Protocol for a randomized pilot study (FIRST STEPS): implementation of the Incredible Years-ASLD® program in Spanish children with autism and preterm children with communication and/or socialization difficulties.

Having access to parenting interventions in the early years is key to improve the developmental outcomes of children with neurodevelopmental problems. The Incredible Years® (IY) Parent Program is a group intervention that has demonstrated efficacy in terms of reducing stress in parents, as well as improving behavioral, emotional, and social outcomes in children. The program has been recently adapted for families of children with autism or language delays (IY-ASLD®). This intervention has not yet been implemented in the Spanish Public Health System, where there is a scarcity of evidence-based interventions being offered to families with young children presenting neurodevelopmental problems. The main aims of this study are to determine the feasibility of implementing the IY-ASLD® program within Spanish Child Mental Health Services and to examine parents' acceptability and satisfaction with the intervention. As a secondary objective, we aim to evaluate its preliminary effectiveness in terms of reducing parental stress and behavioral difficulties in their children. The FIRST STEPS study is a multicenter, pilot randomized controlled trial comparing the IY-ASLD® program with a treatment-as-usual (TAU) condition. Approximately 70 families of children with autism spectrum disorder (ASD) and preterm children with communication and/or socialization difficulties (aged 2-5 years) will be recruited. Families will be assessed prior to randomization and after the intervention. Due to the COVID-19 pandemic, the intervention will consist of 22 weekly online sessions (approximately 6 months). The FIRST STEPS pilot trial will demonstrate the feasibility and acceptability of reliably implementing the IY-ASLD® program within the Spanish Public Health System. The results of this study could represent the first step to inform policymakers in Spain when designing evidence-based healthcare pathways for families of children presenting ASD symptoms or neurodevelopmental difficulties at early stages. TRIAL REGISTRATION: ClinicalTrials.gov NCT04358484 . Registered on 04 April 2020.

Effects of Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation in Children and Adolescents with Prader-Willi Syndrome: A Randomized Crossover Trial.

Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by a wide range of clinical manifestations, including obesity, hyperphagia, and behavioral problems. Bifidobacterium animalis subsp. lactis strain BPL1 has been shown to improve central adiposity in adults with simple obesity. To evaluate BPL1's effects in children with PWS, we performed a randomized crossover trial among 39 patients (mean age 10.4 years). Participants were randomized to placebo-BPL1 (n = 19) or BPL1-placebo (n = 20) sequences and underwent a 12-week period with placebo/BPL1 treatments, a 12-week washout period, and a 12-week period with the crossover treatment. Thirty-five subjects completed the study. The main outcome was changes in adiposity, measured by dual-energy X-ray absorptiometry. Secondary outcomes included lipid and glucose metabolism, hyperphagia, and mental health symptoms. Generalized linear modeling was applied to assess differences between treatments. While BPL1 did not modify total fat mass compared to placebo, BPL1 decreased abdominal adiposity in a subgroup of patients older than 4.5 years (n = 28). BPL1 improved fasting insulin concentration and insulin sensitivity. Furthermore, we observed modest improvements in some mental health symptoms. A follow-up trial with a longer treatment period is warranted to determine whether BPL1 supplementation can provide a long-term therapeutic approach for children with PWS (ClinicalTrials.gov NCT03548480).

Complex post-traumatic stress symptoms in female adolescents: the role of emotion dysregulation in impairment and trauma exposure after an acute sexual assault.

