The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders

Abstract

Depressive episodes are associated not only with changes in neurotransmission in the central nervous system, but also may lead to structural changes in the brain through neuroendocrine, inflammatory, and immunological mechanisms. The aim of this article is to present a new hypothesis connecting the inflammatory theory of depression with IgG food hypersensitivity and leaky gut syndrome. This new potential pathway that may mediate the pathogenesis of depression implies the existence of subsequent developmental stages. Overproduction of zonulin triggered, for example, by gliadin through activation of the epidermal growth factor receptor and protease-activated receptor causes loosening of the tight junction barrier and an increase in permeability of the gut wall ('leaky gut'). This results in a process allowing larger molecules that would normally stay in the gut to cross into the bloodstream and in the induction of IgG-dependent food sensitivity. This condition causes an increased immune response and consequently induces the release of proinflammatory cytokines, which in turn may lead to the development of depressive symptoms. It seems advisable to assess the intestinal permeability using as a marker, for example, zonulin and specific IgG concentrations against selected nutritional components in patients with depression. In the case of increased IgG concentrations, the implementation of an elimination-rotation diet may prove to be an effective method of reducing inflammation. This new paradigm in the pathogenesis of depressive disorders linking leaky gut, IgG-dependent food sensitivity, inflammation, and depression is promising, but still needs further studies to confirm this theory.

Leaky gut biomarkers in depression and suicidal behavior

“…The so‐called gut–brain axis, linking emotional and cognitive brain centers with gastrointestinal function, has recently received substantial attention in relation to psychiatric disorders . This bidirectional crosstalk between the digestive system and the brain could be mediated via changes in gut microbiota resulting in immune activation, potentially generating various types of psychiatric symptoms . Specifically, a leaking gut allows translocation of lipopolysaccharides (LPS), molecules found on the outer membrane of gram‐negative bacteria, from the gut into the circulation.…”

Gluten-Free Diet Regimens and Psychiatric Symptoms

“…Although there is some recent evidence linking major depressive disorder to celiac disease or gluten sensitivity (7,8), the evidence does not have the long history and series of replications found in the literature on schizophrenia (9). We agree with the authors of the letter that celiac disease has been associated with psychiatric disorders other than schizophrenia, including major depressive disorder.…”

The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls

“…On the one hand, a possible cause of the hyperreactivity among patients with MDD may be disruption of gut-microbiome-brain axis, which is related to low-grade inflammation occurring peripherally and in the CNS [ 19 ]. It is suggested that altered gut microbiota could be responsible for increased gut permeability.…”

“…A scenario proposed by Karakula-Juchnowicz et al that links the inflammatory theory of depression with IgG food hypersensitivity and leaky gut syndrome assumes that loss of integrity of the tight-junction barrier could be caused by food antigens [ 19 ]. Overproduction of zonulin triggered, for example, by gliadin through activation of the epidermal growth factor receptor and protease-activated receptor causes loosening of the tight junction barrier and an increase in permeability of the gut wall.…”

“…Increased gut permeability may lead to translocation of food-borne components into blood circulation, resulting in an abnormal immune response and increased levels of circulating pro-inflammatory cytokines, and thus, the development or maintenance of MDD. Elimination of trigger foods may inhibit the pathological response of the immune system and restore the pro/anti-inflammatory balance of the body [ 19 ] (see Figure 1 for an overview).…”