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Contains fulltext : 292321.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Identifying biomarkers of transition to psychosis in individuals at clinical high risk for psychosis (CHR-P) is essential to understanding the mechanisms underlying the disease. Although cross-sectional abnormalities in cortical surface area (CSA) have been demonstrated in individuals at CHR-P who transition to psychosis (CHR-P-T) compared with those who do not (CHR-P-NT), how CSA longitudinally develops remains unclear, especially in younger individuals. We set out to compare CSA in adolescents at CHR-P and healthy controls (HC) over 2 points in time. METHOD: A longitudinal multicenter study was performed in adolescents at CHR-P in comparison to HC and according to transition to psychosis. Magnetic resonance imaging scans were acquired at baseline, at 18-month follow-up, or at the time of transition. Images were pre-processed and hemisphere and regional CSA were computed using FreeSurfer. Between-group analyses were performed with linear mixed-effects models. RESULTS: A total of 313 scans (107 CHR-P and 102 HC) were included in the analysis. At 18 months, the rate of transition to psychosis in CHR-P was 23.4%. Adolescents at CHR-P-T presented greater age-related decrease in CSA in the left parietal and occipital lobes compared with HC, and in the bilateral parietal lobe and right frontal lobe relative to CHR-P-NT. These results were not influenced by antipsychotic treatment, cannabis use, or intelligence quotient (IQ). CONCLUSION: Adolescents at CHR-P that developed a psychotic disorder presented different developmental trajectories of CSA relative to those who did not. A relatively greater decrease in CSA in the parietal and frontal lobes may index clinical transition to psychosis in adolescents at CHR-P.

Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high-risk for the disease (CHR-P). The timing and spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multicentre study including adolescents at CHR-P and healthy controls (HC), aged 10–17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyse between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset.

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of ≤ 18 years (N = 61), 19-24 years (N = 121), and ≥ 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings.

Resumen Introduccion Existe controversia acerca de los criterios DSM-5 para el diagnostico de los trastornos del espectro autista (TEA). En la literatura encontramos resultados discrepantes, siendo el objetivo del estudio determinar la sensibilidad y la especificidad de los criterios DSM-5 para TEA en ninos y adolescentes espanoles. Tambien se determinara la estabilidad del diagnostico al pasar del DSM-IV-TR al DSM-5 y las diferencias clinicas entre TEA y trastorno de la comunicacion social (TCS). Material y metodos El estudio se llevo a cabo en 2017, revisando las historias clinicas de los pacientes evaluados en nuestro servicio. Los items de la entrevista diagnostica para el autismo (Autism Diagnostic Interview-Revised) se ajustaron al DSM-5 y se utilizaron para evaluar la sensibilidad y la especificidad de dicho manual. Resultados La sensibilidad del DSM-5 fue de 0,69-1,00, mayor para el genero femenino, sin diferencias con respecto a la edad y menor para los pacientes con bajo funcionamiento. La especificidad fue de 0,64-0,73. Respecto a la estabilidad, el 83,3% de los casos de autismo diagnosticados con el DSM-IV-TR mantuvieron el diagnostico siguiendo los criterios del DSM-5. En cuanto a las diferencias entre los pacientes diagnosticados de TEA y los diagnosticados de TCS, cabe mencionar que los primeros requirieron mas tratamientos farmacologicos durante su evolucion. Conclusiones Se necesitan mas estudios centrados en el diagnostico de TCS para determinar si la evolucion es diferente a la de los pacientes diagnosticados de TEA. Tambien sera necesario confeccionar nuevas herramientas diagnosticas y terapeuticas para los pacientes con diagnostico de TCS.

Cognitive impairments are proposed as predictors in the differentiation between subjects with psychosis risk syndrome (PRS) who will develop a psychotic disorder (PRS-P) and those who will not (PRS-NP). More in-depth study of the PRS-NP group could contribute to defining the role of cognitive alterations in psychosis. This study aims to analyze cognition of children and adolescents with PRS in terms of their clinical outcome at 18-month follow-up (psychosis, remission, and non-remission) and of determinate predictors of transition to psychosis and remission of PRS. The method is two-site, naturalistic, longitudinal study design, with 98 help-seeking adolescents with PRS and 64 healthy controls (HC). PRS-P (n = 24) and PRS-NP (n = 74) participants were clinically and cognitively assessed at baseline, and when full-blown psychotic disorder had developed or at 18-month follow-up. PRS-P subjects showed lower scores at baseline in processing speed, visuospatial memory, attention, and executive function (cognitive flexibility/processing speed) compared to HC. PRS-NP subjects showed lower baseline scores in verbal working memory and verbal fluency compared to HC. This deficit is also observed in the PRS group of participants still presenting attenuated psychotic symptoms at 18-month follow-up, while PRS subjects in remission showed a similar cognitive profile to HC subjects. Baseline score on processing speed, measured with a coding task, appeared to be a predictive variable for the development of a psychotic disorder. Performance in verbal working memory was predictive of remission in the PRS-NP. Post hoc comparisons indicate the need for careful interpretation of cognitive markers as predictors of psychosis. Cognitive impairments are present in both PRS-P and PRS-NP. Those individuals who recover from PRS show baseline cognitive performance comparable to the HC group. Together with sociodemographic variables, this observation could help in the differentiation of a variety of PRS trajectories in children and adolescents.

