A history of childhood schizophrenia and lessons for autism.

The diagnosis of childhood schizophrenia was widely employed in the U.S. from the 1930s to the late 1970s. In this paper I will provide a history of the diagnosis. Some of the earliest publications on childhood schizophrenia outlined the notion that childhood schizophrenia had different types. I will outline the development of these types, outlining differing symptoms and causes associated with various types. I outline how different types of childhood schizophrenia were demarcated from one another primarily on age of onset and the type of psychosis which was believed to be present. I will outline how various child psychiatrists viewed the types of childhood schizophrenia posited by other child psychiatrists. I will outline the process of abandoning childhood schizophrenia. I use my history to challenge what I believe are misconceptions about childhood schizophrenia. Also, I will use my history to draw lessons for thinking about modern notions of autism. It shows potential problems around formulating psychiatric diagnoses around causes and how compromises might be needed to prevent those problems. Additionally, childhood schizophrenia shows that psychiatrists could formulate subtypes that are not based upon functioning levels and that we can conceive of subtypes as dynamic whereby someone can change which subtype they exhibit over time.

[Controversial issues of diagnosis and theoretical concepts of schizophrenia in childhood]. / Diskussionnye voprosy diagnostiki i teoreticheskie modeli shizofrenii v detskom vozraste.

The article presents modern approaches to classification, presents debatable diagnostic issues, including the differences between domestic approaches to the diagnosis of schizophrenia in childhood from foreign taxonomies. The modern hypothesis of the etiological continuum of schizophrenic and autistic spectrum disorders is discussed, as well as clinical models of manifest stages of schizophrenia in childhood, with an emphasis on the influence of the age factor on the clinic, dynamics and prognosis of diseases.

Identification and treatment of individuals with childhood-onset and early-onset schizophrenia.

Approximately 8 % of patients with schizophrenia are diagnosed before age 18, and 18 % experience their first symptoms before age 18. This narrative review explores the management of patients with early-onset schizophrenia (EOS) and childhood-onset schizophrenia (COS) from diagnosis to their transition to adult care settings. Early diagnosis of schizophrenia in children and adolescents is essential for improving outcomes, but delays are common due to overlapping of symptoms with developmental phenomena and other psychiatric conditions, including substance use, and lack of clinicians' awareness. Once diagnosed, antipsychotic treatment is key, with specific second-generation agents generally being preferred due to better tolerability and their broader efficacy evidence-base in youth. Dosing should be carefully individualized, considering age-related differences in drug metabolism and side effect liability. Clinicians must be vigilant in detecting early non-response and consider switching or dose escalation when appropriate. Since early age of illness onset is a consistent risk factor for treatment-resistant schizophrenia (TRS), clinicians need to be competent in diagnosing TRS and using clozapine. Since COS and EOS are associated with cognitive deficits and impaired functioning, psychosocial interventions should be considered to improve overall functioning and quality of life. Good long-term outcomes depend on continuous treatment engagement, and successful transitioning from pediatric to adult care requires careful planning, early preparation, and collaboration between pediatric and adult clinicians. Targeting functional outcomes and quality of life in addition to symptom remission can improve overall patient well-being. Comprehensive evaluations, age-specific assessments, and targeted interventions are needed to address the unique challenges of EOS and COS.

Low-Dose Clozapine in Early-Onset Resistant Schizophrenia: Case Report and 2-Year Follow-up.

Childhood-onset schizophrenia (COS) is considered a rare and severe form of schizophrenia, with onset before age 13 and only half of affected patients responding to nonclozapine antipsychotics.1 These patients with resistant COS show favorable responses to clozapine, but with higher adverse effects than seen in adults. Some resistant cases respond at a lower dose with minimal adverse effects.2 However, it is unclear which patients will respond to a low dose and how long one should wait before increasing the dose of clozapine. We report a patient with resistant COS who showed a favorable but delayed-onset response to low-dose clozapine.