Background: Adolescents are at high risk of sexual assault compared to any other age group. The pattern of post-traumatic stress symptoms plus life-impairing disturbances in self-organization (emotion dysregulation, negative self-concept and interpersonal problems) is termed Complex Post-Traumatic Stress Disorder (CPTSD). Research about CPTSD after sexual assault in adolescents is limited owing to the challenges associated with assessing this group. This study aims to determine the frequency and structure of CPTSD, and the relationship of emotion dysregulation with impairment and additional trauma exposure among adolescents who have been sexually assaulted. Method: Prospective cohort study of adolescents attending the Sexual Assault Referral Centres serving London over a 2-year period. We conducted cross-sectional analyses (n = 99) on data collected 4-5 months after sexual assault, and Confirmatory Factor Analyses (CFA) and Latent Class Analyses (LCA) to determine the CPTSD profile. CTPSD was defined according to the ICD-11, selecting symptom indicators from the following measures: Strengths and Difficulties Questionnaire (SDQ), Children's Revised Impact of Event Scale (CRIES-13), Short version of the Mood and Feelings Questionnaire (S-MFQ), The Development and Well-Being Assessment (DAWBA). We analysed the association of CPTSD symptom domains with impairment (measured with the SDQ, and the Children's Global Assessment Scale; C-GAS) and with additional trauma exposure. Results: The frequency of ICD-11 PTSD was 59%, and of ICD-11 CPTSD was 40%. CPTSD symptoms showed a strong fit for a correlated 4-factor model, and LCA distinguished a class of participants with high levels of CPTSD symptoms. Emotion dysregulation was associated with impairment in functioning and exposure to trauma beyond other self-organization disturbances and core PTSD symptoms. Conclusions: Disturbances in self-organization are frequent in sexually assaulted adolescents, and emotion dysregulation is associated with impairment and further exposure to trauma. Emotion dysregulation should be considered in preventive and treatment strategies for these vulnerable youth.

Antecedentes: Las adolescentes presentan mayor riesgo de abuso sexual comparadas con cualquier otro grupo de edad. El patrón de síntomas de estrés postraumáticos sumados a las perturbaciones incapacitantes en la autoorganización (desregulación emocional, autoconcepto negativo, y problemas interpersonales) recibe el nombre de trastorno de estrés postraumático complejo (TEPT-C). Las investigaciones en TEPT-C luego de un abuso sexual en adolescentes es limitado dados los desafíos asociados a la evaluación de este grupo. El presente estudio busca determinar la frecuencia y estructura del TEPT-C, y la relación entre la desregulación emocional con deterioro y con exposición a traumas adicionales en mujeres adolescentes en quienes se haya cometido abuso sexual.Métodos: Se realizó un estudio prospectivo de cohortes en adolescentes que acudían a los Centros de Referencia por Abuso Sexual que operan en Londres, durante un periodo de dos años. Condujimos análisis transversales (n = 99) en la información recolectada cuatro a cinco meses después del abuso sexual, además de Análisis Factoriales de Confirmación (AFC) y Análisis de Clases Latentes (ACL) para determinar el perfil del TEPT-C. Se definió al TEPT-C según la CIE-11, seleccionando indicadores de los síntomas a partir de las mediciones siguientes: Cuestionario de Fortalezas y Debilidades (SDQ, por sus siglas en inglés), Escala de Impacto del Evento Revisado para Niños (CRIES-13, por sus siglas en inglés), la Versión Abreviada del Cuestionario de Ánimo y Emociones (S-MFQ, por sus siglas en inglés), la Evaluación del Desarrollo y Bienestar (DAWBA, por sus siglas en inglés). Analizamos la asociación de los dominios de síntomas del TEPT-C con deterioro (medido en la SDQ, y con la Escala de Evaluación Global Infantil; C-GAS, por sus siglas en inglés), y con exposición a traumas adicionales.Resultados: La frecuencia del Trastorno de Estrés Postraumático (TEPT) según la CIE-11 fue de 59%, y de TEPT-C según la CIE-11 fue de 40%. Los síntomas de TEPT-C mostraron un ajuste alto con un modelo correlacionado de cuatro factores, y el ACL distinguió una clase de participantes con alto niveles de síntomas del TEPT-C. El deterioro en el funcionamiento y la exposición a traumas posteriores asociados con la desregulación emocional fueron más allá de las perturbaciones en la autorregulación y en los síntomas nucleares del TEPT.Conclusiones: Las perturbaciones en la autoorganización son frecuentes en adolescentes en quienes se ha cometido un abuso sexual, y la desregulación emocional está asociada con deterioro y con exposición posterior a trauma. La desregulación emocional debería ser considerada en estrategias de prevención y tratamiento para estas jóvenes vulnerables.

A systematic review of short and medium-term mental health outcomes in young people following sexual assault.

