RESUMO
Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown. Forty-seven men (30 CHR-P and 17 healthy controls) received acute challenges of both intranasal oxytocin 40 IU and placebo in two parallel randomised, double-blind, placebo-controlled cross-over studies which had similar but not identical designs. Multi-echo resting-state fMRI data was acquired at approximately 1 h post-dosing. Using a graph theoretical approach, the effects of group (CHR-P vs healthy control), treatment (oxytocin vs placebo) and respective interactions were tested on graph metrics describing the topology of the functional connectome. Group effects were observed in 12 regions (all pFDR < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all pFDR < 0.05) predominantly within the ventral attention network. Our major finding was that many effects of oxytocin on network topology differ across CHR-P and healthy individuals, with significant interaction effects observed in numerous subcortical regions strongly implicated in psychosis onset, such as the thalamus, pallidum and nucleus accumbens, and cortical regions which localised primarily to the default mode network (12 regions, all pFDR < 0.05). Collectively, our findings provide new insights on aberrant functional brain network organisation associated with psychosis risk and demonstrate, for the first time, that oxytocin modulates network topology in brain regions implicated in the pathophysiology of psychosis in a clinical status (CHR-P vs healthy control) specific manner.
Assuntos
Encéfalo , Conectoma , Imageamento por Ressonância Magnética , Ocitocina , Transtornos Psicóticos , Humanos , Ocitocina/farmacologia , Ocitocina/administração & dosagem , Masculino , Conectoma/métodos , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Método Duplo-Cego , Adulto , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Adulto Jovem , Estudos Cross-Over , Administração Intranasal , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Adolescente , RiscoRESUMO
BACKGROUND: Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions. METHODS: The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes. RESULTS: From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed. LIMITATIONS: Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias. CONCLUSIONS: This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms.
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Transtorno do Espectro Autista , Transtorno Autístico , Hipopituitarismo , Hipoplasia do Nervo Óptico , Displasia Septo-Óptica , Humanos , Displasia Septo-Óptica/epidemiologia , Displasia Septo-Óptica/diagnóstico , Displasia Septo-Óptica/genética , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/complicações , Hipoplasia do Nervo Óptico/complicações , Hipopituitarismo/etiologia , Transtorno Autístico/complicaçõesRESUMO
Adults with antisocial personality disorder with (ASPD + P) and without (ASPD - P) psychopathy commit the majority of violent crimes. Empathic processing abnormalities are particularly prominent in psychopathy, but effective pharmacological interventions have yet to be identified. Oxytocin modulates neural responses to fearful expressions in healthy populations. The current study investigates its effects in violent antisocial men. In a placebo-controlled, randomized crossover design, 34 violent offenders (19 ASPD + P; 15 ASPD - P) and 24 healthy non-offenders received 40 IU intranasal oxytocin or placebo and then completed an fMRI morphed faces task examining the implicit processing of fearful facial expressions. Increasing intensity of fearful facial expressions failed to appropriately modulate activity in the bilateral mid-cingulate cortex in violent offenders with ASPD + P, compared with those with ASPD - P. Oxytocin abolished these group differences. This represents evidence of neurochemical modulation of the empathic processing of others' distress in psychopathy.
RESUMO
Humans often act in the best interests of others. However, how we learn which actions result in good outcomes for other people and the neurochemical systems that support this 'prosocial learning' remain poorly understood. Using computational models of reinforcement learning, functional magnetic resonance imaging and dynamic causal modelling, we examined how different doses of intranasal oxytocin, a neuropeptide linked to social cognition, impact how people learn to benefit others (prosocial learning) and whether this influence could be dissociated from how we learn to benefit ourselves (self-oriented learning). We show that a low dose of oxytocin prevented decreases in prosocial performance over time, despite no impact on self-oriented learning. Critically, oxytocin produced dose-dependent changes in the encoding of prediction errors (PE) in the midbrain-subgenual anterior cingulate cortex (sgACC) pathway specifically during prosocial learning. Our findings reveal a new role of oxytocin in prosocial learning by modulating computations of PEs in the midbrain-sgACC pathway.
