Oxytocin Modulates Hippocampal Perfusion in People at Clinical High Risk for Psychosis

Cathy Davies; Yannis Paloyelis; Grazia Rutigliano; Marco Cappucciati; Andrea De Micheli; Valentina Ramella-Cravaro; Umberto Provenzani; Mathilde Antoniades; Gemma Modinos; Dominic Oliver; Daniel Stahl; Silvia Murguia; Fernando Zelaya; Paul  Allen; Sukhi Shergill; Paul Morrison; Steve Williams; David Taylor; Philip McGuire; Paolo Fusar-Poli

doi:10.1038/s41386-018-0311-6

Oxytocin Modulates Hippocampal Perfusion in People at Clinical High Risk for Psychosis

Cathy Davies, Yannis Paloyelis, Grazia Rutigliano, Marco Cappucciati, Andrea De Micheli, Valentina Ramella-Cravaro, Umberto Provenzani, Mathilde Antoniades, Gemma Modinos, Dominic Oliver, Daniel Stahl, Silvia Murguia, Fernando Zelaya, Paul Allen, Sukhi Shergill, Paul Morrison, Steve Williams, David Taylor, Philip McGuire, Paolo Fusar-Poli

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Abstract

Preclinical and human studies suggest that hippocampal dysfunction is a key factor in the onset of psychosis. People at Clinical High Risk for psychosis (CHR-P) present with a clinical syndrome that can include social withdrawal and have a 20-35% risk of developing psychosis in the next 2 years. Recent research shows that resting hippocampal blood flow is altered in CHR-P individuals and predicts adverse clinical outcomes, such as non-remission/transition to frank psychosis. Previous work in healthy males indicates that a single dose of intranasal oxytocin has positive effects on social function and marked effects on resting hippocampal blood flow. The present study examined the effects of intranasal oxytocin on hippocampal blood flow in CHR-P individuals. In a double-blind, placebo-controlled, crossover design, 30 CHR-P males were studied using pseudo-continuous Arterial Spin Labelling on 2 occasions, once after 40IU intranasal oxytocin and once after placebo. The effects of oxytocin on left hippocampal blood flow were examined in a region-of-interest analysis of data acquired at 22-28 and at 30-36 minutes post-intranasal administration. Relative to placebo, administration of oxytocin was associated with increased hippocampal blood flow at both time points (p=.0056; p=.034), although the effect at the second did not survive adjustment for the effect of global blood flow. These data indicate that oxytocin can modulate hippocampal function in CHR-P individuals and therefore merits further investigation as a candidate novel treatment for this group.

Original language	English
Pages (from-to)	1300-1309
Number of pages	10
Journal	Neuropsychopharmacology
Volume	44
Issue number	7
Early online date	9 Jan 2019
DOIs	https://doi.org/10.1038/s41386-018-0311-6
Publication status	Published - 9 Jan 2019

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Oxytocin Modulates Hippocampal Perfusion_DAVIES_Accepted18December2018_GOLD VoR (CC BY)Final published version, 1.93 MBLicence: CC BY

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Davies, C., Paloyelis, Y., Rutigliano, G., Cappucciati, M., De Micheli, A., Ramella-Cravaro, V., Provenzani, U., Antoniades, M., Modinos, G., Oliver, D., Stahl, D., Murguia, S., Zelaya, F., Allen, P., Shergill, S., Morrison, P., Williams, S., Taylor, D., McGuire, P., & Fusar-Poli, P. (2019). Oxytocin Modulates Hippocampal Perfusion in People at Clinical High Risk for Psychosis. Neuropsychopharmacology, 44(7), 1300-1309. https://doi.org/10.1038/s41386-018-0311-6

