The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress.

It is believed that damage to the membranes of brain cells of schizophrenia (SCZ) patients induces the formation of autoantigens and autoantibodies. Nevertheless, the importance of immunological changes leading to the loss of tolerance to self-antigens in the genesis of SCZ has not been established. The MALDI mass spectra of the IgG light chains of 20 healthy donors were relatively homogeneous and characterized by one peak with only one maximum. In contrast to the healthy donors, the MALDI mass spectra of IgG light chains corresponding to 20 SCZ patients demonstrated, similarly to 20 autoimmune systemic lupus erythematosus (SLE) patients, two maxima of a comparable intensity. In addition, the MALDI spectra of the IgG light chains of five SLE and four SCZ patients contained a small additional brightly pronounced peak with remarkably lower molecular mass compared with the main one. DNase autoantibodies (abzymes) can be found in the blood of patients with several autoimmune diseases, while the blood of healthy donors or patients with diseases without a significant disturbance of the immune status does not contain DNase abzymes. Here, we present the first analysis of anti-DNA antibodies and DNase abzymes in the sera of SCZ patients. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of SCZ patients. The sera of approximately 30% of SCZ patients displayed a higher content of antibodies (compared with 37% of SLE) interacting with single- and double-stranded DNA compared with healthy donors. Antibodies with DNase activity were revealed in 80% of the patients. These data indicate that some SCZ patients may show signs of typical autoimmune processes to a certain extent.

Several different theories of schizophrenia (SCZ) were discussed; the causes of this disease are not yet clear. Using ELISA, it was shown that titers of autoantibodies against myelin basic protein (MBP) in SCZ patients are ~1.8-fold higher than in healthy individuals but 5.0-fold lower than in patients with multiple sclerosis. Several rigid criteria were checked to show that the MBP-hydrolyzing activity is an intrinsic property of SCZ IgGs. Approximately 82% electrophoretically homogeneous SCZ IgGs purified using several affinity sorbents including Sepharose with immobilized MBP hydrolyze specifically only MBP but not many other tested proteins. The average relative activity of IgGs from patients with negative symptoms was 2.5-fold higher than that of patients with positive symptoms of SCZ, and it increases with the duration of this pathology. It was shown that abzymes are the earliest statistically significant markers of many autoimmune pathologies. Our findings surmise that the immune systems of individual SCZ patients can generate a variety of anti-MBP abzymes with different catalytic properties, which can attack MBP of the myelin-proteolipid shell of axons. Therefore, autoimmune processes together with other mechanisms can play an important role in SCZ pathogenesis. MBP-hydrolyzing antibodies were previously detected in the blood of 80% to 90% of patients with systemic lupus erythematosus (SLE) and multiple sclerosis (MS). In addition, some similar neuropsychiatric indicators of disease common to SLE, MS, and SCZ were described in the literature. Thus, the destruction of the myelin sheath and the production of MBP-hydrolyzing antibodies can be a common phenomenon for some different diseases.

Background Purpose of study is revealing significant differences in serum proteomes in schizophrenia and bipolar disorder (BD). Results Quantitative mass-spectrometry based proteomic analysis was used to quantify proteins in the blood serum samples after the depletion of six major blood proteins. Comparison of proteome profiles of different groups revealed 27 proteins being specific for schizophrenia, and 18 – for BD. Protein set in schizophrenia was mostly associated with immune response, cell communication, cell growth and maintenance, protein metabolism and regulation of nucleic acid metabolism. Protein set in BD was mostly associated with immune response, regulating transport processes across cell membrane and cell communication, development of neurons and oligodendrocytes and cell growth. Concentrations of ankyrin repeat domain-containing protein 12 (ANKRD12) and cadherin 5 in serum samples were determined by ELISA. Significant difference between three groups was revealed in ANKRD12 concentration ( p = 0.02), with maximum elevation of ANKRD12 concentration (median level) in schizophrenia followed by BD. Cadherin 5 concentration differed significantly ( p = 0.035) between schizophrenic patients with prevailing positive symptoms (4.78 [2.71, 7.12] ng/ml) and those with prevailing negative symptoms (1.86 [0.001, 4.11] ng/ml). Conclusions Our results are presumably useful for discovering the new pathways involved in endogenous psychotic disorders. Electronic supplementary material The online version of this article (10.1186/s12864-019-5848-1) contains supplementary material, which is available to authorized users.

DBS analysis is a reliable tool for blood sampling and performing TDM of clozapine and norclozapine in daily practice and substantially extends the opportunities for TDM of clozapine.

Background Schizophrenia is associated with a lowered life expectancy due to cardiovascular disease. This is, at least in part, related to an increased vulnerability to the development of metabolic syndrome (MetS) in patients with schizophrenia. The dysregulation of apolipoproteins (Apos) may also play a role in the pathogenesis of schizophrenia via their effect on cerebral cholesterol processing. Aim The aim of this study was to investigate serum Apos A1, C3, E, A2 and C2 concentration in schizophrenia patients with or without MetS in comparison to healthy donors. Methods After obtaining informed consent, 53 patients with a diagnosis of paranoid schizophrenia according to ICD-10 criteria (F20) were included. Patients were divided into two groups with (N = 26) and without (N = 27) MetS according to the criteria of the International Diabetes Federation. The control group included 20 mentally and physically healthy subjects. Serum Apos A1, A2, C2, C3 and E were measured using xMAP technology (Luminex). Results Serum ApoA1 was significantly decreased in patients with schizophrenia compared to healthy subjects (p = 0.002); ApoA2 was lower in patients without MetS in comparison to patients with MetS (p = 0.017) and the levels of ApoC3 and ApoC2 were increased in patients with schizophrenia with MetS in comparison with the control group and also with patients without MetS. No other significant differences were established concerning the other assayed apolipoproteins. Conclusions In line with literature data the results of our study suggest that while disturbances in ApoA1 level may play a role in the pathogenesis of schizophrenia, ApoA2, ApoC2, ApoC3 and ApoE may be primarily related to metabolic imbalance.

We present first evidence showing that some electrophoretically homogeneous IgGs from the sera of patients with schizophrenia (36.4%) and their Fab and F(ab)2 fragments as well as from healthy donors (33.3%) possess catalase activity. The relative catalase activity of IgGs from the sera of individual schizophrenia patients (and healthy donors) significantly varied from patient to patient, but the activity of IgGs from healthy donors is on average 15.8-fold lower than that for schizophrenia patients. After extensive dialysis of purified IgGs against EDTA chelating metal ions, the relative catalase activity of IgGs decreases on average approximately 2.5–3.7-fold; all IgGs possess metal-dependent and independent catalase activity. The addition of external Me2+ ions to dialyzed and non-dialyzed IgGs leads to a significant increase in their activity. The best activator of dialyzed and non-dialyzed IgGs is Co2+, the activation by Cu2+, Mn2+, and Ni2+ ions were rare and always lower than by Co2+. Every IgG preparation demonstrates several individual sets of very well expressed pH optima in the pH range from 4.0 to 9.5. These data speak for the individual repertoire of catalase IgGs in every person and an extreme diversity of abzymes in their pH optima and activation by different metal ions. It is known that antioxidant enzymes such as superoxide dismutases, catalases, and glutathione peroxidases represent critical defense mechanisms preventing oxidative modifications of DNA, proteins, and lipids. Catalase activity of human IgGs could probably also play a major role in the protection of organisms from oxidative stress and toxic compounds.