Publications

Burnout is a prevalent and costly work-related condition characterized by four symptom dimensions: cognitive impairment, emotional impairment, mental distance and exhaustion. Although coping, coping flexibility, and cognitive flexibility have been linked to burnout, their unique contributions to its dimensions remain unclear. This longitudinal study used regression analyses to test whether coping, coping flexibility, and cognitive flexibility predict dimensions of burnout two weeks later, adjusting for covariates and baseline burnout. Participants were 337 Australian adults (62% women), aged 18-35, who were working or studying at least three days per week. Evaluation coping flexibility predicted lower cognitive impairment (B = -0.28, p = .003), and adaptive coping flexibility predicted greater exhaustion (B = 0.13, p = .458). Substance use as a coping strategy predicted greater emotional impairment (B = 0.31, p = .040) and behavioral disengagement as a coping strategy predicted greater mental distance (B = 0.26, p = .041) and exhaustion (B = 0.41, p < .001). Cognitive flexibility did not predict dimensions of burnout. Findings indicate that burnout risk is influenced by coping strategy use and coping flexibility, highlighting these as intervention targets.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) plays an important modulatory role in sodium and water homeostasis. Recent studies demonstrated that long-term treatment with GLP-1 receptor agonists (RAs) reduces fluid intake and urine output. To the best of our knowledge, no direct effect of GLP-1 on vasopressin has been observed. This secondary analysis aimed to investigate changes in copeptin levels in euvolemic participants treated with the GLP-1 RA dulaglutide versus placebo.

DESIGN: Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials in 34 patients with primary polydipsia and 20 healthy participants.

METHODS: Participants received a 3-week intervention with dulaglutide (Trulicity) 1.5 mg or placebo (.9% sodium chloride) subcutaneously once weekly. Blood for copeptin analysis was collected at 08:00 after each treatment phase. To estimate the treatment effect of dulaglutide, we derived the absolute within-subject differences of copeptin between dulaglutide and placebo and used the Wilcoxon rank test for statistical analysis.

RESULTS: All 54 participants of the two cross-over trials were included. Median age was 27 years [interquartile range (IQR), 24-37.5 years], and 63% were female. Median body mass index (BMI) was 23 kg/m2 (IQR, 20.8-24.8). After 3-week treatment, dulaglutide was associated with a significant suppression of copeptin with a median within-subject difference of -.7 pmol/L (p = .047), corresponding to a 12% reduction compared to placebo. Treatment-induced changes in copeptin were not significantly correlated with GLP-1-mediated reductions in blood pressure, BMI, or incidence of nausea.

CONCLUSIONS: Our analysis provides evidence that the GLP-1-RA dulaglutide inhibits the vasopressin system and proposes physiological mechanisms that may explain the role of GLP-1 in sodium and water balance.

BACKGROUND: Alcohol consumption was shown to increase endogenous fibroblast growth factor 21 (FGF21), but knowledge about the effect of alcohol cessation on FGF21 is limited. The effects of cigarette smoking and cessation on FGF21 levels are unknown. The objective of this study was to investigate moderate alcohol and cigarette consumption and their cessation on FGF21 levels.

METHODS: This is a secondary analysis of two prospective intervention studies. Study 1: ten healthy men undergoing a beer or water intervention with blood sampling over 720 min. Differences in FGF21 levels between alcohol and water intake were assessed using a mixed-effect model. Study 2: 144 alcohol-drinking men or women undergoing a 12-week intervention of glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide vs placebo on smoking and alcohol cessation. Differences in FGF21 levels after 12 weeks of treatment with GLP-1 in persistent drinkers/smokers compared to those who had stopped drinking/smoking, were assessed using mixed-effect models.

RESULTS: Study 1: FGF21 levels at 240 min following beer intake were higher compared to water intake (1.386.0 pg/mL (95% CI: 934.55; 1,837.44), P < 0.001). Study 2: participants who stopped drinking alcohol had lower FGF21 levels compared to persistent drinkers (-228.65 pg/mL (95% CI: -440.4; -14.6), P = 0.03). Smoking cessation had no effect on FGF21 levels (P = 0.13).

CONCLUSION: Our findings demonstrate a dynamic response in FGF21 levels, with acute moderate alcohol consumption inducing elevated FGF21 levels, and cessation of drinking lowering FGF21 levels, indicative of potential liver recovery. No effect of cigarette smoking cessation on plasma FGF21 levels was observed.