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Ocitocina , Reforço Psicológico , Administração Intranasal , Giro do Cíngulo , Humanos , Aprendizagem , Ocitocina/farmacologiaRESUMO
Intranasal oxytocin is attracting attention as a potential treatment for several brain disorders due to promising preclinical results. However, translating findings to humans has been hampered by remaining uncertainties about its pharmacodynamics and the methods used to probe its effects in the human brain. Using a dose-response design (9, 18 and 36 IU), we demonstrate that intranasal oxytocin-induced changes in local regional cerebral blood flow (rCBF) in the amygdala at rest, and in the covariance between rCBF in the amygdala and other key hubs of the brain oxytocin system, follow a dose-response curve with maximal effects for lower doses. Yet, the effects on local rCBF might vary by amygdala subdivision, highlighting the need to qualify dose-response curves within subregion. We further link physiological changes with the density of the oxytocin receptor gene mRNA across brain regions, strengthening our confidence in intranasal oxytocin as a valid approach to engage central targets. Finally, we demonstrate that intranasal oxytocin does not disrupt cerebrovascular reactivity, which corroborates the validity of haemodynamic neuroimaging to probe the effects of intranasal oxytocin in the human brain. DATA AVAILABILITY: Participants did not consent for open sharing of the data. Therefore, data can only be accessed from the corresponding author upon reasonable request.
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Imageamento por Ressonância Magnética , Ocitocina , Administração Intranasal , Encéfalo , Método Duplo-Cego , Humanos , Ocitocina/farmacologiaRESUMO
Intranasal oxytocin (OT) has been suggested as a putative adjunctive treatment for patients with schizophrenia and autism spectrum disorders (ASD). Here, we examine available evidence from trials investigating the effects of repeated administrations of intranasal OT on the core symptoms of patients with schizophrenia and ASD, focusing on its therapeutic efficacy and heterogeneity of response (meta-ANOVA). Repeated administration of intranasal OT does not improve most of the core symptoms of schizophrenia and ASD, beyond a small tentative effect on schizophrenia general symptoms. However, we found significant moderator effects for dose in schizophrenia total psychopathology and positive symptoms, and percentage of included men and duration of treatment in schizophrenia general symptoms. We found evidence of heterogeneity (increased variance) in the response of schizophrenia negative symptoms to intranasal OT compared with placebo, suggesting that subgroups of responsive and non-responsive patients might coexist. For other core symptoms of schizophrenia, or any of the core symptom dimensions in ASD, the response to repeated treatment with intranasal OT did not show evidence of heterogeneity. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.
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Transtorno do Espectro Autista , Esquizofrenia , Administração Intranasal , Análise de Variância , Transtorno do Espectro Autista/tratamento farmacológico , Humanos , Masculino , Ocitocina/uso terapêutico , Esquizofrenia/tratamento farmacológicoRESUMO
Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addictive behaviours, are limited in efficacy and characterised by increased health risks associated with their pharmacological profile. Preclinical studies have identified oxytocin as a promising pharmacotherapy with anticraving properties for addictive behaviours. Here, we provide the first systematic review of 17 human studies (n = 722; 30% female) investigating the efficacy of intranasal oxytocin to reduce craving or consumption in addictive behaviours. We identify intranasal oxytocin as a method that warrants further investigation regarding its capacity to decrease cue-induced, acute stress-induced or withdrawal-related craving and relapse related to alcohol, cannabis, opioids, cocaine or nicotine, including a potential role as ad hoc medication following exposure to drug-related cues. Future studies should investigate the role of factors such as treatment regimens and sample characteristics, including the role of the amygdala, which we propose as a distinct mechanism mediating oxytocin's anticraving properties.
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Comportamento Aditivo , Fissura , Administração Intranasal , Comportamento Aditivo/tratamento farmacológico , Sinais (Psicologia) , Feminino , Humanos , Masculino , OcitocinaRESUMO
Oxytocin has recently received remarkable attention for its role as a modulator of human behaviour. Here, we aimed to expand our knowledge of the neural circuits engaged by oxytocin by investigating the effects of intranasal and intravenous oxytocin on the functional connectome at rest in 16 healthy men. Oxytocin modulates the functional connectome within discrete neural systems, but does not affect the global capacity for information transfer. These local effects encompass key hubs of the oxytocin system (e.g. amygdala) but also regions overlooked in previous hypothesis-driven research (i.e. the visual circuits, temporal lobe and cerebellum). Increases in levels of oxytocin in systemic circulation induce broad effects on the functional connectome, yet we provide indirect evidence supporting the involvement of nose-to-brain pathways in at least some of the observed changes after intranasal oxytocin. Together, our results suggest that oxytocin effects on human behaviour entail modulation of multiple levels of brain processing distributed across different systems.