Some 70–80% of subjects with psychotic risk syndrome (PRS) have lifetime comorbidity, with depressive disorders being the most common. A high proportion of patients with PRS present nonspecific symptoms which can be confounding factors for diagnosis. Depressive and negative symptoms may be difficult to distinguish and it is important to differentiate them. The aim of this study is to assess the presence of depressive disorder in a child and adolescent sample of PRS and to examine the presence of negative symptoms and detect possible confounding characteristics between them and depressive symptoms. This is a naturalistic multi-site study with subjects who met PRS criteria. A sample of 89 PRS adolescent patients was included. Major depressive disorder (MDD) is the most prevalent comorbid disorder (34.83%). The sample was divided into patients who met criteria for MDD (PRS-MDD, n = 31) and those who did not have this disorder (PRS-ND, n = 44). We obtained significant differences in the attenuated negative symptoms (ANS) between PRS-MDD and PRS-ND (68.18 vs. 90.32%, respectively, p = 0.021). Subjects with MDD presented a higher score in ANS and Hamilton Depression Rating Scale (HDRS). Moreover, we obtained a correlation between negative symptomatology and HDRS score with a higher score on HDRS in subjects with higher negative symptom scores (r = 0.533, p

Network analysis is an important conceptual and analytical approach in mental health research. However, few studies have used network analysis to examine the structure of cognitive performance in psychotic disorders. We examined the network structure of the cognitive scores of a sample of 207 first-episode psychosis (FEP) patients and 188 healthy controls. Participants were assessed using a battery of 10 neuropsychological tests. Fourteen cognitive scores encompassing six cognitive domains and premorbid IQ were selected to perform the network analysis. Many similarities were found in the network structure of FEP patients and healthy controls. Verbal memory, attention, working memory and executive function nodes were the most central nodes in the network. Nodes in both groups corresponding to the same tests tended to be strongly connected. Verbal memory, attention, working memory and executive function were central dimensions in the cognitive network of FEP patients and controls. These results suggest that the interplay between these core dimensions is essential for demands to solve complex tasks, and these interactions may guide the aims of cognitive rehabilitation. Network analysis of cognitive dimensions might have therapeutic implications that deserve further research. © 2022

Objective: To study the differences in early-life characteristics between patients with an early onset of psychotic disorders (EOP, aged < 18 years) versus adult onset of psychotic disorders (AOP, aged >= 18 years) and to identify predictors of earlier onset. Methods: 278 patients with a first episode of psychosis between the ages of 7 and 35 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2009, and December 31, 2011, with diagnoses made for AOP using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and for EOP using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). Early-stage factors such as prenatal, perinatal, and other premorbid factors were registered and compared between EOP and AOP patients. To analyze the association between baseline variables and outcome, univariate and multivariate logistic regression models were used, and the association or odds ratios (ORs) for significant risk factors were calculated. Results: 224 patients with AOP (mean +/- SD age = 25.6 +/- 5.0 years; 65.6% male) and 54 patients with EOP (16.1 +/- 1.7 years; 68.5% male) were included. Univariate analysis revealed significant differences between the groups. Specifically, compared to AOP subjects, EOP patients had more frequent obstetric complications (OCs) (P

El Trastorno de Espectro Autista (TEA) y el Trastorno Obsesivo Compulsivo (TOC) de inicio en la infancia son trastornos del neurodesarrollo con una prevalencia aproximada de entre el 1 y el 3%. Ambos trastornos tienen como característica similar la existencia de comportamientos repetitivos. Objetivos: describir la prevalencia de comportamientos repetitivos de los niños con TEA con la adaptación española del Child Yale-Brown Obsessive-Compulsive Scale por Autism Spectrum Disorder (CY-BOCS-ASD) y comparar el tipo de síntomas y la gravedad con los evaluados en un grupo de comparación con TOC. Metodología: se evaluó mediante el CY-BOCS-ASD una muestra de 39 sujetos con diagnóstico de TEA (confirmado por la Autism Disorder Interview-Revised -ADI-R-) y mediante el Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) 36 sujetos con diagnóstico de TOC siguiendo criterios DSM-IV. Para poder ser incluidos, todos los participantes debían tenir un cociente intelectual >70. Resultados: se obtuvieron puntuaciones más altas en los síntomas obsesivo-compulsivos actuales en el grupo de TOC (12,95+3,45) que en el grupo con TEA (8.23+5.65), (t = -3.632, p = .001). Las compulsiones de limpieza (p=.003), comprobación (p=.001), contaje (p=.001), orden y simetría (p=.004), y miscelánea (p=.001) fueron significativamente más prevalentes en el grupo de TOC. La frecuencia, malestar e interferencia fue mayor en pacientes con TOC que en los pacientes con TEA. Conclusiones: la CY-BOCS-ASD podría ser un instrumento útil para detectar síntomas compulsivos en niños y adolescentes con TEA. Disponer de un instrumento adaptado hará que dicha sintomatología, que requiere un abordaje específico, esté mejor evaluada y considerada en el tratamiento global de los pacientes con TEA.

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

Although psychosocial stress is consistently described as a casual factor for psychosis, the role of recent stressful life events (SLEs) is inconclusive. Studies with subjects with psychosis risk syndrome (PRS), fail to show a large number of SLEs but suggest greater stress sensitivity in these populations. We evaluate the presence of recent SLEs and stress sensitivity, and their relationship with symptoms and functionality in a sample consisting exclusively of help-seeking children and adolescents. Seventy-two 10- to 17-year-old help-seeking subjects who met PRS criteria and forty-two healthy control (HC) subjects participated in a naturalistic multi-site study. Measures of stress included the Stressful Life Events Schedule (SLES) and the G4 item of the Scale for Prodromal Syndromes (SOPS) scale. Child and adolescent PRS subjects presented greater number of SLEs during the previous year, greater total accumulated stress, greater sensitivity to stress, and more impaired tolerance to normal stress than did HC subjects. Stress measures showed a relationship with positive and negative attenuated symptoms, clinical variables and functionality. Our results support the role of stress in the PRS status. It reinforces the suggested differences for clinical presentation of PRS in terms of age, highlighting the importance of gathering data on the under-18 population.

BACKGROUND Developmental stages characterized by greater neural plasticity might be critical periods during which the effects of cognitive training (CT) could theoretically be maximized. However, experiencing a first episode of schizophrenia during childhood or adolescence (ie, early-onset schizophrenia [EOS]) may reduce the brain's ability to benefit from CT. This study examined the effects of EOS versus onset at > 18 years of age (ie, adult-onset schizophrenia [AOS]) as a predictor of response to CT and the relationship between duration of illness and cognitive improvements. METHODS This study is a secondary analysis of data from 2 randomized trials that examined the cognitive effects of neuroscience-informed auditory training (AT) exercises in 84 outpatients with schizophrenia (26 EOS, 58 AOS, recruited between 2004 and 2014). RESULTS There was a significant effect of time in all cognitive domains (F > 10.22, P < .002). The effect of EOS was significant only for verbal learning and memory (F = 5.79, P = .018). AOS increased the mean change score by 5.70 points in this domain, whereas EOS showed no change (t = -2.280, P = .025). However, the difference between AOS and EOS was no longer statistically significant after control for multiple comparisons. Shorter duration of illness was associated with greater improvement in problem solving in the AOS group (r = -0.27, P = .040). CONCLUSIONS Auditory training is effective in improving cognition in both EOS and AOS. Treatment effects in all cognitive domains were similar, with the exception of verbal learning and memory. This result requires replication. Cognitive training provided earlier in the course of the illness results in greater improvements in executive functions. TRIAL REGISTRATION ClinicalTrials.gov identifiers: NCT00312962, NCT00694889​​.

Cognitive reserve (CR) is the premorbid brain capacity to cope with neural damage. People with good CR can tolerate higher levels of pathological brain injuries before displaying clinical symptoms than others. This study aimed to analyze CR in a sample of patients diagnosed with first-episode psychosis (FEP) during childhood or adolescence, comparing them to a community control group (CC) and assessing the predictive value of CR regarding psychosocial functioning, clinical symptoms and neuropsychological variables at the 5-year follow-up. 57 patients diagnosed with FEP during childhood or adolescence and 37 controls completed clinical, neuropsychological, and psychosocial functioning assessments at baseline and 5-year follow-up. CR was assessed in both groups at baseline. The FEP group showed lower CR scores than the CC group. Higher CR in the FEP group was associated with fewer psychotic negative symptoms, total psychotic symptoms and depressive symptoms, higher psychosocial functioning, and less impaired memory and attention at the 5-year follow-up. CR is associated with long-term clinical, neuropsychological and psychosocial functioning outcomes in patients diagnosed with FEP during childhood or adolescence.

The concept of being at risk for psychosis has been introduced both for adults and children and adolescents, but fewer studies have been conducted in the latter population. The aim of this study is to systematically review the articles associated with clinical description, interventions, outcome and other areas in children and adolescents at risk for psychosis. We searched in MEDLINE/PubMed and PsycINFO databases for articles published up to 30/06/16. Reviewed articles were prospective studies; written in English; original articles with Clinical High Risk (CHR) for psychosis samples; and mean age of samples younger than 18 years. From 103 studies initially selected, 48 met inclusion criteria and were systematically reviewed. Studies show that CHR children and adolescents present several clinical characteristics at baseline, with most attenuated positive-symptom inclusion criteria observed, reporting mostly perceptual abnormalities and suspiciousness, and presenting comorbid conditions such as depressive and anxiety disorders. CHR children and adolescents show lower general intelligence and no structural brain changes compared with controls. Original articles reviewed show rates of conversion to psychosis between 17 and 20% at 1 year follow-up and between 7 and 21% at 2 years. While 36% of patients recovered from their CHR status at 6-year follow-up, 40% still met CHR criteria. Studies in children and adolescents with CHR were conducted with different methodologies, assessments tools and small samples. It is important to conduct studies on psychopharmacological and psychological treatment, as well as replication of the few studies found.

Despite evidence supporting the presence of cognitive deficits in children and adolescents with high-functioning autism spectrum disorder (HF-ASD), the nature of these deficits and their clinical and adaptive correlates remain unclear. Moreover, there are few cognitive studies of ASD siblings as a high risk population. We compared 50 children and adolescents with HF-ASD, 22 unaffected siblings of the HF-ASD sample and 34 community controls using an extensive neuropsychological battery. Planning, cognitive flexibility, verbal and working memory, visual local-global processing and emotion recognition are impaired in HF-ASD. Worse cognitive performance, especially in verbal and working memory, was significantly correlated with more severe symptoms and poorer adaptive functioning, also when controlling for intelligence quotient. Results in siblings may suggest an intermediate profile.