Objective: Sexual assault peaks in adolescence, yet sequelae at this age are not well understood. This systematic review aimed to describe mental health outcomes following sexual assault in young people. Method: Two reviewers independently searched databases, screening publications from 1990 to 2018. Inclusion criteria included: longitudinal studies, systematic reviews, and meta-analyses with ≥50% participants aged ten to 24 years; baseline mental health assessment prior to/or <8 weeks post-assault with follow-up ≥ 3 months after the initial assessment.Results: 5 124 titles and abstracts were screened, with 583 papers examined in full. Ten studies met inclusion criteria (sample size 31 to 191). Five studies examined rates of post-traumatic stress disorder (PTSD), reporting rates of up to 95% within one month and up to 60% at 12 months post-assault. Studies evaluating post-traumatic (n = 5) and anxiety (n = 3) symptom scores showed symptoms were highest in the immediate aftermath of the trauma, generally reducing over four to 12 months post-assault. Depressive symptomology appeared to vary between studies (n = 5). However, the majority showed symptoms decreasing over the same time period.Conclusions: Psychopathology is common following sexual assault in young people. Most studies observed reduced rates over time, but there is a paucity of longitudinal research. Psychopathology during the first year after sexual assault is an important treatment target to consider.

Mental and sexual health outcomes following sexual assault in adolescents: a prospective cohort study.

BACKGROUND: Young people are disproportionately affected by sexual assault, yet longitudinal data are sparse. This paper examines the characteristics of adolescents presenting to sexual assault services and mental and sexual health outcomes after an assault. METHODS: This was a prospective cohort study in adolescents aged 13-17 years attending the Sexual Assault Referral Centres serving Greater London, UK, over 2 years. Baseline interviews (T0) were done less than 6 weeks after an assault to collect data on sociodemographic and assault characteristics and psychological symptoms, with follow-up interviews (T1) at 4-5 months after the assault. Four psychological symptom questionnaires were used at T0 and T1: The Child Revised Impact of Events Scale, the Short Mood and Feelings Questionnaire, the Screen for Child Anxiety Related Disorders, and the Strengths and Difficulties Questionnaire. The primary outcome was prevalence of any psychiatric disorder at T1, assessed using the Development and Wellbeing Assessment. Secondary outcomes at T1 were pregnancy, sexually transmitted infections, and sexual health screening since the assault. FINDINGS: Between April 15, 2013, and April 20, 2015, 141 (29%) of 491 eligible young people were recruited to the study (134 females; mean age 15·6 years [SD 1·27]), and 106 (75%) of 141 participants had T1 interviews (99 female). At T0, psychological symptom scores showed that 115 (88%) of 130 females were at risk for depressive disorder, 90 (71%) of 126 were at risk for anxiety disorders, and 116 (91%) of 128 were at risk for post-traumatic stress disorder, with symptoms largely persisting at T1. 68 (80%) of 85 females who had a diagnostic assessment at T1 had a psychiatric disorder, with multiple disorders in 47 (55%) of 85. Anxiety, post-traumatic stress, and major depressive disorders were the commonest diagnoses. Presence of a psychiatric disorder was associated with baseline psychosocial vulnerability (previous social services involvement, mental health service use, self-harm, or sexual abuse), but not assault characteristics. At T1, four (4%) of 105 females had been pregnant since the assault, 14 (12%) of 119 had a sexually transmitted infection diagnosed between T0 and T1, and nine (8%) of 107 reported re-victimisation since the assault. INTERPRETATION: Vulnerable adolescents have the double disadvantage of being at risk for both sexual assault and associated psychiatric disorders, highlighting the need for comprehensive support after an assault. Feasibility and effectiveness of prevention programmes should be investigated. FUNDING: National Institute for Health Research Policy Research Programme grant (115/0001).

Parental bonding in subjects with pathological gambling disorder compared with healthy controls.

The new Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) includes pathological gambling disorder (PGD) in the subgroup of "Addiction and Related Disorders" due to the similarities between PGD and substance-based addictions in neurobiological, psychological, and social risk factors. Family factors as parental rearing attitudes play a crucial role in the development of substance use disorders and PGD. The aim of the present study was to assess the parental bonding during childhood perceived for adults with PGD compared with healthy controls. Twenty males with PGD and 20 control subjects answered the parental bonding instrument, which measures subjects' recollections of parenting on dimensions of care and protection. Subjects with PGD showed significantly lower maternal and paternal care (p = 0.016 and p = 0.031, respectively) than controls, and higher paternal protection (p = 0.003). The most common parental pattern for PGD subjects was the affectionless control (50% for the father and 60% for the mother). Preliminary results suggest that, as previously reported for substance use disorders, an affectionless control parenting style is associated with PGD.