Trauma infantil en esquizofrenia. Implicaciones en los síntomas psicóticos positivos y negativos / Childhood trauma and schizophrenia. Implications for positive and negative psychotic symptomsresumen

La relación entre trauma infantil (TI) y la psicosis está bien establecida y son diversas las teorías sobre los factores que median en esta relación. También son muchos los estudios que exploran la influencia del TI en el curso de la psicosis en distintas áreas. El objetivo de este estudio fue explorar la influencia del TI en la presencia e intensidad de los síntomas psicóticos positivos (SPP) y negativos (SPN) en pacientes con trastornos del espectro esquizofrénico. Se incluyeron un total de 45 pacientes con diagnóstico de esquizofrenia o trastorno esquizoafectivo. Se valoraron datos sociodemográficos, los antecedentes de TI mediante el Childhood Trauma Questionnaire, Short Form (CTQ-SF), así como la intensidad de los síntomas psicóticos positivos y negativos mediante la Positive and Negative Syndrome Scale (PANSS+ y -).De la totalidad de la muestra, 35 pacientes, el 77,8 %, habían padecido algún tipo trauma infantil; el 55,6%, negligencia emocional; el 48,9%, abuso emocional: el 46,7%, negligencia física y el 40,0%, abuso sexual. No encontramos correlación entre CTQ-SF y PANSS+ y sí una relación inversa ente CTQ-SF v PANSS- (Rho -0.300, p=0.045). A diferencia de otros estudios no encontramos una correlación entre el TI y los SPP, a excepción del abuso físico con el ítem de excitación, tal vez debido a la cronicidad de los pacientes de nuestra muestra. La correlación moderada e inversa entre el TI y los SPN sugerimos que podría deberse a que los síntomas psicóticos positivos y negativos surgirían de diátesis distintas. Los síntomas negativos estarían en relación con déficits de neurodesarrollo y no relacionados con el estrés, como se ha sugerido en los síntomas psicóticos positivos. Sin embargo, dado que es trata de un hallazgo poco replicado, es difícil establecer conclusiones claras.(AU)

The relationship between childhood trauma (CT) and psychosis is well established and theories about the factors mediating this relationship are diverse. CT is associated with a worse prognosis of psychosis The aim of this study was to explore the influence of childhood trauma on the presence and intensity of positive (PPS) and negative psychotic symptoms (NPS) in patients with schizophrenic spectrum disorders. Forty-five patients with a diagnosis of schizophrenia or schizo affective disorder were included. Sociodemographic data, childhood trauma history using the Childhood Trauma Questionnaire Short Form (CTQ-SF) and the intensity of positive and negative psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS + and -), were valued. Of the total sample, 35 patients, 77.8%, had suffered some type of childhood trauma; 55.6%, emotional neglect; 48.9%, emotional abuse: 46.7%, physical neglect and 40.0%, sexual abuse. We did not find a correlation between CTQ-SF and PANSS+ and an inverse relationship between CTQ-SF v PANSS- (Rho -0.300, p=0.045). Unlike other studies, we did not find a correlation between CT and PPS, except for physical abuse with the excitation item, perhaps due to the chronicity of patients in our sample. The inverse corre lation between CT and NPS may be due to positive and negative psychotic symptoms arising from different diameters. NPS could be related to neurological development deficits and not related to stress, as suggested in PPS. However, since it is a finding with little replication, it is difficult to draw clear conclusions.(AU

The Triad of Childhood-Onset Schizophrenia, Autism Spectrum Disorder, and Catatonia: A Case Report.

Childhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia with an estimated prevalence of 1/10,000. Schizophrenia and Autism spectrum disorder (ASD) have shared phenotypic features and shared genetic etiology. There is growing research surrounding the co-occurrence of psychomotor syndromes like catatonia with neurodevelopmental disorders like ASD or psychiatric disorders like schizophrenia. In 2013, Shorter and Wachtel described a phenomenon of the 'Iron Triangle' where COS, ASD, and catatonia often co-occur. The Iron Triangle theory is based on observation of historical case literature, which showed that all three diagnoses in the Iron Triangle were routinely assigned to children and adolescents. The pattern of this "Iron Triangle" suggests there may be a single underlying pathology resulting in a unique mixed form of catatonia, autism, and psychosis. We describe the case of a boy with sequential development of COS, ASD, and catatonia who also has syndromic facial and musculoskeletal features. This case highlights overlapping diagnostic features of these three disorders and can help us better understand how "hidden" features of catatonia may occur in patients with COS or ASD but go unrecognized, because they are grouped as features under autism/schizophrenia rather than a distinct diagnosis of catatonia. Further study is warranted to elucidate if this phenotypic pattern constitutes a new single diagnosis that is not well understood, an endophenotype of schizophrenia, or if this is the result of phenomenological overlap between catatonia, ASD, and COS.

Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing.

Childhood-onset schizophrenia (COS) is a rare form of schizophrenia with an onset prior to 13 years of age. Although genetic factors play a role in COS etiology, only a few causal variants have been reported to date. This study presents a diagnostic exome sequencing (ES) in 37 Israeli Jewish families with a proband diagnosed with COS. By implementing a trio/duo ES approach and applying a well-established diagnostic pipeline, we detected clinically significant variants in 7 probands (19 %). These single nucleotide variants and indels were mostly inherited. The implicated genes were ANKRD11, GRIA2, CHD2, CLCN3, CLTC, IGF1R and MICU1. In a secondary analysis that compared COS patients to 4721 healthy controls, we observed that patients had a significant enrichment of rare loss of function (LoF) variants in LoF intolerant genes associated with developmental diseases. Taken together, ES could be considered as a valuable tool in the genetic workup for COS patients.

Impact on the Risk and Severity of Childhood Onset Schizophrenia of Schizophrenia Risk Genetic Variants at the DRD2 and ZNF804A Loci.

The study explored whether schizophrenia risk alleles of the DRD2 rs2514218 and ZNF804A rs1344706 polymorphisms also influenced the risk and severity of childhood-onset schizophrenia (COS) and differentiated it from autism spectrum disorders (ASD). We compared 75 children with COS to 75 children with ASD, 150 patients with adult-onset schizophrenia and 150 healthy individuals. Frequency of the DRD2 T-allele, assumed to be protective against schizophrenia overall, was higher in COS compared to adult-onset schizophrenia and healthy controls. The risk allele A of ZNF804A was associated with greater severity of negative symptoms in COS. The latter result is consistent with the involvement of ZNF804A in the development of severe forms of schizophrenia. The findings regarding DRD2 suggest that the same genetic variants may play different roles in schizophrenia with childhood and adult onset. This warrants further research, since D2 receptor blockade is a general pharmacodynamic property of antipsychotics.

Reprint of: Advanced paternal age and risk of schizophrenia in offspring - Review of epidemiological findings and potential mechanisms.

A large number of studies have examined the association between advanced paternal age (APA) and risk of schizophrenia in offspring. Here we present an overview of epidemiological studies on this subject published since 2000, and systematically summarize their methodologies and results. Next, we discuss evidence to elucidate the potential mechanisms contributing to the association between APA and offspring schizophrenia, considering paternal psychiatric morbidity and genetic liability, maternal factors, and findings from family design studies. We propose that multiple mechanisms, including causal and non-causal pathways, contribute to the observed relationship between APA and schizophrenia in offspring, and conclude by highlighting the need for multi-disciplinary studies in disentangling these complex, non-mutually exclusive mechanisms.

A novel microduplication in INPP5A segregates with schizophrenia spectrum disorder in the family of a patient with both childhood onset schizophrenia and autism spectrum disorder.

Childhood-Onset Schizophrenia (COS) is a very rare and severe psychiatric disorder defined by adult schizophrenia symptoms occurring before the age of 13. We report a microduplication in the 10q26.3 region including part of the Inositol Polyphosphate-5-Phosphatase A (INPP5A) gene that segregates with Schizophrenia Spectrum Disorders (SSDs) in the family of a female patient affected by both COS and Autism Spectrum Disorder (ASD). Phenotyping and genotyping (including CGH-array) were performed for mother, healthy sister, and affected child according to the GenAuDiss protocol (NCT02565524). The duplication size is 324 kb and is present in a patient with COS and in her mother with SSD, but not in the patient's healthy sister. INPP5A encodes a membrane-associated 43 kDa type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. This protein is found both in mouse and human brains and we found that its Drosophila homologue 5PtaseI is specifically expressed in the central nervous system. Hydrolyzed products from InsP3 5-phosphatases mobilize intracellular calcium, which is relevant for dendritic spine morphogenesis in neurons and altered in both schizophrenia and ASD. These may constitute arguments in favor of this gene alteration in the pathophysiology of COS.

[Neurodevelopmental Disorders, Psychiatric Comorbidities and Associated Pathologies in Patients with Childhood-Onset Schizophrenia and Premorbid Autistic Symptoms.] / Atteintes Neurodéveloppementales, Comorbidités Psychiatriques Et Pathologies Associées Chez Des Patients Atteints de Schizophrénie Très Précoce Avec Symptômes Autistiques Prémorbides.