BackgroundLeft-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power.MethodsWe investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.ResultsASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohen’sd= 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.ConclusionAltered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.

Neuropsychological underperformance is well described in young adults at clinical high risk for psychosis, but the literature is scarce on the cognitive profile of at-risk children and adolescents. The aim of this study is to describe the neuropsychological profile of a child and adolescent sample of patients with psychosis risk syndrome (PRS) compared to healthy controls and to analyze associations between attenuated psychotic symptoms and cognitive impairment. Cross-sectional baseline data analysis from a longitudinal, naturalistic, case–control, two-site study is presented. Eighty-one help-seeking subjects with PRS and 39 healthy controls (HC) aged between 10 and 17 years of age were recruited. PRS was defined by: positive or negative attenuated symptoms, Brief Limited Intermittent Psychotic Symptoms (BLIPS), genetic risk (first- or second-degree relative), or schizotypal personality disorder plus impairment in functioning. A neuropsychological battery was administered to assess general intelligence, verbal and visual memory, visuospatial abilities, speed processing, attention, and executive functions. The PRS group showed lower general neuropsychological performance scores at a multivariate level and lower scores than controls in general intelligence and executive functions. Lower scores on executive function and poorer attention were associated with high scores of positive attenuated psychotic symptoms. No association with attenuated negative symptoms was found. This study provides evidence of cognitive impairment in PRS children and adolescents and shows a relationship between greater cognitive impairment in executive functions and attention tasks and severe attenuated positive symptoms. However, longitudinal studies are needed to clarify the nature of cognitive impairment as a possible vulnerability marker.

Adults with psychotic disorders have abnormal connectivity of fronto-temporal networks. However, whether these abnormalities are present in adolescents with early psychosis has not been fully assessed. One-hundred and thirty-nine adolescents aged 12-18 underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging. Following motion correction, data were available for 44 participants with a psychosis risk syndrome, 34 patients with a first episode psychosis (FEP) and 35 healthy controls. Independent component analysis was performed to assess functional networks showing a fronto-temporal scope; this identified a language and a salience network. Mean fractional anisotropy was measured in clusters showing between-group differences in intrinsic functional connectivity (iFC). For the language network, there was a group effect within the right middle/inferior frontal gyrus, explained by reduced iFC in patients with an FEP relative to healthy controls, while in participants with a psychosis risk syndrome values of iFC were intermediate. In this region, values of iFC were positively correlated with mean fractional anisotropy in patients with an FEP. No group differences were observed in the salience network. Reduced iFC of the language network, in association with disrupted white matter microstructure, may characterize FEP during adolescence.

Autism spectrum disorders (ASD) include a range of complex neurodevelopmental disorders with extreme genetic heterogeneity. Exome and target sequencing studies have shown to be an effective tool for the discovery of new ASD genes. The aim of this study was to design an ASD candidate gene panel that covers 44 of the top ASD candidate genes. As a pilot study we performed comprehensive molecular diagnostic testing, including the study of the FMR1 and FMR2 repeat regions, copy number variant analysis in a collection of 50 Spanish ASD cases and mutation screening using targeted next generation sequencing-based techniques in 44 out of the total cohort. We evaluated and clinically selected our cohort, with most of the cases having high functioning ASD without facial dysmorphic features. The results of the present study allowed the detection of copy number and single nucleotide variants not yet identified. In addition, our results underscore the difficulty of the molecular diagnosis of ASD and confirm its genetic heterogeneity. The information gained from this and other genetic screenings is necessary to unravel the clinical interpretation of novel variants.

