Schizophrenia Research最新文献

Background

Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown.

Methods

Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t-tests and correlation analysis.

Results

We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance.

Conclusions

This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ.

Background

Safety behaviors, both positive (maladaptive coping behavior) and negative (avoidance behavior), are used by people with paranoid delusions to avoid perceived threats. Safety behaviors contribute to the persistence of paranoid delusions by preventing disconfirmation of threat beliefs and may influence other psychiatric symptoms. This study investigated how changes in safety behaviors are related to changes in paranoid ideation, social anxiety, depression, cognitive biases and self-esteem over time.

Methods

This study included 116 patients diagnosed with a psychotic disorder (DSM-IV) and at least moderate levels of paranoid ideations (GTPS >40).The data were collected as part of a multi-center randomized controlled trial where patients were randomized to VR-CBT (n = 58) or treatment as usual (TAU; n = 58). Assessments were completed at baseline (T0), after three months (T3) and after six months (T6). For all variables, change scores between T0 and T3 and T3 and T6 were calculated and Pearson correlations between change scores were computed.

Results

A decrease in total safety behavior was related to diminished paranoid ideation, social anxiety, and depression. No significant temporal associations were found between changes in safety behavior and changes in cognitive biases and self-esteem. Similar but less robust results were found for respectively negative safety behavior and positive safety behavior.

Conclusion

Dropping safety behavior can be specifically targeted in behavioral interventions. Whereas there appears to be a relation with reduction in anxiety, paranoia, and depressive symptoms, changes in safety behavior do not seem to align with changes in cognitive thinking processes.

Background

Concern about clozapine-associated neutropenia contributes to clozapine's underutilization and racial disparities in access. People with African ancestry are more likely to have lower normative absolute neutrophil counts (ANC), associated with the Duffy null genetic polymorphism. Recent data on clozapine-associated neutropenia in the US are lacking.

Methods

Patients prescribed clozapine in the Johns Hopkins Medicine electronic medical record (EMR) between 2013 and 2023 were identified. Duffy null Associated Neutrophil Count (DANC) was assigned if there were two ANC's < 2000 cells/μL, >30 days apart, before starting clozapine. Rates of neutropenia, timing of first neutropenia, and demographic differences were explored.

Results

974 received clozapine and had ANC's available, with 63.9 % male, 51.1 % White, and 39 % Black. 287 were presumed to start clozapine during the study period, and were 62.4 % male, 46 % White, and 44.9 % Black. No patients developed severe neutropenia. 59 (6.1 %) developed mild or moderate neutropenia. 19 (6.6 %) new starts had presumed DANC, and none developed neutropenia. 11 of 16 presumed new starts who developed neutropenia did so within eight months. No demographic differences were found between groups for presumed new starts. For non-new starts, where DANC assignment was not possible, Black patients were more likely than White patients to develop neutropenia (OR 3.48, 95 % CI [1.65, 7.73]).

Discussion

To our knowledge, this is the first observational study of clozapine-associated neutropenia in the US in the past decade, and it includes a substantial proportion of Black patients. ANC monitoring requirements may be too strict, contributing to clozapine underutilization.

Impaired visual target detection is a common finding in schizophrenia that is linked to poor functional outcomes. However, the neural mechanisms that contribute to this deficit remain unclear. Recent research in healthy samples has identified relationships between the phase of pre-stimulus electroencephalographic (EEG) activity in the alpha band (8-12 Hz) or theta band (4-7 Hz) and the likelihood of visual target detection with and without attentional cueing, but these effects have not yet been explored in schizophrenia. We performed a study to investigate such effects in schizophrenia (n = 19) and healthy participants (n = 14), using a visual target detection task with attentional cues. We found significant relationships between pre-stimulus EEG phase properties and visual target detection in both groups, but also clear differences in the effects as a function of frequency, group, and attentional cueing. Alpha-band phase effects were relatively uniform across groups and conditions. By contrast, theta-band phase effects showed differences by group and attentional condition which could be consistent with attentional hyperfocusing in the schizophrenia group. Thus, our results elucidate a novel neural mechanism that may help to explain known impairments affecting both visual target detection and attention in schizophrenia.

Schizotypy involves schizophrenia-like traits and symptoms, with the Wisconsin Schizotypy Scales (WSS) being frequently used in previous research. There is some evidence that schizophrenia-spectrum symptom levels, including when using the WSS, might vary both by gender and by race and ethnicity. However, previous research has rarely examined to what extent the WSS show gender and racial bias. Further, this has not been previously examined for the Cognitive Slippage Scale, a measure of disorganized schizotypy. In this study, we examined biases for a subset of items from the WSS in a large sample of undergraduate students (n = 21,829). Using item response theory to test for levels of differential item functioning (DIF), we found some evidence of problematic DIF for all scales, including for negative, positive, and disorganized schizotypy scales. There was evidence of problematic DIF especially by gender and for Black and Multiracial participants. Overall, the current results suggest that gender and/or racial bias on these scales should be an important consideration in using these scales and our results could have implications for assessment of schizophrenia-spectrum symptoms.

Background

In Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients.

Methods

This prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment ‘pre-COVID-19’ (between 16th August 2018 and 15th August 2019), and ‘during-COVID-19’ (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders.

Results

Of 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001).

Conclusions

Early intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required.

Objective

Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ.

Methods

The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively).

Results

Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05).

Conclusion

Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.