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ObjectiveTourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity.MethodsGWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined.ResultsGWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects.ConclusionsModulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.

Trichotillomania/hair pulling disorder (HPD) and excoriation/skin picking disorder (SPD) are childhood-onset, body-focused repetitive behaviors that are thought to share genetic susceptibility and underlying pathophysiology with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We sought to determine the prevalence of DSM-5 HPD and SPD in TS patients, and to identify clinical factors most associated with their co-morbidity with TS. Participants included 811 TS patients recruited from TS specialty clinics for a multi-center genetic study. Patients were assessed using standardized, validated semi-structured interviews. HPD and SPD diagnoses were determined using a validated self-report questionnaire. HPD/SPD prevalence rates were calculated, and clinical predictors were evaluated using regression modeling. 3.8 and 13.0% of TS patients met DSM-5 criteria for HPD and SPD, respectively. In univariable analyses, female sex, OCD, and both tic and obsessive-compulsive symptom severity were among those associated with HPD and/or SPD. In multivariable analyses, only lifetime worst-ever motor tic severity remained significantly associated with HPD. Female sex, co-occurring OCD, ADHD, and motor tic severity remained independently associated with SPD. This is the first study to examine HPD and SPD prevalence in a TS sample using semi-structured diagnostic instruments. The prevalence of HPD and SPD in TS patients, and their association with increased tic severity and co-occurring OCD, suggests that clinicians should screen children with TS and related disorders for HPD/SPD, particularly in females and in those with co-occurring OCD. This study also helps set a foundation for subsequent research regarding HPD/SPD risk factors, pathophysiology, and treatment models.

ObjectiveTourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD).MethodParticipants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms.ResultsSRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone.ConclusionHigher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae.

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39-3.79], p = 1.2 × 10-3) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 × 10-5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6-156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3-45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.

BackgroundClinicians have long considered doubt to be a fundamental characteristic of obsessive-compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been addressed.MethodsParticipants included 1182 adults with OCD who had participated in family and genetic studies of OCD. We used a clinical measure of the severity of doubt, categorized as none, mild, moderate, severe, or extreme. We evaluated the relationship between doubt and OCD clinical features, Axis I disorders, personality and personality disorder dimensions, impairment, and treatment response.ResultsThe severity of doubt was inversely related to the age at onset of OCD symptoms. Doubt was strongly related to the number of checking symptoms and, to a lesser extent, to the numbers of contamination/cleaning and hoarding symptoms. Doubt also was related to the lifetime prevalence of recurrent major depression and generalized anxiety disorder; to the numbers of avoidant, dependent, and obsessive-compulsive personality disorder traits; and to neuroticism and introversion. Moreover, doubt was strongly associated with global impairment and poor response to cognitive behavioral treatment (CBT), even adjusting for OCD severity and other correlates of doubt.ConclusionsDoubt is associated with important clinical features of OCD, including impairment and cognitive-behavioral treatment response.

ObjectivePhenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts.MethodAssessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated.ResultsThe authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not.ConclusionsThe analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

BackgroundHoarding behavior may indicate a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Empirical evidence supports a relationship between hoarding and emotional over-attachment to objects. However, little is known about the relationship between hoarding and parental attachment in OCD.MethodThe study sample included 894 adults diagnosed with DSM-IV OCD who had participated in family and genetic studies of OCD. Participants were assessed for Axis I disorders, personality disorders, and general personality dimensions. The Parental Bonding Instrument (PBI) was used to assess dimensions of perceived parental rearing (care, overprotection, and control). We compared parental PBI scores in the 334 hoarding and 560 non-hoarding participants, separately in men and women. We used logistic regression to evaluate the relationship between parenting scores and hoarding in women, adjusting for other clinical features associated with hoarding.ResultsIn men, there were no significant differences between hoarding and non-hoarding groups in maternal or paternal parenting scores. In women, the hoarding group had a lower mean score on maternal care (23.4 vs. 25.7, p

Objective: The aim of this study was to identify any potential genetic overlap between attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). We hypothesized that since these disorders share a sub-phenotype, they may share common risk alleles. In this manuscript, we report the overlap found between these two disorders. Methods: A meta-analysis was conducted between ADHD and OCD, and polygenic risk scores (PRS) were calculated for both disorders. In addition, a protein-protein analysis was completed in order to examine the interactions between proteins; p-values for the protein-protein interaction analysis was calculated using permutation. Conclusion: None of the single nucleotide polymorphisms (SNPs) reached genome wide significance and there was little evidence of genetic overlap between ADHD and OCD.