Background Functional connectivity (FC) during the resting-state is reduced in schizophrenia, especially within the Default Mode Network (DMN) (Dong 2018), and between the hippocampus, striatum and ventral tegmental area (VTA), which together conform a Midbrain Network (Gangadin 2019). Cross-sectional studies in adult samples have reported altered FC between dopamine synthesizing centers in midbrain and cortical areas in schizophrenia (Martino 2018). Conceptualizing schizophrenia as a neurodevelopmental disorder, we hypothesize that these changes may take place in early ages, prior to the clinical onset of psychosis. Therefore, we aim to examine FC of the DMN and Midbrain networks longitudinally in adolescents at increased risk of developing psychosis compared with youth with early onset psychosis and healthy volunteers (HV). Methods This longitudinal case-control study encompassed adolescents (12.6–18.9 years old) with psychosis risk syndrome (PRS; n=47), first episode of psychosis (FEP; n=59), and age and sex-matched HV (n=34). Fourteen out of the 30 PRS with follow-up assessment developed psychosis (t-PRS). Resting-state fMRI data was available for 88 subjects at baseline and follow-up [no significant differences in relation to drop-outs]: 10 t-PRS re-scanned at 3–12 months (at transition), and 14 PRS who did not transited (nt-PRS), 35 FEP; and 29 HV re-scanned at 10–36 month follow-up. After exclusion due to poor acquisition or excess movement, the final sample encompassed: 27 FEP, 9 t-PRS, 12 nt-PRS and 28 HV. Individual time series were extracted from Regions of Interest (ROI): for the DMN, the medial Prefrontal Cortex (mPFC), precuneus (PC), and bilateral temporo-parietal junction (Schilbach 2016); and for the Midbrain Network, the associative and limbic striatum, VTA and subiculum (Gangadin 2019). The orthogonal parameters of movement, white matter and cerebrospinal fluid (and their derivatives) and head motion scrubbing regressors were regressed out before performing the correlations. Multivariate mixed-effect models were estimated, including group (4), time and group by time interaction as fixed effects; and time and individual variability as random effects. Results There were no significant differences within-network FC. There was a significant group by time interaction in FC between the two networks (p = .02), driven by VTA-PC (pFDR = .02) and VTA-mPFC (pFDR = .04). Post-hoc analyses showed a significant reduction in FC in nt-PRS over time (psFDR ≤ .03), with FEP and t-PRS showing an opposite pattern (psFDR ≤ .01) in both networks. There was a trend-level reduction in FC over time in HV (ps ≤ .09), which showed significant differences relative to FEP (ps ≤ .04) in the VTA-PC and VTA-mPFC, and with t-PRS in the VTA-PC (p = .02). There was no significant difference between HV and nt-PRS. Cumulative dose of antipsychotics was negatively correlated with FC between mPFC-VTA in FEP at follow-up (r = -.41; p = .04); yet group by time effects survived when used as covariable. Sex, socio-economic status or global intelligence quotient did not exert significant effects. Discussion Our findings suggest that the onset of psychosis during adolescence impacts on the age-normative reduction of FC between the DMN and Midbrain networks, characteristic of the network segregation which takes place during typical brain functional development (Satterthwaite 2013). Antipsychotic medication on cortico-subcortical FC appear to have a reversing effect on these findings, although longitudinal group differences in network connectivity persist despite controlling for this effect. Our data sheds light on the changes in the organization of brain function taking place in the early stages of psychosis, coinciding with a key developmental period.

Highlights • Youth with early-onset psychosis displayed deficits in theory of mind performance. • They also showed reduced intrinsic connectivity in the medial prefrontal cortex. • Differences in theory of mind were partially mediated by prefrontal connectivity. • Both measures failed to show the age-positive associations observed in controls. • Onset of psychosis in adolescence may impact development of social cognition., Psychotic disorders are characterized by theory of mind (ToM) impairment. Although ToM undergoes maturational changes throughout adolescence, there is a lack of studies examining ToM performance and its brain functional correlates in individuals with an early onset of psychosis (EOP; onset prior to age 18), and its relationship with age. Twenty-seven individuals with EOP were compared with 41 healthy volunteers using the “Reading-the-Mind-in-the-Eyes” Test, as a measure of ToM performance. A resting-state functional MRI scan was also acquired, in which the default mode network was used to identify areas relevant to ToM processing employing independent component analysis. Group effects revealed worse ToM performance and less intrinsic functional connectivity in the medial prefrontal cortex in EOP relative to healthy volunteers. Group by age interaction revealed age-positive associations in ToM task performance and in intrinsic connectivity in the medial prefrontal cortex in healthy volunteers, which were not present in EOP. Differences in ToM performance were partially mediated by intrinsic functional connectivity in the medial prefrontal cortex. Poorer ToM performance in EOP, coupled with less medial prefrontal cortex connectivity, could be associated with the impact of psychosis during a critical period of development of the social brain, limiting normative age-related maturation.

Background The onset of a psychotic disorder before age 18 (early-onset psychosis, EOP) is a marker of greater clinical severity and poor outcome. There is a lack of studies examining the efficacy of psychological treatment in this population. The Cognitive-Behavioral Social Skills Training (CBSST) is an evidence-based psychological intervention for patients with schizophrenia. OBJECTIVE: To analyze the efficacy of the adolescent version of CBSTT (CBSST-Adolt) versus an active psychological intervention, administered during the critical period, to improve symptoms and functioning in patients with EOP. Methods Randomized controlled trail (RCT) of the adolescent version of the CBSST-Adol compared to an active control intervention. Interventions: The CBSTT-Adol included the 3 original modules (cognitive abilities, social skills, problem-solving skills) but number of sessions was reduced. It was administered in small groups. The active control intervention (PSYCHOED-Adol) included 3 modules (psychoeducation, relapse prevention, healthy life style) with the same format and number of sessions. The language and examples were adapted for adolescents in both interventions. Inclusion criteria: schizophrenia spectrum disorder (schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified), diagnosed before 18; being in the critical period of the illness (first 5 years after the onset); being clinically stabilized (outpatients). Exclusion criteria: IQ Results There were no significant differences in sex or age, but in socioeconomic status (p0.05). There was a similar rate of dropouts during the trail in both branches of the study (31% and 29%, p>0.05). Improvements in clinical symptoms (PANSS total, p=0.045; PANSS positive symptoms, p=0.009) and functioning (GAF, p=0.002; GF:Social, p=0.025, CBI, p=0.020) were found at post-treatment in all sample. However, there was no a superior effect of CBSST-Adol compared to PSYCHOED-Adol in any variable. There was only a trend to a higher improving of the Communication and social contact subscale of the Life Skills Profile in the CBSST-Adol intervention (p=0.061). Discussion The results support the efficacy of psychological intervention improving symptoms and functioning in EOP. We find a similar positive effect after the treatment in both CBSTT-Adol and PSYCHOED-Adol interventions. Main limitations: not having a non-active control group and the sample size.

