Designing a wholly online, multidisciplinary Master of Cancer Sciences degree.

BACKGROUND: Improving oncology-specific knowledge and skills of healthcare professionals is critical for improving the outcomes of people with cancer. Many current postgraduate education offerings may be inaccessible to busy professionals, contain minimal consumer input or do not focus on the multidisciplinary nature of cancer care. In response to these needs, a Master of Cancer Sciences degree was developed. Our aim is to describe the development of the Master of Cancer Sciences. METHODS: We describe the development of the Master of Cancer Sciences, including its theoretical and its pedagogical underpinnings. RESULTS: Our approach to curriculum design was guided by Kern's Six-Step Approach to Medical Curriculum and underpinned by the Seven Principles of Online Learning. These approaches were further underpinned by the Cognitive Theory of Multimedia Learning which informed our approach to audio and visual information design. The pedagogy is interactive, experiential, interprofessional and importantly, includes consumers as educators. In practice, learning activities include peer feedback, multidisciplinary team meeting simulations, group work and clinical role plays. The online environment was visually shaped through infographics, high-quality educational videos and gamification. CONCLUSION: We have designed a Master of Cancer Sciences that is one of the first wholly online, cancer-specific Masters' programs. Its industry-led curriculum using evidence-based pedagogical choices utilises a range of novel digital formats and integrates the consumer perspective to provide a holistic overview of the field. Quantitative and qualitative evaluation of learning outcomes is ongoing.

Assessing mother-infant bonding: reliability of the recorded interaction task.

OBJECTIVE: This study examined the intra- and inter-rater reliability of the Recorded Interaction Task (RIT); a novel tool to assess mother-infant bonding via observational methods. BACKGROUND: Mother-infant bonding describes the reciprocal early emotional connection between mother and infant. Whilst various tools exist to assess mother-infant bonding, many incorrectly confuse this construct with mother-infant attachment. Further, available tools are limited to those that employ self-report methods, thus may reflect perceived behaviour, rather than actual behaviour. The RIT is a novel tool for observational assessment of mother-infant bonding. A standard interaction between mother and infant is recorded, and later assessed against specified bonding-related behaviours. Before its use in research, reliability testing must be undertaken to ensure the RIT may be used consistently. METHODS: The RIT was administered to 15 mother-infant dyads. Participant recordings were assessed by three trained raters at two time points, using the RIT observation scoring sheet. Intra-rater reliability was determined by comparing scores at each time point for each rater. Inter-rater reliability was determined by assessing reliability of scores at the first time point. RESULTS: Strong intra-rater reliability (ICC >0.86) and fair inter-rater reliability (ICC = 0.55) were observed. CONCLUSION: The current findings support the RIT's potential to reliably assess mother-infant bonding.

Novel methods of teaching psychiatry to medical and postgraduate students.

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.

The Recorded Interaction Task: A Validation Study of a New Observational Tool to Assess Mother-Infant Bonding.

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.

Are the protective benefits of vitamin D in neurodegenerative disease dependent on route of administration? A systematic review.

