[Intensive home treatment of adolescents in crisis: treat the parents along with 'psychiatric' adolescents]. / Intensieve thuisbehandeling van jongeren in crisis: behandel ouders mee bij 'psychiatrische' adolescenten.

OBJECTIVE: To investigate whether a new intensive home treatment (IHT) model for adolescents with psychiatric problems is more effective or more efficient than previous treatment methods involving long-term clinical admission. DESIGN: Descriptive, retrospective study. METHOD: The previous treatment model for adolescents in crisis consisted of clinical admission for 6 months or longer. To implement the new treatment model, 4 admission wards with 34 beds were converted to 1 'high & intensive care' (HIC) ward with 7 beds, in combination with IHT care for the family in the home environment. Admission to the HIC is short-term, and the parents are admitted along with their child. The new model was used from May 2013. The number of patients receiving care, the length of treatment, patient satisfaction, the number of beds and the costs were investigated and compared with data from the years 2011 and 2012. RESULTS: In comparison with the previous treatment model, this IHT treatment model revealed that more adolescents could be treated in the course of 1 year (125 compared with 70 per year) with a shorter duration of treatment (2 weeks clinical admission if required and 4 months ambulatory treatment, compared with 6 to 7 months clinical treatment) and with lower costs (€ 28,000 compared with € 55,000) with the same level of patient satisfaction. CONCLUSION: Although initial treatment results are positive, more extensive investigation is required into treatment effectiveness and cost efficiency of the IHT model for adolescents over a longer period of time.

Sensory and sensorimotor gating in children with multiple complex developmental disorders (MCDD) and autism.

Multiple Complex Developmental Disorder (MCDD) is a well-defined and validated behavioral subtype of autism with a proposed elevated risk of developing a schizophrenic spectrum disorder. The current study investigated whether children with MCDD show the same deficits in sensory gating that are commonly reported in schizophrenia, or whether they are indistinguishable from children with autism in this respect. P50 suppression and prepulse inhibition (PPI) of the startle reflex were assessed in children with MCDD (n=14) or autism (n=13), and healthy controls (n=12), matched on age and IQ. All subjects showed high levels of PPI and P50 suppression. However, no group differences were found. No abnormalities in sensory filtering could be detected in children with autism or MCDD. Since sensory gating deficits are commonly regarded as possible endophenotypic markers for schizophrenia, the current results do not support a high level of similarity between schizophrenia and MCDD.

Executive function in MCDD and PDD-NOS: a study of inhibitory control, attention regulation and behavioral adaptivity.

A proportion of children within the autism spectrum is at risk for severe deregulation of thought, emotion and behaviour resulting in (symptoms of) psychotic disorders over the course of development. In an attempt to identify this subgroup, children with PDD-NOS, subtype MCDD (n = 24) were compared to children with PDD-NOS (n = 23) on executive function (EF) skills. Significant differences emerged, always to the disadvantage of the children with PDD-NOS, subtype MCDD on various EF measures. The findings suggest compromised attention regulation and impaired inhibitory control in children with MCDD, which may help explain high levels of thought problems which are frequently observed in these children. Our findings provide evidence for recognizing a PDD subcategory of MCDD that is of specific interest with regard to long-term developmental risks involved.

Overlap of autistic and schizotypal traits in adolescents with Autism Spectrum Disorders.

This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well.

Morphological features in children with autism spectrum disorders: a matched case-control study.

This study was designed to examine morphological features in a large group of children with autism spectrum disorder versus normal controls. Amongst 421 patients and 1,007 controls, 224 matched pairs were created. Prevalence rates and odds ratios were analyzed by conditional regression analysis, McNemar test or paired t-test matched pairs. Morphological abnormalities were significantly more prevalent in patients with autism than in the normal control group and 48 morphological features distinguished patients from controls. Our findings show that morphological features are associated with autism. Exploring potential underlying genetic mechanisms of this association might lead to a better understanding of autism.

Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.

Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70 mg/day) in 32 youths with pervasive developmental disorder (mean age = 8.74, range = 5-16 years) in relation to -759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043 ± 0.017 body mass index-standardized z scores (1.84 ± 1.51 kg) versus 0.64 ± 0.35 z (3.23 ± 1.47 kg) for non-T-allele carriers (p < 0.001). Presence of the rs1414334 C allele played no significant role. Further, weight gain appeared to be associated with younger age and higher doses of risperidone. The current preliminary findings suggest that the variant T allele of the -759C/T HTR2C promoter polymorphism is protective against risperidone-induced weight gain. Younger children and those treated with higher doses of risperidone may be at higher risk for weight gain.

Changes in the developmental trajectories of striatum in autism.

