School bullying in children and adolescents with neurodevelopmental and psychiatric conditions: a systematic review and meta-analysis.

BACKGROUND: Bullying is a common form of violence among children and adolescents. Young people with neurodevelopmental or psychiatric conditions might have an increased risk of bullying victimisation and perpetration. We aimed to assess the odds of bullying involvement and its association with mental health measures in these populations. METHODS: In this systematic review and meta-analysis, we searched PubMed, ERIC, Psychology and Behavioural Sciences Collection, Web of Science Core Collection, PsycArticles, and PsycInfo databases from inception up to Aug 8, 2023, and included articles reporting data on bullying outcomes of current bullying (within the past year) among children and adolescents (aged 4-17 years) with a diagnosis of a neurodevelopmental or psychiatric condtion provided by a health professional. Bullying type was classified as traditional (physical, verbal, or relational) or as cyberbullying (intentional and repeated harm inflicted through electronic devices and social media), and bullying involvement was classified as victimisation, perpetration, and perpetration-victimisation. Mental health measures were collected and the associations with bullying involvement assessed. We used random-effects meta-analyses to estimate prevalence and odds ratios (ORs) for bullying involvement. Heterogeneity was assessed using the I2 statistic, and publication bias was tested with Egger's regression. This study is registered with PROSPERO, CRD42021235043. FINDINGS: We included 212 studies in the meta-analysis. The total sample comprised 126 717 cases (mean age 12·34 years [SD 1·82], 37·6% girls) and 504 806 controls (12·5 years [SD 1·86], 47·6% girls). For traditional bullying, the pooled prevalence was 42·2% (95% CI 39·6-44·9) for victimisation, 24·4% (22·6-26·3) for perpetration, and 14·0% (11·4-17·1) for perpetration-victimisation. For cyberbullying, the prevalence was 21·8% (16·0-28·9) for victimisation, 19·6% (13·4-27·7) for perpetration, and 20·7% (8·4-42·6) for perpetration-victimisation. Compared with controls, young people with neurodevelopmental or psychiatric conditions were more likely to be involved in traditional and cyberbullying as a victim (OR 2·85 [95% CI 2·62-3·09] and 2·07 [1·63-2·61]), perpetrator (2·42 [2·20-2·66] and 1·91 [1·60-2·28]), and perpetrator-victim (3·66 [2·83-4·74] and 1·85 [1·05-3·28]). Bullying involvement was associated with higher scores in mental health measures in young people with neurodevelopmental or psychiatric conditions, particularly internalising symptoms and externalising symptoms. INTERPRETATION: Our study underscores bullying involvement as a prevalent risk factor in young people with neurodevelopmental or psychiatric conditions that might add to their disease burden through its negative effects on mental health. Interventions targeting these vulnerable populations are warranted to improve their mental health and their future social integration. FUNDING: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Consorcio Centro de Investigación Biomédica en Red.

Differences in Patterns of Stimulant Use and Their Impact on First-Episode Psychosis Incidence: An Analysis of the EUGEI Study.

BACKGROUND: Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. METHODS: We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. FINDINGS: Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. INTERPRETATION: Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries.

Aripiprazole for the treatment of schizophrenia: Recommendations of a panel of Spanish experts on its use in clinical practice.

OBJECTIVES: Aripiprazole is an antipsychotic with a partial agonism of dopamine D2 and D3 receptors. This differential mechanism implies a rigorous appraisal of the appropriate therapeutic strategies in certain situations. To answer currently unsolved clinical questions about the use of oral and long-acting injectable (LAI) aripiprazole, we present here an expert consensus from 12 Spanish psychiatrists and a pharmacologist with extensive experience in the use of this antipsychotic. METHODS: Through one face-to-face session and online collaboration, we reached consensus and established practical recommendations based on scientific evidence and clinical experience. We classified the available scientific literature according to SIGN system and attributed a level of evidence to each reviewed article. RESULTS: The recommendations were divided according to (i) chronological dimension (based on previous treatments, including patients naïve or not to antipsychotic treatment and maintenance regimen), and (ii) dimension related to therapeutic options, comprising switches to aripiprazole and the most used combinations with this antipsychotic. CONCLUSIONS: We recommend considering aripiprazole as first treatment option in the early stages of schizophrenia and in patients with affective symptoms and contemplating a switch to aripiprazole LAI in all candidate patients. Importantly, switches from other antipsychotics should consider previous antipsychotic history and exposure to aripiprazole. KEYPOINTSAripiprazole can be considered as first treatment option in early stages of schizophrenia and in patients with significant affective symptoms.Aripiprazole LAI shows better adherence than oral aripiprazole and could be considered in all candidate patients.Before switching to aripiprazole, detailed information about previous antipsychotic history should be gathered.Switch to aripiprazole should be managed differently for aripiprazole naïve and non-naïve patients.Rigorous and controlled studies on antipsychotics in real clinical practice should be carried out.

