Theory of Mind and social functioning among neuropsychiatric disorders:A transdiagnostic study

Social dysfunction is commonly present in neuropsychiatric disorders of schizophrenia (SZ) and Alzheimer's disease (AD). Theory of Mind (ToM) deficits have been linked to social dysfunction in disease-specific studies. Nevertheless, it remains unclear how ToM is related to social functioning across these disorders, and which factors contribute to this relationship. We investigated transdiagnostic associations between ToM and social functioning among SZ/AD patients and healthy controls, and explored to what extent these associations relate to information processing speed or facial emotion recognition capacity. A total of 163 participants were included (SZ: n=56, AD: n=50 and age-matched controls: n=57). Social functioning was assessed with the Social Functioning Scale (SFS) and the De Jong-Gierveld Loneliness Scale (LON). ToM was measured with the Hinting Task. Information processing speed was measured by the Digit Symbol Substitution Test (DSST) and facial emotion recognition capacity by the facial emotion recognition task (FERT). Case-control deficits in Hinting Task performance were larger in AD (rrb = -0.57) compared to SZ (rrb = -0.35). Poorer Hinting Task performance was transdiagnostically associated with the SFS (βHinting-Task = 1.20, p<0.01) and LON (βHinting-Task = -0.27, p<0.05). DSST, but not FERT, reduced the association between the SFS and Hinting Task performance, however the association remained significant (βHinting-Task = 0.95, p<0.05). DSST and FERT performances did not change the association between LON and Hinting Task performance. Taken together, ToM deficits are transdiagnostically associated with social dysfunction and this is partly related to reduced information processing speed

Multivariable prediction of functional outcome after first-episode psychosis:a crossover validation approach in EUFEST and PSYSCAN

Several multivariate prognostic models have been published to predict outcomes in patients with first episode psychosis (FEP), but it remains unclear whether those predictions generalize to independent populations. Using a subset of demographic and clinical baseline predictors, we aimed to develop and externally validate different models predicting functional outcome after a FEP in the context of a schizophrenia-spectrum disorder (FES), based on a previously published cross-validation and machine learning pipeline. A crossover validation approach was adopted in two large, international cohorts (EUFEST, n = 338, and the PSYSCAN FES cohort, n = 226). Scores on the Global Assessment of Functioning scale (GAF) at 12 month follow-up were dichotomized to differentiate between poor (GAF current &lt; 65) and good outcome (GAF current ≥ 65). Pooled non-linear support vector machine (SVM) classifiers trained on the separate cohorts identified patients with a poor outcome with cross-validated balanced accuracies (BAC) of 65-66%, but BAC dropped substantially when the models were applied to patients from a different FES cohort (BAC = 50-56%). A leave-site-out analysis on the merged sample yielded better performance (BAC = 72%), highlighting the effect of combining data from different study designs to overcome calibration issues and improve model transportability. In conclusion, our results indicate that validation of prediction models in an independent sample is essential in assessing the true value of the model. Future external validation studies, as well as attempts to harmonize data collection across studies, are recommended.</p

Comparison between the performance of quantitative flow ratio and perfusion imaging for diagnosing myocardial ischemia

OBJECTIVES This study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)-defined coronary artery disease (CAD).BACKGROUND QFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking.METHODS A total of 208 (624 vessels) patients underwent technetium -99m tetrofosmin SPECT and [15O]H2O PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels).RESULTS QFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively.CONCLUSIONS In this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFRdefined significant CAD compared with perfusion imaging by SPECT or PET. (J Am Coll Cardiol Img 2020;13:1976-85) (c) 2020 by the American College of Cardiology Foundation.Cardiovascular Aspects of Radiolog

Relationships between social withdrawal and facial emotion recognition in neuropsychiatric disorders

Background: Emotion recognition constitutes a pivotal process of social cognition. It involves decoding social cues (e.g., facial expressions) to maximise social adjustment. Current theoretical models posit the relationship between social withdrawal factors (social disengagement, lack of social interactions and loneliness) and emotion decoding. Objective: To investigate the role of social withdrawal in patients with schizophrenia (SZ) or probable Alzheimer's disease (AD), neuropsychiatric conditions associated with social dysfunction. Methods: A sample of 156 participants was recruited: schizophrenia patients (SZ; n = 53), Alzheimer's disease patients (AD; n = 46), and two age-matched control groups (SZc, n = 29; ADc, n = 28). All participants provided self-report measures of loneliness and social functioning, and completed a facial emotion detection task. Results: Neuropsychiatric patients (both groups) showed poorer performance in detecting both positive and negative emotions compared with their healthy counterparts (p < .01). Social withdrawal was associated with higher accuracy in negative emotion detection, across all groups. Additionally, neuropsychiatric patients with higher social withdrawal showed lower positive emotion misclassification. Conclusions: Our findings help to detail the similarities and differences in social function and facial emotion recognition in two disorders rarely studied in parallel, AD and SZ. Transdiagnostic patterns in these results suggest that social withdrawal is associated with heightened sensitivity to negative emotion expressions, potentially reflecting hypervigilance to social threat. Across the neuropsychiatric groups specifically, this hypervigilance associated with social withdrawal extended to positive emotion expressions, an emotionalcognitive bias that may impact social functioning in people with severe mental illness.Education and Child Studie

Prednisolone versus placebo addition in the treatment of patients with recent-onset psychotic disorder: a trial design

