Psychiatry - Research Publications
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ItemEffects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The "Gut Feelings" randomised controlled trial(FRONTIERS MEDIA SA, 2023-02-06)BACKGROUND: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. METHODS: "Gut Feelings" was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. RESULTS: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen's d = -0.60, 95% confidence interval (CI) = -1.18, -0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = -0.19, 95% CI = -0.75, 0.38; p = 0.51) or synbiotic treatments (d = -0.03, 95% CI = -0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. CONCLUSION: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size. CLINICAL TRIAL REGISTRATION: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392.
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ItemA systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia(SPRINGERNATURE, 2022-04)The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.
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ItemThe association between self-reported diet quality and health-related quality of life in rural and urban Australian adolescents(WILEY, 2016-10)OBJECTIVE: This study examines the relationship between diet quality and health-related quality of life (HRQoL) in rural and urban Australian adolescents, and gender differences. DESIGN: Cross-sectional. SETTING: Secondary schools. PARTICIPANTS: 722 rural and 422 urban students from 19 secondary schools. MAIN OUTCOME MEASURES: Self-report dietary-related behaviours, demographic information, HRQoL (AQoL-6D) were collected. Healthy and unhealthy diet quality scores were calculated; multiple linear regression investigated associations between diet quality and HRQoL. RESULTS: Compared to urban students, rural students had higher HRQoL, higher healthy diet score, lower unhealthy diet score, consumed less soft drink and less frequently, less takeaway and a higher proportion consumed breakfast (P < 0.05). Overall, males had higher unhealthy diet score, poorer dietary behaviours but a higher HRQoL score compared to females (P < 0.05). In all students, final regression models indicated: a unit increase in healthy diet score was associated with an increase in HRQoL (unstandardised coefficient(B)±standard error(SE); B = 0.02 ± 0.01(SE); P < 0.02); and a unit increase in unhealthy diet scores was associated with a decrease in HRQoL (-0.01 ± 0.00; P < 0.05). In rural students alone, a unit increase in unhealthy diet score was associated with a decrease in HRQoL (B = -0.01 ± 0.00; P = 0.002), and in urban students a unit increase in healthy diet score was associated with an increase in HRQoL (B = 0.02 ± 0.00; P < 0.001). CONCLUSIONS: Cross-sectional associations between diet quality and HRQoL were observed. Dietary modification may offer a target to improve HRQoL and general well-being; and consequently the prevention and treatment of adolescent health problems. Such interventions should consider gender and locality.
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ItemHow cigarette smoking may increase the risk of anxiety symptoms and anxiety disorders: a critical review of biological pathways(WILEY, 2013-05)Multiple studies have demonstrated an association between cigarette smoking and increased anxiety symptoms or disorders, with early life exposures potentially predisposing to enhanced anxiety responses in later life. Explanatory models support a potential role for neurotransmitter systems, inflammation, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophins and neurogenesis, and epigenetic effects, in anxiety pathogenesis. All of these pathways are affected by exposure to cigarette smoke components, including nicotine and free radicals. This review critically examines and summarizes the literature exploring the role of these systems in increased anxiety and how exposure to cigarette smoke may contribute to this pathology at a biological level. Further, this review explores the effects of cigarette smoke on normal neurodevelopment and anxiety control, suggesting how exposure in early life (prenatal, infancy, and adolescence) may predispose to higher anxiety in later life. A large heterogenous literature was reviewed that detailed the association between cigarette smoking and anxiety symptoms and disorders with structural brain changes, inflammation, and cell-mediated immune markers, markers of oxidative and nitrosative stress, mitochondrial function, neurotransmitter systems, neurotrophins and neurogenesis. Some preliminary data were found for potential epigenetic effects. The literature provides some support for a potential interaction between cigarette smoking, anxiety symptoms and disorders, and the above pathways; however, limitations exist particularly in delineating causative effects. The literature also provides insight into potential effects of cigarette smoke, in particular nicotine, on neurodevelopment. The potential treatment implications of these findings are discussed in regards to future therapeutic targets for anxiety. The aforementioned pathways may help mediate increased anxiety seen in people who smoke. Further research into the specific actions of nicotine and other cigarette components on these pathways, and how these pathways interact, may provide insights that lead to new treatment for anxiety and a greater understanding of anxiety pathogenesis.
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ItemFood policies for physical and mental health(BMC, 2014-05-09)Noncommunicable diseases (NCDs) account for the largest burden of early mortality and are predicted to cost the global community more than US $30 trillion over the next 20 years. Unhealthy dietary habits, in large part driven by substantial changes to global food systems, are recognised as major contributors to many of the common NCDs, including cardiovascular disease, cancer and diabetes. Recent evidence now indicates that unhealthy diets are also risk factors for mental disorders, particularly depression and dementia. This affords substantial scope to leverage on the established and developing approaches to the nutrition-related NCDs to address the large global burden of these mental disorders and reinforces the imperative for governments take substantial actions in regards to improving the food environment and consequent population health via policy initiatives.