Background: The clinical and preclinical exploration of the therapeutic properties of vitamin D have significantly increased in the past decade, owing to the growing associative evidence suggesting vitamin D is neuroprotective. However, whether depletion of vitamin D contributes to the onset of neurological disorders or is a symptom of neurological disease has yet to be defined. Much remains unclear about the causal role of vitamin D and the method of use and forms of vitamin D.Objectives: We sought to quantitatively assess if neuroprotective benefits from vitamin D in neurodegenerative diseases are dependent on route of administration: comparing the effect of endogenously sourced vitamin D from UV exposure to exogenously derived vitamin D through synthetic supplementation.Design: We systematically searched PubMed, Embase and PsycInfo databases which included both pre-clinical and clinical studies investigating vitamin D in neurodegenerative diseases. Articles were subject to strict inclusion criteria and objectively assessed for quality. Additionally, Medline data was analysed to identify trends in topic publications and linguistic characteristics of papers.Results: From a total of 231 screened articles, we identified 73 appropriate for review based on inclusion criteria: original studies that investigated vitamin D levels or levels of vitamin D supplementation in neurodegenerative diseases or investigated past/present sun exposure in disease cohorts. Results indicate there is insufficient evidence to comprehensively reflect on a potential neuroprotective role for vitamin D and if this was dependent on route of administration. The majority of current data supporting neuroprotective benefits from vitamin D are based on pre-clinical and observational studies. Solid evidence is lacking to support the current hypothesis that the beneficial effect of UV exposure results from the synthesis of vitamin D. Sun exposure, independent of vitamin D production, may be protective against multiple Sclerosis, Parkinson's disease and Alzheimer's disease. Yet, further research is required to elucidate the beneficial mechanism of actions of UV exposure. The literature of vitamin D and amyotrophic lateral sclerosis was limited, and no conclusions were drawn. Therefore, in cases where UV-derived vitamin D was hypothesized to be the beneficial mediator in the neuroprotective effects of sun exposure, we propose results are based only on associative evidence.Conclusion: On the basis of this systematic review, strong recommendations regarding therapeutic benefits of vitamin D in neurodegenerative disease cannot be made. It is unclear if vitamin D mediates a protective benefit in neurodegenerative disease or whether it is an associative marker of UV exposure, which may contribute to as of yet unidentified neuroprotective factors.

Measuring opioid dependence in chronic pain patients: A comparison between addiction clinic and pain clinic patient populations.

OBJECTIVE: To compare dependence characteristics between patients with chronic pain treated within an addiction medicine setting with those attending specialist pain clinics. SETTING AND PATIENTS: Forty patients with chronic non-cancer pain taking opioid analgesics for >1 year were recruited from university-affiliated, tertiary teaching hospital clinics; 20 from an addiction medicine clinic (addiction clinic group) and 20 from specialist pain clinics (pain clinic group). DESIGN AND MAIN OUTCOME MEASURES: Data regarding demographics, past and current substance use, pain history and current daily opioid intake were collected. Patients completed three questionnaires: the Severity of Opioid Dependence Questionnaire, Leeds Dependence Questionnaire, and Pain Disability Index. A novel "Opioid Problem Checklist score" assessing drug-related problems was also determined for each patient. RESULTS: The addiction clinic group were younger, more likely to have experienced drug overdose and had a shorter duration of chronic pain. No significant differences in dependence questionnaire scores were found between groups. However, higher Pain Disability Index scores and higher Opioid Problem Checklist scores (indicating more drug-related problems) were found for the addiction clinic group. CONCLUSIONS: Some degree of dependence was present across both addiction and pain clinic groups, supporting the notion a state of dependence can be identified among chronic pain patients taking opioids long term. Aberrant behaviors were not common in the pain clinic sample, suggesting these patients are unlikely to meet Diagnostic and Statistical Manual of Mental Disorders-V criteria for Substance Use Disorder. However, opioid dependence carries significant risks for relapse, chronicity, morbidity and mortality, warranting specific medical management. Management of such risks should be considered routine care in chronic pain patients taking opioids long term.

Chronic stress induces hypersensitivity of murine gastric vagal afferents.

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.

Variability of the cortisol awakening response and morning salivary oxytocin in late adolescence.

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.

Can neuroimmune mechanisms explain the link between ultraviolet light (UV) exposure and addictive behavior?

High ultraviolet (UV) light exposure on the skin acts as a reinforcing stimulus, increasing sun-seeking behavior and even addiction-like sun seeking behavior. However, the physiological mechanisms that underlie this process remain to be defined. Here, we propose a novel hypothesis that neuroimmune signaling, arising from inflammatory responses in UV-damaged skin cells, causes potentiated signaling within the cortico-mesolimbic pathway, leading to increased sun-seeking behaviors. This hypothesized UV-induced, skin-to-brain signaling depends upon cell stress signals, termed alarmins, reaching the circulation, thereby triggering the activation of innate immune receptors, such as toll-like receptors (TLRs). This innate immune response is hypothesized to occur both peripherally and centrally, with the downstream signaling from TLR activation affecting both the endogenous opioid system and the mesolimbic dopamine pathway. As both neurotransmitter systems play a key role in the development of addiction behaviors through their actions at key brain regions, such as the nucleus accumbens (NAc), we hypothesize a novel connection between UV-induced inflammation and the activation of pathways that contribute to the development of addiction. This paper is a review of the existing literature to examine the evidence which suggests that chronic sun tanning resembles a behavioral addiction and proposes a novel pathway by which persistent sun-seeking behavior could affect brain neurochemistry in a manner similar to that of repeated drug use.

