Melbourne School of Professional and Continuing Education - Research Publications
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ItemChronic stress induces hypersensitivity of murine gastric vagal afferents(Wiley, 2019-12-01)Background Stress exposure is known to trigger and exacerbate functional dyspepsia (FD) symptoms. Increased gastric sensitivity to food‐related stimuli is widely observed in FD patients and is associated with stress and psychological disorders. The mechanisms underlying the hypersensitivity are not clear. Gastric vagal afferents (GVAs) play an important role in sensing meal‐related mechanical stimulation to modulate gastrointestinal function and food intake. This study aimed to determine whether GVAs display hypersensitivity after chronic stress, and whether its interaction with leptin was altered by stress. Methods Eight‐week‐old male C57BL/6 mice were exposed to unpredictable chronic mild stress or no stress (control) for 8 weeks. The metabolic rate, gastric emptying rate, and anxiety‐ and depression‐like behaviors were determined. GVA mechanosensitivity, and its modulation by leptin, was determined using an in vitro single fiber recording technique. QRT‐PCR was used to establish the levels of leptin and leptin receptor mRNA in the stomach and nodose ganglion, respectively. Key Results The stressed mice had lower body weight and food intake, and increased anxiety‐like behavior compared to the control mice. The mechanosensitivity of mucosal and tension‐sensitive GVAs was higher in the stressed mice. Leptin potentiated mucosal GVA mechanosensitivity in control but not stressed mice. The expression of leptin mRNA in the gastric mucosa was lower in the stressed mice. Conclusions and Inferences In conclusion, chronic stress enhances GVA mechanosensitivity, which may contribute to the gastric hypersensitivity in FD. In addition, the modulatory effect of leptin on GVA signaling is lost after chronic stress exposure.
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ItemVariability of the cortisol awakening response and morning salivary oxytocin in late adolescence(WILEY, 2018-11)Exogenously administered oxytocin interacts with the hypothalamic-pituitary-adrenal (HPA) axis to modulate endogenous cortisol levels, suggesting a synergistic role for these two hormones in the response to stress, cognitive performance and the development of psycho-behavioural disorders. The cortisol awakening response (CAR) is considered a reliable measure of HPA axis function in humans. However, the CAR appears to vary considerably from day to day and may be strongly influenced by the anticipated demands of the day ahead. The level of variation intrinsic to the CAR is unclear because few studies have examined the CAR in the absence of daily environmental variation. It is not known whether oxytocin has a similar or complementary awakening response. Therefore, over three consecutive days, we examined 12 adolescents (aged 15-17 years) in a highly-controlled sleep laboratory. Saliva was collected on days 4-6 of a 9-day laboratory visit. Cortisol and oxytocin levels were determined by an enzyme-linked immunosorbent assay from saliva sampled at 0, 15, 30 and 45 minutes, and 8 and 12 hours post-awakening. CAR magnitude varied between days and was associated with sleep duration and pre-awakening sleep stage. Conversely, oxytocin levels dropped dramatically in the first 15 minutes post-awakening and were highly consistent across participants and days. Older participants had higher awakening oxytocin concentrations. Although cortisol increases and oxytocin rapidly declines upon awakening, their diurnal variation does not appear to be related at basal, peripheral levels, consistent with a previous finding that exogenously administered oxytocin only modulates cortisol under conditions of stress.
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ItemNovel methods of teaching psychiatry to medical and postgraduate students(LIPPINCOTT WILLIAMS & WILKINS, 2021-09-01)Purpose of review Global burden of mental illness remains at an all-time high and provision of timely good quality care is a challenge globally. Current methods of medical and post-graduate education in psychiatry worldwide have been inadequate in treating those with mental illness. Enormous gaps exist in provision of high-quality teaching, particularly in poorer countries with many having no access to ongoing teaching and training. Recent findings Technology and changes to curriculum design have transformed student experiences and highlighted the value of online learning. There are many models to consider from and we describe the development process for these, which also highlight why some can be superior to classroom-based learning. New innovations have significantly enhanced engagement and reach thereby bringing students across the globe into an interconnected community and putting them in touch with world experts. Although some of these options may be expensive, many can be made affordable and accessible. Summary It is possible to use innovations in online education to ensure high-quality teaching is available globally. A high touch model may be suitable when resources permit, and otherwise low touch scalable models provide options for increasing reach. Together, these models provide optimism for improving standards of global psychiatric training.