Prefrontal abnormalities, executive dysfunction and symptoms severity are modulated by COMT Val158Met polymorphism in first episode psychosis.

INTRODUCTION: Core dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of COMT Val158Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val158Met modulates PFC gray matter reduction, EF deficits and symptom severity at the time of the first psychotic episode. METHODS: The effect of COMT on both EF performance and prefrontal volume (PFC-VOL) was tested in 158 first episode psychosis (FEP) patients and 141 healthy controls (HC) matched for age (range 9-35 years), sex, ethnicity, handedness and COMT Val158Met distribution. EF and PFC-VOL were compared between FEP and HC groups within each polymorphism status (Met/Met versus Val carriers) to assess whether COMT influenced diagnostic differences. Next, correlations between PFC-VOL and EF performance were computed, as well as between both variables and other clinical characteristics of interest (PANSS scores, PAS infancy and premorbid IQ) in the FEP sample. RESULTS: COMT influenced the diagnostic differences mainly in PFC-VOL, but also in EF performance. FEP-Val carriers showed lower EF scores and reduced PFC-VOL compared to the HC group but also poorer EF performance than FEP Met/Met. Poorer EF performance was associated with smaller PFC-VOL, and both were related to increased severity of negative symptoms, poorer premorbid adjustment, and lower estimated premorbid IQ in FEP patients. CONCLUSIONS: Our findings suggest that COMT Val158Met polymorphism might contribute to PFC-VOL reductions, executive dysfunctions and symptom severity in FEP patients.

Leukocyte telomere length in patients with schizophrenia and related disorders: a meta-analysis of case-control studies.

CONTEXT: Telomere length may serve as a biomarker of cellular aging. The literature assessing telomere length in schizophrenia contains conflicting results. OBJECTIVE: To assess differences in leukocyte telomere length (LTL) in peripheral blood in patients with schizophrenia and related disorders and healthy controls and to explore the effect of potential confounding variables. DATA SOURCES: A search of Ovid MEDLINE, and Proquest databases was conducted to identify appropriate studies published from database inception through December 2020. The review protocol was registered with PROSPERO-ID: CRD42021233280. STUDY SELECTION: The initial literature search yielded 192 studies. After study selection in 3 phases, we included 29 samples from 22 studies in the meta-analysis database. DATA EXTRACTION: We used random effects and meta-regression models to derive Cohen d values with pooled 95% confidence intervals (CI) as estimates of effect size (ES) and to test effects of potential moderators. RESULTS: The overall meta-analysis included 4145 patients with schizophrenia and related disorders and 4184 healthy controls and showed that LTL was significantly shorter in patients, with a small to medium effect size (ES, -0.388; 95% CI, -0.492 to -0.283; p < 0.001). Subgroup meta-analyses did not find a significant effect of age or illness duration on differences in LTL in patients with psychosis relative to controls. Meta-regression analyses showed that none of the putative moderators had a significant effect on effect size estimates. CONCLUSIONS: This meta-analysis find further support for the hypothesis of accelerated cellular aging in schizophrenia and related disorders and highlights the need for large longitudinal studies with repeated LTL measurements over time and appropriate assessments of associated factors.

