Negative Symptom Domains Are Associated With Verbal Learning in Adolescents With Early Onset Psychosis

Background: Early-onset psychosis (EOP) is among the leading causes of disease burden in adolescents. Negative symptoms and cognitive deficits predicts poorer functional outcome. A better understanding of the association between negative symptoms and cognitive impairment may inform theories on underlying mechanisms and elucidate targets for development of new treatments. Two domains of negative symptoms have been described in adult patients with schizophrenia: apathy and diminished expression, however, the factorial structure of negative symptoms has not been investigated in EOP. We aimed to explore the factorial structure of negative symptoms and investigate associations between cognitive performance and negative symptom domains in adolescents with EOP. We hypothesized that (1) two negative symptom factors would be identifiable, and that (2) diminished expression would be more strongly associated with cognitive performance, similar to adult psychosis patients.Methods: Adolescent patients with non-affective EOP (n = 169) were included from three cohorts: Youth-TOP, Norway (n = 45), Early-Onset Study, Norway (n = 27) and Adolescent Schizophrenia Study, Mexico (n = 97). An exploratory factor analysis was performed to investigate the underlying structure of negative symptoms (measured with the Positive and Negative Syndrome Scale (PANSS)). Factor-models were further assessed using confirmatory factor analyses. Associations between negative symptom domains and six cognitive domains were assessed using multiple linear regression models controlling for age, sex and cohort. The neurocognitive domains from the MATRICS Consensus Cognitive Battery included: speed of processing, attention, working memory, verbal learning, visual learning, and reasoning and problem solving.Results: The exploratory factor analysis of PANSS negative symptoms suggested retaining only a single factor, but a forced two factor solution corroborated previously described factors of apathy and diminished expression in adult-onset schizophrenia. Results from confirmatory factor analysis indicated a better fit for the two-factor model than for the one-factor model. For both negative symptom domains, negative symptom scores were inversely associated with verbal learning scores.Conclusion: The results support the presence of two domains of negative symptoms in EOP; apathy and diminished expression. Future studies on negative symptoms in EOP should examine putative differential effects of these symptom domains. For both domains, negative symptom scores were significantly inversely associated with verbal learning.

Tracing Links Between Early Auditory Information Processing and Negative Symptoms in Schizophrenia: An ERP Study

Background: Negative symptoms represent a heterogeneous dimension with a strong impact on functioning of subjects with schizophrenia (SCZ). Five constructs are included in this dimension: anhedonia, asociality, avolition, blunted affect, and alogia. Factor analyses revealed that these symptoms cluster in two domains: experiential domain (avolition, asociality, and anhedonia) and the expressive deficit (alogia and blunted affect), that might be linked to different neurobiological alterations. Few studies investigated associations between N100, an electrophysiological index of early sensory processing, and negative symptoms, reporting controversial results. However, none of these studies investigated electrophysiological correlates of the two negative symptom domains.Objectives: The aim of our study was to evaluate, within the multicenter study of the Italian Network for Research on Psychoses, the relationships between N100 and negative symptom domains in SCZ.Methods: Auditory N100 was analyzed in 114 chronic stabilized SCZ and 63 healthy controls (HCs). Negative symptoms were assessed with the Brief Negative Symptom Scale (BNSS). Repeated measures ANOVA and correlation analyses were performed to evaluate differences between SCZ and HCs and association of N100 features with negative symptoms.Results: Our findings demonstrated a significant N100 amplitude reduction in SCZ compared with HCs. In SCZ, N100 amplitude for standard stimuli was associated with negative symptoms, in particular with the expressive deficit domain. Within the expressive deficit, blunted affect and alogia had the same pattern of correlation with N100.Conclusion: Our findings revealed an association between expressive deficit and N100, suggesting that these negative symptoms might be related to deficits in early auditory processing in SCZ.