Background Controversy exists regarding the DSM-5 criteria for autism spectrum disorders (ASD). Given the mixed results that have been reported, our main aim was to determine DSM-5 sensitivity and specificity in a child and adolescent Spanish sample. As secondary goals, we assessed the diagnostic stability of DSM-IV-TR in DSM-5, and clinical differences between children diagnosed with an ASD or a social (pragmatic) communication disorder (SPCD). Methods This study was carried out in 2017, reviewing the medical records of patients evaluated in our service. Items from a parent report measure of ASD symptoms (Autism Diagnostic Interview-Revised) were matched to DSM-5 criteria and used to assess the sensitivity and specificity of the DSM-5 criteria and current DSM-IV criteria when compared with clinical diagnoses. Results DSM-5 sensitivity ranged from .69 to 1.00, and was higher in females. By age, the DSM-5 and DSM-IV-TR criteria showed similar sensitivity. In the case of intellectual quotient, DSM-5 criteria sensitivity was lower for those in the “low-functioning” category. DSM-5 specificity ranged from .64 to .73, while DSM-5 specificity was similar for all phenotypic subgroups. With respect to stability, 83.3% of autism disorder cases retained a diagnosis of ASD using the DSM-5 criteria. With regard to differences between ASD and SPCD, we found that patients diagnosed with ASD received more pharmacological treatment than those diagnosed with SPCD. Conclusions Further research is required to confirm our results. Studies focusing on the SPCD phenotype will be necessary to determine outcome differences with ASD and the most effective diagnostic and therapeutic tools.

Most individuals with autism spectrum disorders often fail in tasks of theory of mind (ToM). However, those with normal intellectual functioning known as high functioning ASD (HF-ASD) sometimes succeed in mentalizing inferences. Some tools have been developed to more accurately test their ToM abilities. The aims of this study were to examine the psychometric properties of the Spanish version of Stories of Everyday Life Test (SEL) in a sample of 29 children and adolescents with HF-ASD and 25 typically developing controls and to compare their performance. The Spanish-SEL demonstrated good internal consistency, strong convergence with clinical severity and another ToM test, and adequate discriminant validity from intellectual capability and age, identifying the condition of 70 % of participants.

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology. Electronic supplementary material The online version of this article (10.1007/s10803-018-3510-4) contains supplementary material, which is available to authorized users.

Aim Despite the interest in psychosis risk syndrome (PRS) in children and adolescents, information on the syndrome in this population is scarce. Methods Prospective naturalistic multi-site study in which 10- to 17-year-old help-seeking subjects who met PRS criteria (positive or negative attenuated symptoms; brief limited intermittent psychotic symptoms; genetic risk or schizotypal personality disorder plus impairment in functioning) were included, along with 45 age and sex-matched healthy controls (HC). All subjects were clinically and functionally assessed. Results Ninety-one PRS subjects (PRSS) with a mean age of 15.5 ± 1.4 met inclusion criteria (IC). Compared with HC, PRSS presented worse global and academic functioning in the previous year, had experienced more psychiatric and psychological problems, and presented gestational ages outside the normal range. More than 80% of PRSS met ≥2 IC, with 65.9% having one Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis, and 61.7% of those having ≥2 diagnoses. Some 49.5% of PRSS had a first- or second-degree family history (FH) of psychosis. Patients with first- and second-degree FH do not differ in their clinical expression. Conclusions Children and adolescents with PRS are a patient group with a pattern of neurodevelopmental impairment and clinical complexity similar to patients with schizophrenia spectrum disorders, highlighting the importance of assessing these variables in child and adolescent samples. PRSS with first- and second-degree relatives with FH do not present differences in their clinical presentation, suggesting that including these two groups of patients in the genetic risk criteria would enrich knowledge of these criteria.

Objective This study explored whether age moderated cognitive, symptom, and functional changes over a 12-week compensatory cognitive training (CCT) intervention for participants with severe mental illnesses. CCT focused on the cognitive domains of attention, learning, prospective memory, and executive functioning, often impaired in this population. Method Seventy-seven unemployed individuals (46 participants with severe mood disorders and 31 participants with schizophrenia/schizoaffective disorder; mean age = 44 years) received CCT for 12 weeks in the context of a supported employment program. Participants were administered cognitive, symptom severity, and functional measures at baseline and 3-, 6-, and 12-month follow-ups, as well as at 18 and 24 months for symptom/functional measures. Mixed effects models, controlling for diagnosis, examined whether age impacted the trajectories of change following CCT. Results Analyses showed several significant time by age interactions; younger participants improved more over time on category fluency, β = -.280, t(42.10) = -2.76, p = .008, and financial capacity (UCSD Performance-Based Skills Assessment), β = -.194, t(54.02) = -2.21, p = .031, whereas older participants showed greater reduction in positive symptom severity (Positive and Negative Syndrome Scale), β = -.109, t(78.35) = -2.34, p = .022, and less functional decline on the Independent Living Skills Survey, β = .118, t(109.77) = 2.05, p = .043. Conclusions and implications for practice Age moderated the effects of CCT over time on measures of cognition, symptom severity, and functioning. Younger participants improved on objective measures of verbal processing speed and financial capacity, whereas older participants showed reduced positive symptom severity and less decline in self-reported daily functioning. These findings suggest that CCT may differentially benefit persons with severe mental illnesses depending on age. (PsycINFO Database Record