Neuropsychological effects of maintenance treatment with Clozapine in Treatment-Resistant Psychotic Disorder.

INTRODUCTION: Clozapine is a second-generation antipsychotic drug that is mainly prescribed for treatment-resistant psychotic disorder. It is known to have several undesirable side effects, including cognitive functional complaints, such as memory or attention. The aim of this work is to study if reduction of the dosage within the therapeutic margins could improve cognitive performance of Clozapine treated patients. To do so, a study was made of the relationship between Clozapine plasma levels and neuropsychological performance in patients undergoing Clozapine monotherapy. MATERIAL AND METHODS: This is a single-blind design study of the correlation between Clozapine plasma levels and neuropsychological testing in a sample of 19 patients with treatment-resistant psychotic disorder in whom Clozapine was the only psychotropic drug. Spearman correlations were carried out between neuropsychological variables and Clozapine plasma levels. Additionally, the sample was divided into two groups between patients with high Clozapine plasma drug levels (Clz pl≥300µg/L) and low ones (Clz pl<300 µg/L). MANOVA was performed to determine neuropsychological differences between the two groups. Subsequently, a linear regression model was carried out to predict neuropsychological performance. RESULTS: There was no significant Spearman correlation between neuropsychological scores and Clozapine plasma levels (p>0.1). MANOVA showed no significant differences between the two groups in any of the tests administered, although there was a trend towards significance in the number on attempts of the Card Sorting Test (WCST), where subjects with high levels of Clozapine showed worse performance (F=3.86; df=1.17; p=0.07). The linear regression model showed that only plasma levels significantly predicted executive performance, explaining 31% of the variance (F=3.62; df=2.16; p=0.05). CONCLUSION: No relationship between plasma levels of Clozapine and cognitive performance has been found. This result suggests that it is not desirable to reduce a relevant dose of Clozapine in patients with cognitive complaints.

Efectos neuropsicológicos del tratamiento de mantenimiento con Clozapina en el Trastorno Psicótico Resistente / Neuropsychological effects of maintenance treatment with Clozapine in Treatment-Resistant Psychotic Disorder

Introducción. La Clozapina es un antipsicótico de segunda generación, indicado en casos de trastorno psicótico resistente al tratamiento convencional. Presenta varios efectos secundarios, entre ellos, las quejas sobre la función cognitiva como la memoria o la atención. El objetivo es estudiar si la reducción de la dosis dentro de los márgenes terapéuticos podría mejorar el rendimiento cognitivo de los pacientes tratados con clozapina. Para ello se estudia la relación entre la concentración plasmática de Clozapina y el rendimiento cognitivo en pacientes en monoterapia con Clozapina. Material y Métodos. El estudio es un diseño simple ciego de correlación entre niveles plasmáticos de Clozapina y rendimiento neuropsicológico en una muestra de 19 pacientes con trastorno psicótico resistente en monoterapia con Clozapina. Se realizaron correlaciones de Spearman entre variables neuropsicológicas y niveles plasmáticos. Adicionalmente, la muestra se dividió entre pacientes con niveles plasmáticos altos (Clz pl≥300μg/L) y bajos (Clz pl<300μg/L) de Clozapina. Se llevó a cabo una MANOVA para determinar diferencias entre grupos. Se realizó un análisis de regresión lineal para predecir el rendimiento neuropsicológico. Resultados. No se halló ninguna correlación significativa entre las pruebas neuropsicológicas y los niveles plasmáticos de Clozapina (p>0.1). La MANOVA no mostró diferencias significativas entre los dos grupos en ninguna de las pruebas administradas, aunque sí se observó una tendencia a la significación en los análisis univariantes donde en el número de intentos del Test de Clasificación de Tarjetas (WCST)los sujetos con niveles altos de Clozapina mostraron un peor rendimiento (F=3.86; gl=1.17; p=0.07). El modelo de regresión lineal mostró que el único factor significativo fueronlos niveles plasmáticos, explicando un 31% de la varianza (F=3.62; gl=2.16; p=0.05). Conclusiones. No se evidencia relación entre los niveles plasmáticos de Clozapina y el rendimiento cognitivo. Este resultado sugiere que no es conveniente reducir de forma relevante la dosis de Clozapina en pacientes que se quejan de disfunciones cognitivas

