Risk factors of deficit and non-deficit schizophrenia: Results from a cross-sectional study.

AIM: It has been observed that deficit and non-deficit schizophrenia (SCZ-D and SCZ-ND) might be characterized by different risk factors. Therefore, the present study aimed to assess as to whether previously reported risk factors of schizophrenia are specifically associated with SCZ-D and SCZ-ND. METHOD: This study was based on a cohort of 118 stable outpatients with schizophrenia. A diagnosis of SCZ-D was established using the Schedule for the Deficit Syndrome (SDS). Risk factors were recorded using structured interview, the Operational Criteria for Psychotic Illness (OPCRIT) checklist and the Traumatic Experience Checklist (TEC). The following risk factors were explored: male sex, a history of schizophrenia in first-degree relatives, seasonality of birth, birth weight <3000g, delivery by cesarean section, a history of childhood trauma (emotional abuse, emotional neglect, physical abuse and sexual abuse) as well as substance abuse (other than nicotine) and cigarette smoking at psychosis onset. RESULTS: Individuals with SCZ-D were more likely to be males as well as reported higher rates of birth weight <3000g and any categories of childhood trauma. In turn, substance abuse (other than nicotine) at psychosis onset was significantly more frequent in patients with SCZ-ND. Binary logistic regression, controlling for multiple comparisons, revealed similar findings, except for the association with any categories of childhood trauma that appeared to be not significant. CONCLUSION: Our findings partially replicate differential patterns of risk factors for SCZ-D (male sex and birth weight <3000g) and SCZ-ND (substance abuse at psychosis onset), likely attributable to the effects of timing of exposure.

Neurodevelopmental aspects of adverse childhood experiences in psychosis: Relevance of the allostatic load concept.

Previous studies have shown that neurodevelopmental characteristics of adverse childhood experiences (ACEs), such as their accumulation and minimal age at exposure, might moderate their impact on clinical expression of psychosis. However, it remains unknown as to whether specific neurodevelopmental characteristics of ACEs are associated with biological alterations observed in psychosis. In this study, we tested the hypothesis that younger minimal age at exposure as well as greater accumulation and severity of ACEs are associated with systemic biological dysregulations captured by the allostatic load (AL) index in patients with psychosis. The present study included 65 inpatients with psychotic disorders and 56 healthy controls (HCs). A total of 15 biomarkers were used to measure the AL index. Individuals with psychosis had significantly higher AL index as well as they reported greater accumulation and severity of ACEs compared to HCs. After adjustment for age, sex, the number of education years and the dosage of antipsychotics, greater accumulation of ACEs and younger minimal age at exposure were significantly associated with higher AL index in patients with psychosis. None of neurodevelopmental characteristics of ACEs was associated with the AL index in HCs. Our findings indicate that greater accumulation of ACEs and younger minimal age at exposure are related to biological dysregulations captured by the AL index in patients with psychosis. Future studies investigating the role of ACEs in the pathophysiology of psychosis need to consider their neurodevelopmental characteristics. It is also important to further explore timing of exposure to indicate critical developmental periods related to psychosis risk and better inform potential interventions.

The Relationship between Cognitive Functions and Psychopathological Symptoms in First Episode Psychosis and Chronic Schizophrenia.

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.

Psychopathology and Stem Cell Mobilization in Ultra-High Risk of Psychosis and First-Episode Psychosis Patients.

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.

Adverse Childhood Experiences and Methylation of the FKBP5 Gene in Patients with Psychotic Disorders.

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.