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Methamphetamine (MA)‐induced psychosis (MIP) is associated with increased oxidative toxicity (especially lipid peroxidation) and lowered antioxidant defences. Advanced glycation end products (AGEs) cause oxidative stress upon ligand binding to AGE receptors (RAGEs). There is no data on whether MA use may cause AGE–RAGE stress or whether the latter is associated with MIP. This case–control study recruited 60 patients with MA use disorder and 30 normal controls and measured serum levels of oxidative stress toxicity (OSTOX, lipid peroxidation), antioxidant defences (ANTIOX), magnesium, copper, atherogenicity, AGE and soluble RAGE (sRAGE) and computed a composite reflecting AGE–RAGE axis activity. MA dependence and use were associated with elevated levels of AGE, sRAGE, OSTOX/ANTIOX, Castelli Risk Index 1 and atherogenic index of plasma. Increased sRAGE concentrations were strongly correlated with dependence severity and MA dose. Increased AGE–RAGE stress was correlated with OSTOX, OSTOX/ANTIOX and MA‐induced intoxication symptoms, psychosis, hostility, excitement and formal thought disorders. The regression on AGE–RAGE, the OSTOX/ANTIOX ratio, decreased magnesium and increased copper explained 54.8% of the variance in MIP symptoms, and these biomarkers mediated the effects of increasing MA concentrations on MIP symptoms. OSTOX/ANTIOX, AGE–RAGE and insufficient magnesium were found to explain 36.0% of the variance in the atherogenicity indices. MA causes intertwined increases in AGE–RAGE axis stress and oxidative damage, which together predict the severity of MIP symptoms and increased atherogenicity. [ABSTRACT FROM AUTHOR]

Objective: Suicide is a leading cause of death worldwide. Identifying factors associated with suicidality (suicidal ideation [SI]/suicidal behavior) could increase our understanding of the pathophysiological underpinnings of suicide and improve its prevention. Methods: We conducted a systematic review (PubMed/PsycInfo/Cochrane databases, up to September 2020) and random‐effect meta‐analysis including observational studies comparing peripheral C‐reactive protein (CRP) levels in suicidal versus non‐suicidal patients affected by any psychiatric disorder and healthy controls (HC). Primary outcome was the CRP standardized mean difference (SMD) between patients with high suicidality versus those with absent or low suicidality. Secondary outcomes were SMD of CRP levels between those with suicide attempt versus no suicide attempt, as well as between those with (high) versus low or absent SI. Quality of included studies was measured with Newcastle‐Ottawa scale. Results: Out of initial 550 references, 21 observational studies involving 7682 subjects (7445 with mood disorders or first‐episode psychosis, 237 HC) were included. A significant association of CRP levels with suicidality (SMD 0.688, 95% CI 0.476–0.9, p < 0.001) emerged. CRP levels were higher in individuals with high SI (SMD 1.145, 95% CI 0.273–2.018, p = 0.010) and in those with suicide attempt (SMD 0.549, 95%CI 0.363–0.735, p < 0.001) than non‐suicidal individuals (either patients or HC). Main analyses were confirmed in sensitivity analysis (removing HC), and after adjusting for publication bias. The cross‐sectional design of included studies, and the high heterogeneity of diagnosis and treatment limit the generalizability of these results. Median quality of included studies was high. Conclusion: CRP is associated with higher suicidality in patients with mental disorders. Large cohort studies longitudinally monitoring CRP levels are needed to explore its longitudinal association with suicidality. [ABSTRACT FROM AUTHOR]

Abstract: Rationale: Deficit schizophrenia, as defined by the Schedule for Deficit Syndrome, may represent a distinct diagnostic class defined by neurocognitive impairments coupled with changes in IgA/IgM responses to tryptophan catabolites (TRYCATs). Adequate classifications should be based on supervised and unsupervised learning rather than on consensus criteria. Methods: This study used machine learning as means to provide a more accurate classification of patients with stable phase schizophrenia. Results: We found that using negative symptoms as discriminatory variables, schizophrenia patients may be divided into two distinct classes modelled by (A) impairments in IgA/IgM responses to noxious and generally more protective tryptophan catabolites, (B) impairments in episodic and semantic memory, paired associative learning and false memory creation, and (C) psychotic, excitation, hostility, mannerism, negative, and affective symptoms. The first cluster shows increased negative, psychotic, excitation, hostility, mannerism, depression and anxiety symptoms, and more neuroimmune and cognitive disorders and is therefore called “major neurocognitive psychosis” (MNP). The second cluster, called “simple neurocognitive psychosis” (SNP) is discriminated from normal controls by the same features although the impairments are less well developed than in MNP. The latter is additionally externally validated by lowered quality of life, body mass (reflecting a leptosome body type), and education (reflecting lower cognitive reserve). Conclusions: Previous distinctions including “type 1” (positive)/“type 2” (negative) and DSM‐IV‐TR (eg, paranoid) schizophrenia could not be validated using machine learning techniques. Previous names of the illness, including schizophrenia, are not very adequate because they do not describe the features of the illness, namely, interrelated neuroimmune, cognitive, and clinical features. Stable‐phase schizophrenia consists of 2 relevant qualitatively distinct categories or nosological entities with SNP being a less well‐developed phenotype, while MNP is the full blown phenotype or core illness. Major neurocognitive psychosis and SNP should be added to the DSM‐5 and incorporated into the Research Domain Criteria project. [ABSTRACT FROM AUTHOR]

Aim: We aimed to delineate the effects of immunoglobulin (Ig)M‐mediated autoimmune responses directed against malondialdehyde (MDA) and nitroso (SNO) adducts on nitro‐oxidative stress and depressive and physiosomatic symptoms (DPSS) at the end of term. Methods: IgM responses to MDA, NO (nitroso) adducts formed by nitrosylation, and NO2 tyrosine formed by nitration were measured as well as hydroperoxides (ferrous oxidation xylenol orange), advanced protein oxidation products (AOPP), and NO metabolite (NOx) levels in women at the end of term pregnancy and in normal controls. Results: IgM responses to MDA were significantly and inversely associated with AOPP, ferrous oxidation xylenol orange, and NOx and DPSS. IgM responses to NO adducts were significantly and inversely associated with DPSS and positively with NOx levels. There were significant associations between IgM responses to MDA, NO adducts, and NO2 tyrosine. The DPSS score was predicted by AOPP and a lifetime history of premenstrual syndrome (both positively) and IgM responses to NO adducts (inversely). Furthermore, 71.8% of the variance in the index of nitro‐oxidative stress was explained by lowered IgM responses to MDA, antioxidant levels (zinc, total radical trapping parameter), and inflammatory mediators. Conclusion: Lowered levels of IgM responses to MDA during pregnancy are accompanied by a reduced regulation of nitro‐oxidative processes thereby explaining increased oxidative and nitrosative stress biomarkers in association with DPSS. IgM responses to NO adducts, which reflect nitrosylation as a consequence of increased NO production, regulate DPSS symptoms at the end of term and are a trait marker of major depression. IgM responses to MDA are a key part of the compensatory anti‐inflammatory responses system. [ABSTRACT FROM AUTHOR]