INTRODUCTION: Childhood-Onset Schizophrenia (COS) is a rare (1/40000), severe and neurodevelopmental form of schizophrenia beginning before 13 years of age. Little is known about comorbidities and specific COS-related disorders. Thus, the objective of our study was to evaluate them from a psychiatric, neurodevelopmental and somatic perspective. METHOD: This is an ancillary study of the GenAuDiss protocol. A standardized psychiatric interview (K-SADS-PL DSM5) and a neuropsychological assessment (WISC-V/WAIS-IV) were carried out in outpatients with COS as well as a medical history collection concerning pregnancy, perinatal period, development, biography and medical and psychiatric, personal, and family history. RESULTS: 20 outpatients were included. The mean age of onset of COS was 8.90 years (+/- 2.30). Psychiatric comorbidities (DSM5) were Attention Deficit Hyperactivity Disorder (15/20 patients), Anxiety Disorders (14/20) and Autism Spectrum Disorder (13/20). The average IQ was 70.26 (+/- 18.09). A language delay and a break in school career were noted in 18/20 patients. Finally, the main associated somatic disorder was asthma (15/20 patients). DISCUSSION: We highlighted in our patients with COS a high frequency of comorbidities including at least one systematic psychiatric disorder. However, although COS is a severe condition impacting the patient, his family and society, its management remains essentially symptomatic. In clinical practice, it is necessary to look for all these comorbidities and to manage them in order to improve the overall quality of care.

INTRODUCTION: La schizophrénie très précoce (STP) est une forme rare (1/40000), grave et neurodéveloppementale de schizophrénie débutant avant 13 ans. Les comorbidités et atteintes associées spécifiques des STP étant peu étudiées, l'objectif de notre étude a été de les évaluer sur le plan psychiatrique, neurodéveloppemental et somatique. MÉTHODE: Il s'agit d'une étude ancillaire du protocole GenAuDiss. Un entretien psychiatrique standardisé (K-SADS-PL DSM5) et un bilan neuropsychologique (WISC-V/WAIS-IV) ont été effectués chez les patients atteints de STP ainsi qu'une anamnèse concernant la grossesse, la périnatalité, le développement, la biographie et les antécédents médicaux et psychiatriques, personnels et familiaux. RÉSULTATS: 20 sujets ont été inclus. L'âge moyen de début du trouble était de 8,90 ans (+/−2,30). Les comorbidités psychiatriques (DSM5) étaient le Trouble Déficitaire de l'Attention avec Hyperactivité (15/20 patients), les troubles anxieux (14/20) et le Trouble du Spectre de l'Autisme (13/20). Le QI moyen était de 70,26 (+/−18,09). Un retard de langage et une rupture de parcours scolaire étaient notés chez 18/20 patients. Enfin, l'affection somatique principale associée était l'asthme (15/20 patients). DISCUSSION: Nous avons mis en évidence chez nos patients atteints de STP une fréquence élevée de comorbidités dont au moins un trouble psychiatrique systématique. Or, bien que la schizophrénie infantile soit une pathologie de pronostic sévère impactant le patient, sa famille et la société, sa prise en charge demeure essentiellement symptomatique. En pratique clinique, il apparaît nécessaire de rechercher systématiquement ces comorbidités et de les prendre en charge pour améliorer la qualité globale des soins.

Comparison of clinical characteristics and treatment efficacy in childhood-onset schizophrenia and adolescent-onset schizophrenia in mainland China: A retrospective study.

AIM: The comparative study of childhood-onset schizophrenia (COS) and adolescent-onset schizophrenia (AOS) is scarce. This study aimed to examine the differences in clinical presentations and treatment efficacy between COS and AOS and further analyse the factors affecting the efficacy of early-onset schizophrenia (EOS). METHODS: A total of 582 electronic medical records of inpatients with EOS (216 COS and 366 AOS inpatients) between 2012 and 2019 were retrospectively analysed. The positive and negative syndrome scale (PANSS) was used to assess psychotic symptoms. Logistic regression analysis was performed to analyse the predictors of efficacy. RESULTS: The mean age of onset of EOS was 12.87 ± 2.19 years. The importance of better diagnosing COS appeared in a longer illness course, more frequently insidious onset, less frequent delusions, more severe negative symptoms and bizarre behaviours than AOS. Besides, COS had more frequent visual hallucinations and impulsive behaviours than AOS. After hospitalization, the improvement rate of psychotic symptoms in COS and AOS were 38.3% and 47.8%, respectively. The difference of efficacy between the two groups was statistically significant. Days of hospitalization, age of onset, presence of flat affect, PANSS total and negative score at admission were predictors of treatment efficacy in EOS individuals. CONCLUSIONS: COS inpatients suffer more obvious negative symptoms, bizarre behaviours, visual hallucinations and impulsive behaviours and worse efficacy than AOS inpatients. The severity of negative symptoms and age of onset seem the most noteworthy predictors of efficacy. These findings highlight the importance of early detection and early intervention.