Antagonising TLR4-TRIF signalling before or after a low-dose alcohol binge during adolescence prevents alcohol drinking but not seeking behaviour in adulthood.

Adolescents frequently engage in risky behaviours such as binge drinking. Binge drinking, in turn, perturbs neurodevelopment reinforcing reward seeking behaviour in adulthood. Current animal models are limited in their portrayal of this behaviour and the assessment of neuroimmune involvement (specifically the role of Toll-like receptor 4 (TLR4)). Therefore, the aims of this project were to develop a more relevant animal model of adolescent alcohol exposure and to characterise its effects on TLR4 signalling and alcohol-related behaviours later life. Balb/c mice received a short (P22-P25), low dose alcohol binge during in early adolescence, and underwent tests to investigate anxiety (elevated plus maze), alcohol seeking (conditioned place preference) and binge drinking behaviour (drinking in the dark) in adulthood. Four doses of alcohol during adolescence increased alcohol-induced conditioned place preference and alcohol intake in adulthood. However, this model did not affect basal elevated plus maze performance. Subsequent analysis of nucleus accumbal mRNA, revealed increased expression of TLR4-related mRNAs in mice who received alcohol during adolescence. To further elucidate the role of TLR4, (+)-Naltrexone, a biased TLR4 antagonist was administered 30 min before or after the adolescent binge paradigm. When tested in adulthood, (+)-Naltrexone treated mice exhibited reduced alcohol intake however, alcohol seeking and anxiety behaviour was unaltered. This study highlights that even a small amount of alcohol, when given during a critical neurodevelopmental period, can potentiate alcohol-related behaviours and TLR4 activation later in life. Interestingly, attenuation of TLR4 before or after adolescent alcohol exposure reduced only binge alcohol intake in adulthood.

The efficacy of (+)-Naltrexone on alcohol preference and seeking behaviour is dependent on light-cycle.

Circadian rhythm affects drug-induced reward behaviour and the innate immune system. Peaks in reward-associated behaviour and immune responses typically occur during the active (dark) phase of rodents. While the role of the immune system, specifically, Toll-like receptor 4 (TLR4, an innate immune receptor) in drug-induced reward is becoming increasingly appreciated, it is unclear whether its effects vary according to light-cycle. Therefore, the aim of this study was to characterise the effects of the phase of the light-cycle and the state of the innate immune system on alcohol reward behaviour and subsequently determine whether the efficacy of targeting the immune component of drug reward depends upon the light-cycle. This study demonstrates that mice exhibit greater alcohol-induced conditioned place preference and alcohol two-bottle choice preference during the dark cycle. This effect overlapped with elevations in reward-, thirst- and immune-related genes. Administration of (+)-Naltrexone, a TLR4 antagonist, reduced immune-related gene mRNA expression and alcohol preference with its effects most pronounced during the dark cycle. However, (+)-Naltrexone, like other TLR4 antagonists exhibited off-target side effects, with a significant reduction in overall saccharin intake - an effect likely attributable to a reduction in tyrosine hydroxylase (Th) mRNA expression levels. Collectively, the study highlights a link between a time-of-day dependent influence of TLR4 on natural and alcohol reward-like behaviour in mice.

Oxytocin as an Indicator of Psychological and Social Well-Being in Domesticated Animals: A Critical Review.

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.

Adversity impacting on oxytocin and behaviour: timing matters.