Background High-risk symptoms for psychosis (HRS) and substantial functional impairment occurs early in the course of psychosis (Fusar-Poli et al., 2015). Many patients with HRS are adolescents who are still living at home and are highly reliant on their relatives for support. Objectives: (1) To compare the family burden of caregivers of adolescents with HRS with carers of an age and gender matched healthy control group (HC), (2) to examine the relationships between different family burden aspects and high-risk symptoms for psychosis in the HRS sample. Methods Sample: 68 HRS subjects (15.3 ± 1.7 years, 66% females) and 42 HC subjects (15.5 ± 1.5 years, 66% females) from a prospective longitudinal study including help-seeking subjects who met HRS criteria (Child and Adolescent Psychiatry and Psychology departments of Hospital Clínic and Sant Joan de Déu, Barcelona, Spain). Inclusion criteria: age 10–17 years, meeting criteria for 1) attenuated positive or negative symptoms in the previous 12-months, 2) brief intermittent psychotic symptoms, 3) first or second degree relative with schizophrenia or schizotypical disorder plus impairment of functioning. Exclusion criteria: IQ-9.35, p-5.59, p

Background Adolescents with early-onset schizophrenia (EOS) have marked deficits in their functional outcome. However, few short and reliable instruments for assessing real-world functioning have been specifically validated in EOS. The Life Skills Profile (LSP) is a brief scale widely used in schizophrenia and considered one of the optimal instruments for assessing real-world daily living skills. The purpose of this study was to examine the usefulness and the feasibility of the LSP to assess daily living skills in EOS. Methods The sample included 53 clinically and pharmacologically stabilized adolescent patients with EOS and 53 healthy adolescents. Content review of the scale and internal consistency analysis were conducted in the EOS group. A subgroup of 30 patients was re-assessed over a 10-day interval to establish the test–retest reliability. Measures of functional outcome were used to assess convergent validity, and measures of intelligence and symptoms were used to assess divergent validity. Discriminant validity was analyzed through logistic analysis and the receiver-operating characteristic curve. Results The LSP and its subscales showed high reliability, adequate internal consistency and adequate convergent and divergent validity. The LSP was also found to be a sensitive instrument for detecting differences between patients and healthy adolescents, correctly classifying 84% of the sample. The estimated area under the curve was 0.925 (95% CI 0.875–0.976). Conclusions The LSP showed adequate psychometric characteristics in adolescents with EOS and appeared to be a valid, reliable and time-efficient instrument for use in clinical practice and research settings to assess real-world daily-living skills in EOS.

The objective of this study was to examine whether cognitive change and age predicted work outcome in the context of supported employment (SE) and compensatory cognitive training (CCT) in severe mental illness. Forty unemployed outpatients receiving SE (7 young [20-35 years], 15 middle-aged [36-50 years], and 18 older [51-66 years] patients) completed cognitive assessments at baseline and after 12 weeks of CCT. Logistic regression analyses showed that improvement in attention/vigilance significantly predicted work attainment (B = 2.35, SE = 1.16, p = 0.043). Young and older participants were more likely to obtain work than middle-aged participants (B = 4.03, SE = 1.43, p = 0.005; B = 2.16, SE = 0.93, p = 0.021, respectively). Improved attention and age group (young and old) were associated with better work outcomes after SE + CCT. Improving attention may be an important target for improving work outcome in severe mental illness. Middle-aged individuals may need additional support to return to work.

Previous studies have shown high rates of comorbid disorders in children and adolescents with autism spectrum disorder, but failed to compare them with general population and few of them have identified predictors of comorbidity. This study compared the rates of psychiatric disorders in 50 children and adolescents with autism spectrum disorder, 24 of their siblings, 32 controls from general population and 22 of their siblings. Children and adolescent with autism spectrum disorder and their siblings had higher rates of attention deficit and hyperactivity disorder compared to controls. Lower socioeconomic status and intelligence quotient were the main risk factors. The contribution of socioeconomic status and intelligence quotient to increase the risk of developing comorbidity in autism spectrum disorder and psychopathology in their siblings deserves further study.

Cognition and clinical variables are known to be among the most predictive factors of real-world social functioning and daily living skills in adult-onset schizophrenia. Fewer studies have focused on their impact in adolescents with early-onset schizophrenia (EOS). The aim of this study is to examine the relationships and the predictive value of cognition and clinical variables on real-world daily living skills in a sample of adolescents with EOS. Cognitive, clinical and real-world everyday living skills measures were administered to 45 clinically and pharmacologically stabilized adolescent outpatients with EOS and 45 healthy control subjects matched by age and sex. Multi-variant analyses to compare cognitive and real-world functioning profiles between patients and controls and regression analysis to identify predictors of real-world functioning scores in patients were used. Adolescents with EOS showed a generalized cognitive and real-world daily living skills dysfunction. Several cognitive and clinical variables significantly correlated with real-world daily living skills functioning but only the processing speed and executive functions emerged as independent predictors of everyday living skills scores, explaining 25.1% of the variance. Slowness in processing information and executive dysfunction showed a significant impact on real-world daily living skills in EOS, independently from clinical symptoms and other cognitive variables. Nevertheless, much of the variance in the daily living skills measure remained unaccounted for, suggesting that other factors were involved as well in this young population.