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Conectoma , Ocitocina/fisiologia , Administração Intranasal , Administração Intravenosa , Adulto , Estudos Cross-Over , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Masculino , Ocitocina/administração & dosagem , Adulto JovemRESUMO
Single measurements of salivary and plasmatic oxytocin are used as indicators of the physiology of the oxytocin system. However, questions remain about whether they are sufficiently stable to provide valid trait markers of the physiology of the oxytocin system, and whether salivary oxytocin can accurately index its plasmatic concentrations. Using radioimmunoassay, we measured baseline plasmatic and/or salivary oxytocin from two independent datasets. We also administered exogenous oxytocin intravenously and intranasally in a triple dummy, within-subject, placebo-controlled design and compared baseline levels and the effects of routes of administration. Our findings question the use of single measurements of baseline oxytocin concentrations in saliva and plasma as valid trait markers of the physiology of the oxytocin system in humans. Salivary oxytocin is a weak surrogate for plasmatic oxytocin. The increases in salivary oxytocin observed after intranasal oxytocin most likely reflect unabsorbed peptide and should not be used to predict treatment effects.
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Técnicas de Diagnóstico Endócrino , Sistema Endócrino/metabolismo , Ocitocina/sangue , Saliva/metabolismo , Administração Intranasal , Administração Intravenosa , Adolescente , Adulto , Biomarcadores/sangue , Humanos , Masculino , Ocitocina/administração & dosagem , Valor Preditivo dos Testes , Radioimunoensaio , Reprodutibilidade dos Testes , Fatores de Tempo , Adulto JovemRESUMO
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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Ocitocina , Transtornos Psicóticos , Administração Intranasal , Sistema Nervoso Autônomo , Frequência Cardíaca , Humanos , Masculino , Transtornos Psicóticos/tratamento farmacológicoRESUMO
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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Ocitocina , Transtornos Psicóticos , Administração Intranasal , Encéfalo/diagnóstico por imagem , Estudos Cross-Over , Método Duplo-Cego , Emoções , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos Psicóticos/tratamento farmacológicoRESUMO
Advances in the treatment of bulimia nervosa and binge-eating disorder (BN/BED) have been marred by our limited understanding of the underpinning neurobiology. Here we measured regional cerebral blood flow (rCBF) to map resting perfusion abnormalities in women with BN/BED compared with healthy controls and investigate whether intranasal oxytocin (OT), proposed as a potential treatment, can restore perfusion in disorder-related brain circuits. Twenty-four women with BN/BED and 23 healthy women participated in a randomized, double-blind, crossover, placebo-controlled study. We used arterial spin labelling MRI to measure rCBF and the effects of an acute dose of intranasal OT (40 IU) or placebo over 18-26 min post dosing, as we have previously shown robust OT-induced changes in resting rCBF in men in a similar time-window (15-36 min post dosing). We tested for effects of treatment, diagnosis and their interaction on extracted rCBF values in anatomical regions-of-interest previously implicated in BN/BED by other neuroimaging modalities, and conducted exploratory whole-brain analyses to investigate previously unidentified brain regions. We demonstrated that women with BN/BED presented increased resting rCBF in the medial prefrontal and orbitofrontal cortices, anterior cingulate gyrus, posterior insula and middle/inferior temporal gyri bilaterally. Hyperperfusion in these areas specifically correlated with eating symptoms severity in patients. Our data did not support a normalizing effect of intranasal OT on perfusion abnormalities in these patients, at least for the specific dose (40 IU) and post-dosing interval (18-26 min) examined. Our findings enhance our understanding of resting brain abnormalities in BN/BED and identify resting rCBF as a non-invasive potential biomarker for disease-related changes and treatment monitoring. They also highlight the need for a comprehensive investigation of intranasal OT pharmacodynamics in women before we can fully ascertain its therapeutic value in disorders affecting predominantly this gender, such as BN/BED.