PRODUCTION OF AFFIRMATIVE, NEGATIVE AND INTERROGATIVE SENTENCES IN SCHIZOPHRENIA

Language disorder is one of the most significant symptom domains which characterize Schizophrenia Disorder. The aim of the present study considering these language problems is to find out the number of the affirmative, negative and interrogative sentences on schizophrenia patients’ spontaneous speech and reveal whether their depression, doubts and sceptical behaviours affect their speech. Fifty patients with schizophrenia diagnosed according to DSM-IV criteria were included into the study and compared to fifty healthy subjects matched for age, sex and education level with the patients participated in the study. The subjects’ speech was evaluated by using subject-based narration and free verbal narration tests. As a result of the statistical and linguistic analyses, significant differences were found between schizophrenic patients’ and healthy subjects’ speech in terms of between affirmative, negative and interrogative sentence use. The results indicate that the patients' excessive use of negative and interrogative sentences is related to their feature of attributing negatively to the events and emotions they experience.

A meta-analysis on the effect of telemedicine on the management of attention deficit and hyperactivity disorder in children and adolescents

Introduction This study aims to report the effect sizes of telemedicine treatments on the symptom domains of paediatric ADHD. Methods In this systematic review and meta-analysis, electronic databases, i.e. PubMed, Scopus, Web of Science and Embase, were searched for articles published up to December 2020. The inclusion criteria were as follows: children or adolescents diagnosed for ADHD or other hyperkinetic disorders; randomized controlled trials (RCTs); efficacy established with parents and teachers or self-rating scales at least for one of the following domains: inattention, cognitive function, hyperactivity, hyperactivity/impulsivity or oppositional behaviours. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. Results From 310 records reduced to 228 after removing duplicates, overall 12 studies were fulfilled our inclusion criteria. They consisted of 708 participants (358 with telemedicine intervention and 350 controls). The telemedicine interventions varied from computerized training programmes with phone calls to videoconferencing programmes, virtual reality classrooms or games. The most applicable method consisted of computerized training programmes with phone calls. Pooling results of all studies with available data on each subscale showed a significant effect of telemedicine on inattention/cognitive function (standardized mean difference (SMD) = 0.26, 95% CI: 0.16, 0.36), hyperactivity/impulsivity (SMD = 0.29, 95% CI: 0.06, 0.52), and oppositional behaviours (SMD = 0.72, 95% CI: 0.24, 1.20) subscales in ADHD. Almost all studies had an overall unclear risk of bias. The source of outcome assessment (parents, teachers or self-report questionnaire) was addressed as a potential confounding factor. In almost all symptom domains, the satisfaction from the treatment was higher in parents than in teachers. Conclusions The clinical effects of telemedicine on the treatment of ADHD showed a small effect size for inattention/cognitive function, hyperactivity/impulsivity and oppositional behaviours.

"Predictors of Negative Symptom Domains in Outpatients with Schizophrenia: A Cross-Sectional Study"

"Background: Current research suggests that negative symptoms may not be a unitary construct. Factor analytic studies typically found evidence for a two-factor solution of the negative symptom domain: the expressive and the volitional deficit. This study aimed to investigate whether the two-factor solution of negative symptoms is supported across different instruments of evaluation: PANSS and NSA-16 in outpatients with schizophrenia and to explore the relationship between these domains and sociodemographic, clinical, and metabolic outcomes, routinely assessed in daily practice.Another aim was to determine clinical predictors of negative symptoms domains among these variables. Materials and methods: 107 patients with schizophrenia were included in this cross-sectional study. The Principal Component Analysis was used to identify negative symptom domains and Spearman's rank correlation coefficient and multiple regression analyses were used to assess the relationship between the negative symptom domains and clinical variables. Results: PCA indicated a two-component solution explaining 85.2% of the variance for the NSA-16 subscales, reflecting an expressive deficit and an experiential deficit component. Age of onset of the disease and the cognitive deficit were significant predictors of the expressive deficit , body mass index and the number of admissions in the hospital for the experiential deficit. Conclusions: The current findings indicate that the expressive deficit and the experiential deficit should be considered as distinct domains of the psychopathology and should be rated separately"