Introduction High rates of psychopathology and worse performance in cognitive areas have been described in high risk (HR) first degree relatives of subjects with schizophrenia. The present study aimed to examine clinical and neuropsychological characteristics in two different groups of first degree relatives of patients with schizophrenia – one of siblings (HRs), and one of offspring (HRo) – and compare them with healthy controls (HC). Methods Participants were 30 HRo, 26 HRs and 33 HC, all aged between 7 and 16 years. Clinical and neuropsychological assessments were completed by all participants. Results No significant differences were observed between HR groups in DSM-IV diagnoses. The most prevalent diagnosis in both HR samples was attention deficit/hyperactivity disorder (ADHD) followed by oppositional defiant disorder and generalized anxiety disorder. Both HR groups obtained worse scores than HC on prodromal symptoms, premorbid adjustment and behavioral problem scales. In cognitive areas, HRo performed worse than HC on most WISC-IV index scores, logical memory, visual memory and perceptual organization, whereas HRs only performed worse in WISC-IV indexes, logical memory and perceptual organization. Most of these differences remained stable after controlling for ADHD. The comparison between HRo and HRs showed significant differences in prodromal symptoms and working memory after controlling for ADHD. Conclusion Similar abnormalities in HRo and HRs were found in relation to clinical and neuropsychological variables. Subtle differences were found between HR groups with HRo showing difficulties in more clinical and neuropsychological areas than HRs and HC. This suggests that, the specific kind of family relationship should to be taken into account in future HR research.

While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.

Background Dysfunctional attitudes such as defeatist performance beliefs (DPB) and asocial beliefs (AB) have been linked to negative symptoms and functional outcome in chronic schizophrenia (Campellone et al., 2016; Grant and Beck, 2010) and in adults with recent onset schizophrenia (Ventura et al., 2014). Adolescents with early-onset psychosis (EOP) are at major risk of having persistent negative symptoms (Puig et al., 2017) but no previous study has examined dysfunctional attitudes in this population. We aimed: (1) to examine if more DPB and AB were present in adolescents with EOP compared with normal controls, and (2) to study the relationships between DPB and AB with symptoms and functioning. Methods Sample: 15 adolescents with EOP (11♀, age=15.33 ± 1.23) and 10 healthy controls (8♀, age=15.60 ± 1.51), participants in a trial about cognitive and behavioral social skills treatment in EOP developing in Hospital Clínic of Barcelona (baseline data). Patients were under antipsychotic meds. Inclusion criteria: having an early-onset schizophrenia spectrum disorder diagnosed between 9–18 years-old (schizophrenia, schizoaffective disorder, psychosis n.o.s.); being within the 5 first years after the disease onset; clinical stability. Exclusion criteria: IQ6.67, p3.02, p

Negative symptomatology and neurocognitive variables have been considered good predictors of functional outcome in schizophrenia. Specifically, secondary verbal memory has been proposed to be one of the main predictors of psychosocial functioning. In this study, negative symptoms and memory performance were analyzed for associations with psychosocial function. Linear regression methods were used to analyze the value of verbal memory and negative symptomatology as predictors of everyday life skills in a sample of 29 DSM-IV schizophrenia outpatients with predominant negative symptoms. We also took into account the role of gender in the analyses. Secondary verbal memory was found to explain 40% of the variance in psychosocial functioning, independently of gender, whereas the negative symptoms predicted 26%. When both variables were combined, the explained variance was about 49%. These results support the hypothesis that cognitive variables are better predictors than symptomatology. Finally, secondary verbal memory is a good predictor of psychosocial functioning in chronic schizophrenia with predominant negative symptomatology.

The present study evaluated the efficacy of a group therapy program in improving psychosocial adjustment to HIV infection, and tried to identify variables predictive of greater improvement. The outcome of 47 completing patients was analyzed, comparing the measures between T1 (1 month before therapy), and T2 (first session), and between T2 and T3 (last session) using the Wilcoxon matched-pairs signed-ranks test for each dimension of the Psychosocial Adjustment to Illness Scale (PAIS). The therapy consisted of 16 weekly 2-hour sessions following a structured time-limited cognitive-behavioral group psychotherapy program. During the intervention (between T2 and T3) a significant improvement was observed in health care orientation, vocational environment, domestic environment, sexual relation, extended family relationships, social environment, and total PAIS. There were no changes during baseline (between T1 and T2) in any of the PAIS subscales, or in the total PAIS score. Sexual route of transmission was independently associated with an improvement in health care orientation (beta = 2.525). Time since HIV diagnosis (beta = 0.022) and being employed (beta = 2.548) were independently associated with an improvement in adjustment to vocational environment. Men who have sex with men showed a poorer improvement in adjusting to family relations after the intervention (beta = -2.548). Finally, a lower CD4 count (beta = -0.005) and being employed (beta = 3.054) were independently associated with an improvement in adjustment to social environment. Our psychotherapy program improved psychosocial functioning in a heterogeneous sample of HIV-1-infected patients referred to a consultation-liaison psychiatry unit.