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ItemThe Recorded Interaction Task: A Validation Study of a New Observational Tool to Assess Mother-Infant Bonding(WILEY, 2021-03)INTRODUCTION: Mother-infant bonding describes the early emotional connectedness between a mother and her infant. The quality of the mother-infant bond early in life is related to the subsequent quality of the child's attachment, the quality of further mother-infant interactions, and various other social outcomes across the child's life span. The Recorded Interaction Task (RIT) was developed to assess mother-infant bonding using observational methods in a naturalistic but standardized setting, thus addressing shortcomings of previous self-report tools. The RIT focusses on the common interaction between mother and infant (aged 2 to 5 months old), during a diaper (nappy) change. The interaction is video recorded and later assessed. The RIT must be validated before it can be used to assess mother-infant bonding in future research or in clinical practice. METHODS: Face and content validity of the RIT were assessed by a panel of 6 experts in bonding and assessment of maternal and infant behavior. The RIT and self-reported Postpartum Bonding Questionnaire (PBQ) were administered to 15 mother-infant dyads with the correlation between their scores used to assess convergent validity. RESULTS: Acceptable face and content validity of the RIT was demonstrated. A weak correlation between the RIT and PBQ (r = -0.13) and their subscales (r = -0.22) were observed. A strong correlation between the RIT maternal behavior and infant behavior subscales was recorded (r = 0.69). DISCUSSION: The RIT appears to be a viable tool for the observational assessment of mother-infant bonding. Reliability testing and piloting will be required before the RIT can be used in future research or clinical practice.
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ItemToll-like receptor 4: innate immune regulator of neuroimmune and neuroendocrine interactions in stress and major depressive disorder(FRONTIERS MEDIA SA, 2014-09-30)Major depressive disorder (MDD) poses one of the highest disease burdens worldwide. Yet, current treatments targeting serotonergic and noradrenaline reuptake systems are insufficient to provide long-term relief from depressive symptoms in most patients, indicating the need for new treatment targets. Having the ability to influence behavior similar to depressive symptoms, as well as communicate with neuronal and neuroendocrine systems, the innate immune system is a strong candidate for MDD treatments. Given the complex nature of immune signaling, the main question becomes: What is the role of the innate immune system in MDD? The current review presents evidence that toll-like receptor 4 (TLR4), via driving both peripheral and central immune responses, can interact with serotonergic neurotransmission and cause neuroendocrine disturbances, thus integrating with widely observed hallmarks of MDD. Additionally, through describing the multi-directional communication between immune, neural and endocrine systems in stress, TLR4-related mechanisms can mediate stress-induced adaptations, which are necessary for the development of MDD. Therefore, apart from exogenous pathogenic mechanisms, TLR4 is involved in immune changes as a result of endogenous stress signals, playing an integral part in the pathophysiology, and could be a potential target for pharmacological treatments to improve current interventions for MDD.
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ItemOxytocin as an Indicator of Psychological and Social Well-Being in Domesticated Animals: A Critical Review(FRONTIERS MEDIA SA, 2017-09-13)Oxytocin is often portrayed as a hormone specific to social behavior, reflective of positive welfare states, and linked to mental states. Research on oxytocin in domesticated animal species has been few to date but is rapidly increasing (in dog, pig, cattle, sheep), with direct implications for animal welfare. This review evaluates the evidence for the specificity of oxytocin as an indicator of: 1. Social, 2. Positive, and 3. Psychological well-being. Oxytocin has most often been studied in socially relevant paradigms, with a lack of non-social control paradigms. Oxytocin research appears biased toward investigating positive valence, with a lack of control in valence or arousal. Oxytocin actions are modulated by the environmental and social contexts, which are important factors to consider. Limited evidence supports that oxytocin's actions are linked to psychological states; nevertheless whether this is a direct effect of oxytocin per se remains to be demonstrated. Overall, it is premature to judge oxytocin's potential as an animal welfare indicator given the few and discrepant findings and a lack of standardization in methodology. We cover potential causes for discrepancies and suggest solutions through appropriate methodological design, oxytocin sampling or delivery, analysis and reporting. Of particular interest, the oxytocinergic system as a whole remains poorly understood. Appreciation for the differences that social contact and group living pose in domesticated species and the way they interact with humans should be key considerations in using oxytocin as a psychosocial indicator of well-being.
