Major depression is reportedly characterized by increased activity of the hypothalamic-pituitary-adrenal (HPA) axis and by in vivo immune activation. The present study was carried out in order to investigate the relationships between HPA-axis activity and in vivo immune function in depression. Towards this end the following parameters were measured: 24 h urinary cortisol (UC) excretion; basal and post-dexamethasone (DST) plasma cortisol, beta-endorphin/beta-lipotropin (beta END/beta LPH) and dexamethasone concentrations; and leucocyte subsets (i.e. lymphocytes, neutrophils, monocytes, CD4+, CD4+CD45RA+, CD4+CD45RO+, CD8+, CD8+CD57+, CD8+CD57-, HLA-DR+, CD25+ T cells, HLA-DR+, CD19+, CD20+, and CD21+ B cells) both pre- and post-DST. Dexamethasone administration (1 mg orally) induced leucocytosis, lymphocytopaenia, monocytopaenia and neutrophilia. HPA-axis non-suppressors exhibited a relative resistance to the enhancing (e.g. neutrophils) or depressant (e.g. lymphocytes, CD4+ T cells) effects of dexamethasone. There were significant correlations between UC excretion and the number of percentage of lymphocytes, monocytes, CD4+CD45RA+ and CD8+CD57- T cells (negatively) and neutrophils (positively). It is concluded that multiple and complex intertwined relationships between HPA-axis hyperactivity and systemic immune stimulation participate in the pathophysiology or pathogenesis of major depression.
Depression is accompanied by activation of immuno-inflammatory and oxidative and nitrosative stress (IO&NS) pathways, and increased IgM/IgA responses to lipopolysaccharide (LPS) of gram-negative commensal bacteria. The latter suggests that bacterial translocation has caused IgM/IgA responses directed against LPS. Bacterial translocation may drive IO&NS responses.To examine the associations between IgM/IgA responses to LPS and IO&NS measurements, including plasma/serum interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin, lysozyme, oxidized LDL (oxLDL) antibodies, peroxides, and IgM (auto)immune responses against malondialdehyde (MDA), azelaic acid, phophatidyl inositol (Pi), NO-tryptophan and NO-tyrosine in depressed patients and controls.We found significant positive associations between IgM/IgA responses to LPS and oxLDL antibodies, IgM responses against MDA, azelaic acid, Pi, NO-tryptophan, and NO-tyrosine. The IgA responses to LPS were correlated with lysozyme. There were no significant positive correlations between the IgM/IgA responses to LPS and IL-1 and neopterin.The findings show that in depression there is an association between increased bacterial translocation and lysozyme production, an antibacterial compound, O&NS processes, and autoimmune responses directed against O&NS generated neoantigenic determinants. It is suggested that bacterial translocation may drive IO&NS pathways in depression and thus play a role in its pathophysiology.
The purpose of this study is to describe how to use the precision nomothetic psychiatry approach to (a) delineate the associations between schizophrenia symptom domains, including negative symptoms, psychosis, hostility, excitation, mannerism, formal thought disorders, psychomotor retardation (PHEMFP), and cognitive dysfunctions and neuroimmunotoxic and neuro-oxidative pathways and (b) create a new endophenotype class based on these features. We show that all symptom domains (negative and PHEMFP) may be used to derive a single latent trait called overall severity of schizophrenia (OSOS). In addition, neurocognitive test results may be used to extract a general cognitive decline (G-CoDe) index, based on executive function, attention, semantic and episodic memory, and delayed recall scores. According to partial least squares analysis, the impacts of adverse outcome pathways (AOPs) on OSOS are partially mediated by increasing G-CoDe severity. The AOPs include neurotoxic cytokines and chemokines, oxidative damage to proteins and lipids, IgA responses to neurotoxic tryptophan catabolites, breakdown of the vascular and paracellular pathways with translocation of Gram-negative bacteria, and insufficient protection through lowered antioxidant levels and impairments in the innate immune system. Unsupervised machine learning identified a new schizophrenia endophenotype class, named major neurocognitive psychosis (MNP), which is characterised by increased negative symptoms and PHEMFP, G-CoDe and the above-mentioned AOPs. Based on these pathways and phenome features, MNP is a distinct endophenotype class which is qualitatively different from simple psychosis (SP). It is impossible to draw any valid conclusions from research on schizophrenia that ignores the MNP and SP distinctions.
Abstract Background Amnestic mild cognitive impairment (aMCI) is characterized by changes in lipids and oxidative stress (OS). It is crucial to exclude patients with major depression (MDD) to accurately evaluate these biomarkers in aMCI. Aims To examine lipid and oxidative stress biomarkers associated with aMCI versus normal controls. Methods We performed a case-control analysis involving 61 individuals with aMCI (without MDD) and 60 healthy controls. We assessed the severity of aMCI, distress symptoms of old age, and lipid/OS biomarkers. Results The levels of serum -SH groups were significantly higher in individuals with aMCI, while the levels of malondialdehyde (MDA) were significantly lower in the same group. Serum advanced oxidation protein products, glutathione, and folic acid did not show any notable variations. In individuals with aMCI, we observed an elevated apolipoprotein B (ApoB)/ApoA ratio, as well as decreased levels of high-density lipoprotein cholesterol (HDL), ApoA, and a reverse cholesterol transport (RCT) index. The simultaneous presence of aMCI and subclinical depressive symptoms is marked by elevated levels of triglycerides and ApoB, as well as decreased levels of ApoA and HDL. A significant portion of the variability (24.9%) in a quantitative MCI severity score can be attributed to -SH groups, age (positively), MDA and education (inversely). Discussion The alterations in MDA and -SH levels in aMCI may potentially disrupt redox signaling, which can affect cell signaling and homeostatic setpoints. The interaction between aMCI and subclinical depressive symptoms can lead to increased atherogenicity and reduced antiatherogenic protection.
The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with "chronic fatigue syndrome."The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this "chronic fatigue spectrum" should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.
This paper reports on the development of a videotape "Depression ... the answers" for use in cognitive behavioral therapy with depressed inpatients. 17 patients evaluated the videotape. The described psychoeducational video program was constructed as an introduction for, an opening to, and as a facilitation and clarification of the psychotherapeutic and pharmacological treatments.
Summary The alterations in the inflammatory response system (IRS) appear to be quite different between OCD and anorexia nervosa and are also different from the changes observed in major depression. In anorexia nervosa, there is some evidence for increased production of monocytic cytokines, i.e. tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6), and decreased production of Th-1 like cytokines, i.e. IL-2 and IFNγ. In the same patients there are also signs of immunosuppression, e.g. lowered numbers of CD4 and CD8 T cells and increased production of transforming growth factor-beta (TGFβ). The increased production of monocytic cytokines may be the consequence of the hyponutritional status of those patients. The diminished production of the Th-1 like cytokines may be the consequence of at least four different factors: 1) the deficiency in nutritional factors; 2) neuroendocrine disorders, such as increased Cortisol production; 3) the increased TGFβ production; and 4) lower serum dipeptidyl peptidase activity. In OCD no consistent or specific alterations in the IRS are observed. There is no evidence that IRS activation may play a role in the pathophysiology of OCD and anorexia nervosa.
