The well-being of medical students: A biopsychosocial approach.

OBJECTIVE: Mental health problems among medical students have been widely reported, but the predisposing and perpetuating factors and biological concomitants are poorly understood. Adopting a biopsychosocial approach, we studied well-being in a group of Australian medical students, focusing on sleep, autonomic and immune mechanisms, as well as mental, social and physical well-being, health-related behaviours, and daily functioning. METHODS: Fourth-year medical students (N = 151) completed comprehensive assessments, including laboratory-based and nocturnal autonomic monitoring via ambulatory bioharness, a psychiatric diagnostic interview, and questionnaires assessing sleep quality and psychosocial and physical well-being. A blood sample was taken to quantify the inflammatory marker C-reactive protein. Sleep, mood and activity was additionally monitored daily for 7 days. RESULTS: A sizable minority of students reported diminished physical, mental and psychosocial well-being. We also found concerning levels of sleep disturbance and social and occupational impairment in a subset of students. The strong co-occurrence of problems across symptom domains supported a biopsychosocial interdependence of health and well-being states. Maladaptive coping behaviours were apparent, notably hazardous alcohol consumption, which was associated with a clinically significant elevation in C-reactive protein levels (> 3 mg/L). We documented, for the first time, significantly diminished nocturnal heart rate variability in medical students with a mental health diagnosis. Nocturnal heart rate variability was strongly associated with sleep quality, daytime autonomic stress reactivity, as well as occupational and social functioning. CONCLUSION: Well-being is a multifaceted phenomenon firmly interlinked with sleep, autonomic and immune function, health behaviours and functional outcomes. Our novel findings supported a key role for nocturnal autonomic function in promoting sleep quality and mental well-being. Interventions could focus on sleep hygiene and health behaviours as a buffer for well-being and teach more adaptive strategies for coping with the stresses of medical training.

The effect of short-term exposure to energy-matched diets enriched in fat or sugar on memory, gut microbiota and markers of brain inflammation and plasticity.

Short-term exposure to high-energy diets impairs memory but there is little data on the relative contributions of fat and sugar to these deficits or the mechanisms responsible. Here, we investigated how these different macronutrients affect memory, neuroinflammation and neuroplasticity markers and the gut microbiota. Rats were fed matched purified diets for 2weeks; Control, Sugar, Saturated Fatty Acid (SFA) or Polyunsaturated Fatty Acid (PUFA), which varied only in the percentage of energy available from sugar and the amount and type of fat. Rats consuming SFA and Sugar were impaired on hippocampal-dependent place recognition memory compared to Controls and PUFA rats, despite all rats consuming similar amounts of energy. All rats performed comparably on the object recognition task. Hippocampal and hypothalamic inflammatory markers were not substantially affected by the diets and there was no change in the neuroplasticity marker, brain-derived neurotrophic factor. Each of the diets significantly altered the microbial composition in distinct ways. Specifically, the relative abundance of 89 taxa differed significantly between groups with the majority of these changes accounted for by the Clostridiales order and within that, Lachnospiraceae and Ruminococcaceae. These taxa showed a range of macronutrient specific correlations with place memory. In addition, Distance based Linear Models found relationships between memory, inflammation-related hippocampal genes and the gut microbiota. In conclusion, our study shows that the macronutrient profile of the diet is crucial for diet-induced memory deficits and suggests a possible link between diet, the gut microbiota and hippocampal inflammatory genes.

Short exposure to a diet rich in both fat and sugar or sugar alone impairs place, but not object recognition memory in rats.

High energy diets have been shown to impair cognition however, the rapidity of these effects, and the dietary component/s responsible are currently unclear. We conducted two experiments in rats to examine the effects of short-term exposure to a diet rich in sugar and fat or rich in sugar on object (perirhinal-dependent) and place (hippocampal-dependent) recognition memory, and the role of inflammatory mediators in these responses. In Experiment 1, rats fed a cafeteria style diet containing chow supplemented with lard, cakes, biscuits, and a 10% sucrose solution performed worse on the place, but not the object recognition task, than chow fed control rats when tested after 5, 11, and 20 days. In Experiment 2, rats fed the cafeteria style diet either with or without sucrose and rats fed chow supplemented with sucrose also performed worse on the place, but not the object recognition task when tested after 5, 11, and 20 days. Rats fed the cafeteria diets consumed five times more energy than control rats and exhibited increased plasma leptin, insulin and triglyceride concentrations; these were not affected in the sucrose only rats. Rats exposed to sucrose exhibited both increased hippocampal inflammation (TNF-α and IL-1ß mRNA) and oxidative stress, as indicated by an upregulation of NRF1 mRNA compared to control rats. In contrast, these markers were not significantly elevated in rats that received the cafeteria diet without added sucrose. Hippocampal BDNF and neuritin mRNA were similar across all groups. These results show that relatively short exposures to diets rich in both fat and sugar or rich in sugar, impair hippocampal-dependent place recognition memory prior to the emergence of weight differences, and suggest a role for oxidative stress and neuroinflammation in this impairment.

