Neurochemical effects of oxytocin in people at clinical high risk for psychosis

Davies, Cathy; Rutigliano, Grazia; Micheli, Andrea Ilario De; Stone, James; Ramella-Cravaro, Valentina; Provenzani, Umberto; Cappucciati, Marco; Scutt, Eleanor; Paloyelis, Yannis; Oliver, Dominic; Murguia, Silvia; Zelaya, Fernando; Allen, Paul; Shergill, Sukhwinder S.; Morrison, Paul; Williams, Steven; Taylor, David; Lythgoe, David J.; McGuire, Philip; Fusar‐Poli, Paolo

doi:10.1016/j.euroneuro.2019.03.008

Cited by 9 publications

(16 citation statements)

References 89 publications

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“…While this study demonstrated that acute OT administration modulates key brain regions during inferring others' social emotions, OT effects on functional outcomes in CHR-P subjects need to be tested in future longer-term clinical trials. Furthermore, in terms of the neurophysiological mechanisms by which OT has its effects, we previously reported that OT modulates cerebral (hippocampal) perfusion in CHR-P patients 35 , but did not appear to modulate regional concentrations of neurochemical metabolites 36 . The mechanisms by which OT increases neural efficiency in CHR-P individuals therefore warrants further research.…”

Section: Discussionmentioning

confidence: 96%

“…Intranasal OT administration followed recommended guidelines and a protocol adopted by a previous study conducted at our institute 49 . As done in our previous studies 35,36 , participants self-administered one puff (4 IU) of intranasal OT or matched placebo every 30 s, alternating between nostrils, until 40 IU had been administered. See refs.…”

Section: Methodsmentioning

confidence: 99%

“…The study received National Research Ethics Service approval (14/LO/1692) and all subjects gave written informed consent. The participants and OT administration have previously been described in our Arterial Spin Labelling (ASL) 35 and magnetic resonance spectroscopy ( 1 H-MRS) 36 studies. Sample size was estimated using G*Power 3 to detect neurochemical effects based on a previous 1 H-MRS study 37 , which indicated that a sample size of 30 was sufficient to detect a medium within-subject effect size (d z = 0.53), when alpha=0.05 and power=80%.…”

Section: Participantsmentioning

confidence: 99%

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Acute oxytocin effects in inferring others’ beliefs and social emotions in people at clinical high risk for psychosis

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Social deficits are key hallmarks of the Clinical High Risk for Psychosis (CHR-P) state and of established psychotic disorders, and contribute to impaired social functioning, indicating a potential target for interventions. However, current treatments do not significantly ameliorate social impairments in CHR-P individuals. Given its critical role in social behaviour and cognition, the oxytocinergic (OT) system is a promising target for novel interventions in CHR-P subjects. In a double-blind, placebo-controlled, crossover design, 30 CHR-P males were studied using functional magnetic resonance imaging (fMRI) on two occasions, once after 40IU self-administered intranasal OT and once after placebo. A modified version of the Sally-Anne task was used to assess brain activation during inferring others' beliefs and social emotions. The Reading the Mind in the Eyes Test was acquired prior to the first scan to test whether OT effects were moderated by baseline social-emotional abilities. OT did not modulate behavioural performances but reduced activation in the bilateral inferior frontal gyrus compared with placebo while inferring others' social emotions. Furthermore, the relationship between brain activation and task performance after OT administration was moderated by baseline social-emotional abilities. While task accuracy during inferring others' social emotion increased with decreasing activation in the left inferior frontal gyrus in CHR-P individuals with low social-emotional abilities, there was no such relationship in CHR-P individuals with high social-emotional abilities. Our findings may suggest that acute OT administration enhances neural efficiency in the inferior frontal gyrus during inferring others' social emotions in those CHR-P subjects with low baseline social-emotional abilities.

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

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Acute oxytocin effects in inferring others’ beliefs and social emotions in people at clinical high risk for psychosis

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“…Participants were randomly allocated to a treatment order (oxytocin/placebo or placebo/oxytocin). After drug administration, participants were guided to a magnetic resonance imaging (MRI) scanner (data already reported 47,78 or to be reported in forthcoming publications). During the MRI session, we acquired, in the following order, two arterial spin-labelling resting-state scans, two runs of BOLD fMRI during a theory-of-mind task 79 , then two structural scans (T1 and FLAIR), a resting-state BOLD fMRI and a magnetic resonance spectroscopy scan at the end.…”

Section: Study Design and Procedures Chr-p Samplementioning

confidence: 99%

“…In contrast with schizophrenia, the number of intranasal oxytocin studies conducted with people at CHR-P until now is surprisingly scarce. We have previously shown that a single acute dose of intranasal oxytocin (40 IU) modulates hippocampal perfusion (a key element of our current models of the neurobiological mechanisms underlying the onset of psychosis) 45 – 47 and increases the levels of choline in the anterior cingulate cortex of men at CHR-P 48 . However, while oxytocin has long been recognised for its roles in the regulation of the cardiovascular and ANSs 49 – 51 , we are still unclear about whether intranasal oxytocin might address the ANS dysfunction observed along the psychosis spectrum.…”

Section: Introductionmentioning

confidence: 99%

Intranasal oxytocin increases heart-rate variability in men at clinical high risk for psychosis: a proof-of-concept study

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Autonomic nervous system (ANS) dysfunction (i.e., increased sympathetic and/or decreased parasympathetic activity) has been proposed to contribute to psychosis vulnerability. Yet, we still lack directed therapeutic strategies that improve ANS regulation in psychosis or at-risk states. The oxytocin system constitutes a potential therapeutic target, given its role in ANS regulation. However, whether intranasal oxytocin ameliorates autonomic regulation during emerging psychosis is currently unknown. We pooled together two datasets, one of 30 men at clinical high risk for psychosis (CHR-P), and another of 17 healthy men, who had participated in two double-blinded, placebo-controlled, randomised, crossover MRI studies with similar protocols. All participants self-administered 40 IU of intranasal oxytocin or placebo using a nasal spray. We recorded pulse plethysmography during a period of 8 min at about 1 h post dosing and estimated heart rate (HR) and high-frequency HR variability (HF-HRV), an index of cardio-parasympathetic activity. CHR-P and healthy men did not differ at resting HR or HF-HRV under placebo. We found a significant condition × treatment effect for HF-HRV, showing that intranasal oxytocin, compared with placebo, increased HF-HRV in CHR-P but not in healthy men. The main effects of treatment and condition were not significant. In this proof-of-concept study, we show that intranasal oxytocin increases cardio-parasympathetic activity in CHR-P men, highlighting its therapeutic potential to improve autonomic regulation in this clinical group. Our findings support the need for further research on the preventive and therapeutic potential of intranasal oxytocin during emerging psychosis, where we lack effective treatments.

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Prevention of Psychosis

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IMPORTANCE Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. OBJECTIVE To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. EVIDENCE REVIEW Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes.FINDINGS In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. CONCL...

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Neurochemical effects of oxytocin in people at clinical high risk for psychosis

Cited by 9 publications

References 89 publications

Acute oxytocin effects in inferring others’ beliefs and social emotions in people at clinical high risk for psychosis

Acute oxytocin effects in inferring others’ beliefs and social emotions in people at clinical high risk for psychosis

Intranasal oxytocin increases heart-rate variability in men at clinical high risk for psychosis: a proof-of-concept study

Prevention of Psychosis

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