Psychosis Prognosis Predictor: A continuous and uncertainty-aware prediction of treatment outcome in first-episode psychosis.

INTRODUCTION: Machine learning models have shown promising potential in individual-level outcome prediction for patients with psychosis, but also have several limitations. To address some of these limitations, we present a model that predicts multiple outcomes, based on longitudinal patient data, while integrating prediction uncertainty to facilitate more reliable clinical decision-making. MATERIAL AND METHODS: We devised a recurrent neural network architecture incorporating long short-term memory (LSTM) units to facilitate outcome prediction by leveraging multimodal baseline variables and clinical data collected at multiple time points. To account for model uncertainty, we employed a novel fuzzy logic approach to integrate the level of uncertainty into individual predictions. We predicted antipsychotic treatment outcomes in 446 first-episode psychosis patients in the OPTiMiSE study, for six different clinical scenarios. The treatment outcome measures assessed at both week 4 and week 10 encompassed symptomatic remission, clinical global remission, and functional remission. RESULTS: Using only baseline predictors to predict different outcomes at week 4, leave-one-site-out validation AUC ranged from 0.62 to 0.66; performance improved when clinical data from week 1 was added (AUC = 0.66-0.71). For outcome at week 10, using only baseline variables, the models achieved AUC = 0.56-0.64; using data from more time points (weeks 1, 4, and 6) improved the performance to AUC = 0.72-0.74. After incorporating prediction uncertainties and stratifying the model decisions based on model confidence, we could achieve accuracies above 0.8 for ~50% of patients in five out of the six clinical scenarios. CONCLUSION: We constructed prediction models utilizing a recurrent neural network architecture tailored to clinical scenarios derived from a time series dataset. One crucial aspect we incorporated was the consideration of uncertainty in individual predictions, which enhances the reliability of decision-making based on the model's output. We provided evidence showcasing the significance of leveraging time series data for achieving more accurate treatment outcome prediction in the field of psychiatry.

Longitudinal assessment of ventricular volume trajectories in early-stage schizophrenia: evidence of both enlargement and shrinkage.

BACKGROUND: Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. METHODS: We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. RESULTS: Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. CONCLUSION: Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.

Time is the enemy: Negative symptoms are related to even slight differences in the duration of untreated psychosis.

BACKGROUND: Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AIMS: We aimed to identify factors from the baseline visit (V1) - with a mean illness duration of 0.47 years (SD = 0.45) - that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/- 0.45). METHOD: Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. RESULTS: DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/- 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. CONCLUSION: The results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.

The influence of antibiotic treatment on the behavior and gut microbiome of adult rats neonatally insulted with lipopolysaccharide.

The present study investigated whether neonatal exposure to the proinflammatory endotoxin lipopolysaccharide (LPS) followed by an antibiotic (ATB)-induced dysbiosis in early adulthood could induce neurodevelopmental disorders-like behavioral changes in adult male rats. Combining these two stressors resulted in decreased weight gain, but no significant behavioral abnormalities were observed. LPS treatment resulted in adult rats' hypoactivity and induced anxiety-like behavior in the social recognition paradigm, but these behavioral changes were not exacerbated by ATB-induced gut dysbiosis. ATB treatment seriously disrupted the gut bacterial community, but dysbiosis did not affect locomotor activity, social recognition, and acoustic reactivity in adult rats. Fecal bacterial community analyses showed no differences between the LPS challenge exposed/unexposed rats, while the effect of ATB administration was decisive regardless of prior LPS exposure. ATB treatment resulted in significantly decreased bacterial diversity, suppression of Clostridiales and Bacteroidales, and increases in Lactobacillales, Enterobacteriales, and Burkholderiales. The persistent effect of LPS on some aspects of behavior suggests a long-term effect of early toxin exposure that was not observed in ATB-treated animals. However, an anti-inflammatory protective effect of ATB cannot be assumed because of the increased abundance of pro-inflammatory, potentially pathogenic bacteria (Proteus, Suttrella) and the elimination of the bacterial families Ruminococcaceae and Lachnospiraceae, which are generally considered beneficial for gut health.

Registered report: How open do you want your science? An international investigation into knowledge and attitudes of psychology students.

