Belief Updating and Paranoia in Individuals with Schizophrenia

Background and Hypothesis: Persecutory delusions are among the most common delusions in schizophrenia and represent the extreme end of the paranoia continuum. Paranoia is accompanied by significant worry and distress. Identifying cognitive mechanisms underlying paranoia is critical for advancing treatment. We hypothesized that aberrant belief updating, which is related to paranoia in human and animal models, would also contribute to persecutory beliefs in individuals with schizophrenia. Study Design: Belief updating was assessed in 42 schizophrenia and 44 healthy participants, using a 3-option probabilistic reversal learning (3-PRL) task. Hierarchical Gaussian filter (HGF) was used to estimate computational parameters of belief updating. Paranoia was measured using the Positive and Negative Syndrome Scale (PANSS) and the revised Green et al. Paranoid Thoughts Scale (R-GPTS). Unusual thought content was measured with the Psychosis Symptom Rating Scale (PSYRATS) and the Peters et al. Delusions Inventory (PDI-21). Worry was measured using the Dunn Worry Questionnaire. Results: Consistent with prior work, paranoia was significantly associated with elevated win-switch rate, prior on volatility and sensitivity to volatility in both schizophrenia and across the whole sample. These relationships were specific to paranoia and did not extend to unusual thought content or measures of anxiety. We did, however, find a significant indirect effect of paranoia on the relationship between prior beliefs about volatility and worry. Conclusions: This work provides evidence that relationships between belief updating parameters and paranoia extend to schizophrenia, may be specific to persecutory beliefs, and contribute to theoretical models implicating worry in the maintenance of persecutory delusions.

Properties of Two-Locus Genealogies and Linkage Disequilibrium in Temporally Structured Samples

Archaeogenetics has been revolutionary, revealing insights into demographic history and recent positive selection in many organisms. However, most studies to date have ignored the non-random association of genetic variants at different loci (i.e., linkage disequilibrium, LD). This may be in part because basic properties of LD in samples from different times are still not well understood. Here, we derive several results for summary statistics of haplotypic variation under a model with time-stratified sampling: 1) The correlation between the number of pairwise differences observed between time-staggered samples (ΠΔt) in models with and without strict population continuity; 2) The product of the LD coeficient, D, between ancient and modern samples, which is a measure of haplotypic similarity between modern and ancient samples; and 3) The expected switch rate in the Li and Stephens haplotype copying model. The latter has implications for genotype imputation and phasing in ancient samples with modern reference panels. Overall, these results provide a characterization of how haplotype patterns are affected by sample age, recombination rates, and population sizes. We expect these results will help guide the interpretation and analysis of haplotype data from ancient and modern samples.

Meta-analysis of Salt Valproate Prevent Switch Associated with Antidepressants in Chinese Depressive Patients

Objective: to study the efficacy of valproate in preventing switch rate related to antidepressant in depressive patients. Methods: The related literature were searched in Chinese Biomedical Database(CBM), China National Knowledge Infrastructure(CNKI) , WANFANG database,and Chinese Social Sciences Citation Index(CSSCI) from 1 January 2005 to 1 January 2020 The rate of switch between groups was synthesized and discussed.Result:A total of 549 subjects were included in 7 studies,in which in 279 cases are in combination group and 270 cases are in group of monotherapy by antidepressant . The results showed switch rate of valproate group was 0.11%,switch rate of antidepressant group was 11.11%, which was very different (OR=0.13 ,95% CI: 0.05–0.35) and also indicated that valproate reduced switch rate was 99%[ (11.11%-0.11%)/11.11%]. In sodium valproate group, switch rate was 0%，while switch rate in antidepressant was 5.7%( OR=0.18,95%CI=0.04-0.84,Z=2.18,P=0.03). In magnesium valproate group, switch rate was 2.2%,while switch rate in antidepressant was16.92% ( OR=0.11,95%CI=0.03-0.39,Z=3.47, P=0.0005).Conclusion:The salt valproate can reduced switch rate related to antidepressant in depressive patients.

Resetting of Auditory and Visual Segregation Occurs After Transient Stimuli of the Same Modality

In the presence of a continually changing sensory environment, maintaining stable but flexible awareness is paramount, and requires continual organization of information. Determining which stimulus features belong together, and which are separate is therefore one of the primary tasks of the sensory systems. Unknown is whether there is a global or sensory-specific mechanism that regulates the final perceptual outcome of this streaming process. To test the extent of modality independence in perceptual control, an auditory streaming experiment, and a visual moving-plaid experiment were performed. Both were designed to evoke alternating perception of an integrated or segregated percept. In both experiments, transient auditory and visual distractor stimuli were presented in separate blocks, such that the distractors did not overlap in frequency or space with the streaming or plaid stimuli, respectively, thus preventing peripheral interference. When a distractor was presented in the opposite modality as the bistable stimulus (visual distractors during auditory streaming or auditory distractors during visual streaming), the rate of percept switching was not significantly different than when no distractor was presented. Conversely, significant differences in switch rate were observed following within-modality distractors, but only when the pre-distractor percept was segregated. Due to the modality-specificity of the distractor-induced resetting, the results suggest that conscious perception is at least partially controlled by modality-specific processing. The fact that the distractors did not have peripheral overlap with the bistable stimuli indicates that the perceptual reset is due to interference at a locus in which stimuli of different frequencies and spatial locations are integrated.