Case-control study of neuropsychiatric symptoms following COVID-19 hospitalization in 2 academic health systems

Neuropsychiatric symptoms may persist following acute COVID-19 illness, but the extent to which these symptoms are specific to COVID-19 has not been established. We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID-19 between March 2020 and May 2021, and compared them to individuals hospitalized for other indications during this period. Natural language processing was applied to narrative clinical notes to identify neuropsychiatric symptom domains up to 150 days following hospitalization. Among 6,619 individuals hospitalized for COVID-19 drawn from a total of 42,961 hospital discharges, the most commonly documented symptom domains between 31 and 90 days after initial positive test were fatigue (13.4%), mood and anxiety symptoms (11.2%), and impaired cognition (8.0%). In models adjusted for sociodemographic features and hospital course, none of these were significantly more common among COVID-19 patients; indeed, mood and anxiety symptoms were less frequent (adjusted OR 0.72 95% CI 0.64-0.92). Between 91 and 150 days after positivity, most commonly-detected symptoms were fatigue (10.9%), mood and anxiety symptoms (8.2%), and sleep disruption (6.8%), with impaired cognition in 5.8%. Frequency was again similar among non-COVID-19 post-hospital patients, with mood and anxiety symptoms less common (aOR 0.63, 95% CI 0.52-0.75). Neuropsychiatric symptoms were common up to 150 days after initial hospitalization, but occurred at generally similar rates among individuals hospitalized for other indications during the same period. Post-acute sequelae of COVID-19 thus may benefit from standard if less-specific treatments developed for rehabilitation after hospitalization.

Error-related negativity predicts increases in anxiety in a sample of clinically anxious female children and adolescents over 2 years

Background: An increased neural response to making errors has emerged as a biomarker of anxiety. Error negativity (Ne) or errorrelated negativity (ERN) is an event-related potential generated when people commit errors; the Ne/ERN is greater among people with anxiety and predicts increases in anxiety. However, no previous study has examined whether the Ne/ERN can be used as a prognostic indicator among people with current anxiety. The present study addressed this gap by examining whether the Ne/ERN prospectively predicts increases in anxiety symptoms in clinically anxious children and adolescents. Methods: The sample included 34 female participants between the ages of 8 and 14 years who met the criteria for a clinical anxiety disorder based on clinical interview. The Ne/ERN was measured using a flanker task. Results: Increased Ne/ERN at baseline predicted increases in total anxiety symptoms 2 years later, even when accounting for baseline symptoms. The Ne/ERN predicted increases in the symptom domains of generalized anxiety, social anxiety and harm avoidance/perfectionism, but not panic, separation anxiety, school avoidance or physical symptoms. Limitations: The sample size was small, which may have inflated the false discovery rate. To mitigate this possibility, we used multiple self-report measures, and the results for the 2 measures (as well as their symptom domains) converged. Conclusion: These data suggest that the Ne/ERN can delineate specific risk trajectories, even among those who already meet the criteria for a clinical anxiety disorder. Considering the need for prognostic markers among people with clinical anxiety, the current findings are an important and novel extension of previous work.

Selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for anxiety, obsessive-compulsive, and stress disorders: A 3-level network meta-analysis

Background Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis. Methods and findings We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies’ databases. No restriction was made regarding comorbidities with any other mental disorder, participants’ age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration’s risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). Medication (SSRI or SNRI) was more effective than placebo for the aggregate measure of internalizing symptoms (SMD −0.56, 95% CI −0.62 to −0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials. Conclusions In this study, we observed that SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This 3-level network meta-analysis contributes robust evidence to the ongoing discussion about the true benefit of antidepressants, with a significantly larger quantity of data and higher statistical power than previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy.