In Search of Biomarkers to Guide Interventions in Autism Spectrum Disorder: A Systematic Review.

OBJECTIVE: The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. METHODS: A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included. RESULTS: A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis." CONCLUSIONS: There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.

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

The Positive and Negative Syndrome Scale for Schizophrenia Autism Severity Scale (PAUSS) in young people with autism and schizophrenia.

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.

Developmental Differences Between Schizophrenia and Bipolar Disorder.

Ample evidence supports a neurodevelopmental origin in some cases of schizophrenia (SZ). More inconsistent information is available for bipolar disorder (BD). We herein review studies with a focus on premorbid (adjustment and functionality) and early developmental milestones that include both SZ and BD patients. A search was performed in the PubMed electronic database, retrieving 619 abstracts; 30 were ultimately included in this systematic review. Eight prospective cohorts, 15 retrospective studies, and 7 studies based on national registries. Psychomotor developmental deviations and general adjustment problems characterize the childhood of subjects later diagnosed with SZ or BD; they are more marked in those later diagnosed with SZ vs BD, earlier onset vs later onset, and psychotic vs nonpsychotic disorders. Cognitive impairment follows a linear risk trend for SZ and a U-shaped trend for BD. Social isolation and visuoperceptual/reading anomalies more frequently antecede SZ. Pervasive developmental disorders increase the risk for both SZ and BD, more so in cases with normal intelligence. The predictive risk of each isolated developmental marker is low, but a significant percentage of subjects with SZ and a minority of adults with BD showed signs of premorbid abnormalities in childhood. The great limitation is still the lack of studies comparing SZ and BD that include psychotic and nonpsychotic bipolar cases separately. There are many cases, even in childhood/adolescent SZ, where no premorbid anomalies are found, and immunological disorders or other etiologies should be searched for. At least in cases with clear neurodevelopmental markers, rare genetic variants should be investigated.