BACKGROUND: The symptom severity of a substantial group of schizophrenia patients (30-40%) does not improve through pharmacotherapy with antipsychotic medication, indicating a clear need for new treatment options to improve schizophrenia outcome. Meta-analyses, genetic studies, randomized controlled trials, and post-mortem studies suggest that immune dysregulation plays a role in the pathophysiology of schizophrenia. Some anti-inflammatory drugs have shown beneficial effects on the symptom severity of schizophrenia patients. Corticosteroids are effective in various chronic inflammatory and autoimmune disorders. Prednisolone, a potent glucocorticosteroid, has minor mineral-corticosteroid potencies and can adequately pass the blood-brain barrier

A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort

[Background] We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN).[Method] Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study.[Results] The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period.[Conclusions] This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice.PSYSCAN was supported as part of the European Funding 7th Framework Programme (grant number 603196).Peer reviewe

Supplements to: A naturalistic cohort study of first-episode schizophrenia spectrum disorder: a description of the early phase of illness in the PSYSCAN cohort

Suppl. Figure 1. Percentage of FES patients in symptomatic remission throughout the study.Suppl. Figure 2. Percentage of FES patients in functional remission throughout the study.Suppl. Figure 3. Clustered boxplot displaying the mean depression scores per time point (measured using the Hamilton Depression Rating Scale) in the subgroup meeting criteria for a depressive episode at baseline (assessed through the SCID-I) versus the subgroup without a depressive episode at baseline.Suppl. Table 1. Baseline demographics and clinical characteristics of study completers and drop-outs.Suppl. Table 2. Number of patients in symptomatic and functional remission throughout the period of follow-up.Suppl. Table 3. Generalized linear mixed models: pairwise contrasts for symptomatic and functional remission.Suppl. Table 4. Linear mixed models: estimated marginal means for PANSS, GAF, SOFAS, CGI, GF-S, GF-R and HAM-D.Suppl. Table 5. Linear mixed models: estimates of fixed effect time on PANSS, GAF, SOFAS, CGI, GF-S, GF-R and HAM-D.Suppl. Table 6. Number of patients admitted to the hospital since the previous visit due to psychotic symptoms and due to psychiatric reasons in general.Suppl. Table 7. Substances used at least once in the past three months (WHO-ASSIST).Suppl. Table 8. Number of patients reporting daily or almost daily substance use in the past three months, separated per time point and substance category (WHO-ASSIST).Suppl. Table 9. Number of patients reporting daily or almost daily substance use in the past three months, separated for the group of symptomatic remitters and non-remitters at month 12.Suppl. Table 10. Baseline demographics and clinical characteristics of symptomatic remitters and non-remitters at month 12.Suppl. Table 11. Summary of sociodemographics and baseline clinical characteristics of FES participants, separated per country.Suppl. Table 12. Number of FES patients in symptomatic remission throughout the period of follow-up, separated per country.Suppl. Table 13. Number of FES patients in functional remission throughout the period of follow-up, separated per country.Suppl. Table 14. Number of FES patients admitted to the hospital for psychiatric reasons throughout the period of follow-up, separated per country.Suppl. Table 15. Number of FES patients admitted to the hospital for psychosis throughout the period of follow-up, separated per country.Suppl. Table 16. Number of FES patients using antipsychotic medication throughout the period of follow-up, separated per country.Suppl. Table 17. Overview of subjects not meeting eligibility criteria.Suppl. Table 18. Number of patients in symptomatic and functional remission throughout the period of follow-up when using alternative definitions.Suppl. Table 19. Generalized linear mixed models: pairwise contrasts for symptomatic and functional remission when using alternative definitions.Peer reviewe

Understanding Pitch Perception as a Hierarchical Process with Top-Down Modulation

Pitch is one of the most important features of natural sounds, underlying the perception of melody in music and prosody in speech. However, the temporal dynamics of pitch processing are still poorly understood. Previous studies suggest that the auditory system uses a wide range of time scales to integrate pitch-related information and that the effective integration time is both task- and stimulus-dependent. None of the existing models of pitch processing can account for such task- and stimulus-dependent variations in processing time scales. This study presents an idealized neurocomputational model, which provides a unified account of the multiple time scales observed in pitch perception. The model is evaluated using a range of perceptual studies, which have not previously been accounted for by a single model, and new results from a neurophysiological experiment. In contrast to other approaches, the current model contains a hierarchy of integration stages and uses feedback to adapt the effective time scales of processing at each stage in response to changes in the input stimulus. The model has features in common with a hierarchical generative process and suggests a key role for efferent connections from central to sub-cortical areas in controlling the temporal dynamics of pitch processing

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals

Priorities, satisfaction and treatment goals in psychosis patients: an online consumer's survey

An insight into preferences, satisfaction and treatment goals of patients is important for reaching treatment alliance and may increase the success of initiated treatment. Participants from the Netherlands,with at least one psychotic episode, were asked to fill in an online questionnaire. Participants ranked their priorities in treatment content, stated whether they were satisfied on these items and ranked a list of treatment goals. 462 respondents ranked their treatment preferences regarding treatment content(mean age: 40.3 years; mean duration of illness: 13.5 years). Items ranked most important: “prompt assistance, preferably in own environment”, “attention for medication”, “appropriate attitude of the professional caregiver”. More than 50 % rated “unsatisfied” or “very unsatisfied” for: “practical help in resocialization”, “aid to acquire autonomy” and “help with physical health”. 345 participants ranked treatment goals (mean age: 40.4 years; mean duration of illness: 13.7 years). Items ranked most important: “reducing apathy and lack of initiative”, “reducing disturbing or unusual experiences”, “reducing confusion and concentration problems”. Psychiatric services should pay great attention to early outpatient intervention with supportive counseling and an appropriate attitude of the caregiver with attention for medication use. Improvement is warranted for practical assistance, help in regaining autonomy and help with physical healt