Prefrontal abnormalities, executive dysfunction and symptoms severity are modulated by COMT Val158Met polymorphism in first episode psychosis / Modulación de alteraciones prefrontales por el polimorfismo COMT Val158Met en los primeros episodios psicóticos

Introduction: Core dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of COMT Val158Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val158Met modulates PFC gray matter reduction, EF deficits and symptom severity at the time of the first psychotic episode.Methods: The effect of COMT on both EF performance and prefrontal volume (PFC-VOL) was tested in 158 first episode psychosis (FEP) patients and 141 healthy controls (HC) matched for age (range 9–35 years), sex, ethnicity, handedness and COMT Val158Met distribution. EF and PFC-VOL were compared between FEP and HC groups within each polymorphism status (Met/Met versus Val carriers) to assess whether COMT influenced diagnostic differences. Next, correlations between PFC-VOL and EF performance were computed, as well as between both variables and other clinical characteristics of interest (PANSS scores, PAS infancy and premorbid IQ) in the FEP sample.Results: COMT influenced the diagnostic differences mainly in PFC-VOL, but also in EF performance. FEP-Val carriers showed lower EF scores and reduced PFC-VOL compared to the HC group but also poorer EF performance than FEP Met/Met. Poorer EF performance was associated with smaller PFC-VOL, and both were related to increased severity of negative symptoms, poorer premorbid adjustment, and lower estimated premorbid IQ in FEP patients.Conclusions: Our findings suggest that COMT Val158Met polymorphism might contribute to PFC-VOL reductions, executive dysfunctions and symptom severity in FEP patients. (AU)

Introducción: Algunas de las alteraciones descritas en los trastornos psicóticos incluyen una hipoactividad dopaminérgica en la corteza prefrontal (CPF), déficits en la función ejecutiva (FE) y reducción de la materia gris en la CPF. La variante Val del polimorfismo COMT Val158Met se asocia con una menor disponibilidad dopaminérgica en la CPF. Sin embargo, está aún pendiente de determinar la forma en la que COMT modula la materia gris de la CPF, la FE y la gravedad de los síntomas en el momento del primer episodio psicótico (PEP).Métodos: El efecto de COMT en el rendimiento de la FE y el volumen prefrontal (VOL-CPF) se evaluó en 158 pacientes con PEP y 141 controles sanos (CS) emparejados por edad (9-35 años), sexo, etnia y distribución de COMT. La FE y el VOL-CPF se compararon entre los grupos de PEP y CS, y en función de la variante alélica del polimorfismo (Met/Met versus portadores Val) para evaluar si COMT modula las diferencias diagnósticas. Además, se llevaron a cabo correlaciones entre FE y VOL-CPF, así como entre ambas variables y las puntuaciones en la PANSS, el ajuste premórbido y el CI premórbido.Resultados: COMT moduló las diferencias diagnósticas en VOL-CPF y el rendimiento de FE. Los PEP portadores de la variante Val presentaron menores puntuaciones en FE y reducción del VOL-CPF en comparación con el grupo CS, y menor rendimiento de FE que los PEP Met/Met. Un menor rendimiento en FE se asoció con un menor VOL-CPF, y ambas variables estaban relacionadas con un incremento en la gravedad de síntomas negativos, un peor ajuste premórbido y un menor CI premórbido en pacientes con PEP.Conclusiones: Nuestros hallazgos evidencian que el polimorfismo COMT Val158Met podría contribuir a la reducción del VOL-CPF, la disfunción ejecutiva y la gravedad de los síntomas en los pacientes con PEP. (AU)

Cortical thinning over two years after first-episode psychosis depends on age of onset.

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15-35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe.

Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis.

BACKGROUND: There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. METHODS: We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses. RESULTS: We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles. LIMITATIONS: Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms. CONCLUSIONS: Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.

The impact of cognitive reserve, cognition and clinical symptoms on psychosocial functioning in first-episode psychoses.

