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As core symptoms of schizophrenia, cognitive deficits contribute substantially to poor outcomes. Early life stress (ELS) can negatively affect cognition in patients with schizophrenia and healthy controls, but the exact nature of the mediating factors is unclear. Therefore, we investigated how ELS, education, and symptom burden are related to cognitive performance.
The sample comprised 215 patients with schizophrenia (age, 42.9 ± 12.0 years; 66.0 % male) and 197 healthy controls (age, 38.5 ± 16.4 years; 39.3 % male) from the PsyCourse Study. ELS was assessed with the Childhood Trauma Screener (CTS). We used analyses of covariance and correlation analyses to investigate the association of total ELS load and ELS subtypes with cognitive performance.
ELS was reported by 52.1 % of patients and 24.9 % of controls. Independent of ELS, cognitive performance on neuropsychological tests was lower in patients than controls (p < 0.001). ELS load was more closely associated with neurocognitive deficits (cognitive composite score) in controls (r = −0.305, p < 0.001) than in patients (r = −0.163, p = 0.033). Moreover, the higher the ELS load, the more cognitive deficits were found in controls (r = −0.200, p = 0.006), while in patients, this correlation was not significant after adjusting for PANSS.
ELS load was more strongly associated with cognitive deficits in healthy controls than in patients. In patients, disease-related positive and negative symptoms may mask the effects of ELS-related cognitive deficits. ELS subtypes were associated with impairments in various cognitive domains. Cognitive deficits appear to be mediated through higher symptom burden and lower educational level.
Background
Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.
Aims
We investigated employment and relationship status changes among patients across the affective and psychotic spectrum – in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.
Method
The sample from the longitudinal multicentric PsyCourse Study comprised 1260 patients with affective and psychotic spectrum disorders and 441 controls (mean age ± s.d., 39.91 ± 12.65 years; 48.9% female). Multistate models (Markov) were used to analyse transitions in employment and relationship status, focusing on transition intensities. Analyses contained multiple multistate models adjusted for age, gender, job or partner, diagnostic group and Global Assessment of Functioning (GAF) in different combinations to analyse the impact of the covariates on the hazard ratio of changing employment or relationship status.
Results
The clinical group had a higher hazard ratio of losing partner (hazard ratio 1.46, P < 0.001) and job (hazard ratio 4.18, P < 0.001) than the control group (corrected for age/gender). Compared with controls, clinical groups had a higher hazard of losing partner (affective group, hazard ratio 2.69, P = 0.003; psychotic group, hazard ratio 3.06, P = 0.001) and job (affective group, hazard ratio 3.43, P < 0.001; psychotic group, hazard ratio 4.11, P < 0.001). Adjusting for GAF, the hazard ratio of losing partner and job decreased in both clinical groups compared with controls.
Conclusion
Patients face an increased hazard of job loss and relationship dissolution compared with healthy controls, and this is partially conditioned by the diagnosis and functional level. These findings underscore a high demand for destigmatisation and support for individuals in managing their functional limitations.
Adverse childhood experiences (ACE) contribute significantly to mental disorders. While existing research has primarily focused on specific diagnostic categories, a comprehensive understanding of how childhood trauma interacts with biological factors, symptom severity and functioning requires a broader perspective. Therefore, this study adopted a cross-diagnostic approach to examine the impact of ACE on quality of life (QoL), psychosocial functioning, and symptom burden by analyzing data from the PsyCourse Study, a longitudinal, multicenter research project conducted in Germany and Austria. We used multivariate linear regression models and cluster analysis to evaluate data from 725 participants with affective and psychotic disorders and healthy controls who completed the self-assessed Childhood Trauma Screener (CTS) during the course of the study. The results showed that across diagnoses, QoL was significantly impacted by ACE, particularly emotional neglect. An ablation study revealed that 2.3% to 6.2% of the variability in QoL domains could be attributed to ACE. Across diagnoses, symptoms of depression were significantly associated with ACE, especially emotional abuse, but psychotic and manic symptoms were not. Polygenic risk scores (PRS) did not emerge as significant predictors for any examined outcomes. Cluster analysis revealed distinct symptom profiles: Averaged over time, patients with less trauma exposure were rather in the subclinical than in the clinically ill clusters. We conclude that the pervasive influence of ACE on disease severity should be considered when evaluating and treating patients with affective and psychotic disorders.
The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder
(2020)
Genetische Studien an forensisch Untergebrachten? Klinische, ethische und juristische Überlegungen
(2024)
Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.
Association between mitochondria-related genes and cognitive performance in the PsyCourse Study
(2023)
Older Adults with Bipolar Disorder (OABD) represent a heterogeneous group, including those with early and late onset of the disorder. Recent evidence shows both groups have distinct clinical, cognitive, and medical features, tied to different neurobiological profiles. This study explored the link between polygenic risk scores (PRS) for bipolar disorder (PRS-BD), schizophrenia (PRS-SCZ), and major depressive disorder (PRS-MDD) with age of onset in OABD. PRS-SCZ, PRS-BD, and PRS-MDD among early vs late onset were calculated. PRS was used to infer posterior SNP effect sizes using a fully Bayesian approach. Demographic, clinical, and cognitive variables were also analyzed. Logistic regression analysis was used to estimate the amount of variation of each group explained by standardized PRS-SCZ, PRS-MDD, and PRS-BD. A total of 207 OABD subjects were included (144 EOBD; 63 LOBD). EOBD showed higher PRS-BD compared to LOBD (p = 0.005), while no association was found between age of onset and PRS-SCZ or PRS-MDD. Compared to LOBD, EOBD individuals also showed a higher likelihood for suicide attempts (p = 0.01), higher presence of psychotic symptoms (p = 0.003), higher prevalence of BD-I (p = 0.002), higher rates of familiarity for any psychiatric disorder (p = 0.004), and lower processing speed measured with Trail-Making Test part A (p = 0.03). OABD subjects with an early onset showed a greater genetic burden for BD compared to subjects with a late onset. These findings contribute to the notion that EOBD and LOBD may represent different forms of OABD, particularly regarding the genetic predisposition to BD.