Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system

Dysregulations in the brain serotonergic system and exposure to environmental stressors have been implicated in the development of major depressive disorder. Here, we investigate the interactions between the stress and serotonergic systems by characterizing the behavioral and biochemical effects of chronic stress applied during early-life or adulthood in wild type (WT) mice and mice with deficient tryptophan hydroxylase 2 (TPH2) function. We showed that chronic mild stress applied in adulthood did not affect the behaviors and serotonin levels of WT and TPH2 knock-in (KI) mice. Whereas, maternal separation (MS) stress increased anxiety-and depressive-like behaviors of WT mice, with no detectable behavioral changes in TPH2, KI mice. Biochemically, we found that MS WT mice had reduced brain serotonin levels, which was attributed to increased expression of monoamine oxidase A (MAO A). The increased MAO A expression was detected in MS WT mice at 4 weeks old and adulthood. No change in TPH2 expression was detected. To determine whether a pharmacological stressor, dexamethasone (Dex), will result in similar biochemical results obtained from MS, we used an in vitro system, SH-SY5Y cells, and found that Dex treatment resulted in increased MAO A expression levels. We then treated WT mice with Dex for 5 days, either during postnatal days 7-11 or adulthood. Both groups of Dex treated WT mice had reduced basal corticosterone and glucocorticoid receptors expression levels. However, only Dex treatment during PND7-11 resulted in reduced serotonin levels and increased MAO A expression. Just as with MS WT mice, TPH2 expression in PND7-11, Dex-treated WT mice was unaffected. Taken together, our findings suggest that both environmental and pharmacological stressors affect the expression of MAO A, and not TPH2, when applied during the critical postnatal period. This leads to long-lasting perturbations in the serotonergic system, and results in anxiety-and depressive-like behaviors.

Should patients in a persistent vegetative state be allowed to die? Guidelines for a new standard of care in Australian hospitals

In this article we will be arguing in favour of legislating to protect doctors who bring about the deaths of PVS patients, regardless of whether the death is through passive means (e.g. the discontinuation of artificial feeding and respiration) or active means (e.g. through the administration of pharmaceuticals known to hasten death in end-of-life care). We will first discuss the ethical dilemmas doctors and lawmakers faced in the more famous PVS cases arising in the US and UK, before exploring what the law should be regarding such patients, particularly in Australia. We will continue by arguing in favour of allowing euthanasia in the interests of PVS patients, their families, and finally the wider community, before concluding with some suggestions for how these ethical arguments could be transformed into a set of guidelines for medical practice in this area.

Persistent and contemporaneous effects of job stressors on mental health: a study testing multiple analytic approaches across 13 waves of annually collected cohort data

OBJECTIVES: This study investigated the extent that psychosocial job stressors had lasting effects on a scaled measure of mental health. We applied econometric approaches to a longitudinal cohort to: (1) control for unmeasured individual effects; (2) assess the role of prior (lagged) exposures of job stressors on mental health and (3) the persistence of mental health.

METHODS: We used a panel study with 13 annual waves and applied fixed-effects, first-difference and fixed-effects Arellano-Bond models. The Short Form 36 (SF-36) Mental Health Component Summary score was the outcome variable and the key exposures included: job control, job demands, job insecurity and fairness of pay.

RESULTS: Results from the Arellano-Bond models suggest that greater fairness of pay (β-coefficient 0.34, 95% CI 0.23 to 0.45), job control (β-coefficient 0.15, 95% CI 0.10 to 0.20) and job security (β-coefficient 0.37, 95% CI 0.32 to 0.42) were contemporaneously associated with better mental health. Similar results were found for the fixed-effects and first-difference models. The Arellano-Bond model also showed persistent effects of individual mental health, whereby individuals' previous reports of mental health were related to their reporting in subsequent waves. The estimated long-run impact of job demands on mental health increased after accounting for time-related dynamics, while there were more minimal impacts for the other job stressor variables.

CONCLUSIONS: Our results showed that the majority of the effects of psychosocial job stressors on a scaled measure of mental health are contemporaneous except for job demands where accounting for the lagged dynamics was important.