The extent to which the phenotype of children comorbid for velocardiofacial syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS-only has not been studied. The sample consisted of 41 children (20 females) with VCFS, ranging in age from 6.5 years to 15.8 years. Eight children with VCFS met formal DSM-IV diagnostic criteria for autism based upon the ADI-R. These eight plus an additional nine participants met diagnostic criteria for an autistic spectrum disorder (VCFS + ASD). Ninety-four percent of the children with VCFS + ASD had a co-occurring psychiatric disorder while 60% of children with VCFS had a psychiatric disorder. Children with VCFS + ASD had larger right amygdala volumes. All other neuroanatomic regions of interest were statistically similar between the two groups.

Although Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism [Tierney et al., 2001], the incidence of SLOS and other sterol disorders among individuals with autism spectrum disorders (ASD) is unknown. This study investigated 1) the incidence of biochemically diagnosed SLOS in blood samples from a cohort of subjects with ASD from families in which more than one individual had ASD and 2) the type and incidence of other sterol disorders in the same group. Using gas chromatography/mass spectrometry, cholesterol and its precursor sterols were quantified in one hundred samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had sterol levels consistent with SLOS, 19 samples had total cholesterol levels lower than 100 mg/dL, which is below the 5 th centile for children over age 2 years. These findings suggest that, in addition to SLOS, there may be other disorders of sterol metabolism or homeostasis associated with ASD. KeywordsSmith-Lemli-Opitz syndrome; hypocholesterolemia; Autism Genetic Resource Exchange; Asperger disorder; pervasive developmental disorder Smith-Lemli-Opitz syndrome (SLOS, MIM 270400) is an autosomal recessive malformation syndrome caused by a deficiency of the last step of cholesterol biosynthesis, 7-dehydrocholesterol reductase (DHCR7) [Tint et al, 1994]. Principal abnormalities include a typical facial appearance, microcephaly, hypotonia, cleft palate, hypogenitalism, 2-3 toe syndactyly, and a characteristic behavioral profile including autism, usually accompanied by mental retardation. The enzymatic deficiency manifests biochemically in blood and all tissues as a reduced level of cholesterol and increased levels of 7-dehydrocholesterol (7DHC) and its isomer, 8-dehydrocholesterol (8DHC), although a few very mildly affected patients have normal plasma cholesterol levels despite increases in 7DHC and 8DHC. This NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript sterol abnormality in turn affects the synthesis and metabolism of various sterol-derived compounds, including bile acids, adrenal steroids, neurosteroids, and the structure of sterolrich membranes, such as myelin, the plasma membrane, and various subcellular organelles.SLOS is a relatively common genetic disorder with an estimated incidence among those of European ancestry of approximately 1 in 50,000 births. SLOS has a wide spectrum of clinical and biochemical severity, from functionally normal individuals to malformed fetuses that die in utero [Lowry and Yong, 1980;Kelley and Hennekam, 2000]. Although the combined carrier frequency for several common DHCR7 null alleles of about 1.25% predicts an incidence of 1 in 25,000 births in European-derived populations, about 50% of conceptuses appear to be lost early in pregnancy [Kelley and Herman, 2001]. Most SLOS individuals who survive the newborn period are compound heterozygotes for a common DHCR7 null mutation and a mild...

Cholesterol is essential for neuroactive steroid production, growth of myelin membranes, and normal embryonic and fetal development. It also modulates the oxytocin receptor, ligand activity and G-protein coupling of the serotonin-1A receptor. A deficit of cholesterol may perturb these biological mechanisms and thereby contribute to autism spectrum disorders (ASDs), as observed in Smith-Lemli-Opitz syndrome (SLOS) and some subjects with ASDs in the Autism Genetic Resource Exchange (AGRE). A clinical diagnosis of SLOS can be confirmed by laboratory testing with an elevated plasma 7DHC level relative to the cholesterol level and is treatable by dietary cholesterol supplementation. Individuals with SLOS who have such cholesterol treatment display fewer autistic behaviours, infections, and symptoms of irritability and hyperactivity, with improvements in physical growth, sleep and social interactions. Other behaviours shown to improve with cholesterol supplementation include aggressive behaviours, self-injury, temper outbursts and trichotillomania. Cholesterol ought to be considered as a helpful treatment approach while awaiting an improved understanding of cholesterol metabolism and ASD. There is an increasing recognition that this single-gene disorder of abnormal cholesterol synthesis may be a model for understanding genetic causes of autism and the role of cholesterol in ASD.

Pediatricians regularly care for children who have experienced child maltreatment. Child maltreatment is a risk factor for a broad range of mental health problems. Issues specific to child maltreatment make addressing emotional and behavioral challenges among maltreated children difficult. This clinical report focuses on 2 key issues necessary for the care of maltreated children and adolescents in pediatric settings: trauma-informed assessments and the role of pharmacotherapy in maltreated children and adolescents. Specific to assessment, current or past involvement of the child in the child welfare system can hinder obtaining necessary information or access to appropriate treatments. Furthermore, trauma-informed assessments can help identify the need for specific interventions. Finally, it is important to take both child welfare system and trauma-informed assessment approaches into account when considering the use of psychotropic agents because there are critical diagnostic and systemic issues that affect the prescribing and discontinuing of psychiatric medications among children with a history of child maltreatment.

Mania and bipolar disorder have been reported in adolescents and adults with velocardiofacial syndrome (VCFS; also known as 22q11.2 deletion syndrome). Children with VCFS have a high prevalence of attention-deficit/hyperactivity disorder (ADHD), which may constitute a risk factor for the eventual development of bipolar disorder in this population. Therefore, we sought to determine whether children with VCFS exhibit more manic symptoms than community controls that also may have learning disorders and ADHD. The study population consisted of 86 children with VCFS and 36 community controls from ages 9 to 15 years, using measures of Young Mania Rating Scale-Parent Version, Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), Child Behavior Checklist (CBCL), and Wechsler Intelligence Scale for Children-3rd edition (WISC-III). The results indicate that manic symptoms were not more prevalent in VCFS than in a community sample of children with learning disorders and ADHD. However, after accounting for symptoms of depression and ADHD, we found that manic symptoms in VCFS predicted uniquely to scores on four Child Behavior Checklist (CBCL) subscales, including anxiety, somatization, thought, and conduct problems. In contrast, manic symptoms in controls predicted uniquely to conduct problems only. Accordingly, our findings of severe behavioral impairment in youth with VCFS and manic symptoms suggest that these children may warrant more intensive monitoring and treatment relative to youth with VCFS and ADHD only.

One hundred twenty-seven 7-, 9-, and 11-year-old children were presented large or small samples of own-gender enhancing or other-gender enhancing observations. Children read arguments based on the observations, rated argument intelligence, judged the number of other children to whom the observations could be generalized, and provided verbal justifications for their judgments. Own-gender reasoning biases declined with age; these declines were, however, partially accounted for by declines in the strength of self-reported gender affiliations. Reasoning biases--demonstrated by problem-to-problem shifts in reasoning quality-were constrained by sample size, indicating a modest degree of rationality even among 7-year-olds. Specifically, biases co-existed with reasonably limited generalizations from small samples of own-gender evidence and with reasonably extensive generalizations from large samples of other-gender evidence. Children were thus able to satisfy motivations for own-gender favoritism and reason in accord with the law of large numbers. Several explanations of the findings-based on changes in the salience of gender, multiple classification skills, and the ability to reason independently from beliefs-are offered.

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