Angela Cosenza

Open trial of risperidone in 24 young children with pervasive developmental disorders

OBJECTIVE To describe tolerability and efficacy of risperidone in very young children with pervasive developmental disorders. METHOD Twenty-four children aged 3.6 to 6.6 years (mean 4.6 years +/- 8 months) enrolled during 1999 and 2000 participated in a 16-week open-label trial with risperidone monotherapy. Outcome measures included the Childrens Psychiatric Rating Scale (CPRS), Childhood Autism Rating Scale (CARS), Clinical Global Impression-Improvement (CGI-I), and Childrens Global Assessment Scale (C-GAS). RESULTS Two subjects did not complete the trial because of side effects. The optimal dose was 0.5 mg/day. After the treatment a 21% improvement in CPRS and a 14% improvement in CARS total scores was found. Items related to behavioral control (hyperactivity, fidgetiness, rhythmic motions) and affect regulation (lability of affect, angry affect) improved more than 25%. Based on improvement of at least 25% on the CPRS and a score of 1 or 2 on the CGI-I, eight subjects were considered responders. Functional impairment (C-GAS) improved more than 25%. Thirteen subjects (54%) were free of any side effects; in the other participants risperidone was well tolerated. Only three subjects had a weight gain greater than 10%. CONCLUSIONS Low-dose risperidone may positively affect symptoms in young autistic children, improving disruptive/hyperactive behavior and affective dysregulation. Further controlled studies in this age group are warranted.

The CBCL 1.5-5 and the identification of preschoolers with autism in Italy.

AIMS To study the potential use of child behaviour checklist (CBCL) 1.5-5 scales for the early identification of preschoolers at risk of autism. METHODS CBCL scores of three groups of preschoolers were compared: (1) an experimental group of 101 preschoolers with autism spectrum disorder (ASD); (2) a control group of 95 preschoolers with other psychiatric disorders (OPD); (3) a control group of 117 preschoolers with typical development (TD). One-way analysis of variance (ANOVA), logistic regression with odds ratio (OR) and receiver operating characteristic (ROC) analyses were performed. RESULTS ANOVA revealed that ASD and OPD had significantly higher scores in almost all CBCL scales than TD. ASD presented significantly higher scores than OPD on Withdrawn, Attention Problems and Pervasive Developmental Problems (PDP) scales. Logistic regression analysis demonstrated that these same CBCL scales have validity in predicting the presence of an ASD towards both TD and OPD. ROC analysis indicated high sensitivity and specificity for PDP (0.85 and 0.90) and Withdrawn (0.89 and 0.92) scales when ASD is compared to TD. Specificity (0.60 for PDP and 0.65 for Withdrawn) decreases when comparing ASD and OPD CONCLUSIONS: The PDP and Withdrawn scales have a good predictive validity so that they could be proposed as a first-level tool to identify preschoolers at risk of autism in primary care settings. Problems regarding the lower specificity when comparing ASD v. OPD are discussed.

Prolactin levels in young children with pervasive developmental disorders during risperidone treatment.

Although hyperprolactinemia is a common side effect during risperidone treatment in adult patients, no information is available on young children. The aim of this study is to report on serum prolactin levels in 25 young autistic children (22 males and 3 females, age range 3.9-7 years, mean age 4.10 years) during treatment with risperidone (dosage range 0.25-0.90 mg/day, mean dosage 0.52 mg/day). Prolactin levels were measured at baseline and after 10 weeks of treatment. The clinical outcome measure used was the Clinical Global Impression-Improvement. Serum prolactin was 9.77 +/- 3.94 ng/mL at baseline and 25.92 +/- 13.9 ng/mL during the 10th week of treatment (p < 0.001). Six children (24%) showed prolactin levels lower than 15 ng/mL, which is the upper normal level; eight children (28%) had prolactin levels higher than two times the upper limit (30 ng/mL). Hyperprolactinemia did not show significant correlations with age, weight, or risperidone dosage. There was no relation with clinical outcome. Dose reduction of risperidone resulted in a decrease of prolactin levels. None of the children showed clinical signs of hyperprolactinemia. Given the paucity of available data on potential effects of long-term hyperprolactinemia, a monitoring of prolactin during treatment with risperidone and other typical and atypical antipsychotics may be warranted.