BACKGROUND: Functional impairment is a defining feature of psychotic disorders. A range of factors has been shown to influence functioning, including negative symptoms, cognitive performance and cognitive reserve (CR). However, it is not clear how these variables may affect functioning in first-episode psychosis (FEP) patients. This 2-year follow-up study aimed to explore the possible mediating effects of CR on the relationship between cognitive performance or specific clinical symptoms and functional outcome. METHODS: A prospective study of non-affective FEP patients was performed (211 at baseline and 139 at follow-up). CR was entered in a path analysis model as potential mediators between cognitive domains or clinical symptoms and functioning. RESULTS: At baseline, the relationship between clinical variables or cognitive performance and functioning was not mediated by CR. At follow-up, the effect of attention (p = 0.003) and negative symptoms (p = 0.012) assessed at baseline on functioning was partially mediated by CR (p = 0.032 and 0.016), whereas the relationship between verbal memory (p = 0.057) and functioning was mediated by CR (p = 0.014). Verbal memory and positive and total subscales of PANSS assessed at follow-up were partially mediated by CR and the effect of working memory on functioning was totally mediated by CR. CONCLUSIONS: Our results showed the influence of CR in mediating the relationship between cognitive domains or clinical symptoms and functioning in FEP. In particular, CR partially mediated the relationship between some cognitive domains or clinical symptoms and functioning at follow-up. Therefore, CR could improve our understanding of the long-term functioning of patients with a non-affective FEP.

Relación entre empleo y bienestar emocional en personas con trastorno mental grave / Relationship between employment and emotional state in people with severe mental disorder

Las personas con un diagnóstico de trastorno mental grave (TMG) tienen tasas de desempleo notablemente superiores a las de la población general. Esto se asocia con mayor riesgo de exclusión social y de marginalidad, y favorece la cronicidad de las dificultades personales y sociales. Este estudio observacional pretende evaluar la relación entre el empleo y el estado emocional subjetivo en personas con TMG. El estudio incluyó 744 participantes (304 con TMG usuarias de recursos de rehabilitación psicosocial, 168 personas con TMG con empleo protegido y 272 personas sin TMG con empleo ordinario), con una edad media de 41.9 años y 50.1% mujeres. De los 744 participantes, 577 (77.6%) tuvieron empleo remunerado (409 (60.9%) empleo ordinario y 168 (29.1%) empleo protegido); 244 (32.8%) comunicaron que tenían un diagnóstico de psicosis y 400 (53.8%) que tenían reconocida la discapacidad. Las personas con empleo tuvieron mejores valores de bienestar psicológico subjetivo (p=0.013) que las personas sin empleo, independientemente del diagnóstico o de la discapacidad. Sin embargo, no hubo diferencias significativas en bienestar psicológico subjetivo entre las personas con empleo ordinario y con empleo protegido (p=0.687). Como conclusión, las personas con empleo remunerado tuvieron mayor bienestar psicológico subjetivo que las personas sin empleo, independientemente del diagnóstico, de la discapacidad o de que el empleo fuera ordinario o protegido. (AU)

People with a diagnosis of severe mental disorder (SMD) have significantly higher unemployment rates than the general population. This is associated with a greater risk of social exclusion and marginalization, and favors the chronicity of personal and social difficulties. This observational study aims to assess the relationship between employment and subjective emotional state in people with a SMD diagnosis. The study included 744 participants (304 with a SMD diagnosis who were users of psychosocial rehabilitation resources, 168 with a SMD diagnosis with supported employment, and 272 people without diagnosis of SMD with ordinary (non-supported) employment), with a mean age of 41.9 years and 50.1% women. Out of the 744 participants, 577 (77.6%) had an employment (409 (60.9%) ordinary employment and 168 (29.1%) supported employment), 244 (32.8%) reported that they have a diagnosis of psychosis and 400 (53.8%) that they have a recognized disability. People with an employment had better subjective psychological well-being values than people without an employment (p=0.013), regardless of diagnosis or disability. There were no significant differences in subjective psychological well-being between people with ordinary employment and people with supported employment (p=0.687). In conclusion, people with a paid employment had higher subjective psychological well-being than people without an employment, regardless of diagnosis, disability or whether the employment was ordinary or supported. (AU)

Fronto-Parietal Gray Matter Volume Loss Is Associated with Decreased Working Memory Performance in Adolescents with a First Episode of Psychosis.