BACKGROUND: Exogenous oxytocin (OT) reduces reward-driven food intake. Less is known about endogenous OT and eating behaviour. Preclinical studies suggest peripheral OT levels may reflect the opposite of central appetite-related OT activity. In healthy females, circulating OT declines after eating. Whether this pattern exists in obesity and how endogenous OT relates to hedonic eating remains unclear. We hypothesised that OT would decrease postprandially in adults with obesity and that higher OT exposure, reflecting lower central OT signalling, would correlate with greater reward-driven caloric intake.

METHODS: Sixty-one adults with obesity (56% female; age [mean ± SE] 33.55 ± 0.81 years; BMI 36.77 ± 0.62 kg/m2) consumed a standardised meal following an overnight fast. OT was measured in peripheral blood pre-meal and 30, 60, and 120 min post-meal. Area under the curve (AUC) was calculated to capture OT exposure. Postprandial hedonic eating drive was assessed via visual analogue scales (VAS) and Cookie Taste Test (CTT). Meal-related OT dynamics were analysed using linear mixed effects models, relationships between OT exposure and hedonic eating drive were examined with linear regression and mediation analyses.

RESULTS: OT levels did not change in response to the meal. Greater OT AUC was associated with reduced postprandial satisfaction (p = 0.008, d = 1.00) and higher CTT caloric intake (p = 0.036, d = 0.62). The relationship between OT AUC and CTT caloric intake was mediated by OT's effect on postprandial satisfaction (p = 0.014, proportion mediated = 53.28%).

CONCLUSIONS: In obesity, OT levels did not change postprandially. Greater OT exposure was linked to lower satisfaction and increased hedonic eating, suggesting dysregulated OT signalling in obesity potentially contributing to overeating.

BACKGROUND: The menopausal transition (MT) represents a period of increased risk for depressive symptoms. Emergence of these symptoms may reflect dysregulations in affect caused by fundamental MT characteristics, particularly sleep disturbance, estradiol decline, and vasomotor symptoms (VMS). Using an experimental paradigm mimicking menopause, we examined the effects of MT-related characteristics on affect.

METHODS: 38 premenopausal women without affective disorders completed a 6-day experimental paradigm comprising 2 nights of unfragmented sleep followed by 3 nights of provoked sleep fragmentation, during the high-estradiol mid-to-late-follicular menstrual phase. A subset (n = 27) repeated the paradigm after leuprolide-suppressed estradiol (low-estradiol). Positive affect (PA) and negative affect (NA) ratings were obtained daily using the Positive and Negative Affect Schedule.

RESULTS: Sleep fragmentation adversely influenced PA and NA acutely after one night of fragmentation (p < 0.007). This effect persisted following 3 nights of sleep fragmentation for NA (p = 0.02), but not PA (p = 0.46). Conversely, estradiol suppression increased PA (p = 0.0.03) but not NA (p = 0.51). In the low-estradiol condition, women who developed VMS trended toward having a more pronounced and sustained reduction in PA over three nights of sleep fragmentation compared to those who did not (p = 0.09).

CONCLUSIONS: Our findings show that MT-related characteristics significantly disrupt both positive and negative affect, potentially underlying emergence of depressive symptoms during this reproductive stage. We observed differential effects on positive and negative affect, with sleep fragmentation having a greater effect on NA and estradiol and VMS having a greater effect on PA, suggesting benefit for tailoring interventions that target specific types of affect regulation.

BACKGROUND: Australia has one of the highest rates of cannabis use globally, yet the concentration of Δ9-tetrahydrocannabinol (THC) of illicit street cannabis has not been formally assessed in over a decade. We aimed to comprehensively profile the concentration of THC, cannabidiol (CBD) and other cannabinoids in contemporary illicit street cannabis in regional Australia, assess variation over time, and examine how the amount of THC relates to consumer's perceived product strength.

METHODS: Participants donated two 1-gram samples of cannabis at 3 different timepoints (i.e., 6 samples total) ∼9-weeks apart, over 5 months. High-performance liquid chromatography quantified the concentrations of THC, CBD, cannabigerol, cannabichromene, cannabinol, tetrahydrocannabivarin, and their plant-based carboxylic acid precursors (THCA, CBDA, CBGA, CBNA, THCVA) in percentage and milligrams.