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Transtorno da Compulsão Alimentar , Bulimia Nervosa , Encéfalo/diagnóstico por imagem , Bulimia Nervosa/diagnóstico por imagem , Bulimia Nervosa/tratamento farmacológico , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Ocitocina , PerfusãoRESUMO
BACKGROUND: Previous research has found that exogenous oxytocin administration has the potential to modulate attentional biases in women with anorexia nervosa. Recent work has indicated that attentional biases to food may reinforce the recurrent binge eating behaviour characterising bulimia nervosa and binge eating disorder. To date, however, no study has yet investigated the effect of oxytocin on attentional biases to palatable food in women with bulimia nervosa and binge eating disorder. METHODS: The present study employed a single-session cross-over design to test the hypothesis that a divided dose of 64 IU of intranasal oxytocin, administered as one intranasal dose of 40 IU of oxytocin followed by a top-up of 24 IU of oxytocin 80 minutes later, vs placebo administration administered in the same dosing schedule would reduce attentional biases towards food images in a dot probe task. We hypothesised that oxytocin administration would reduce vigilance towards food to a greater degree in women with bulimia nervosa or binge eating disorder vs healthy comparison women. Twenty-five women with bulimia nervosa or binge eating disorder and 27 comparison women without history of an eating disorder were recruited to take part in the study. RESULTS: In contrast to our hypothesis, there was no main effect of diagnosis on attentional bias to food (fixed effect = 5.70, P = 0.363), nor a significant interaction between diagnosis and drug condition (fixed effect =-14.80, P = 0.645). There was a main effect of drug condition, such that oxytocin increased vigilance towards food vs neutral images in the dot probe task (fixed effect = 10.42, P = 0.044). A correlation analysis revealed that this effect was moderated by attentional bias in the placebo condition, such that greater avoidance of food stimuli in the placebo condition was associated with a greater increase in vigilance induced by oxytocin. CONCLUSIONS: The findings of the present study add to a mixed body of literature investigating the therapeutic effects of oxytocin in women. Future research would benefit from dose-response studies investigating the optimal dose of oxytocin for modulating the attentional processing of palatable food in populations with eating disorders.
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Viés de Atenção/efeitos dos fármacos , Transtorno da Compulsão Alimentar/psicologia , Bulimia Nervosa/psicologia , Alimentos , Ocitocina/farmacologia , Administração Intranasal , Adolescente , Adulto , Estudos Cross-Over , Feminino , Humanos , Estimulação Luminosa , Projetos Piloto , Adulto JovemRESUMO
Previous theoretical models of bulimia nervosa (BN) and binge eating disorder (BED) have implicated cross-domain risk-taking behaviour as a significant maintenance factor in both disorders. The present study aimed to test this hypothesis by administering the Balloon Analogue Risk Task (BART) to 25 women with BN or BED and 27 healthy comparison women without a history of an eating disorder. Furthermore, we tested the effect of a divided dose of 64 IU of oxytocin on risk-taking behaviour in the BART. Contrary to our hypothesis, women with BN or BED did not exhibit baseline differences in performance on the BART in the placebo condition (t = 1.42, df = 50, P = 0.161, d = 0.39). Oxytocin did not have a main effect on performance in the BART (F = 0.01, df = 1, P = .907, η2partial < 0.001); however, there was an interaction, such that participants in the BN/BED participant group, compared to the healthy comparison group, demonstrated safer behaviour on the BART in the oxytocin condition, but not in the placebo condition (F = 4.29, df = 1, P = 0.044, η2partial = 0.082). These findings cast doubt on the common assumption that individuals with BN and BED exhibit greater risk-taking behaviour in all domains and add to the evidence that oxytocin plays a functional role in modulating behaviours that entail trade-offs between reward approach and risk in humans. We recommend that future dose-response studies investigate the effect of oxytocin on reward approach behaviour further in women with recurrent binge eating behaviour, as well as the clinical significance of this effect.
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Transtorno da Compulsão Alimentar/psicologia , Bulimia Nervosa/psicologia , Ocitocina/farmacologia , Assunção de Riscos , Administração Intranasal , Adulto , Transtorno da Compulsão Alimentar/patologia , Transtorno da Compulsão Alimentar/fisiopatologia , Encéfalo/efeitos dos fármacos , Bulimia Nervosa/patologia , Bulimia Nervosa/fisiopatologia , Estudos Cross-Over , Método Duplo-Cego , Emoções/efeitos dos fármacos , Feminino , Humanos , Imageamento por Ressonância Magnética , Ocitocina/administração & dosagem , Testes Psicológicos , Recompensa , Adulto JovemRESUMO
Alterations in neurochemical metabolites are thought to play a role in the pathophysiology of psychosis onset. Oxytocin, a neuropeptide with prosocial and anxiolytic properties, modulates glutamate neurotransmission in preclinical models but its neurochemical effects in people at high risk for psychosis are unknown. We used proton magnetic resonance spectroscopy (1H-MRS) to examine the effects of intranasal oxytocin on glutamate and other metabolites in people at Clinical High Risk for Psychosis (CHR-P) in a double-blind, placebo-controlled, crossover design. 30 CHR-P males were studied on two occasions, once after 40IU intranasal oxytocin and once after placebo. The effects of oxytocin on the concentration of glutamate, glutamate+glutamine and other metabolites (choline, N-acetylaspartate, myo-inositol) scaled to creatine were examined in the left thalamus, anterior cingulate cortex (ACC) and left hippocampus, starting approximately 75, 84 and 93 min post-dosing, respectively. Relative to placebo, administration of oxytocin was associated with an increase in choline levels in the ACC (p=.008, Cohen's dâ¯=â¯0.54). There were no other significant effects on metabolite concentrations (all p>.05). Our findings suggest that, at â¼75-99 min post-dosing, a single dose of intranasal oxytocin does not alter levels of neurochemical metabolites in the thalamus, ACC, or hippocampus in those at CHR-P, aside from potential effects on choline in the ACC.
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Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Ocitocina/administração & dosagem , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/metabolismo , Administração Intranasal , Adolescente , Adulto , Estudos Cross-Over , Método Duplo-Cego , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Transtornos Psicóticos/diagnóstico por imagem , Fatores de Risco , Tálamo/efeitos dos fármacos , Tálamo/metabolismo , Adulto JovemRESUMO
INTRODUCTION: Anorexia nervosa (AN) is an eating disorder characterised by restriction of energy intake, fears of gaining weight and related body image disturbances. The oxytocinergic system has been proposed as a pathophysiological candidate for AN. Oxytocin is a neuropeptide involved in bodily processes (eg, breast feeding) and in the onset of social behaviours (eg, bonding). Studies investigating the effect of intranasal oxytocin (IN-OT) in AN showed that it can improve attentional bias for high-calorie food and fat bodies stimuli, and related stress. However, less is known about the effect of IN-OT on bodily awareness and body image distortions, key features of the disorder linked to its development, prognosis and maintenance. Here, we aim to investigate the effect of IN-OT on the perception of affective, C-tactile-optimal touch, known to be impaired in AN and on multisensory integration processes underlying a body ownership illusion (ie, rubber hand illusion). For exploratory purposes, we will also investigate the effect of IN-OT on another interoceptive modality, namely cardiac awareness and its relationship with affective touch. DESIGN, METHODS AND ANALYSIS: Forty women with AN and forty matched healthy controls will be recruited and tested in two separate sessions; self-administering IN-OT (40 IU) or placebo, intranasally, in a pseudo-randomised manner. The data from this double-blind, placebo-controlled, cross-over study will be analysed using linear mixed models that allow the use of both fixed (treatment levels) and random (subjects) effects in the same analysis. To address our main hypotheses, separate analyses will be run for the affective touch task, where the primary outcome dependent variable will be the pleasantness of the touch, and for the rubber hand illusion, where we will investigate multisensory integration quantified as subjective embodiment towards the rubber hand. In the latter, we will manipulate the synchronicity of touch and the size of the hand. ETHICS AND DISSEMINATION: Ethics approval has been obtained by National Research Ethics Service NRES Committee London (Queen's Square Committee, ref number 14/LO/1593). The results will be disseminated through conference presentations and publication in peer-reviewed journals.
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Anorexia Nervosa , Transtornos Dismórficos Corporais , Ocitocina/administração & dosagem , Sensação , Tato/efeitos dos fármacos , Administração Intranasal , Adolescente , Adulto , Anorexia Nervosa/tratamento farmacológico , Anorexia Nervosa/fisiopatologia , Anorexia Nervosa/psicologia , Transtornos Dismórficos Corporais/tratamento farmacológico , Transtornos Dismórficos Corporais/fisiopatologia , Transtornos Dismórficos Corporais/psicologia , Imagem Corporal , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Ocitócicos/administração & dosagem , Estimulação Física , Sensação/efeitos dos fármacos , Sensação/fisiologiaRESUMO
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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Hipocampo/irrigação sanguínea , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Ocitocina/administração & dosagem , Transtornos Psicóticos/fisiopatologia , Administração Intranasal , Adolescente , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Transtornos Psicóticos/sangue , Fatores de Risco , Adulto JovemRESUMO
The current study aimed to test the influence of oxytocin on palatable food intake, 24-h caloric consumption, and stress in women with bulimia nervosa and binge eating disorder. We recruited 25 women with DSM-5 bulimia nervosa or binge eating disorder, and 27 weight-matched comparison women without history of an eating disorder. We employed a double-blind, placebo-controlled crossover design in which each participant attended the lab for two experimental sessions, receiving a divided dose of 64IU intranasal oxytocin in one session and equivalent volume of placebo nasal spray in the opposite session. The order of administration was pseudo-randomised across participants. We hypothesised that a divided dose of 64IU intranasal oxytocin administration would reduce subjective hunger, the immediate consumption of palatable food, 24-h calorie consumption, and the incidence of binge eating when compared to placebo. We also hypothesised that oxytocin administration would be associated with lower levels of stress and salivary cortisol, and that there would be an interaction with participant group such that oxytocin would reduce eating behaviour and stress to a greater degree in women with bulimia nervosa or binge eating disorder, compared to women without history of an eating disorder. We did not find a significant effect of oxytocin on any of the measurements of eating behaviour, subjective stress, or salivary cortisol. We recommend that future studies test the dose-response effect of oxytocin on eating behaviours and stress in human populations with eating disorders to further clarify the moderating factors for oxytocin's effect on eating.
Assuntos
Transtorno da Compulsão Alimentar/psicologia , Bulimia Nervosa/psicologia , Comportamento Alimentar , Ocitocina/farmacologia , Estresse Psicológico/complicações , Método Duplo-Cego , Ingestão de Energia , Feminino , Humanos , Hidrocortisona/metabolismo , Modelos Lineares , Ocitocina/administração & dosagem , Saliva/metabolismo , Escala Visual Analógica , Adulto JovemRESUMO
Multisensory integration processes are fundamental to our sense of self as embodied beings. Bodily illusions, such as the rubber hand illusion (RHI) and the size-weight illusion (SWI), allow us to investigate how the brain resolves conflicting multisensory evidence during perceptual inference in relation to different facets of body representation. In the RHI, synchronous tactile stimulation of a participant's hidden hand and a visible rubber hand creates illusory body ownership; in the SWI, the perceived size of the body can modulate the estimated weight of external objects. According to Bayesian models, such illusions arise as an attempt to explain the causes of multisensory perception and may reflect the attenuation of somatosensory precision, which is required to resolve perceptual hypotheses about conflicting multisensory input. Recent hypotheses propose that the precision of sensorimotor representations is determined by modulators of synaptic gain, like dopamine, acetylcholine, and oxytocin. However, these neuromodulatory hypotheses have not been tested in the context of embodied multisensory integration. The present, double-blind, placebo-controlled, crossover study ( n = 41 healthy volunteers) aimed to investigate the effect of intranasal oxytocin (IN-OT) on multisensory integration processes, tested by means of the RHI and the SWI. Results showed that IN-OT enhanced the subjective feeling of ownership in the RHI, only when synchronous tactile stimulation was involved. Furthermore, IN-OT increased an embodied version of the SWI (quantified as estimation error during a weight estimation task). These findings suggest that oxytocin might modulate processes of visuotactile multisensory integration by increasing the precision of top-down signals against bottom-up sensory input.