Cognitive maturation during adolescence is modulated by brain maturation. However, it is unknown how these processes intertwine in early onset psychosis (EOP). Studies examining longitudinal brain changes and cognitive performance in psychosis lend support for an altered development of high-order cognitive functions, which parallels progressive gray matter (GM) loss over time, particularly in fronto-parietal brain regions. We aimed to assess this relationship in a subsample of 33 adolescents with first-episode EOP and 47 matched controls over 2 years. Backwards stepwise regression analyses were conducted to determine the association and predictive value of longitudinal brain changes over cognitive performance within each group. Fronto-parietal GM volume loss was positively associated with decreased working memory in adolescents with psychosis (frontal left (B = 0.096, p = 0.008); right (B = 0.089, p = 0.015); parietal left (B = 0.119, p = 0.007), right (B = 0.125, p = 0.015)) as a function of age. A particular decrease in frontal left GM volume best predicted a significant amount (22.28%) of the variance of decreased working memory performance over time, accounting for variance in age (14.9%). No such association was found in controls. Our results suggest that during adolescence, EOP individuals seem to follow an abnormal neurodevelopmental trajectory, in which fronto-parietal GM volume reduction is associated with the differential age-related working memory dysfunction in this group.

Humanization in mental health plans in Spain. / La humanización en los planes de salud mental en España.

INTRODUCTION: Mental health (MH) care has important challenges, especially in the field of humanization. Our objectives were to identify the humanization measures in MH plans of the Spanish autonomous communities (CCAA) and the priorities to be developed in this area. MATERIAL AND METHODS: A large and multidisciplinary group of people involved in MH care participated in a consensus, according to a modified Delphi method, based on «design thinking¼, in three phases: (1) identification of humanization measures in MH plans of CCAA; (2) analysis of the implementation of these measures; and (3) identification of humanization priorities in MH. RESULTS: Fourteen of the 17 CCAA have current MH plans. They contained four types of humanization measures: (1) improvement of the quality of care; (2) promotion of user participation; (3) campaigns against stigma and discrimination; (4) caring for especially vulnerable people. Implementation of measures ranged from 6.3% (i.e.: specific budget) to 100%, with an average of 64.1%. We identified priority issues, operationalized in 5 proposals: (1) information campaigns; (2) multidisciplinary meeting forums; (3) platforms of support entities; (4) strategies on MH education; (5) humanization in study plans. CONCLUSIONS: Some MH plans include humanization among their objectives, but partially. The implementation of humanization proposals such as those identified in this study is essential to achieve a high-quality MH care.

Cognitive clusters in first-episode psychosis.

Impairments in a broad range of cognitive domains have been consistently reported in some individuals with first-episode psychosis (FEP). Cognitive deficits can be observed during the prodromal stage. However, the course of cognitive deficits is still unclear. The aim of this study was to identify cognitive subgroups over time and to compare their sociodemographic, clinical and functional profiles. A total of 114 patients with Schizophrenia Spectrum Disorders were included in the present study. We assessed subjects through psychiatric scales and eight neuropsychological tests at baseline and at two-year follow-up visit. We performed the Partition Around Medoids algorithm with all cognitive variables. Furthermore, we performed a logistic regression to identify the predictors related to the different cognitive clusters at follow-up. Two distinct subgroups were found: the first cluster characterized by cognitive impairment and a second cluster had relatively intact cognition in comparison with norms. Up to 54.7% of patients with cognitive deficits at baseline tended to improve during the first two years of treatment. Patients with intact cognition at follow-up had a higher socioeconomic status, later age of onset, lower negative symptoms and a higher cognitive reserve (CR) at baseline. CR and age of onset were the baseline variables that predicted cognitive impairment. This research allows us to obtain a better understanding of the heterogeneous profile of psychotic disorders. Identifying the characteristics of patients who will present a cognitive impairment could improve early detection and intervention. These results suggest that enhancing CR could contribute to improving the course of the illness.

The Role of Premorbid IQ and Age of Onset as Useful Predictors of Clinical, Functional Outcomes, and Recovery of Individuals with a First Episode of Psychosis.

BACKGROUND: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown. METHODS: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ ≥ 85) and age of onset (early onset < 18 years; adult onset ≥ 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates. RESULTS: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset patients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms (d = 0.59), poorer functioning (d = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%). CONCLUSIONS: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup.

The role of depression in the prediction of a "late" remission in first-episode psychosis: An analysis of the OPTiMiSE study.

OBJECTIVE: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES). METHODS: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" remitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period. RESULTS: Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR) = 4.186, 95% confidence interval (CI) = 2.082-8.416, p < 0.001) and older age (OR = 1.081, 95% CI = 1.026-1.138, p = 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019). CONCLUSION: Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01248195, https://clinicaltrials.gov/ct2/show/NCT01248195.

