Altered methylation of the FKBP5 gene has been observed in various mental disorders and attributed to the effects of adverse childhood experiences (ACEs). However, the level of FKBP5 methylation has not been investigated in patients with psychotic disorders. Therefore, in this study we aimed to determine the FKBP5 methylation in patients with psychosis and controls, taking into account the effects of ACEs. Participants were 85 patients with psychotic disorders, including first-episode psychosis (FEP) patients and acutely relapsed schizophrenia (SCZ-AR) patients, as well as 56 controls. The level of four CpG sites at the FKBP5 gene was determined in the peripheral blood leukocytes using pyrosequencing. After controlling for potential confounding factors, the level of FKBP5 methylation at one out of four tested CpG sites was significantly lower in FEP patients compared to other groups of participants. Significant main effects of parental antipathy and sexual abuse on the level of FKBP5 methylation were observed at the differentially methylated CpG site. Participants reporting this category of ACEs had significantly lower levels of FKBP5 methylation at this CpG site. Lower levels of FKBP5 methylation were associated with better cognitive performance and higher functional capacity in patients with psychosis. In controls, lower methylation of FKBP5 was related to worse performance of immediate memory and language skills. Our findings suggest that hypomethylation of the FKBP5 appears at early stages of psychosis and might be associated with a history of ACEs as well as less severe clinical manifestation.

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been implicated in the development of psychosis and subthreshold psychotic symptoms commonly referred to as psychotic-like experiences (PLEs). The exact mechanisms linking the HPA axis responses with the emergence of PLEs remain unknown. The present study aimed to explore real-life associations between stress, negative affect, salivary cortisol levels (a proxy of the HPA axis activity) as well as PLEs together with their underlying cognitive biases (i.e., threat anticipation and aberrant salience). The study was based on the experience sampling method scheduled over 7 consecutive days in the sample of 77 drug-naïve, young adults (18–35 years). The saliva samples were collected with each prompt to measure cortisol levels. A temporal network analysis was used to explore the directed associations of tested variables. Altogether, 3234 data entries were analyzed. Data analysis revealed that salivary cortisol levels did not directly predict next-moment fluctuations of PLEs. However, higher salivary cortisol levels were associated with higher next-moment levels of PLEs through the effects on threat anticipation and negative affect. In turn, PLEs appeared to predict cortisol levels through the effects on negative affect and event-related stress. Negative affect and threat anticipation were the most central nodes in the network. There might be bidirectional associations between the HPA axis responses and PLEs. Threat anticipation and negative affect might be the most important mediators of these associations. Interventions targeting these mediators might hold promise for disrupting the connection between the HPA axis dysregulation and PLEs.

Background and objective: According to the diathesis-stress model, disturbances of the hypothalamic-pituitary-adrenal (HPA) axis are thought to play a role in the development, onset, and progression of psychosis. The aim of this paper is to present the available body of evidence on the...

Background/Objectives: Recent evidence suggests that gut microbiota plays an important role in anxiety and stress-related disorders through interactions along the gut–brain axis. Our aim was to determine the microbiological diversity of intestinal microorganisms in individuals with acute and remission phases of PD when compared to healthy individuals. Another aim was also to analyze the differences in the metabolic pathways occurring in the intestinal microbiota of individuals from the three analyzed groups. Methods: A diagnosis was established using the Mini-International Neuropsychiatric Interview (M.I.N.I). The gut’s microbiota composition was analyzed through bacterial 16S rRNA gene sequencing (V1–V2 regions). The clinical evaluations included a BMI measurement, Short Form-36 Health Survey (SF-36), Hamilton Anxiety Scale (HAM-A), Montgomery–Åsberg Depression Rating Scale (MADRS), Columbia-Suicide Severity Rating Scale (C-SSRS), and State-Trait Anxiety Inventory (STAI). Results: We recruited 62 participants (31 PD and 31 controls). After conducting quality control filtering, data from 54 participants were analyzed (25 PD, 11 acute, 14 remission, and 29 controls). Observed richness was lower in the acute PD (63) group than in the control (74) and remission (66) (p = 0.038) groups, whereas the Shannon and Simpson indices and beta diversity (PERMANOVA) were not significantly different. The Ruminococcus gnavus group was enriched in acute PD; no other deconfounded differences in microbial composition were detected. Predicted functional differences were detected by edgeR only and included the pathways that are related to steroid biosynthesis and innate immune signaling. Conclusions: Distinct gut microbial signatures were associated with PD, implicating both the metabolic and inflammatory pathways in disease pathophysiology.

Although regenerative and inflammatory processes are involved in the etiopathogenesis of many psychiatric disorders, their roles are poorly understood. We investigate the potential role of stem cells (SC) and factors influencing the trafficking thereof, such as complement cascade (CC) components, phospholipid substrates, and chemokines, in the etiology of schizophrenia. We measured sphingosine-1-phosphate (S1P), stromal-derived factor 1 (SDF-1), and CC cleavage fragments (C3a, C5a, and C5b-C9; also known as the membrane attack complex) in the peripheral blood of 49 unrelated patients: 9 patients with ultra-high risk of psychosis (UHR), 22 patients with first-episode psychosis (FEP), and 18 healthy controls (HC). When compared with the HC group, the UHR and FEP groups had higher levels of C3a. We found no significant differences in hematopoietic SC, very small embryonic-like stem cell (VSEL), C5a, S1P, or SDF-1 levels in the UHR and FEP groups. However, among FEP patients, there was a significant positive correlation between VSELs (CD133+) and negative symptoms. These preliminary findings support the role of the immune system and regenerative processes in the etiology of schizophrenia. To establish the relevance of SC and other factors affecting the trafficking thereof as potential biomarkers of schizophrenia, more studies on larger groups of individuals from across the disease spectrum are needed.