The endogenous oxytocin system plays a vital role in facilitating parturition, lactation and social interaction in humans and other mammals. It also impacts on a number of important endocrine, immune and neurotransmitter systems. A well-regulated oxytocin system has been proposed to increase resilience, and therefore reduce the likelihood of an individual developing mental illness or substance dependence. This review discusses the adverse external influences that can modulate oxytocin receptor and protein levels and impact on substance use and mental health. The paper highlights the impact of adversity such as poor maternal care, parental substance use and child abuse or neglect. We review clinical and preclinical data on the impact of adversity on the basis of the time of exposure from infancy and early childhood, to adolescence, adulthood to older age. Previous research suggests that dysregulation of the endogenous oxytocin system may be implicated in determining susceptibility to stress, anxiety, addiction and mental health conditions. The impact of external influence seems to be strongest in specific time periods where the system shows experience-based development or natural fluctuations in oxytocin levels. Interventions that target the oxytocin system during or soon after exposure to adversity may prove protective.

Early social environment affects the endogenous oxytocin system: a review and future directions.

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.

Oxytocin treatment in pediatric populations.

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.

Toll-like receptor 4: innate immune regulator of neuroimmune and neuroendocrine interactions in stress and major depressive disorder.

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.

Reduced response to the thermal grill illusion in chronic pain patients.

OBJECTIVE: Sensory illusions may reveal fundamental features of the nervous system. The thermal grill illusion is such a pain illusion, where interlaced warm and cool temperature bars (thermal grill) produce a paradoxical burning sensation. Previous studies have only systematically investigated the thermal grill illusion in pain-free volunteers. The objective of this study was to investigate whether the response to the thermal grill illusion was tolerable in patients with chronic pain and whether the response differed between patients with chronic pain and pain-free volunteers. SUBJECTS: Sixteen pain-free participants and 18 chronic pain patients (seven not receiving opioids and 11 receiving opioids). METHODS: The thermal grill response was investigated using a custom-built thermal grill. Heat and cold pain thresholds were also determined. RESULTS: Chronic pain patients reported less intense pain, heat, and unpleasantness to the thermal grill compared with pain-free participants; in particular, there was an overall main effect for significantly less heat from the thermal grill compared with pain-free participants (P = 0.016). At the 22/38°C combination, although the majority of pain-free participants experienced the illusion to some degree, the majority of pain patients in both groups did not (median pain score 0). Although perceived heat from the thermal grill was significantly lower in chronic pain patients, both heat and cold pain thresholds did not differ among the three populations. CONCLUSIONS: This preliminary data suggest that the thermal grill response may provide insights into pain sensitivity that are not detected by conventional thermal quantitative sensory testing.

Individual differences underlying susceptibility to addiction: Role for the endogenous oxytocin system.

Recent research shows that the effects of oxytocin are more diverse than initially thought and that in some cases oxytocin can directly influence the response to drugs and alcohol. Large individual differences in basal oxytocin levels and reactivity of the oxytocin system exist. This paper will review the literature to explore how individual differences in the oxytocin system arise and examine the hypothesis that this may mediate some of the individual differences in susceptibility to addiction and relapse. Differences in the oxytocin system can be based on individual factors, e.g. genetic variation especially in the oxytocin receptor, age or gender, or be the result of early environmental influences such as social experiences, stress or trauma. The paper addresses the factors that cause individual differences in the oxytocin system and the environmental factors that have been identified to induce long-term changes in the developing oxytocin system during different life phases. Individual differences in the oxytocin system can influence effects of drugs and alcohol directly or indirectly. The oxytocin system has bidirectional interactions with the stress-axis, autonomic nervous system, neurotransmitter systems (e.g. dopamine, serotonin and GABA/glutamate) and the immune system. These systems are all important, even vital, in different phases of addiction. It is suggested that early life adversity can change the development of the oxytocin system and the way it modulates other systems. This in turn could minimise the negative feedback loops that would normally exist. Individuals may show only minor differences in behaviour and function unless subsequent stressors or drug use challenges the system. It is postulated that at that time individual differences in oxytocin levels, reactivity of the system or interactions with other systems can influence general resilience, drug effects and the susceptibility to develop problematic drug and alcohol use.