Assessment of School Anti-Bullying Interventions: A Meta-analysis of Randomized Clinical Trials.

Importance: Bullying is a prevalent and modifiable risk factor for mental health disorders. Although previous studies have supported the effectiveness of anti-bullying programs; their population impact and the association of specific moderators with outcomes are still unclear. Objective: To assess the effectiveness of school anti-bullying interventions, their population impact, and the association between moderator variables and outcomes. Data Sources: A search of Ovid MEDLINE, ERIC, and PsycInfo databases was conducted using 3 sets of search terms to identify randomized clinical trials (RCTs) assessing anti-bullying interventions published from database inception through February 2020. A manual search of reference lists of articles included in previous systematic reviews and meta-analyses was also performed. Study Selection: The initial literature search yielded 34 798 studies. Included in the study were articles that (1) assessed bullying at school; (2) assessed the effectiveness of an anti-bullying program; (3) had an RCT design; (4) reported results; and (5) were published in English. Of 16 707 studies identified, 371 met the criteria for review of full-text articles; 77 RCTs were identified that reported data allowing calculation of effect sizes (ESs). Of these, 69 independent trials were included in the final meta-analysis database. Data Extraction and Synthesis: Random-effects and meta-regression models were used to derive Cohen d values with pooled 95% CIs as estimates of ES and to test associations between moderator variables and ES estimates. Population impact number (PIN), defined as the number of children in the total population for whom 1 event may be prevented by an intervention, was used as an estimate of the population impact of universal interventions targeting all students, regardless of individual risk. Main Outcomes and Measures: The main outcomes are the effectiveness (measured by ES) and the population impact (measured by the PIN) of anti-bullying interventions on the following 8 variable categories: overall bullying, bullying perpetration, bullying exposure, cyberbullying, attitudes that discourage bullying, attitudes that encourage bullying, mental health problems (eg, anxiety and depression), and school climate as well as the assessment of potential assocations between trial or intervention characteristics and outcomes. Results: This study included 77 samples from 69 RCTs (111 659 participants [56 511 in the intervention group and 55 148 in the control group]). The weighted mean (range) age of participants in the intervention group was 11.1 (4-17) years and 10.8 (4-17) years in the control group. The weighted mean (range) proportion of female participants in the intervention group was 49.9% (0%-100%) and 50.5% (0%-100%) in the control group. Anti-bullying interventions were efficacious in reducing bullying (ES, -0.150; 95% CI, -0.191 to -0.109) and improving mental health problems (ES, -0.205; 95% CI, -0.277 to -0.133) at study end point, with PINs for universal interventions that target the total student population of 147 (95% CI, 113-213) and 107 (95% CI, 73-173), respectively. Duration of intervention was not statistically significantly associated with intervention effectiveness (mean [range] duration of interventions, 29.4 [1 to 144] weeks). The effectiveness of anti-bullying programs did not diminish over time during follow-up (mean [range] follow-up, 30.9 [2-104] weeks). Conclusions and Relevance: Despite the small ESs and some regional differences in effectiveness, the population impact of school anti-bullying interventions appeared to be substantial. Better designed trials that assess optimal intervention timing and duration are warranted.

The Positive and Negative Syndrome Scale for Schizophrenia Autism Severity Scale (PAUSS) in young people with autism and schizophrenia / Escala PAUSS (escala de gravedad del autismo derivada de la PANSS - escala de síndrome positivo y negativo para la esquizofrenia) en una muestra de jóvenes con autismo y esquizofrenia

