A 32 year longitudinal study of child and adolescent pathways to well-being in adulthood

The purpose of the study was to investigate the relative importance of child and adolescent social and academic pathways to well-being in adulthood (32-years) indicated by a sense of meaning, social engagement, positive coping and prosocial values. Data were drawn from a 15 wave (32-year) longitudinal study of the health and development of around 1000 New Zealanders (Dunedin Multidisciplinary Health and Development Study, New Zealand). Moderate continuity in social connectedness (0.38) and high continuity in academic ability (0.90) was observed across childhood and adolescence. Adolescent social connectedness was a better predictor of adult well-being than academic achievement (0.62 vs. 0.12). There was evidence of an indirect pathway from adolescent academic achievement to adult well-being through social connectedness (0.29). Indicators of well-being in adulthood appear to be better explained by social connection rather than academic competencies pathways. Implications for promoting longer term well-being during the school years are discussed.

The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications

In some patients with major depressive disorder (MDD), individual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems, inflammatory, oxidative and nitrosative stress pathways, neurotrophins and regulation of neurogenesis, cortisol and the hypothalamic–pituitary–adrenal axis modulation, mitochondrial dysfunction and epigenetic and dietary influences. Evidence-based novel treatments informed by this knowledge are discussed.

New drug targets in depression : inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

This paper reviews new drug targets in the treatment of depression and new drug candidates to treat depression. Depression is characterized by aberrations in six intertwined pathways: (1) inflammatory pathways as indicated by increased levels of proinflammatory cytokines, e.g. interleukin-1 (IL-1), IL-6, and tumour necrosis factor α. (2) Activation of cell-mediated immune pathways as indicated by an increased production of interferon γ and neopterin. (3) Increased reactive oxygen and nitrogen species and damage by oxidative and nitrosative stress (O&NS), including lipid peroxidation, damage to DNA, proteins and mitochondria. (4) Lowered levels of key antioxidants, such as coenzyme Q10, zinc, vitamin E, glutathione, and glutathione peroxidase. (5) Damage to mitochondria and mitochondrial DNA and reduced activity of respiratory chain enzymes and adenosine triphosphate production. (6) Neuroprogression, which is the progressive process of neurodegeneration, apoptosis, and reduced neurogenesis and neuronal plasticity, phenomena that are probably caused by inflammation and O&NS. Antidepressants tend to normalize the above six pathways. Targeting these pathways has the potential to yield antidepressant effects, e.g. using cytokine antagonists, minocycline, Cox-2 inhibitors, statins, acetylsalicylic acid, ketamine, ω3 poly-unsaturated fatty acids, antioxidants, and neurotrophic factors. These six pathways offer new, pathophysiologically guided drug targets suggesting that novel therapies could be developed that target these six pathways simultaneously. Both nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators and glycogen synthase kinase-3 (GSK-3) inhibitors target the six above-mentioned pathways. GSK-3 inhibitors have antidepressant effects in animal models of depression. Nrf2 activators and GSK-3 inhibitors have the potential to be advanced to phase-2 clinical trials to examine whether they augment the efficacy of antidepressants or are useful as monotherapy.

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers.

Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways

There is now evidence that depression, as characterized by melancholic symptoms, anxiety, and fatigue and somatic (F&S) symptoms, is the clinical expression of peripheral cell-mediated activation, inflammation and induction of oxidative and nitrosative stress (IO&NS) pathways and of central microglial activation, decreased neurogenesis and increased apoptosis. This review gives an explanation for the multiple “co-morbidities” between depression and a large variety of a) brain disorders related to neurodegeneration, e.g. Alzheimer’s, Parkinson’s and Huntington’s disease, multiple sclerosis and stroke; b) medical disorders, such as cardiovascular disorder, chronic fatigue syndrome, chronic obstructive pulmonary disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, inflammatory bowel disease, irritable bowel syndrome, leaky gut, diabetes type 1 and 2, obesity and the metabolic syndrome, and HIV infection; and c) conditions, such as hemodialysis, interferon-α-based immunotherapy, the postnatal period and psychosocial stressors. The common denominator of all those disorders/conditions is the presence of microglial activation and/or activation of peripheral IO&NS pathways. There is evidence that shared peripheral and / or central IO&NS pathways underpin the pathophysiology of depression and the previously mentioned disorders and that activation of these IO&NS pathways contributes to shared risk. The IO&NS pathways function as a smoke sensor that detect threats in the peripheral and central parts of the body and signal these threats as melancholic, anxiety, and fatigue and somatic (F&S) symptoms. The presence of concomitant depression is strongly associated with a lower quality of life and increased morbidity and mortality in medical disorders. This may be explained since depression contributes to increased (neuro)inflammatory burden and may therefore drive the inflammatory and degenerative progression. It is concluded that the activation of peripheral and / or central IO&NS pathways may explain the co-occurrence of depression with the above disorders. This shows that depression belongs to the spectrum of inflammatory and degenerative disorders.

Reasons for referral to bone densitometry in men and women aged 20-49 years : population-based data

Introduction Osteoporosis poses a significant public health problem for ageing Australians. However, approximately 25 % of Australian adults aged 20–49 years have osteopenia, a precursor condition to osteoporosis. Despite this, little is known about bone density testing in this age group.

Methods Reasons for referral to dual energy X-ray absorptiometry (DXA) were examined in 2,264 patients aged 20–49 years, referred in 2001–2010 to the Geelong Bone Densitometry Service, Geelong Hospital, Victoria. Referral reasons were determined from clinical indication codes derived from patient records. Age, sex and bone mineral density (BMD) T scores were ascertained for each patient.

Results The most common reason for referral for women reflected glucocorticoid use, and for men reflected fracture. Compared to women, men were more likely to have been referred because of minimal trauma fracture or low BMD (41.7 versus 27.1 %, p < 0.001). No further differences were identified between the sexes, with similar numbers of referral observed for secondary osteoporosis, and monitoring of drug therapy. At the spine, and for all indications, men had a significantly greater BMD deficit compared to women (all p ≤ 0.002). After age adjustment, men who were tested due to fracture or glucocorticoid reasons had significantly greater BMD at the total hip (p ≤ 0.03). No further associations were seen after age adjustment between referral reason and BMD.

Conclusions Our study presents the first data examining reasons for referral to DXA among Australians aged 20–49 years. Understanding health service utilisation regarding bone health in young adults is fundamental to understanding future risk, informing effective public health messages and raising awareness of osteoporosis.

Measuring pathways to university : success factors in construction management education

Past research has shown that many students find navigating pathways from TAFE to university difficult. This paper proposes a framework for evaluating the success of the pathways. Student enrolled in higher education courses responded to a questionnaire on the nature of their experiences in VET and how this impacted on their decision to articulate to university. The survey covered a sample of three universities across Australia. The results showed that students generally had positive experiences, but that some pathways had better outcomes than others. The framework developed in this research is capable of identifying issue that lead to poor outcomes. The results indicate that matrix developed contained three factors that were good measures of the success of the pathways. The paper concludes by suggesting that universities need a greater awareness of the impact of pathways on identifying pipelines for their students.