POS0488 THE IMPACT OF ANTINUCLEAR ANTIBODIES INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA AGENTS ON THE LONG-TERM TREATMENT OUTCOMES IN RHEUMATOID ARTHRITIS PATIENTS

Background:The seroconversion of antinuclear antibodies (ANA) induced by anti-tumour necrosis factor alpha (anti-TNF-α) therapy remains a matter of concern in various inflammatory conditions namely rheumatoid arthritis. However, evidence is still scarce regarding the impact of these autoantibodies on the clinical response to treatment in these patients.Objectives:This study aimed to explore the impact of ANA induced by anti-TNF-α therapy on the outcomes of treatment in patients with rheumatoid arthritis over two years of follow-up.Methods:An observational retrospective cohort study was conducted with two years of follow-up. Patients diagnosed with rheumatoid arthritis, according to the American College of Rheumatology (ACR) criteria, and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα agent as first biologic between 2003 and 2018 were included. Patients with positive ANA (titer ≥100) and/or positive anti-double stranded DNA (anti-dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. Disease Activity Score for 28 joints (DAS28), DAS28 delta, Health Assessment Questionnaire (HAQ), HAQ delta were assessed at baseline, 6, 12, 18 and 24 months. Clinical response was evaluated by EULAR criteria and three response categories were defined: good, mild and no response. The rate of switch of biological treatment was assessed over 24 months. To examine the differences between groups with and without ANA seroconversion independent samples t test for normally distributed continuous data, Mann-Whitney U-tests for non-normally distributed continuous data and Chi-square tests for categorical data were used. Logistic regression models were used to assess the effects of ANA seroconversion on clinical response to treatment over 6, 12, 18 and 24 months.Results:A total of 185 patients (mean age of 49.3±10.9 years old; 85.4% female) with a median follow-up of 7 [4-14] years were included. We found an ANA seroconversion rate (titer ≥100) of 77.3% (n=143) with median time of 36 [15-72.3] months. There were no differences among groups regarding age, gender, disease duration, be seropositivity or not (for rheumatoid factor and/or anti-citrullinated protein antibodies) and have an erosive disease or not. DAS28 delta was significantly different (p=0.035) between group with positive ANA (2.01±1.29) and negative ANA (1.15±1.51) at 6 months. DAS28 was significantly different (p=0.014) between group with positive ANA (5.06±3.39) and negative ANA (3.99±1.43) at 12 months. No statistically significant differences were found in the DAS28, DAS28 delta, HAQ, HAQ delta at 18 and 24 months and in the EULAR response at any time. Switch rate was significantly different between patients with ANA seroconversion (median 1[0-1]) versus absence of seroconversion (median 0[0-1]), p=0.025. In the regression model ANA seroconversion did not predict switch rate and EULAR response over time.Conclusion:This study showed that the majority of patients with rheumatoid arthritis treated with an anti-TNF-α agent developed ANA and that their presence may be associated with worse clinical results (DAS28) at 6 and 12 months. In fact, previous research suggested that a decrease in anti-TNF-α drug concentration due to the production of autoantibodies may lead to worse outcomes of treatment. Moreover, our data demonstrated that patients with ANA seroconversion had a higher switch rate. Despite these results, there are no differences in the EULAR response between the two groups and ANA seroconversion did not predict this response over time. Therefore, ANA induced by anti-TNF-α agents should be monitored in patients with rheumatoid arthritis and its impact on treatment must be considered. Further research is needed to explore these results through large-scale prospective studies.Disclosure of Interests:None declared

Can Salt Valproate Prevent Switch Associated With Antidepressants in Depressive Patients?Meta-analysis From Chinese Data (Preprint)

BACKGROUND There are many ways to strengthen the effects of treatment for depressive patients,in which, add on mood stabilizer is one of these many ways. And at same time,it was very common that antidepressant induce switch to mania.Does the mood stabilizer can prevent the switch?This study is that assessment the difference between combination treatment of valproate and antidepressant and monotherapy antidepressant. OBJECTIVE to assess the preventing switch effect of valproate in depressive patients treated by antidepressant METHODS We searched Chinese Biomedical Database(CBM), China National Knowledge Infrastructure(CNKI) , WANFANG database,and Chinese Social Sciences Citation Index(CSSCI) in Chinese to find literature from 1 January 2005 to 1 January 2020 related to the study in model of “comparison of switch rate between combination treatment of valproate and antidepressant and monotherapy of antidepressant in depressive patients” ,among which results such as comments, letters, reviews and case reports were excluded. The rate of switch between groups was synthesized and discussed. RESULTS A total of 549 subjects were included in 7 studies,in which in 279 cases are in combination group and 270 cases are in group of monotherapy by antidepressant . Random effect model is used to account for the data by Revman 5.2. The results showed that the switch rate of valproate group was 0.11%(3/279),switch rate of antidepressant group was 11.11%( 30/270), which was very different in switch rate(OR=0.13 ,95% CI: 0.05–0.35) and also indicated that valproate reduced switch rate was 99%[ (11.11%-0.11%)/11.11%]. In sodium valproate group, switch rate was 0%，while switch rate in antidepressant was 5.7%( OR=0.18,95%CI=0.04-0.84),which was significantly different(Z=2.18,P=0.03). In magnesium valproate group, switch rate was 2.2%,while switch rate in antidepressant was16.92%( OR=0.11,95%CI=0.03-0.39),which was significantly different(Z=3.47,P=0.0005). CONCLUSIONS The salt valproate can reduced switch rate related to antidepressant in depressive patients. In this study, salt valproate reduce 99% switch rate. CLINICALTRIAL NO