Introduction. Clozapine is a second-generation antipsychotic drug that is mainly prescribed for treatment-resistant psychotic disorder. It is known to have several undesirable side effects, including cognitive functional complaints, such as memory or attention. The aim of this work is to study if reduction of the dosage within the therapeutic margins could improve cognitive performance of Clozapine treated patients. To do so, a study was made of the relationship between Clozapine plasma levels and neuropsychological performance in patients undergoing Clozapine monotherapy. Material and Methods. This is a single-blind design study of the correlation between Clozapine plasma levels and neuropsychological testing in a sample of 19 patients with treatment-resistant psychotic disorder in whom Clozapine was the only psychotropic drug. Spearman correlations were carried out between neuropsychological variables and Clozapine plasma levels. Additionally, the sample was divided into two groups between patients with high Clozapine plasma drug levels (Clz pl.300ƒÊg/L) and low ones (Clz pl<300ƒÊg/L). MANOVA was performed to determine neuropsychological differences between the two groups. Subsequently, a linear regression model was carried out to predict neuropsychological performance. Results. There was no significant Spearman correlation between neuropsychological scores and Clozapine plasma levels (p>0.1). MANOVA showed no significant differences between the two groups in any of the tests administered, although there was a trend towards significance in the number on attempts of the Card Sorting Test (WCST), where subjects with high levels of Clozapine showed worse performance (F=3.86; df=1.17; p=0.07). The linear regression model showed that only plasma levels significantly predicted executive performance, explaining 31% of the variance (F=3.62; df=2.16; p=0.05). Conclusion. No relationship between plasma levels of Clozapine and cognitive performance has been found. This result suggests that it is not desirable to reduce a relevant dose of Clozapine in patients with cognitive complaints

Exploring the interaction between childhood maltreatment and temperamental traits on the severity of borderline personality disorder.

BACKGROUND: Childhood maltreatment and temperamental traits play a role in the development of Borderline Personality Disorder (BPD). The aim of the present study was to assess the involvement and the interrelationship of both factors in the clinical severity of BPD. METHOD: The self-reported history of childhood trauma, psychobiological temperamental traits, and severity of BPD symptoms were evaluated in 130 subjects with BPD. RESULTS: Approximately 70% of the sample reported some form of abuse or neglect. Childhood maltreatment inversely correlated with sociability, but no correlation was observed with the other temperamental traits. The regression model showed that neuroticism-anxiety and aggression-hostility traits, as well as emotional abuse, were risk factors independently associated with the severity of BPD. Sexual abuse was not associated with the severity of the disorder. Finally, the interaction between high neuroticism-anxiety traits and the presence of severe emotional abuse was associated with BPD severity. CONCLUSION: These results suggest that the interaction between temperamental traits and childhood emotional abuse has an influence not only on the development but also on the severity of BPD. Further studies are needed to identify more biological and environmental factors associated with the severity of the disorder.

Asenapine in the treatment of borderline personality disorder: an atypical antipsychotic alternative.

Many individuals with borderline personality disorder (BPD) receive medical treatment in clinical practice, although to date, there are no drugs specifically available for BPD. The recent Cochrane guideline suggests a benefit from using second-generation antipsychotics such as olanzapine or aripiprazole; nevertheless, side effects limit their use. Asenapine is a novel FDA-approved atypical antipsychotic for schizophrenia and bipolar disorder. However, it has not yet been tested for BPD. The goal of this observational open-label study was to assess the safety, tolerability and efficacy of asenapine in a series of cases of patients with BPD. Twelve individuals with BPD were recruited and treated with asenapine during an 8-week period. Eight individuals completed the study; a significant improvement was observed in the CGI-BPD (P<0.001) and BSL-23 (P<0.048) scales for BPD symptomatology. Besides, there was a significant improvement in the general psychopathology domains (BPRS, P<0.004), whereas no significant differences were observed in depressive symptoms. No serious adverse effects were reported and a significant weight reduction was observed (P=0.002). Asenapine appears to be a safe and effective agent in the treatment of patients with BPD, especially when other alternatives are not tolerated. These preliminary findings should be replicated in a controlled clinical trial.