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title = "Oxytocin Modulates Hippocampal Perfusion in People at Clinical High Risk for Psychosis",

abstract = "Preclinical and human studies suggest that hippocampal dysfunction is a key factor in the onset of psychosis. People at Clinical High Risk for psychosis (CHR-P) present with a clinical syndrome that can include social withdrawal and have a 20-35% risk of developing psychosis in the next 2 years. Recent research shows that resting hippocampal blood flow is altered in CHR-P individuals and predicts adverse clinical outcomes, such as non-remission/transition to frank psychosis. Previous work in healthy males indicates that a single dose of intranasal oxytocin has positive effects on social function and marked effects on resting hippocampal blood flow. The present study examined the effects of intranasal oxytocin on hippocampal blood flow in CHR-P individuals. In a double-blind, placebo-controlled, crossover design, 30 CHR-P males were studied using pseudo-continuous Arterial Spin Labelling on 2 occasions, once after 40IU intranasal oxytocin and once after placebo. The effects of oxytocin on left hippocampal blood flow were examined in a region-of-interest analysis of data acquired at 22-28 and at 30-36 minutes post-intranasal administration. Relative to placebo, administration of oxytocin was associated with increased hippocampal blood flow at both time points (p=.0056; p=.034), although the effect at the second did not survive adjustment for the effect of global blood flow. These data indicate that oxytocin can modulate hippocampal function in CHR-P individuals and therefore merits further investigation as a candidate novel treatment for this group.",

author = "Cathy Davies and Yannis Paloyelis and Grazia Rutigliano and Marco Cappucciati and {De Micheli}, Andrea and Valentina Ramella-Cravaro and Umberto Provenzani and Mathilde Antoniades and Gemma Modinos and Dominic Oliver and Daniel Stahl and Silvia Murguia and Fernando Zelaya and Paul Allen and Sukhi Shergill and Paul Morrison and Steve Williams and David Taylor and Philip McGuire and Paolo Fusar-Poli",

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Davies, C , Paloyelis, Y, Rutigliano, G, Cappucciati, M, De Micheli, A, Ramella-Cravaro, V, Provenzani, U, Antoniades, M, Modinos, G , Oliver, D , Stahl, D, Murguia, S, Zelaya, F, Allen, P, Shergill, S , Morrison, P , Williams, S , Taylor, D , McGuire, P & Fusar-Poli, P 2019, 'Oxytocin Modulates Hippocampal Perfusion in People at Clinical High Risk for Psychosis', Neuropsychopharmacology, vol. 44, no. 7, pp. 1300-1309. https://doi.org/10.1038/s41386-018-0311-6

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AU - Davies, Cathy

AU - Paloyelis, Yannis

AU - Rutigliano, Grazia

AU - Cappucciati, Marco

AU - De Micheli, Andrea

AU - Ramella-Cravaro, Valentina

AU - Provenzani, Umberto

AU - Antoniades, Mathilde

AU - Modinos, Gemma

AU - Oliver, Dominic

AU - Stahl, Daniel

AU - Murguia, Silvia

AU - Zelaya, Fernando

AU - Allen, Paul

AU - Shergill, Sukhi

AU - Morrison, Paul

AU - Williams, Steve

AU - Taylor, David

AU - McGuire, Philip

AU - Fusar-Poli, Paolo

PY - 2019/1/9

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N2 - Preclinical and human studies suggest that hippocampal dysfunction is a key factor in the onset of psychosis. People at Clinical High Risk for psychosis (CHR-P) present with a clinical syndrome that can include social withdrawal and have a 20-35% risk of developing psychosis in the next 2 years. Recent research shows that resting hippocampal blood flow is altered in CHR-P individuals and predicts adverse clinical outcomes, such as non-remission/transition to frank psychosis. Previous work in healthy males indicates that a single dose of intranasal oxytocin has positive effects on social function and marked effects on resting hippocampal blood flow. The present study examined the effects of intranasal oxytocin on hippocampal blood flow in CHR-P individuals. In a double-blind, placebo-controlled, crossover design, 30 CHR-P males were studied using pseudo-continuous Arterial Spin Labelling on 2 occasions, once after 40IU intranasal oxytocin and once after placebo. The effects of oxytocin on left hippocampal blood flow were examined in a region-of-interest analysis of data acquired at 22-28 and at 30-36 minutes post-intranasal administration. Relative to placebo, administration of oxytocin was associated with increased hippocampal blood flow at both time points (p=.0056; p=.034), although the effect at the second did not survive adjustment for the effect of global blood flow. These data indicate that oxytocin can modulate hippocampal function in CHR-P individuals and therefore merits further investigation as a candidate novel treatment for this group.

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Oxytocin Modulates Hippocampal Perfusion in People at Clinical High Risk for Psychosis

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