RESULTS: Thirty-seven participants donated 127 cannabis samples. On average, one cannabis gram contained 34.8 mg THC (6.96 Standard THC units), 12.00 % total THC (THC+(THCA*0.877)), and 0.30 % total CBD (CBD+(CBDA*0.877)). THC concentrations remained stable across participants' current and past samples over time (p > 0.05). Finally, no correlation was found between participants' subjective assessments of cannabis strength and THC or total THC content in the same product (p > 0.05).

CONCLUSIONS: Contemporary illicit street cannabis in regional Australia is high in THC and low in CBD. The concentration of THC is lower than international trends but appears to have increased compared to reports on illicit Australian cannabis collected over 10 years ago, while low concentrations of CBD have remained stable over time. Perceived cannabis strength may be influenced by factors beyond measurable THC concentrations, such as individual tolerance, consumption methods, or consumer expectations.

Existing models are currently inadequate in explaining the relationship between habitual decision-making and different expressions of addictive behaviors. The current study investigates the role of psychological distress as a key factor in disrupting decision-making processes in the context of substance and behavioral addictions. A large community sample (N = 668) completed a gamified two-stage task to investigate the link between model-free (habitual) task behavior and a wide range of addictive behaviors. Addictive behaviors included substance use (alcohol, nicotine, and illicit drug use) and behavioral addictions (problematic use of the internet, addictive eating, shopping, and gambling). The relationship between habitual task behavior and addictive engagement was investigated using structural equation modelling with a bifactor latent variable structure, which was modeled and tested; one for substance use and one for behavioral addictions. For participants with higher levels of psychological distress, greater habitual task behavior was a significant predictor of behavioral addiction risk (β = -0.188, SE = 2.061, p = .016), specifically problematic use of the internet (β = -0.148, SE = 0.045, p = .018) and eating behaviors (β = -0.191, SE = 0.016, p < .001). These findings support our proposition that psychological distress disrupts cognitive control, leading to a greater reliance on habitual decision-making and non-substance addictive behaviors. This highlights the potential importance of habit-based interventions in combination with stress-reduction and mental health-promoting techniques to improve outcomes and minimize harm, especially in the context of behavioral addictions.

Sex differences in the prevalence of substance use disorders (SUD) are well recognized. While a greater proportion of males endorse consuming substances and SUDs, the gap between the sexes has been narrowing over time, due to an increased rate of substance use among females. Yet, the mechanisms underlying sex differences in SUD are unclear, and evidence is lacking to inform the development of personalised preventions and treatment for males and females. The neuroscientific evidence to date is inadequate to explain sex differences in SUD, due to a range of methodological issues (eg, study design, recruitment, and statistical modelling). A harmonised multidisciplinary approach that considers sex at each stage of the research cycle is required to create new mechanistic knowledge and to inform the identification of prevention and treatment targets for males and females with an SUD.

Individual differences in neural circuits underlying emotional regulation, motivation, and decision-making are implicated in many psychiatric illnesses. Interindividual variability in these circuits may manifest, at least in part, as individual differences in impulsivity at both normative and clinically significant levels. Impulsivity reflects a tendency towards rapid, unplanned reactions to internal or external stimuli without considering potential negative consequences coupled with difficulty inhibiting responses. Here, we use multivariate brain-based predictive models to explore the neural bases of impulsivity across multiple behavioral scales, neuroanatomical features (cortical thickness, surface area, and gray matter volume), and sexes (females and males) in a large sample of youth from the Adolescent Brain Cognitive Development (ABCD) Study at baseline (n = 9,099) and two-year follow-up (n = 6,432). Impulsivity is significantly associated with neuroanatomical variability, and these associations vary across behavioral scales and neuroanatomical features. Impulsivity broadly maps onto cortical thickness in dispersed regions (e.g., inferior frontal, lateral occipital, superior frontal, entorhinal), as well as surface area and gray matter volume in specific medial (e.g., parahippocampal, cingulate) and polar (e.g., frontal and temporal) territories. Importantly, while many relationships are stable across sexes, others are sex-specific. These results highlight the complexity of the relationships between neuroanatomy and impulsivity across scales, features, sexes, and time points in youth. These findings suggest that neuroanatomy, in combination with other biological and environmental factors, reflects a key driver of individual differences in impulsivity in youth. As such, neuroanatomical markers may help identify youth at increased risk for developing impulsivity-related illnesses. Furthermore, this work emphasizes the importance of adopting a multidimensional and sex-specific approach in neuroimaging and behavioral research.