Maltodextrin can produce similar metabolic and cognitive effects to those of sucrose in the rat.

In the context of the well-documented metabolic and behavioural effects of supplementing rats' diets with access to a sucrose solution, the aim of this study was to compare the impact of 10% sucrose with that of an isoenergetic (10.4%) solution of hydrolysed starch, maltodextrin. This polysaccharide is metabolised at least as rapidly as sucrose and is also very palatable to rats, but does not contain fructose. Each of three experiments contained three groups: one given a sucrose solution, one given a maltodextrin solution and a control group maintained on standard chow and water alone. In Experiment 1 the sucrose and maltodextrin groups were given their supplementary drinks for 2 h each day, while in Experiments 2 and 3 these groups had 24-h access to their supplements. Ad libitum access to maltodextrin produced at least as rapid weight gain as sucrose and in Experiment 2 retroperitoneal fat mass was greater in the two carbohydrate groups than in the control group. Moreover, in Experiment 3, impaired performance on a location recognition task was also found in both carbohydrate groups after only 17 days on the diets. These results indicate that the harmful effects of excess sucrose consumption can also be produced by another rapidly absorbed carbohydrate that does not contain fructose.

Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome.

STUDY OBJECTIVES: Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS. METHODS: Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants' homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality. RESULTS: Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep. Poorer self-reported wellbeing and sleep quality was associated with reduced parasympathetic signaling during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS. CONCLUSIONS: Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS.

Personalised relaxation practice to improve sleep and functioning in patients with chronic fatigue syndrome and depression: study protocol for a randomised controlled trial.

BACKGROUND: Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) are both debilitating but heterogeneous conditions sharing core features of fatigue, unrefreshing sleep, and impaired functioning. The aetiology of these conditions is not fully understood, and 'best-practice' treatments are only moderately effective in relieving symptoms. Unrecognised individual differences in the response to such treatments are likely to underlie poor treatment outcomes. METHODS/DESIGN: We are undertaking a two-group, parallel, randomised controlled trial (RCT) comparing the effects of a personalised relaxation intervention on sleep quality, daytime symptoms, and functioning in patients with CFS (n = 64) and MDD (n = 64). Following identification of the method that best enhances autonomic responding (such as heart rate variability), participants randomised to the active intervention will practise their recommended method nightly for 4 weeks. All participants will keep a sleep diary and monitor symptoms during the trial period, and they will complete two face-to-face assessments, one at baseline and one at 4 weeks, and a further online assessment to evaluate lasting effects of the intervention at 2 months. Assessments include self-report measures of sleep, wellbeing, and function and monitoring of autonomic responses at rest, in response to the relaxation method and during nocturnal sleep. Treatment outcomes will be analysed using linear mixed modelling. DISCUSSION: This is the first RCT examining the effects of a personalised relaxation intervention, pre-tested to maximise the autonomic relaxation response, in patients with unrefreshing sleep and fatigue attributed to CFS or MDD. Detailed monitoring of sleep quality and symptoms will enable sensitive detection of improvements in the core symptoms of these debilitating conditions. In addition, repeated monitoring of autonomic functioning can elucidate mechanisms underlying potential benefits. The findings have translational potential, informing novel, personalised symptom management techniques for these conditions, with the potential for better clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR), ACTRN12616001671459 . Registered on 5 December 2016.

Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions.

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

Why is obesity such a problem in the 21st century? The intersection of palatable food, cues and reward pathways, stress, and cognition.

Changes in food composition and availability have contributed to the dramatic increase in obesity over the past 30-40 years in developed and, increasingly, in developing countries. The brain plays a critical role in regulating energy balance. Some human studies have demonstrated increased preference for high fat and high sugar foods in people reporting greater stress exposure. We have examined neurochemical changes in the brain in rodent models during the development of obesity, including the impact of obesity on cognition, reward neurocircuitry and stress responsiveness. Using supermarket foods high in fat and sugar, we showed that such a diet leads to changes in neurotransmitters involved in the hedonic appraisal of foods, indicative of an addiction-like capacity of foods high in fat and/or sugar. Importantly, withdrawal of the palatable diet led to a stress-like response. Furthermore, access to this palatable diet attenuated the physiological effects of acute stress (restraint), indicating that it could act as a comfort food. In more chronic studies, the diet also attenuated anxiety-like behavior in rats exposed to stress (maternal separation) early in life, but these rats may suffer greater metabolic harm than rats exposed to the early life stressor but not provided with the palatable diet. Impairments in cognitive function have been associated with obesity in both people and rodents. However, as little as 1 week of exposure to a high fat, high sugar diet selectively impaired place but not object recognition memory in the rat. Excess sugar alone had similar effects, and both diets were linked to increased inflammatory markers in the hippocampus, a critical region involved in memory. Obesity-related inflammatory changes have been found in the human brain. Ongoing work examines interventions to prevent or reverse diet-induced cognitive impairments. These data have implications for minimizing harm caused by unhealthy eating.