[A clinical case of continuous schizophrenia with onset in early childhood]. / Klinicheskii sluchai nepreryvnotekushchei shizofrenii s nachalom v rannem detskom vozraste.

Cases of very early-onset schizophrenia are poorly described in the modern literature due to the ambiguous attribution of these conditions to a number of schizophrenic disorders. The diagnosis is complicated by the atypical presentation of the disease in early childhood. This clinical case reflects the manifestation, dynamics and outcome of the disease, which is important for early diagnosis and initiation of adequate drug intervention and habilitation.

Expansion of the GRIA2 phenotypic representation: a novel de novo loss of function mutation in a case with childhood onset schizophrenia.

Childhood-onset schizophrenia (COS) is a rare form of schizophrenia with an onset before 13 years of age. There is rising evidence that genetic factors play a major role in COS etiology, yet, only a few single gene mutations have been discovered. Here we present a diagnostic whole-exome sequencing (WES) in an Israeli Jewish female with COS and additional neuropsychiatric conditions such as obsessive-compulsive disorder (OCD), anxiety, and aggressive behavior. Variant analysis revealed a de novo novel stop gained variant in GRIA2 gene (NM_000826.4: c.1522 G > T (p.Glu508Ter)). GRIA2 encodes for a subunit of the AMPA sensitive glutamate receptor (GluA2) that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. GluA2 subunit mutations are known to cause variable neurodevelopmental phenotypes including intellectual disability, autism spectrum disorder, epilepsy, and OCD. Our findings support the potential diagnostic role of WES in COS, identify GRIA2 as possible cause to a broad psychiatric phenotype that includes COS as a major manifestation and expand the previously reported GRIA2 loss of function phenotypes.

Second-Generation Antipsychotic Drugs for Children and Adolescents.

The effectiveness and safety of antipsychotics have not been fully established in children and adolescents. Many antipsychotics approved for use in adults are prescribed off-label to children and adolescents. We investigated the effectiveness and tolerability of antipsychotics for children and adolescents with schizophrenia and bipolar disorder. A literature review of the empirical evidence regarding the use of antipsychotics, particularly second-generation antipsychotics, in children and adolescents showed that these drugs were safe and effective for this population. Antipsychotics were similarly effective for treatment of schizophrenia and bipolar disorder in children and adolescents. When prescribing antipsychotics to this population, clinicians should consider adverse events and the discontinuation rate in treated patients. However, the current evidence shows a lack of consensus regarding the use of antipsychotics in children and adolescents.

Sleep neurophysiology in childhood onset schizophrenia.

Altered sleep neurophysiology has consistently been reported in adult patients with schizophrenia. Converging evidence suggests that childhood onset schizophrenia (COS), a rare but severe form of schizophrenia, is continuous with adult onset schizophrenia. The aim of the current study was to characterize sleep neurophysiology in COS. An overnight sleep electroencephalogram (EEG) was recorded in 17 children and adolescents with COS (16 years ± 6.6) and 17 age and gender-matched controls. Non-rapid eye movement (NREM) and rapid eye movement (REM) sleep EEG power and coherence for the frequency bands delta (1.6-4.8 Hz), theta (5-8.4 Hz), alpha (8.6-11 Hz), beta 1 (16.4-20.2 Hz) and beta 2 (20.4-24.2 Hz) were compared between COS patients and controls. COS patients exhibited significant and widespread deficits in beta power during NREM and REM sleep. With regard to coherence, we found increases in COS patients across brain regions, frequency bands and sleep states. This study demonstrates the utility of the sleep EEG for studying vulnerable populations and its potential to aid diagnosis.