Aripiprazole Monotherapy in Children and Young Adolescents with Pervasive Developmental Disorders: A Retrospective Study

AbstractBackground: Pervasive developmental disorders (PDDs) are severe psychiatric disorders characterized by impairment in social interactions, in verbal and non-verbal communication, and by restricted and stereotyped patterns of interest and behaviour, with onset in the first 3 years of life. The appropriate use of pharmacotherapy can improve some aberrant symptoms and behaviours and increase the person’s response to non-pharmacological interventions. Objective: To describe clinical outcomes, or symptom changes, and adverse effects during naturalistic treatment with aripiprazole monotherapy in children with PDDs and severe behavioural disorders (such as aggression against self and/or others, hostility, hyperactivity, severe impulsiveness). Method: This retrospective naturalistic study included 34 patients (23 males and 11 females, age range 4.5–15 years, mean age 10.2 ± 3.3 years), admitted during 2006–2007, diagnosed according to DSM-IV criteria and followed up for 4–12 months (mean 7.0 ± 3.6 months). Outcome measures were three global measures of clinical and functional impairment and improvement from baseline: the Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) scales; the Children’s Global Assessment Scale (C-GAS); and the Childhood Autism Rating Scale (CARS), a specific measure of PDD symptoms. Results: The mean baseline CGI-S was 5.7 ± 0.8 (markedly ill/severely ill). The mean final dosage of aripiprazole was 8.1 ±4.9 mg/day. At the endpoint, 11 patients (32.4%) were ‘much improved’ or ‘very much improved’ (CGI-I score of 1 or 2), 12 patients (35.3%) were ‘minimally improved’ (CGI-I score of 3) and 10 (29.4%) were ‘unchanged’ or ‘worsened’ (CGI-I score of 4 or 5). C-GAS and CARS scores significantly improved (p <0.0001, effect sizes 0.59 and 0.62, respectively). Nine patients (26.5%) experienced moderate to severe agitation, which was associated with self-injurious behaviours in five of these patients, and five patients presented with sleep disorders. Twelve patients (35.3%) discontinued medication during the follow-up because of lack of efficacy or adverse effects. Conclusions: In these severely impaired children with PDDs, aripiprazole monotherapy was associated with a significant improvement in maladaptive behaviours in one-third of patients. Agitation and insomnia were the most frequent adverse effects. Further controlled studies in larger samples to explore possible predictors of efficacy are warranted.

Risperidone Monotherapy in Preschool Children With Pervasive Developmental Disorders

The aim of this preliminary study was to examine the short-term efficacy and safety of the atypical antipsychotic risperidone in preschool autistic children. The sample consisted of 10 subjects (7 males and 3 females) aged 39/12 to 66/12 years (mean age 4.7 years). A 16-week open-label trial with risperidone monotherapy was initiated at a starting dose of 0.25 mg daily and was increased to a maximum dose of 0.50 mg (0.027 mg/kg daily). Outcome measures were the Childhood Autism Rating Scale, the Childrens Psychiatric Rating Scale, Clinical Global Impression (improvement score), and the Childrens Global Assessment of Functioning. Two subjects did not complete the trial because of side effects (tachycardia and flushes, fever and hyporexia). After the 16-week treatment, data from the eight children who completed the trial indicated a modest improvement in the Childhood Autism Rating Scale total score, Childrens Psychiatric Rating Scale total score, and Childrens Global Assessment of Functioning. According to the Clinical Global Impression, the global improvement score for four subjects was much improved or very much improved; the score for the other four children was minimally improved. None of the children exhibited behavioral deterioration. The side effects in the eight children were not severe. (J Child Neurol 2001;16:395-400).

Gray Matter Alterations in Young Children with Autism Spectrum Disorders: Comparing Morphometry at the Voxel and Regional Level.

Sophisticated algorithms to infer disease diagnosis, pathology progression and patient outcome are increasingly being developed to analyze brain MRI data. They have been successfully implemented in a variety of diseases and are currently investigated in the field of neuropsychiatric disorders, including autism spectrum disorder (ASD). We aim to test the ability to predict ASD from subtle morphological changes in structural magnetic resonance imaging (sMRI).