ObjectiveTo identify heritable symptom-based subtypes of Tourette syndrome (TS).MethodsForty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined.ResultsA 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18)).ConclusionsExpanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.

ImportanceTourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (

Georges Gilles de la Tourette, in describing the syndrome that now bears his name, observed that the condition aggregated within families. Over the last three decades, numerous studies have confirmed this observation, and demonstrated that familial clustering is due in part to genetic factors. Recent studies are beginning to provide clues about the underlying genetic mechanisms important for the manifestation of some cases of Tourette Disorder (TD). Evidence has come from different study designs, such as nuclear families, twins, multigenerational families, and case-control samples, together examining the broad spectrum of genetic variation including cytogenetic abnormalities, copy number variants, genome-wide association of common variants, and sequencing studies targeting rare and/or de novo variation. Each of these classes of genetic variation holds promise for identifying the causative genes and biological pathways contributing to this paradigmatic neuropsychiatric disorder.

Compared to studies in adults, there have been few studies of hoarding in children and adolescents with obsessive-compulsive disorder (OCD). In the current study, we evaluated OCD clinical features, Axis I disorders, and social reciprocity scores in 641 children and adolescents with OCD, of whom 163 (25%) had hoarding compulsions and 478 did not. We found that, as a group, youth with hoarding had an earlier age at onset and more severe lifetime OCD symptoms, poorer insight, more difficulty making decisions and completing tasks, and more overall impairment. The hoarding group also had a greater lifetime prevalence of panic disorder, specific phobia, Tourette disorder, and tics. As measured with the Social Reciprocity Scale, the hoarding group had more severe deficits in parent-rated domains of social communication, social motivation, and restricted interests and repetitive behavior. In a multivariable model, the overall social reciprocity score, age at onset of OCD symptoms, symmetry obsessions, and indecision were independently related to hoarding in these children and adolescents with OCD. These features should be considered as candidate risk factors for the development of hoarding behavior in pediatric OCD.

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

A recent study by Persico et al. [2001: Mol Psychiatry 6:150-159] suggests alleles of a CGG polymorphism, just 5' of the reelin gene (RELN) initiator codon, confer liability for autism, especially alleles bearing 11 or more CGG repeats (long alleles). The association is consistent across both a case-control and family-based sample. We attempted to replicate their finding using a larger, independent family-based sample from the NIH Collaborative Programs of Excellence in Autism (CPEA) Network. In our data, allele transmissions to individuals with autism versus unaffected individuals are unbiased, both when alleles are classified by repeat length and when they are classified into long/short categories. Because of the apparent linkage of autism to chromosome 7q, particularly related to the development of language, we also evaluate the relationship between Reelin alleles and the age at which autism subjects use their first word or first phrase. Neither is significantly associated with Reelin alleles. Our results are not consistent with a major role for Reelin alleles in liability to autism.

A recent study by Ingram et al. [2000b: Teratology 62:393-405] suggests a (His)73(Arg) polymorphism (A:G) in HOXA1 contributes substantially to a liability for autism. Using 68 individuals diagnosed with Autism Spectrum Disorders, they found a significant dearth of G homozygotes and biased transmission of G alleles from parents to affected offspring, especially from mothers. Because the connection between HOXA1 and liability to autism is compelling, we attempted to replicate their finding using a larger, independent sample from the Collaborative Programs of Excellence in Autism (CPEA) network. In our data, genotype frequencies conform to Hardy-Weinberg equilibrium; allele transmissions meet Mendelian expectations; and there is no obvious sex-biased allele transmission. Based on our sample size, calculations suggest that we would have at least 95% power to detect linkage and association even if the A:G polymorphism were to account for only 1% of the heritability of autism. Therefore, although we cannot exclude the possibility that the samples in the two studies are intrinsically different, our data from our sample argue against a major role for HOXA1 (His)73(Arg) in liability to autism.

