Metabolic syndrome and major depression

Abstract

Major depression is associated with a 4-fold increased risk for premature death, largely accounted by cardiovascular disease (CVD). The relationship between depression and CVD is thought to be mediated by the so-called metabolic syndrome (MeS). Epidemiological studies have consistently demonstrated a co-occurrence of depression with MeS components, ie, visceral obesity, dyslipidemia, insulin resistance, and hypertension. Although the exact mechanisms linking MeS to depression are unclear, different hypotheses have been put forward. On the one hand, MeS could be the hallmark of the unhealthy lifestyle habits of depressed patients. On the other, MeS and depression might share common alterations of the stress system, including the hypothalamus-pituitary-adrenal (HPA) axis, the autonomic nervous system, the immune system, and platelet and endothelial function. Both the conditions induce a low grade chronic inflammatory state that, in turn, leads to increased oxidative and nitrosative (O&NS) damage of neurons, pancreatic cells, and endothelium. Recently, neurobiological research revealed that peripheral hormones, such as leptin and ghrelin, which are classically involved in homeostatic energy balance, may play a role in mood regulation. Metabolic risk should be routinely assessed in depressed patients and taken into account in therapeutic decisions. Alternative targets should be considered for innovative antidepressant agents, including cytokines and their receptors, intracellular inflammatory mediators, glucocorticoids receptors, O&NS pathways, and peripheral mediators.

KBP-042 improves bodyweight and glucose homeostasis with indices of increased insulin sensitivity irrespective of route of administration

“…Elevated leptin levels due to increased leptin resistance are observed as a function of obesity both in rodents and humans (Friedman and Halaas, 1998;Koch et al, 2013;Marazziti et al, 2013). The resistance towards leptin in this study was confirmed in a food intake test where leptin alone did not alter the food intake in HFD rats.…”

Bidirectional Prospective Associations of Metabolic Syndrome Components With Depression, Anxiety, and Antidepressant Use

“…Consequently, it remains unclear as to whether, over time, psychopathology impairs components of the metabolic syndrome, or vice versa. Each direction is biologically plausible, since the development and progression of both psychopathology and metabolic dysregulation are associated with a range of detrimental biological processes, including altered autonomic and neuroendocrine stress functioning, low grade inflammation, cellular aging, and oxidative and nitrosative damage 16, 17, 18. Thus, the pathophysiology of psychopathology may increase the risk of metabolic dysregulation, and vice versa.…”

Association of paraoxonase-1 activity and major depressive disorder in patients with metabolic syndrome

“…MS could be the consequence of unhealthy lifestyle habits in patients with MDD as well. It also could be hypothesized that MS and MDD share common pathophysiologic mechanisms including increased activity of the stress-induced hypothalamus-pituitary-adrenal axis, abnormal autonomic nervous system activity, stress-mediated gene expression, and release of pro-inflammatory cytokines [18].…”