Stress, inflammation, and cellular vulnerability during early stages of affective disorders: biomarker strategies and opportunities for prevention and intervention

The mood disorder prodrome is conceptualized as a symptomatic, but not yet clinically diagnosable stage of an affective disorder. Although a growing area, more focused research is needed in the pediatric population to better characterize psychopathological symptoms and biological markers that can reliably identify this very early stage in the evolution of mood disorder pathology. Such information will facilitate early prevention and intervention, which has the potential to affect a person’s disease course.This review focuses on the prodromal characteristics, risk factors, and neurobiological mechanisms of mood disorders. In particular, we consider the influence of early-life stress, inflammation, and allostatic load in mediating neural mechanisms of neuroprogression. These inherently modifiable factors have known neuroadaptive and neurodegenerative implications, and consequently may provide useful biomarker targets. Identification of these factors early in the course of the disease will accordingly allow for the introduction of early interventions which augment an individual’s capacity for psychological resilience through maintenance of synaptic integrity and cellular resilience. A targeted and complementary approach to boosting both psychological and physiological resilience simultaneously during the prodromal stage of mood disorder pathology has the greatest promise for optimizing the neurodevelopmental potential of those individuals at risk of disabling mood disorders.

Gastrointestinal microbiota in autistic spectrum disorder

In this thesis, gut bacteria of children with autism were examined. The results provided new information and a compelling picture of the gut bacteria of children with autism and gastrointestinal symptomatology. The mechanisms that underlie gut dysfunction might involve factors like stress-induced changes in gut physiology associated with autism.

Gratitude : a basis for positive psychology interventions with a clinical population

This thesis includes a literature review that summarises the types of psychological research that have been conducted into gratitude, including the research conceptualising and developing assessments around it and exploring its associations with wellbeing, personality, social interaction, and health. The review focuses specifically on the research examining the relationship of gratitude to anxiety, depression and sleep, providing an outline of current theories about the relationship of positive affect to wellbeing, and a summary of the evidence to date. It is noted that there is comparatively little research on the impact of gratitude on anxiety and sleep but promising findings about the role of gratitude in the treatment of depression. Taken together, it is argued, the current research supported the need for trials of gratitude interventions specifically with clinical populations. Finally, the review looks at the literature of experimental interventions using gratitude. Particular emphasis is given to what has been learnt through these trials that might guide the focus and design of future research.

There follows the report of a randomized wait-list controlled pre-post trial of a gratitude diary intended to extend the research into the efficacy of gratitude diaries in the treatment of clinical populations with depression, anxiety and sleep difficulties. It was hypothesised that after completing a brief gratitude diary for three weeks, participants would have lower scores on measures of depression, anxiety, and perceived sleep difficulties, and higher scores on a measure of life satisfaction. These results were also expected to be evident at three-week follow-up. In a randomised waitlist-controlled trial with repeated measures pre-, post- and follow-up design, participants (N=109, from Australia) aged 18-64 years with a current self-reported diagnosis of an anxiety disorder and/or depression, took part in a self-help study via the internet. After completing the diary participants had lower scores on measures of depression, anxiety and perceived sleep difficulties and higher scores on a measure of subjective wellbeing than immediately pre-intervention. In addition, they had improved scores on a measure of stress. At three-week follow-up scores on depression and perceived sleep difficulties were no longer significantly different from pre-intervention, however improvements for subjective wellbeing and stress at post-intervention were maintained. At follow-up scores for anxiety had not only been maintained but had improved significantly beyond post-intervention results. This trial provides support for the use of gratitude diaries as a short-term intervention with a clinical population. Different patterns of anxiety and depression scores raise the possibility that gratitude interventions work differently to address depression and anxiety symptoms and provide support for the idea that gratitude interventions may have sustainable effects on anxiety symptoms.

Neurobiology of schizophrenia spectrum disorders: The role of oxidative stress

Mitochondrial dysfunction and oxidative stress are increasingly implicated in the pathophysiology of schizophrenia. The brain is the body's highest energy consumer, and the glutathione system is the brain's dominant free radical scavenger. In the current paper, we review the evidence of central and peripheral nervous system anomalies in the oxidative defences of individuals with schizophrenia, principally involving the glutathione system. This is reflected by evidence of the manifold consequences of oxidative stress that include lipid peroxidation, protein carboxylation, DNA damage and apoptosis - all potentially part of the process of neuroprogression in the disorder. Importantly, oxidative stress is amenable to intervention. We consider the clinical potential of some possible interventions that help reduce oxidative stress, via augmentation of the glutathione system, particularly N-acetyl cysteine. We argue that a better understanding of the mechanisms and pathways underlying oxidative stress will assist in developing the therapeutic potential of this area.

Police officers' perceptions of the challenges involved in internet child exploitation investigation

Purpose
The purpose of this paper is to explore police officers’ perceptions of the challenges and work stressors of working in Internet Child Exploitation (ICE) investigation.

Design/methodology/approach
Participants were a heterogeneous sample of 32 ICE investigators across nine Australian jurisdictions. Officers’ perceptions of ICE work were elicited via individual, open-ended, anonymous, telephone interviews, which focused on both the nature and impact of work-related stressors and challenges.

Findings
Thematic analysis revealed that viewing ICE material was not perceived to be a major stressor or particularly traumatic facet of ICE investigation. Rather, the challenges related to three areas; work relationships, workload and resources and the physical environment. Participants also suggested some improvements to their work environment which could reduce the impact of these challenges.

Practical implications
The stressors identified by ICE investigators in this study place physical, psychological and social restrictions on investigative capacity. Modifications to the workplace environment that facilitate more effective professional collaboration, reduce workload and enhance investigator efficiency and functionality of the physical work environment would likely reduce the potential for harm associated with ICE investigation and improve ICE investigators’ capacity to perform their role.

Originality/value

Acute effect of sorghum flour-containing pasta on plasma total polyphenols, antioxidant capacity and oxidative stress markers in healthy subjects: a randomised controlled trial

SUMMARY
Background & aims
It has been previously reported that pasta containing wholegrain sorghum flour exhibits high content of polyphenols and antioxidant capacity and hence might enhance antioxidant status and reduce markers of oxidative stress in vivo; however no clinical studies have yet been reported. Therefore, the present study assessed the effect of pasta containing red or white wholegrain sorghum flour on plasma total polyphenols, antioxidant capacity and oxidative stress markers in humans. The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN: 12612000324819).

Methods
In a randomised crossover design, healthy subjects (n = 20) consumed three test meals of control pasta (CP), 30% red sorghum pasta (RSP) or 30% white sorghum pasta (WSP), 1–2 wk apart. The test meals were consumed as breakfast after an overnight fast. Blood samples were obtained at fasting and 2 h after consumption and analysed for total polyphenols, antioxidant capacity, superoxide dismutase (SOD) activity, protein carbonyl and 8-isoprostanes.

Results
Compared to baseline, the 2 h post-prandial levels following the RSP meal of plasma polyphenols, antioxidant capacity and SOD activity were significantly (P < 0.001) higher while the protein carbonyl level was significantly lower (P = 0.035). Furthermore, net changes in polyphenols, antioxidant capacity and SOD activity were significantly (P < 0.001) higher while protein carbonyl were significantly (P = 0.035) lower following consumption of the RSP meal than the CP meal.

Conclusion
The results demonstrated that pasta containing red wholegrain sorghum flour enhanced antioxidant status and diminished marker of oxidative stress in healthy subjects.

Towards stage specific treatments: Effects of duration of illness on therapeutic response to adjunctive treatment with N-acetyl cysteine in schizophrenia.

Schizophrenia is a chronic and often debilitating disorder in which stage of illness appears to influence course, outcome, prognosis and treatment response. Current evidence suggests roles for oxidative, neuroinflammatory, neurotrophic, apoptotic, mitochondrial and glutamatergic systems in the disorder; all targets of N-acetyl cysteine (NAC). A double blind, placebo controlled trial suggested NAC to be beneficial to those diagnosed with schizophrenia. The current manuscript aims to investigate duration of the illness as a key factor that may be modulating the response to NAC in the participants who took part in the study. A sample of 121 participants were randomized in a double fashion to 24weeks (placebo=62; NAC=59). Clinical and functional variables were collected over the treatment period. Duration of the illness at baseline was grouped into <10years, 10-<20years and >20years. Mixed Model Repeated Measures Analysis was used to explore the effect of illness duration on response to treatment with NAC. A significant interaction between duration of the illness and response to treatment with NAC was consistently found for positive symptoms and functional variables, but not for negative or general symptoms or for side effects related outcomes. The pattern of changes suggests this mediator effect of duration of illness in response to treatment is more evident in those participants with 20years or more of illness duration. Our results suggest a potential advantage of adjunctive NAC over placebo on functioning and positive symptoms reduction in those patients with chronic schizophrenia. This has potential for suggesting stage specific treatments.

SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study.

The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case-control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide < 6 ppm. SLC6A4 gene STin2 VNTR polymorphism was assessed using a Multiplex-PCR-based method. At baseline, participants were evaluated using the Fagerström Test for Nicotine Dependence (FTND) and the ASSIST scale.

Staging systems in bipolar disorder: an International Society for Bipolar Disorders Task Force report

We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined.

Are urinary porphyrins a valid diagnostic biomarker of autism spectrum disorder?

A fundamental challenge to the timely diagnosis of Autism Spectrum Disorder (ASD) is the reliance on the observation of a set of aberrant behavior. Consequently, the diagnostic process requires that the child reach an age where the behaviors would typically be exhibited. The identification of a reliable biological marker (biomarker) could be of considerable benefit to the diagnostic process. As a diagnostic biomarker, porphyrins present an attractive prospect as previous studies have reported consistent findings of children with ASD showing significant elevations in porphyrin levels in contrast to controls. Furthermore, there is some evidence that ASD severity may be associated with porphyrins, which would be a valuable characteristic of any ASD biomarker. Importantly, for practical use, porphyrins can be tested non-invasively via a sample of urine. The present study sought to investigate whether porphyrin profiles can reliably be used to (a) differentiate ASD cases from healthy controls; and (b) predict ASD severity. The study compared the porphyrin levels of three groups of children aged 2-6 years: Group 1-children diagnosed with ASD (n = 70); Group 2-healthy, normally developing siblings of children diagnosed with ASD (n = 36); and Group 3-healthy, normally developing children with no known blood relative diagnosed with ASD (n = 54). The results of logistic regression analyses failed to find support for the hypotheses that porphyrin levels could be used as a valid tool to detect ASD cases or predict severity. Autism Res 2014, 7: 535-542. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.