We evaluated social anxiety (SA) symptoms in parents of children with autism spectrum disorders (ASDs; N = 131) and community parents (N = 597) using the Social Phobia and Anxiety Inventory (SPAI). SA was significantly more common in ASD than control mothers (15.6 vs. 6.7 %) and more equal between the ASD and control fathers (3.3 vs. 4.8 %). The ASD mothers scored significantly higher than control mothers on all SPAI scales. ASD fathers scored significantly higher than control fathers on the somatic, cognitive, avoidance and agoraphobic symptoms of SA. It is of clinical import to support ASD parents' well-being as their psychiatric features may contribute greatly to their children's emotional development and the well-being of the whole family.

Background: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with onset in childhood and is characterized by obsessions (recurrent, intrusive, persistent thoughts, impulses and/or ideas that often cause anxiety or distress) and compulsions (ritualized and stereotypic behaviours or mental acts that are often performed to relieve anxiety or distress associated with obsessions). Although OCD is a heritable disorder, its complex molecular etiology is poorly understood. Methods: We combined enrichment analyses and an elaborate literature review of the top-ranked genes emerging from the 2 published genome-wide association studies of OCD and candidate genes implicated through other evidence in order to identify biological processes that, when dysregulated, increase the risk for OCD. Results: The resulting molecular protein landscape was enriched for proteins involved in regulating postsynaptic dendritic spine formation-- and hence synaptic plasticity--through insulin-dependent molecular signalling cascades. Limitations: This study is a first attempt to integrate molecuar information from different sources in order to identify biological mechanisms underlying OCD etiology. Our findings are constrained by the limited information from hypothesis-free studies and the incompleteness and existing limitations of the OCD literature and the gene function annotations of gene enrichment tools. As this study was solely based on in silico analyses, experimental validation of the provided hypotheses is warranted. Conclusion: Our work suggests a key role for insulin and insulin-related signalling in OCD etiology and--if confirmed by independent studies--could eventually pave the way for the development of novel OCD treatments., Introduction Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects an estimated 2.5% of the world's population (1,2) and is characterized by obsessive and/or compulsive behaviours. (3) Obsessive behaviours include [...]

It is not known whether reproductive factors early in the mother's life influence risk of autism spectrum disorders (ASD). We assessed maternal age at menarche, menstrual cycle characteristics during adolescence, oral contraceptive use prior to first birth, body shape, and body mass index (BMI) in association with ASD using binomial regression in a cohort study of 61,596 women, including 743 cases. Overall, early life factors were not associated with ASD, though early age at menarche (RR for age 10 or less = 1.54, 95% CI 1.18, 2.02, p = 0.0002) and BMI at age 18 of greater than or equal to 30 (RR 2.03, 95% CI 1.34, 3.08, p = 0.0008) were significantly associated with increased risk of ASD. Further work should investigate the potential influence of these factors.

The contributions of cognitive style and organization to processing and recalling a complex novel stimulus were examined by comparing the Rey Osterrieth Complex Figure (ROCF) test performance of children, adolescents, and adults with ASD to clinical controls (CC) and non-impaired controls (NC) using the "Developmental Scoring System." The ROCF task involves a complex structure with strong organizational or integrative processing demands. The individuals with ASD relied on a predominantly part-oriented strategy to cope with the complexity of the task and did not make the typical developmental shift to a configurational approach. Both processing style and organization (whether pieces of information were perceived as connected to one another in a meaningful way) contributed to structural recall in the ASD group.

The aim of the study was to examine psychiatric symptoms in high-functioning adolescents with autism spectrum disorders reported by multiple informants. Forty-three 11- to 17-year-old adolescents with Asperger syndrome (AS) or high-functioning autism (HFA) and 217 typically developed adolescents completed the Youth Self-Report (YSR), while their parents completed the Child Behavior Checklist (CBCL). Teachers of adolescents with AS/HFA completed the Teacher Report Form (TRF). The informants reported significantly more psychiatric symptoms, especially withdrawn, anxious/depressed, social and attention problems, in adolescents with AS/HFA than in controls. In contrast to findings in the general population, the psychiatric problems of adolescents with AS/HFA are well acknowledged by multiple informants, including self-reports. However, anxiety and depressive symptoms were more commonly reported by adolescents with AS/HFA and their teachers than their parents, indicating that some emotional distress may be hidden from their parents. (Contains 4 tables.)