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ItemPop, heavy metal and the blues: secondary analysis of persistent organic pollutants (POP), heavy metals and depressive symptoms in the NHANES National Epidemiological Survey(BMJ PUBLISHING GROUP, 2014)OBJECTIVES: Persistent environmental pollutants, including heavy metals and persistent organic pollutants (POPs), have a ubiquitous presence. Many of these pollutants affect neurobiological processes, either accidentally or by design. The aim of this study was to explore the associations between assayed measures of POPs and heavy metals and depressive symptoms. We hypothesised that higher levels of pollutants and metals would be associated with depressive symptoms. SETTING: National Health and Nutrition Examination Survey (NHANES). PARTICIPANTS: A total of 15 140 eligible people were included across the three examined waves of NHANES. PRIMARY AND SECONDARY OUTCOME MEASURES: Depressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9), using a cut-off point of 9/10 as likely depression cases. Organic pollutants and heavy metals, including cadmium, lead and mercury, as well as polyfluorinated compounds (PFCs), pesticides, phenols and phthalates, were measured in blood or urine. RESULTS: Higher cadmium was positively associated with depression (adjusted Prevalence Ratios (PR)=1.48, 95% CI 1.16 to 1.90). Higher levels of mercury were negatively associated with depression (adjusted PR=0.62, 95% CI 0.50 to 0.78), and mercury was associated with increased fish consumption (n=5500, r=0.366, p<0.001). In addition, several PFCs (perfluorooctanoic acid, perfluorohexane sulfonic acid, perfluorodecanoic acid and perfluorononanoic acid) were negatively associated with the prevalence of depression. CONCLUSIONS: Cadmium was associated with an increased likelihood of depression. Contrary to hypotheses, many of persistent environmental pollutants were not associated or negatively associated with depression. While the inverse association between mercury and depressive symptoms may be explained by a protective role for fish consumption, the negative associations with other pollutants remains unclear. This exploratory study suggests the need for further investigation of the role of various agents and classes of agents in the pathophysiology of depression.
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ItemThe impact of maternal smoking during pregnancy on depressive and anxiety behaviors in children: the Norwegian Mother and Child Cohort Study(BMC, 2015-02-03)BACKGROUND: Maternal smoking during pregnancy (MSDP) is associated with multiple adverse childhood outcomes including externalizing behaviors. However, the association between MSDP and internalizing (anxiety and depressive) behaviors in offspring has received less investigation. We aimed to assess the association between MSDP and childhood internalizing (anxiety and depressive) behaviors in a very large, well-characterized cohort study. METHODS: We assessed the association between MSDP and internalizing behaviors in offspring utilizing information drawn from 90,040 mother-child pairs enrolled in the Norwegian Mother and Child Cohort Study. Mothers reported smoking information, including status and frequency of smoking, twice during pregnancy. Mothers also reported their child's internalizing behaviors at 18 months, 36 months, and 5 years. Associations between MSDP and childhood internalizing behaviors, including dose-response and timing of smoking in pregnancy, were assessed at each time point. RESULTS: MSDP was associated with increased internalizing behaviors when offspring were aged 18 months (B = 0.11, P <0.001) and 36 months (B = 0.06, P <0.01), adjusting for numerous potential confounders. Higher rates of smoking (e.g., >20 cigarettes per day) were associated with higher levels of internalizing behaviors. Maternal smoking during early pregnancy appeared to be the critical period for exposure. CONCLUSIONS: We found evidence supporting a potential role for MSDP in increasing internalizing (anxiety and depressive) behaviors in offspring. We also found evidence supportive of a possible causal relationship, including dose-dependency and support for a predominant role of early pregnancy exposure. Further investigation utilizing genetically informed designs are warranted to assess this association.
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ItemPrevention of mental disorders: evidence, challenges and opportunities(BIOMED CENTRAL LTD, 2014-05-09)Modelling studies suggest that less than 30% of the burden of mental disorders can be averted, even with optimal care and access to services. This points to the need to reduce the incidence of mental disorders, utilising evidence-based prevention strategies and policy action. In this cross-journal article collection (http://www.biomedcentral.com/series/PMD), the case for prevention is made by identifying initiatives with established efficacy, as well as opportunities and targets for the prevention of mental disorders in early life, in the workplace and at the population level. These articles provide reviews, systematic and narrative, outlining the evidence base for prevention approaches, as well as comment and debate designed to prompt discussion and a reconsideration of strategies for prevention. Barriers to expanding the research into prevention include the reluctance of governments and funding bodies to invest in research and policy action that may take many years to manifest benefits. The case for the cost-effectiveness of preventing mental disorders needs to be strongly argued and new cross-disciplinary, intersectoral initiatives and policies developed for the prevention of mental disorders across the lifespan.
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ItemThe Microbiome and Mental Health: Looking Back, Moving Forward with Lessons from Allergic Diseases(KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2016-05)Relationships between gastrointestinal viscera and human emotions have been documented by virtually all medical traditions known to date. The focus on this relationship has waxed and waned through the centuries, with noted surges in interest driven by cultural forces. Here we explore some of this history and the emerging trends in experimental and clinical research. In particular, we pay specific attention to how the hygiene hypothesis and emerging research on traditional dietary patterns has helped re-ignite interest in the use of microbes to support mental health. At present, the application of microbes and their structural parts as a means to positively influence mental health is an area filled with promise. However, there are many limitations within this new paradigm shift in neuropsychiatry. Impediments that could block translation of encouraging experimental studies include environmental forces that work toward dysbiosis, perhaps none more important than westernized dietary patterns. On the other hand, it is likely that specific dietary choices may amplify the value of future microbial-based therapeutics. Pre-clinical and clinical research involving microbiota and allergic disorders has predated recent work in psychiatry, an early start that provides valuable lessons. The microbiome is intimately connected to diet, nutrition, and other lifestyle variables; microbial-based psychopharmacology will need to consider this contextual application, otherwise the ceiling of clinical expectations will likely need to be lowered.
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