Dynamic cognitive flexibility

Cognitive flexibility, or the ability to flexibly switch between different task sets, is often operationalized using performance on voluntary task switching (VTS) paradigms. In VTS paradigms, performance is commonly measured by examining reaction time, accuracy, the effects of switching tasks on reaction time and accuracy, and the rate at which participants choose to switch tasks. Previous literature has frequently examined these measures in terms of overall task averages. Instead, the current work examines whether these measures change during task performance, as well as the degree to which individual differences in these changes might inform individual differences in external measures. A series of three experiments, two of which utilized publicly available datasets from previous publications, examined changes in these measures throughout the performance of different VTS paradigms administered by different labs. In the first two experiments, significant group-level declines in switch rates were present, consistent with increased effort avoidance and early fatigue effects. In the third experiment, no such decline was present at a group level; however, subject-level changes in switch rates were related to scores on BIS/BAS subscales, while subject average switch rates were not. The current work suggests that examining changes in switch rates throughout a task might provide valuable information not captured by average switch rates that future VTS studies might wish to explore. Future work should attempt to clarify the conditions in which group-level declines in switch rate can be produced as well as which cognitive mechanisms might underlie these declines.

Adaptation is influenced by the complexity of environmental change during evolution in a dynamic environment

The environmental conditions of microorganisms’ habitats may fluctuate in unpredictable ways, such as changes in temperature, carbon source, pH, and salinity to name a few. Environmental heterogeneity presents a challenge to microorganisms, as they have to adapt not only to be fit under a specific condition, but they must also be robust across many conditions and be able to deal with the switch between conditions itself. While experimental evolution has been used to gain insight into the adaptive process, this has largely been in either unvarying or consistently varying conditions. In cases where changing environments have been investigated, relatively little is known about how such environments influence the dynamics of the adaptive process itself, as well as the genetic and phenotypic outcomes. We designed a systematic series of evolution experiments where we used two growth conditions that have differing timescales of adaptation and varied the rate of switching between them. We used lineage tracking to follow adaptation, and whole genome sequenced adaptive clones from each of the experiments. We find that both the switch rate and the order of the conditions influences adaptation. We also find different adaptive outcomes, at both the genetic and phenotypic levels, even when populations spent the same amount of total time in the two different conditions, but the order and/or switch rate differed. Thus, in a variable environment adaptation depends not only on the nature of the conditions and phenotypes under selection, but also on the complexity of the manner in which those conditions are combined to result in a given dynamic environment.

How About Effect of Lithium Carbonate on Preventive Switch Induced by Antidepressants in Patients With Depressive Episode? Chinese Data Analysis

Background: Although mania or hypomania was defined as indispensable for bipolar disorder, depressive episodes are more common and impairing, with proven response to treatments.So the prevention switch was a important affair in clinical psychiatryMethods: We searched CBM, CNKI, WANFANG and CSSCI in Chinese to find literature from July 1 2000 to July 31 2020 related to the study in model of “comparison of switch rate between combination treatment of lithium and antidepressant and monotherapy of antidepressant in patients with depressive episode”, among which results such as comments, letters, reviews and case reports were excluded. The rate of switch between groups was synthesized and discussed. Result: A total of 695 subjects were included in 9 studies. Random effect model is used to account for the data by Revman 5.2. The results showed that the switch rate of lithium carbonate was 8.28%(29/350),switch rate of antidepressant was 25.29%(87/344), which was very different in switch rate(OR=0.25, 95% CI: 0.16–0.39) and also indicated that lithium reduced switch rate was 67.25%(25.29%-8.28%/25.29%). In bipolar depression group, lithium reduced switch rate was 68.11%(25.84%-8.24%/25.84%). In depression group, lithium reduced switch rate was 67.34%(25.29%-8.26%/25.29%). In group of patients treated by SSRI, lithium reduced switch rate was 60.3%(29.85%-11.85%/29.85%).In group of patients treated by TCA, lithium reduced switch rate was 73.14%(22.28%-6.01%/22.28%). Conclusion: As typical mood stabilizer, lithium carbonate can reduced switch rate related to antidepressant in patients with depressive episode.