Depression is a multicausal disorder and has been associated with the risk to develop cancer, dementia, diabetes, epilepsy and stroke. As a metabolic disorder depression has been associated with obesity, diabetes, insulin sensitivity, neuropeptide Y, glucose regulation, poor glycemic control, glucagone-like peptide-1, cholezystokinin, ghrelin, leptin, the endocannabinoid system, insulin-like growth factor and gastrin-releasing peptide. As a cardiovascular disease a close relationship exists between depression and blood pressure, heart rate, norepinephrine, sympathetic tone, vascular resistance, blood viscosity, plasma volume, intima thickness and atherosclerosis. Additionally blood coagulation, fibrinolysis, D-dimers, plasminogen activator inhibitor-1 protein, platelet activation, VEGF, plasma nitric oxide and its synthase are changed in depressed patients. As an endocrinological and stress disorder depression has been connected with the concentration of free T4, TSH, CRH, arginine vasopressin, corticotrophin, corticosteroid release and ACTH. Depression as an inflammatory disorder is mediated by pro-inflammatory cytokines, interleukin-1, interleukin-6, TNF-alpha, soluble interleukin-2 receptors, interferon-alpha, interleukin 8, interleukin-10, hs-CRP, acute phase proteins, haptoglobin, toll like receptor 4, interleukin-1beta, mammalian target of rapamycin pathway, substance P, cyclooxygenase-2, prostaglandin-E2, lipid peroxidation levels and acid sphingomyelinase. Nutritional factors might influence depression risk, i.e. the consumption of folate, omega-3 fatty acids, monounsaturated fatty acids, olive oil, fish, fruits, vegetables, nuts, legumes, vitamin B6 and vitamin B12. The neurodegenerative hypothesis of depression explains decreased hippocampal volumes in depressed patients and changes of neurotrophic support by BDNF, erythropoietin, GDNF, FGF-2, NT3, NGF and growth hormone. In this context, a fast neuroprotective and antidepressant effect has also been observed by ketamine, which acts via the glutamatergic system. Hence, GABA, AMPA, EAAT, NMDA- and metabotropic glutamate receptors (mGluR1 to mGluR8) have gained interest in depression recently. Alternative, causative or also easy available treatment strategies beyond serotonin and noradrenaline reuptake inhibition might be a major topic of future psychiatric care. In this review, an attempt is made to overview concepts of the disease and search for perspectives on antidepressant treatment strategies beyond approved medications.

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Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies

Salivary cortisol as a biomarker in stress research.

The cortisol awakening response (CAR): Facts and future directions

The Adaptive Calibration Model of stress responsivity.

http://anthro.vancouver.wsu.edu/media/Course_files/anth-260-edward-h-hagen/chida-and-steptoe-2009-cortisol-awakening-response-and-psychosocial-factors-a-systematic-review-and-meta-analysis-1.pdf

Cortisol awakening response and psychosocial factors: a systematic review and meta-analysis.

The awakening cortisol response (ACR) is a discrete and distinctive part of the cortisol circadian cycle. In healthy adults salivary free cortisol concentrations increase by between 50 and 160% in the first 30 min immediately post-awakening (approximate average increase of 9 nmol/l, range 4-15 nmol/l, estimated to be equivalent to about three secretory episodes). However there are no agreed norms for the absolute concentrations of free cortisol in saliva either immediately post-awakening (range of 4.7-18.5 nmol/l) or 30 min post-awakening (range of 8.6-21.9 nmol/l). This review explores reasons for these discrepancies in normative data including confounding factors such as gender, age, awakening time, light and participant adherence. Although the physiological role of the ACR has not been clearly defined evidence is discussed that suggests it is under a distinct regulatory influence, different from the rest of the diurnal cortisol secretory cycle. Despite the difficulties associated with its measurement a range of studies have demonstrated an association between the ACR and psychosocial variables, stress and health. However it remains unclear whether positive affect and good health are consistently associated with larger or smaller awakening responses. It is early days in the search for the role and significance of the ACR. Its putative role in the regulation of physiological function across the day (e.g. the immune system) and its sensitivity to psychosocial variables make it a prime candidate as an intermediary linking mind and health.

The awakening cortisol response: Methodological issues and significance

The cortisol awakening response: more than a measure of HPA axis function.

The cortisol awakening response (CAR) is a crucial point of reference within the healthy cortisol circadian rhythm, with cortisol secretion typically peaking between 30 and 45 min post awakening This chapter reviews the history of investigation into the CAR and highlights evidence that its regulation is relatively distinct from cortisol secretion across the rest of the day It is initiated by awakening, under the influence of the hypothalamic suprachiasmatic nucleus, and "fine tuned" by a direct neural input to the adrenal cortex by the sympathetic nervous system This chapter also examples the CAR in relation to other awakening-induced processes, such as restoration of consciousness, attainment of full alertness, changes in other hormones, changes in the balance of the immune system, and mobilization of the motor system, and speculates that there is a role for the CAR in these processes

The cortisol awakening response in context.

Suspected non-adherence and weekend versus week day differences in the awakening cortisol response

http://www.lampe-de-luminotherapie.com/wp-content/uploads/effets-luminotherapie.pdf

Lisa Thorn

Papers

The awakening cortisol response: Methodological issues and significance

The cortisol awakening response: more than a measure of HPA axis function.

The cortisol awakening response in context.

Suspected non-adherence and weekend versus week day differences in the awakening cortisol response

The effect of dawn simulation on the cortisol response to awakening in healthy participants.