- cortical functional connectivity prior to psychosis predicts conversion and correlates with rate of GM decline, but we do not know if rs-dysconnectivity is progressive during the prodrome. Furthermore, in NAPLS2, plasma markers of pro-inflammatory cytokines at baseline predicted the rate of GM loss in converters; these same markers also correlated with rs-dysconnectivity. We do not yet know whether these inflammatory markers drive the changes in brain structure/function or are consequences of these changes. Similarly, higher levels of cortisol, and lower mismatch negativity predicted psychosis and the rate of PFC GM decline and were correlated with each other and with measures of rs-connectivity and cytokines. This application is a competitive renewal for a nine-site, longitudinal study aimed at identifying the brain processes underlying the progression of the clinical syndromes that characterize the psychosis prodrome. The goals are: 1) to determine the pre-onset trajectories of GM decline and disrupted resting-state brain connectivity in CHR individuals who develop psychosis using MRI, and 2) to identify inflammatory and plasticity mechanisms associated with transition to psychosis. Over a two-year period, the study will repeatedly measure these indicators, and at the same time examine changes in physiological indices of brain function, social and cognitive functioning, and symptom progression. The multi-site collaboration will follow large CHR (n= 378) and demographically matched comparison (n= 162) samples that will undergo comprehensive assessments of biological and behavioral changes. This approach will answer important questions about the origins of the brain changes that give rise to psychosis and will provide insights into likely approaches to halting or mitigatig the pathological process and advance our understanding of risk prediction, both critical steps in prevention.


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: 2022 ( Subtotal = -$1,455 )
2022	2018	GOVERNORS OF THE UNIVERSITY OF CALGARY, THE	2500 UNIVERSITY DR NW	CALGARY	AB			CAN	Mental Health Research Grants	001	10	8/25/2022	NON-COMPETING CONTINUATION	$20
2022	2018	GOVERNORS OF THE UNIVERSITY OF CALGARY, THE	2500 UNIVERSITY DR NW	CALGARY	AB			CAN	Mental Health Research Grants	000	10	8/8/2022	NON-COMPETING CONTINUATION	-$1,475
														Subtotal = -$1,455

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	GOVERNORS OF THE UNIVERSITY OF CALGARY, THE	2500 UNIVERSITY DR NW	CALGARY	AB	T2N 1N4		CAN	Mental Health Research Grants	000	10	5/5/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	GOVERNORS OF THE UNIVERSITY OF CALGARY, THE	2500 UNIVERSITY DR NW	CALGARY	AB	T2N 1N4		CAN	Mental Health Research Grants	000	10	4/12/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $279,173 )
2018	2018	GOVERNORS OF THE UNIVERSITY OF CALGARY, THE	2500 UNIVERSITY DR NW	CALGARY	AB	T2N 1N4		CAN	Mental Health Research Grants	000	10	6/29/2018	NON-COMPETING CONTINUATION	$279,173
														Subtotal = $279,173

Issue Date FY: 2017 ( Subtotal = $339,799 )
2017	2017	GOVERNORS OF THE UNIVERSITY OF CALGARY, THE	2500 UNIVERSITY DR NW	CALGARY	AB	T2N 1N4		CAN	Mental Health Research Grants	000	9	6/30/2017	NON-COMPETING CONTINUATION	$339,799
														Subtotal = $339,799

Issue Date FY: 2016 ( Subtotal = $493,867 )
2016	2016	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA				CAN	Mental Health Research Grants	000	8	6/20/2016	NON-COMPETING CONTINUATION	$493,867
														Subtotal = $493,867

Issue Date FY: 2015 ( Subtotal = $500,479 )
2015	2015	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA				CAN	Mental Health Research Grants	001	7	8/10/2015	SUPPLEMENT FOR EXPANSION	$45,652
2015	2015	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA				CAN	Mental Health Research Grants	000	7	7/29/2015	NON-COMPETING CONTINUATION	$454,827
														Subtotal = $500,479

Issue Date FY: 2014 ( Subtotal = $456,081 )
2014	2014	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA				CAN	Mental Health Research Grants	000	6	9/25/2014	COMPETING CONTINUATION	$456,081
														Subtotal = $456,081

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA		00000		CAN	Mental Health Research Grants	000	5	4/10/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $366,131 )
2012	2012	UNIVERSITY OF CALGARY	2500 UNIVERSITY DR NW	CALGARY, ALBERTA				CAN	Mental Health Research Grants	000	5	3/30/2012	NON-COMPETING CONTINUATION	$366,131
														Subtotal = $366,131

Issue Date FY: 2011 ( Subtotal = $546,402 )
2011	2011	UNIVERSITY OF CALGARY	2500 UNIVERSITY DR NW	CALGARY, ALBERTA				CAN	Mental Health Research Grants	002	4	8/19/2011	NON-COMPETING CONTINUATION	$448,413
2011	2011	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA		00000		CAN	Mental Health Research Grants	005	4	9/13/2011	NON-COMPETING CONTINUATION	$0
2011	2011	UNIVERSITY OF CALGARY	2500 UNIVERSITY DR NW	CALGARY, ALBERTA				CAN	Mental Health Research Grants	003	4	9/1/2011	SUPPLEMENT FOR EXPANSION	$97,989
2011	2010	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA		00000		CAN	Mental Health Research Grants	004	3	9/2/2011	NON-COMPETING CONTINUATION	$0
2011	2009	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA		00000		CAN	Mental Health Research Grants	000	2	7/11/2011	NON-COMPETING CONTINUATION	$0
2011	2009	UNIVERSITY OF CALGARY	**	CALGARY, ALBERTA		00000		CAN	Mental Health Research Grants	001	2	8/10/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $546,402

Issue Date FY: 2010 ( Subtotal = $437,618 )
2010	2010	UNIVERSITY OF CALGARY	2500 UNIVERSITY DR NW	CALGARY, ALBERTA				CAN	Mental Health Research Grants	000	3	4/23/2010	NON-COMPETING CONTINUATION	$437,618
														Subtotal = $437,618

Issue Date FY: 2009 ( Subtotal = $450,555 )
2009	2009	UNIVERSITY OF CALGARY	2500 UNIVERSITY DR NW	CALGARY, ALBERTA				CAN	Mental Health Research Grants	001	2	7/22/2009	NON-COMPETING CONTINUATION	$355,754
2009	2008	UNIVERSITY OF CALGARY	2500 UNIVERSITY DR NW	CALGARY, ALBERTA				CAN	Mental Health Research Grants	000	1	12/9/2008	NEW	$94,801
														Subtotal = $450,555

Grand Total All Awards = $3,868,650

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"7/9" Predictors and Mechanisms of Conversion to Psychosis

Award Number: U01MH081984

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/30/2008

PERIOD OF PERFORMANCE END DATE: 01/31/2021

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