INTRODUCTION: Schizophrenia spectrum disorders (SSD) share symptoms with autism spectrum disorders (ASD). Autistic phenotypic profiles in SSD may be associated with a poor prognosis. We aimed to assess the evidences for reliability and convergent validity of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Autism Severity Scale (PAUSS) in a sample of young people with ASD and SSD, and to use the PAUSS to explore correlates of "autistic profiles" in the SSD sample. MATERIALS AND METHODS: ASD (n=33, age=13-27 years) and SSD subjects (n=26, age=16-35 years) underwent PANSS, Autism Diagnostic Observation Schedule-Generic (ADOS-G), Autism Diagnostic Interview-Revised (ADI-R), and Social Responsiveness Scale (SRS) assessments. We derived PAUSS total/domain scores from the PANSS and applied these back-to-back with ADOS calibrated severity scores (CSS), ADI-R current behavior algorithm (CBA) scores, and SRS scores. RESULTS: Our results show evidence for an acceptable PAUSS score reliability and convergent validity both in the ASD and SSD samples. PAUSS total and socio-communication scores significantly correlated with ADOS Overall/Social Affect CSS, both in ASD and in SSD. SSD with higher PAUSS scores ("autistic-SSD") showed Overall/Social Affect CSS scores positioned in between ASD and "non-autistic SSD". The PAUSS total score was significantly associated with global functioning in SSD (adjusted R2=0.311). CONCLUSIONS: There seems to be evidence for the reliability and validity of PAUSS scores for quantifying autism symptom severity transdiagnostically and to identify "autistic phenotypes" in adolescents/young adults with SSD

INTRODUCCIÓN: Los trastornos del espectro de la esquizofrenia (TEE) comparten síntomas con los trastornos del espectro del autismo (TEA). En individuos con TEE, perfiles fenotípicos "autistas" parecen estar asociados con un peor pronóstico. Nuestro objetivo fue evaluar la evidencia de fiabilidad y validez convergente de la PAUSS (escala de gravedad del autismo derivada de la escala de síndrome positivo y negativo para la esquizofrenia [PANSS]) en una muestra de jóvenes con TEA y TEE, y utilizar la PAUSS para explorar correlatos de "perfiles autistas" en la muestra de TEE. MATERIALES Y MÉTODOS: En sujetos con TEA (n = 33, edad = 13-27 años) y TEE (n = 26, edad = 16-35 años) se llevaron a cabo las siguientes evaluaciones: la PANSS, la Escala de Observación para el Diagnóstico del Autismo - Genérica (ADOS-G), la Entrevista para el Diagnóstico del Autismo-Revisada (ADI-R), y la Escala de Sensibilidad Social (SRS). Se derivaron de la PANSS las puntuaciones totales/dominio de la PAUSS y se correlacionaron con las puntaciones CSS (gravedad total calibrada) del ADOS, con las puntuaciones del algoritmo de comportamiento actual (CBA) del ADI-R y con las puntuaciones de la SRS. RESULTADOS: Nuestros resultados muestran una evidencia de fiabilidad y validez convergente de la PAUSS aceptables tanto en la muestra TEA como en la TEE. Las puntuaciones totales y del dominio social-comunicación de la PAUSS correlacionaban positiva y significativamente con las puntuaciones CSS total y afectividad social, respectivamente, tanto en la muestra TEA como en la TEE. Los individuos TEE con puntuaciones PAUSS más elevadas ("TEE autistas") mostraban puntuaciones CSS total y afectividad social situadas entre las de los individuos TEA y los "TEE-no autistas". En individuos TEE, la puntuación total PAUSS mostraba una asociación significativa con el funcionamiento global (R2 ajustado = 0.311). CONCLUSIONES: Parece haber evidencia de fiabilidad y validez de las puntuaciones de la PAUSS para cuantificar la gravedad de sintomatología autista a nivel transdiagnóstico, así como para identificar "fenotipos autistas" en adolescentes / adultos jóvenes con TEE

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis.

BACKGROUND: Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms. METHODS: We searched ClinicalTrials.gov , CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a random-effects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317 . RESULTS: Eighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8-12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = - 0.32, 95% CI [- 0.39, - 0.25], in repetitive behaviors - 0.23[- 0.32, - 0.15] and in scales measuring overall core symptoms - 0.36 [- 0.46, - 0.26]. Overall, 19%, 95% CI [16-22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain. LIMITATIONS: About 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers. CONCLUSIONS: Placebo response in ASD was substantial and predicted by design- and participant-related factors, which could inform the design of future trials in order to improve the detection of efficacy in core symptoms. Potential solutions could be the minimization and careful selection of study sites as well as rigorous participant enrollment and the use of measurements of change not solely dependent on caregivers.