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ItemCortisol-induced increases of plasma oxytocin levels predict decreased immediate free recall of unpleasant words.(Frontiers Media SA, 2012)Cortisol and oxytocin have been shown to interact in both the regulation of stress responses and in memory function. In the present study we administered cortisol to 35 healthy female subjects in a within-subject double-blind placebo-controlled design, while measuring oxytocin levels, adrenocorticotropic hormone (ACTH) levels, and free recall of pleasant and of unpleasant words. We found that cortisol administration suppressed ACTH levels and (1) induced a decrease in oxytocin associated with ACTH suppression and (2) an increase in oxytocin that was independent from ACTH suppression. This cortisol-induced increase in plasma oxytocin was associated with a selective decrease in immediate free recall of unpleasant words from primacy positions. The present results add to evidence that cortisol-induced increases in oxytocin could mediate some of the effects of stress and cortisol on memory, and possibly play a role in the regulation of the hypothalamo-pituitary-adrenal stress response. This mechanism could significantly impact affective and social behaviors, in particular during times of stress.
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ItemCommentary: Intranasal Oxytocin Treatment Increases Eye-Gaze Behavior toward the Owner in Ancient Japanese Dog Breeds(Frontiers Media, 2018-08-17)
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ItemOxytocin treatment in pediatric populations(FRONTIERS MEDIA SA, 2014-10-16)The role of endogenous oxytocin as neuromodulator of birth, lactation and social behaviors is well-recognized. Moreover, the use of oxytocin as a facilitator of social and other behaviors is becoming more and more accepted. Many positive effects have been attributed to intranasal oxytocin administration in animals and humans; with current research highlighting encouraging advances in its potential for use in mental health disorders. The new frontier will be investigating the effective use of oxytocin in pediatric populations. Limited animal data is available on this. Large-scale human studies focusing on autism are currently under way, but many other possibilities seem to lie in the future. However, we need to know more about the risks and effects of repeated use on the developing brain and body. This paper will provide an overview of the current understanding of the role of endogenous oxytocin and its related neuropeptide systems in influencing behaviors, in particular attachment, and will review (a) the literature on the use of intranasal oxytocin in young animals, children (age range birth-12 years) and adolescents (age range 13-19 years), (b) the expected benefits and risks based on the current research, and (c) the risks of oxytocin in children with severe psychopathology and early life trauma. The paper will conclude with a clinical perspective on these findings.
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ItemEarly social environment affects the endogenous oxytocin system: a review and future directions(FRONTIERS MEDIA SA, 2015-03-11)Endogenous oxytocin plays an important role in a wide range of human functions including birth, milk ejection during lactation, and facilitation of social interaction. There is increasing evidence that both variations in the oxytocin receptor (OXTR) and concentrations of oxytocin are associated with differences in these functions. The causes for the differences that have been observed in tonic and stimulated oxytocin release remain unclear. Previous reviews have suggested that across the life course, these differences may be due to individual factors, e.g., genetic variation (of the OXTR), age or sex, or be the result of early environmental influences, such as social experiences, stress, or trauma partly by inducing epigenetic changes. This review has three aims. First, we briefly discuss the endogenous oxytocin system, including physiology, development, individual differences, and function. Second, current models describing the relationship between the early life environment and the development of the oxytocin system in humans and animals are discussed. Finally, we describe research designs that can be used to investigate the effects of the early environment on the oxytocin system, identifying specific areas of research that need further attention.