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.

Detailed time course of the cortisol awakening response in healthy participants

Assessment of the cortisol awakening response: Real-time analysis and curvilinear effects of sample timing inaccuracy

The adrenal hormones cortisol and dehydroepiandrosterone (DHEA) share a common secretagogue: adrenocorticotropic hormone; however, secretion of these hormones can be dissociated suggesting subtle individual regulation at the level of the adrenal gland. We examined differences in the diurnal patterns of cortisol and DHEA secretion in healthy adolescent girls, with the aim of informing the possibility of exploiting these differences to aid interpretation of data from clinical populations in which these patterns can become dysregulated. Fifty-six healthy females aged 10-18 years provided saliva samples at 0 and 30 min (morning samples) and 12 h post-awakening on 2 consecutive weekdays. For morning salivary cortisol in relation to morning DHEA concentrations, correlational analysis revealed only a trend (p = 0.054). Similarly, the association between evening cortisol and DHEA was characterised as a trend (p = 0.084). Mean morning DHEA concentrations showed more day-to-day consistency than equivalent cortisol samples (r = 0.829 for DHEA and 0.468 for cortisol; z = 3.487, p < 0.0005). Unlike the cortisol pattern, characterised by a marked awakening response (cortisol awakening response, CAR), a significant rise in DHEA concentration post-awakening was not evident. Finally, there was a strong association between morning and evening concentrations of DHEA, not found for cortisol. The study shows differences in cortisol and DHEA secretion in the post-awakening period and informs work that seeks to examine correlates of dysregulated hypothalamic-pituitary-adrenal axis function. Parallel examination of both hormones enables enhanced interpretation of aberrant patterns of the CAR, i.e. an exploration of whether dysregulation affects both hormones (reflecting overall steroidogenic capacity) or cortisol alone (CAR-specific mechanisms).

Differences between diurnal patterns of salivary cortisol and dehydroepiandrosterone in healthy female adolescents

Retrieval-induced forgetting (RIF) refers to the finding that the retrieval of a memory trace suppresses the retrieval of rival memory traces, and there is evidence that RIF reflects the effects of cognitive inhibition. The Attentional Control Theory (ACT) postulates that cognitive inhibition will be impaired by a high level of state anxiety, but the effect of anxiety on RIF has not previously been investigated. A sample of 116 participants were tested on the RIF procedure, and were also administered the Spielberger State Anxiety Inventory and the Big Five Personality Inventory. The results indicated a significant negative correlation between RIF scores and state anxiety, and a significant positive correlation between RIF scores and extraversion. However, a multiple regression analysis identified extraversion as the main predictor of RIF performance. None of the other personality factors correlated with RIF scores. These findings are consistent with the predictions of the ACT.

Lisa Thorn

Papers

Detailed time course of the cortisol awakening response in healthy participants

Assessment of the cortisol awakening response: Real-time analysis and curvilinear effects of sample timing inaccuracy

Differences between diurnal patterns of salivary cortisol and dehydroepiandrosterone in healthy female adolescents

The relationship between retrieval-induced forgetting, anxiety, and personality

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy.