Metabolic Syndrome, Alzheimer Disease, Schizophrenia, and Depression: Role for Leptin, Melatonin, Kynurenine Pathways, and Neuropeptides

Biological phenotypes underpin the physio‐somatic symptoms of somatization, depression, and chronic fatigue syndrome

“…d) The diagnosis major depression is not externally validated, but rather is clinically and biologically heterogenous. e) These results have treatment implications for many depression/somatization-associated disorders, including ME/CFS, but also PTSD, schizophrenia (149), inflammatory bowel disease, fibromyalgia, and eating disorders, as well as for the high association of depression/somatization with the etiology and course of neurodegenerative disorders, such as Alzheimer's and multiple sclerosis (150). All of these disorders are classically difficult to successfully manage.…”

Increased breakdown of kynurenine towards its neurotoxic branch in bipolar disorder

“…Emerging evidence suggests that immune-inflammatory activity and tryptophan catabolites (TRYCATs) changes are involved in the etiology as well as in the course of BD. TRYCATs are proposed to be mediators of immune-inflammatory activity and also neurodegeneration [ 7 ]. Depression and mania are accompanied by the activation of immune inflammatory pathways like increased levels of pro-inflammatory cytokines which are connected to alterations in the TRYCAT metabolism [ 8 ].…”

The gut–brain axis: The role of melatonin in linking psychiatric, inflammatory and neurodegenerative conditions

“…Many, if not most, other major psychiatric disorders, are associated with high levels of stress and depression, as well as with heightened levels of O&NS and immune-inflammatory activation, including mania in bipolar disorder, schizophrenia [25] and posttraumatic stress disorder (PTSD) [26]. The autoimmune consequences arising from this suggest that there are neuroprogressive changes to the biological underpinnings of such depressionassociated disorders, which recent work supports [27,28].…”

“…As well as being a powerful antioxidant melatonin also induces the synthesis of endogenous antioxidants, thereby making a significant contribution to cellular oxidant status across a range of organs and tissues. Pineal melatonin is commonly decreased across a wide range of medical disorders, including depression-associated conditions, such as schizophrenia [71] and Alzheimer's disease [72], with melatonin proposed to have some efficacy in the management of such conditions [25]. Single nucleotide polymorphisms in the molecules and receptors of the melatoninergic pathway are modelled as mediating their disease susceptibility effects predominantly via pineal melatonin dysregulation.…”

“…Such direct effects of gut bacteria on the host melatoninergic pathways and the question of bacterial melatonin synthesis will be important to determine. Given the importance of tryptophan availability and its regulation of serotonin and melatonin, as well as glia and immune responses, it is likely that gut bacteria will have a significant impact on key processes driving changes in neuroinflammation [1,2,25]. The role of gut melatonin in neuroinflammatory conditions such as Alzheimer's disease is urgently in need of investigation.…”