We examined social anxiety and internalizing symptoms using the Social Phobia and Anxiety Inventory for Children (SPAI-C), the Social Anxiety Scale for Children -Revised (SASC-R), and the Child Behavior Checklist (CBCL) in a sample of fifty-four high-functioning subjects with autism or Asperger syndrome (HFA/AS) (M = 11.2 plus or minus 1.7 years) and 305 community subjects (M = 12.2 plus or minus 2.2 years). Children and adolescents completed the SPAI-C and SASC-R, and their parents completed the CBCL Internalizing scale. Adolescents with HFA/AS scored higher than the community sample on all measures. Behavioural avoidance and evaluative social anxiety increased by age within the HFA/AS group, whereas behavioural avoidance decreased by age in control participants. Data support that HFA/AS in adolescents may be associated with clinically relevant social anxiety symptoms.

Background: A minority of patients with attention-deficit hyperactivity disorder (ADHD) do not respond favorably to methylphenidate. This has been partially associated with homozygosity for the Dopamine transporter (DAT1) 10-repeat allele and the presence of one or two Dopamine D4 receptor (DRD4) 7-repeat alleles. This study examined the sibling correlation of methylphenidate response rate and the possible association between response rate and these risk alleles. Methods: A sample of 82 Dutch children with ADHD, from 54 families, (including 30 singletons and 28 sib pairs), who used methylphenidate, was phenotyped according to DSM-IV criteria. Patients were members of affected sib pairs and were genotyped for DAT1 and DRD4. The sibling Intraclass Correlation Coefficient for methylphenidate response rate was calculated. The association between individual response rates and the risk alleles was examined using linear regression techniques. Results: The Intraclass Correlation Coefficient was significant (r = 0.563, p = 0.001). No evidence was found establishing an association between methylphenidate response and DAT1-homozygosity. There was a positive trend towards association with the presence of one or two DRD4-7R alleles. Conclusions: The sibling correlation may indicate a familial clustering of methylphenidate response. This response is possibly associated with the presence of one or two alleles at the DRD4-7R locus, but not with DAT1-10R homozygosity in the Dutch population.

Objective: To examine the implications for research of the use of three alternative definitions for Asperger syndrome (AS). Differences across the three nosologic systems were examined in terms of diagnostic assignment, IQ profiles, comorbid symptoms, and familial aggregation of social and other psychiatric symptoms. Method: Standard data on diagnosis, intellectual functioning, comorbidity patterns, and family history were obtained on 65 individuals screened for a very high probability of having autism without mental retardation (or higher functioning autism, FHA) or AS. Diagnoses of AS were established based on three different approaches: DAM-IV, presence/absence of communicative phrase speech by 3 years, and a system designed to highlight prototypical features of AS. Results: Agreement between the three diagnostic systems was poor. AS could be differentiated from FHA (but not from PD-NOS) on the basis of IQ profiles in two of the three systems. Differences in patterns of comorbid symptomatology were obtained in two of the three systems, although differences were primarily driven by the PD-NOS category. Only one of the approaches yielded differences relative to aggregation of the broader phenotype in family members. Conclusions: Diagnostic assignments of AS based on three commonly used approaches have low agreement and lead to different results in comparisons of IQ profiles, patterns of comorbidity, and familial aggregation of psychiatric symptoms across the approach specific resultant groups of FHA, AS, and PD-NOS.

This study of hyperlexia in 80 children with developmental delays found no significant differences in the frequency of hyperlexia in girls compared with boys; a significantly elevated frequency of hyperlexia in children diagnosed with pervasive developmental disorders (PDD) compared with children with non-PDD diagnoses; and a similar range of IQ and developmental outcomes for children with and without hyperlexia. (Contains references.) (Author/DB)

This paper examines the validity of Asperger syndrome as a condition apart from high-functioning autism. Potential differences between Asperger syndrome and autism is possible if both are strictly defined. The importance of genetic factors in Asperger syndrome is stressed. Research on the nosological validity of this condition and its relationship to the pervasive developmental disorder spectrum is urged. (DB)