BACKGROUND: Repetitive and stereotyped behavior has been associated with striatum in various neuropsychiatric disorders. However, striatal involvement has not yet been shown conclusively in autism. Issues include the use of neuroleptic medication and differences in mean age between samples, where conflicting results may reflect differences in developmental stage between samples. The objective was to examine brain development in a homogeneous sample of subjects with high-functioning autism. METHODS: Magnetic resonance measures of brain structure of 188 individuals (99 subjects with high-functioning autism and 89 typically developing, matched control subjects) aged between 6 years and 25 years were compared. Measurements included the volume of brain structures, including striatum, as well as voxel-based assessment of gray matter density. RESULTS: Developmental trajectories of the caudate nucleus, putamen, and nucleus accumbens differed between subjects with autism and control subjects. Results were not accounted for by overall changes in brain volume or neuroleptic medication. The development of the caudate nucleus differed from typical most, as its volume increased with age in autism, while it decreased for control subjects. Voxel-based analysis showed that changes in striatum localized to the head of the caudate nucleus. Overall, caudate nucleus volume was associated with repetitive behavior in autism. CONCLUSIONS: We report changes in striatal development in autism, while caudate volume is associated with repetitive behaviors. This emphasizes the importance of striatum in the etiology of autism, in particular in the development of repetitive behavior that characterizes the disorder.

No evidence for structural brain changes in young adolescents at ultra high risk for psychosis.

OBJECTIVE: The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing of these changes has not been established. We investigated structural brain changes in a sample of young adolescents (12-18 years) at ultra high-risk for psychosis (UHR). METHODS: Structural MRI data from young UHR subjects (n=54) and typically developing, matched controls (n=54) were acquired with a 1.5 Tesla scanner and compared. RESULTS: None of the measures differed between UHR subjects and controls. CONCLUSIONS: Our results do not support the presence of gross neuroanatomical changes in young UHR subjects. This suggests that early changes are too subtle to detect with conventional imaging techniques. Therefore, changes observed in older cohorts may only onset later developmentally or occur secondary to prodromal symptoms.

Smooth pursuit eye movement (SPEM) in patients with multiple complex developmental disorder (MCDD), a subtype of the pervasive developmental disorder.

OBJECTIVE: Multiple complex developmental disorder (MCDD) is a well-defined and validated behavioural subtype of pervasive developmental disorder-not otherwise specified (PDD-NOS) and is thought to be associated with a higher risk of developing a schizophrenic spectrum disorder. The question was addressed whether patients with MCDD show the same psychophysiological abnormalities as seen in patients with schizophrenia. METHOD: Smooth pursuit eye movement (pursuit gain and saccadic parameters) was measured in children with either MCDD (n=18) or autism (n=18), and in age- and IQ-matched controls (n=36), as well as in a group of adult patients with schizophrenia (n=14) and a group of adult controls (n=17). RESULTS: We found the expected effect of lower velocity gain and increased number of saccades in schizophrenic patients. Children with MCDD also showed a lower velocity gain compared to controls children. In contrast, velocity gain was similar in autistic subjects and controls. No differences for velocity gain were found in a direct comparison between MCDD and autism. Saccadic parameters were not significantly different from controls in either MCDD or autistic subjects. CONCLUSION: Children with MCDD, like schizophrenic adults, show a reduced velocity gain, which could indicate that schizophrenia spectrum disorders and MCDD share (at least to some degree) a common neurobiological background.

Prolactin release in children treated with risperidone: impact and role of CYP2D6 metabolism.

OBJECTIVE: Little is known about the role of CYP2D6 polymorphism in risperidone-induced prolactin release in children. METHOD: Twenty-five children (aged 5-15 years) with pervasive developmental disorders were genotyped for CYP2D6 polymorphisms. Serum prolactin, risperidone, and 9-hydroxyrisperidone were assessed at baseline and after 8 weeks of risperidone treatment (mean dosage, 0.06 +/- 0.03 mg/kg/d). After 24 weeks of treatment, prolactin was measured in a subsample of 15 children. Adverse effects were evaluated using a clinician-rated survey. RESULTS: Mean +/- SD prolactin levels increased from 7.8 +/- 8.0 ng/mL at baseline to 33.2 +/- 12.8 ng/mL at week 8 (P < 0.001), with a slight decrease to 28.8 +/- 13.6 ng/mL at week 24. At week 8, serum prolactin level was positively correlated with dose per kilogram (r = 0.648, P < 0.001), number of functional CYP2D6 genes (J = 2.117, P = 0.034), and serum 9-hydroxyrisperidone concentration (r = 0.664, P = 0.001) and was negatively correlated with the risperidone/9-hydroxyrisperidone ratio (r = -0.571, P = 0.004) but not with risperidone concentration (r = -0.243, P = 0.264) nor age (r = 0.072, P = 0.733). Prolactin elevation was not associated with adverse effects. CONCLUSIONS: Low-to-intermediate doses of risperidone induced a 4-fold prolactin increase in children without a clear development of tolerance up to 6 months. CYP2D6 ultrarapid metabolism may be a risk factor for more pronounced prolactin elevation.

Neuropsychological effects of risperidone in children with pervasive developmental disorders: a blinded discontinuation study.

OBJECTIVE: Little is known about the neuropsychological effects of risperidone in children with pervasive developmental disorders. METHOD: Twenty-four children (aged 5-17 years) with pervasive developmental disorders and co-morbid disruptive behavior who responded favorably to open-label treatment with risperidone as part of a previously described controlled discontinuation study completed two different computerized attention tasks at baseline, weeks 4, 8, and 24 of open-label treatment, and, at 8 weeks after random assignment to either placebo or risperidone. The primary efficacy measures were response latencies to visually presented stimuli requiring two different types of attention-controlled processing, i.e., focused and divided attention. RESULTS: About half of the clinical responders did not produce valid performance measures. These could be shown to be of younger mental age and less adaptive as measured by the Vineland Behavior Scales. For the valid task performers divided attention (serial search in working memory) was shown to regress in the placebo group (n = 7), while in the risperidone group (n = 7) there was further improvement. No such group difference was found for focused attention. CONCLUSIONS: The study suggests a beneficial effect of risperidone after several months of treatment, enhancing divided attention in children with pervasive developmental disorders.

Autonomic and neuroendocrine responses to a psychosocial stressor in adults with autistic spectrum disorder.

Objective of the study was to replicate in adults our previous findings of decreased heart rate and normal endocrine responses to stress in autistic children and to elucidate the discrepancy between autonomic and endocrine stress responses by including epinephrine, norepinephrine, oxytocin and vasopressin measurements. Ten autistic spectrum disorder (ASD) adults were compared to 14 healthy controls in their response to a psychosocial stressor (public speaking). ASD patients showed decreased heart rate, but normal cortisol responses, consistent with our prior findings in children. No differences in norepinephrine, epinephrine, oxytocin or vasopressin responses to stress were found. However, in contrast to previous findings in low functioning autistic children, ASD adults showed increased basal oxytocin levels, which may be related to developmental factors.

Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study.

OBJECTIVE: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. METHOD: Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe tantrums, aggression, or self-injurious behavior, started 8-week open-label treatment with risperidone. Responders (n = 26) continued treatment for another 16 weeks, followed by a double-blind discontinuation (n = 24; two patients discontinued treatment because of weight gain) consisting of either 3 weeks of taper and 5 weeks of placebo only or continuing use of risperidone. Relapse was defined as a significant deterioration of symptoms based on clinical judgment and a parent questionnaire. RESULTS: Risperidone was superior to placebo in preventing relapse: this occurred in 3 of 12 patients continuing on risperidone versus 8 of 12 who switched to placebo (p = .049). Weight gain, increased appetite, anxiety, and fatigue were the most frequently reported side effects. CONCLUSIONS: This study indicates the effectiveness of risperidone during a period of several months, reducing disruptive behavior in about half of the children with autism spectrum disorders. The results provide a rationale for the continuing use of risperidone beyond 6 months, although considerable weight gain can limit the use of this agent.

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

BACKGROUND: To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. METHOD: Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. RESULTS: Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. CONCLUSIONS: High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

Magnetic resonance imaging studies on autism and childhood-onset schizophrenia in children and adolescents - a review.

OBJECTIVE: To find out whether the neurodevelopmental disorders autism and childhood-onset schizophrenia have a common developmental pathway and whether the abnormalities detected are 'disorder-specific', by reviewing magnetic resonance imaging (MRI) studies. METHODS: As a result of a Medline search, we were able to access 28 studies on autism and 12 studies on childhood-onset schizophrenia, which focused on children and adolescents. RESULTS: Larger lateral ventricles were found to be a common abnormality in both disorders. 'Disorder-specific' abnormalities in patients with autism were larger brains, a larger thalamic area, and a smaller right cingulate gyrus. Subjects with childhood-onset schizophrenia were found to have smaller brains, a smaller amygdalum and thalamus, and a larger nucleus caudatus. In subjects with childhood-onset schizophrenia, abnormalities appeared to progress over a limited period of time. CONCLUSIONS: Because the study designs varied so much, the results should be interpreted cautiously. Before abnormalities found in the disorders can be designated as equal or 'disorder-specific', it will be essential to perform large longitudinal and cross-sectional follow-up studies.