Functional outcomes and patient satisfaction following inpatient treatment for childhood-onset schizophrenia spectrum disorders vs non-psychotic disorders in children in the United Kingdom.

AIM: The aim of this study was to compare clinical characteristics and treatment outcomes between children with Childhood-onset schizophrenia spectrum disorders (COSS) and children with other severe non-psychotic psychiatric conditions (non-COSS), all admitted to a national mental health inpatient children's unit. METHODS: We conducted a retrospective study of all children discharged from a national children's inpatient unit in the United Kingdom, between 2009 and 2018. We compared functional and treatment outcomes and satisfaction with treatment in COSS with non-COSS in the whole sample and separately for male and female patients. RESULTS: A total of 211 children (55% boys) were included in the sample. The mean age on admission was 129.7 months (10.8 years; age range, 6-12).Twenty cases were diagnosed with COSS (9.5%). In the whole sample, COSS patients had significantly lower Children's Global Assessment Scale (CGAS) scores on admission compared to non-COSS (P = .006). There was a trend towards children with COSS as a group having a longer admission (M = 194.6 days, SD = 125.4) compared to non-COSS (M = 135.8 days, SD = 86.2), (P = .053). Females with COSS seemed to have more significant differences compared to females with non-COSS, in particular, longer admissions (P = .016) and worse CGAS scores at discharge (P = .04), whilst in males, these differences seemed to be attenuated. CONCLUSIONS: Children with COSS have lower functioning at the point of inpatient admission and possibly longer admissions, but similar satisfaction with treatment at discharge from hospital compared with non-COSS. Females with COSS may have worse functional outcomes compared to non-COSS at discharge.

Association of family history of schizophrenia and history of obstetric complications at birth: relationship with age at onset and psychopathology dimensions in a Nigerian cohort.

BACKGROUND: The nature of the association between obstetric complications (OCs) at birth and the genetic aetiology of schizophrenia remains unclear, as some authors suggest that it is an independent risk factor while others support either interactionism or an epiphenomenon perspective. OBJECTIVE: To examine the association of family history of schizophrenia (FHS) with history of OCs, with a view to assessing whether this relationship moderates clinical phenotypes such as symptom dimensions and age at onset of illness. METHODS: This study examined OCs among schizophrenia probands using the Obstetric Complications Scale. An inquiry into family history was performed using the Family history method. Psychopathological symptom dimensions were assessed using standard scales. Data were analyzed to examine the interaction of FHS and history of OCs with age at onset and symptom dimensions, using ANCOVA. RESULTS: FHS was significantly associated with the disorganized symptoms dimension (p=0.03). History of OCs was significantly associated with earlier age at onset (p=0.007). However, in ANCOVA, the effect of the interaction between FHS and history of OCs was not significant for age at onset and symptom dimensions (P = 0.059). CONCLUSION: FHS was significantly associated with disorganization syndrome, and OCs was significantly associated with age at onset.

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

Sleep spindle activity in childhood onset schizophrenia: Diminished and associated with clinical symptoms.

Neuroimaging studies of childhood onset schizophrenia (COS), a rare yet severe form of schizophrenia with an onset before the age of 13 years, have shown continuity with adult onset schizophrenia. Previous research in adult patients has shown reduced sleep spindle activity, transient oscillations in the sleep electroencephalogram (EEG) generated through thalamocortical loops. The current study examines sleep spindle activity in patients with COS. Seventeen children and adolescents with COS (16 years ±6.6) underwent overnight sleep EEG recordings. Sleep spindle activity was compared between patients with COS and age and gender matched controls and correlated with clinical symptom severity. We found pronounced deficits in sleep spindle amplitude, duration, density and frequency in patients with COS (effect size = 0.61 to 1.96; dependent on metric and EEG derivation). Non-rapid eye movement (NREM) sleep EEG power and coherence in the sigma band (11-16 Hz) corresponding to spindle activity were also markedly diminished in patients with COS as compared to controls. Furthermore, the degree of deficit in power and coherence of spindles was strongly associated with clinician rated hallucinations and positive symptoms over widespread cortical regions. Our finding of diminished spindle activity and its association with hallucinations likely reflect dysfunction of the thalamocortical circuits in children and adolescents with COS. Given the relative ease of sleep EEG recordings in vulnerable populations, this study highlights the potential of such recordings to characterize brain function in schizophrenia.