Somatic Overgrowth Predisposes to Seizures in Autism Spectrum Disorders

Background Comorbidity of Autism Spectrum Disorders with seizures or abnormal EEG (Autism-Epilepsy Phenotype) suggests shared pathomechanisms, and might be a starting point to identify distinct populations within the clinical complexity of the autistic spectrum. In this study, we tried to assess whether distinct subgroups, having distinctive clinical hallmarks, emerge from this comorbid condition. Methods Two-hundred and six individuals with idiopathic Autism Spectrum Disorders were subgrouped into three experimental classes depending on the presence of seizures and EEG abnormalities. Neurobehavioral, electroclinical and auxological parameters were investigated to identify differences among groups and features which increase the risk of seizures. Our statistical analyses used ANOVA, post-hoc multiple comparisons, and the Chi-squared test to analyze continuous and categorical variables. A correspondence analysis was also used to decompose significant Chi-squared and reduce variables dimensions. Results The high percentage of children with seizures (28.2% of our whole cohort) and EEG abnormalities (64.1%) confirmed that the prevalence of epilepsy in Autism Spectrum Disorders exceeds that of the general population. Seizures were associated with severe intellectual disability, and not with autism severity. Interestingly, tall stature (without macrocephaly) was significantly associated with EEG abnormalities or later onset seizures. However, isolated macrocephaly was equally distributed among groups or associated with early onset seizures when accompanied by tall stature. Conclusions Tall stature seems to be a phenotypic “biomarker” of susceptibility to EEG abnormalities or late epilepsy in Autism Spectrum Disorders and, when concurring with macrocephaly, predisposes to early onset seizures. Growth pattern might act as an endophenotypic marker in Autism-Epilepsy comorbidity, delineating distinct pathophysiological subtypes and addressing personalized diagnostic work-up and therapeutic approaches.

Application of the Repetitive Behavior Scale-Revised - Italian version - in preschoolers with autism spectrum disorder

Restricted repetitive and stereotyped patterns of behavior, interests, and activities (RRB) are mandatory features for a diagnosis of Autism Spectrum Disorder (ASD) according to the Diagnostic and Statistical Manual of mental disorders-fifth edition (DSM-5). Despite the strong diagnostic role of RRB, their expressiveness and their relationship with other clinical/demographic features in ASD is not fully elucidated. The Italian version of the Repetitive Behavior Scale-Revised (RBS-R) was applied to a relatively large sample of preschool-aged children with ASD who underwent a comprehensive clinical assessment. The relationship between RRB and sex, age, non-verbal IQ, autism severity, as well as the diagnostic accuracy of the RBS-R were explored. Stereotyped and Ritualistic/Sameness behaviors were the most common RRB in preschoolers with ASD, without widespread differences between males and females. No significant correlations between RRB and chronological age, or non-verbal IQ were detected. The expressiveness of ritualistic/sameness behaviors positively correlated with autism severity, assessed through the Calibrated Severity Score (CSS) derived from the Autism Diagnostic Observation Schedule (ADOS). Receiver Operator Characteristic (ROC) analysis showed high diagnostic accuracy using the Global Rating Score, which represents the judgment of the parents of as the RRB affect the childs life. However, while the Global Rating Score performed well, the remaining subscales did not. This investigation extends the limited research on early pattern and associated features of RRB in young children with ASD. The use of the RBS-R may increase the knowledge of the RRB complexity and variability and in turn improve the diagnostic and therapeutic procedures within the autistic spectrum.

Behavioral Phenotype of ASD Preschoolers with Gastrointestinal Symptoms or Food Selectivity

This study investigated the prevalence and type of gastrointestinal (GI) and food selectivity (FS) symptoms in 163 preschoolers with ASD, and their possible links with core ASD features and emotional/behavioural problems. 40.5% of children with ASD had at least one severe GI symptom or FS. Preschoolers with and without GI symptoms and with and without FS were significantly different on several emotional/behavioural problems and restrictive/repetitive behaviours, whereas they did not differ significantly on performance IQ and autistic severity. The GI plus FS group presented with Sleep Problems, Self-injurious Behaviors and Anxiety Problems. Results indicated the need for early identification of GI disturbances and FS in order to design tailored intervention for these symptoms frequently associated to challenging behaviours in ASD.