The use of Open Science practices is often proposed as a way to improve research practice, especially in psychology. Open Science can increase transparency and therefore reduce questionable research practices, making research more accessible to students, scholars, policy makers, and the public. However, little is known about how widespread Open Science practices are taught and how students are educated about these practices. In addition, it remains unknown how informing students about Open Science actually impacts their understanding and adoption of such practices. This registered report proposes the validation of a questionnaire. The aim is to survey how much psychology students know about Open Science and to assess whether knowledge of and exposure to Open Science in general-be it through university curricula or social media-influences attitudes towards the concept and intentions to implement relevant practices.

Activity of New Synthetic (2-Chloroethylthio)-1,4-naphthoquinones in Prostate Cancer Cells.

Development of resistance to currently available standard therapies in advanced prostate cancer (PCa) emphasizes the need for novel therapeutic options. Here, we report the synthesis of new hybrid molecules consisting of 2-chloroethylthio and 1,4-naphthoquinone pharmacophores and describe their activity in PCa. In screening analyses, the introduction of one 2-chloroethylthio group improved the anticancer properties of 1,4-naphthoquinones, whereas the introduction of a second 2-chloroethylthio moiety rather decreased activity. Two most promising of the synthesized compounds, 30 and 32, were highly active in different human PCa cell lines harboring varying resistance profiles at nanomolar concentrations. The generated data suggest that the compounds are capable of mitochondria targeting, cytotoxic ROS induction, and DNA damage, which resulted in apoptosis presumably executed in a caspase-dependent manner. The substances synergized with the clinically approved PARP inhibitor olaparib and resensitized AR-V7-expressing PCa cells to antiandrogen enzalutamide, as well as to a combination of enzalutamide and an AKT inhibitor. This was at least in part exerted via down-regulation of AR-V7 expression and inhibition of AR signaling. Mild antagonism was observed in combination with platinum- or taxane-based chemotherapy, which was putatively related to treatment-induced activation of p38, JNK1/2, ERK1/2, MEK1/2, and AKT, functioning as potential pro-survival factors. Thus, the synthesized (2-chloroethylthio)-1,4-naphthoquinone derivatives exhibit promising anticancer properties in vitro, suggesting their further development as potential therapeutics for the treatment of castration-resistant PCa.

The general fault in our fault lines.

Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.

Driver eye movements in relation to unfamiliar traffic signs: An eye tracking study.

Traffic signs are an integral part of the traffic control plan and they provide road users with necessary information on the upcoming situation. This paper aims to examine the level of understanding of traffic sign imagery used in different countries and to track participants' eye movement when they encounter unfamiliar signs. Tobii eye tracking glasses were used to track gaze differences between familiar and unfamiliar traffic signs. Our findings show that sign characteristics (such as the amount of information on the sign) and the observer's knowledge of the sign meaning have a significant impact on eye behaviour. Signs containing more information (loaded with more content) and unfamiliar to the participant systematically produced the longest overall and average fixations and gazing duration. Given that longer gaze time for unfamiliar traffic signs presents a potential traffic hazard, we evaluated the need for standardization of traffic signs.

Study Protocol on Cognitive Performance in Bulgaria, Croatia, and the Netherlands: The Normacog Brief Battery.

The Normacog Brief Battery (NBB) provides a comprehensive overview of an individual's cognitive functioning within a short amount of time. It was originally developed for the Spanish population in Spain. However, there is a considerable need for brief batteries in clinical neuropsychological assessment, especially in eastern European countries. Cultural background and other individual characteristics-such as age, level of education, and sex-are shown to influence both cognition and patients' performance on neuropsychological tests. Therefore, it is important to develop understanding of how and why culture impacts on cognitive testing and determine which sociodemographic variables affect cognitive performance. The current study aims to translate, adapt, and standardize the NBB in Bulgaria, Croatia, and the Netherlands, and to analyze the effect of sex, age, and education level on cognitive performance between these three countries. This brief battery assesses eleven cognitive domains, including those most currently relevant in cognition such as premorbid intelligence, attention, executive function, processing speed, and memory. The translation and adaptation of the battery for different cultures will be done using the back-translation process. After exclusion criteria, the current study will include a total sample of 300 participants (≥18 years old). The samples of 100 participants per country will be balanced through the consideration of their age and level of education. Effects of the sociodemographic variables (age, level of education, and sex) on cognitive performance are expected. Furthermore, this relationship is expected to differ across countries. A multivariate hierarchical linear regression will be used and exploratory analysis will be carried out to investigate further effects. The results will be particularly valuable for future research and assessment in cognitive performance. The growing demand for accurate and fast neuropsychological assessment shows the importance of creating a universal brief assessment tool for wider cross-cultural application.