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Background: An increasing number of women are utilizing fertility treatments, but little is known about their relation to autism spectrum disorders (ASD). Methods: To determine the association between maternal fertility therapy use and risk of having a child with ASD, we conducted a nested case-control study within the Nurses' Health Study II (n = 116,430). Maternally reported diagnoses of ASD were confirmed through a supplementary questionnaire and, in a subgroup, the Autism Diagnostic Interview-Revised. Controls were randomly selected by frequency matching to case children's year of birth. Associations were examined by self-reported infertility and type of therapy using conditional logistic regression. Results: In all, 9% of the 507 cases and 7% of 2,529 controls indicated fertility therapy use for the index pregnancy. No significant associations with self-reported fertility therapies or history of infertility were seen in primary analyses. In subgroup analyses of women with maternal age ≥35 years (n = 1,020), artificial insemination was significantly associated with ASD; ovulation inducing drug (OID) use was significantly associated in crude but not adjusted analyses (odds ratio 1.81, 95% CI 0.96-3.42). Results were similar by diagnostic subgroup, though within the advanced maternal age group, OID and artificial insemination were significantly associated with Asperger syndrome and pervasive developmental disorder not-otherwise specified, but not autistic disorder. Conculsion: Assisted reproductive therapy and history of infertility did not increase risk of having a child with ASD in this study. However, the associations observed with OID and artificial insemination among older mothers, for whom these exposures are more common, warrant further investigation. [ABSTRACT FROM AUTHOR]

The authors examined pregnancy and obstetric complications in association with autism spectrum disorders (ASD) in children of participants from the Nurses' Health Study II, a prospective national cohort with information collected through biennial mailed questionnaires since 1989. Logistic regression was used to obtain crude and adjusted odds ratios for ASD, and by diagnostic subgroup. Seven hundred and ninety-three cases were reported among 66,445 pregnancies. Pregnancy complications and obstetric suboptimality factors were assessed by maternal report of occurrence in first birth and, in secondary analyses, in any birth. Complications and a suboptimality score were significantly associated with having a child with ASD (OR 1.49, 95% CI 1.26, 1.77, P<0.0001 for pregnancy complications in first birth and 2.76, 95% CI 2.04, 3.74, P<0.0001 comparing individuals with four or more obstetric suboptimality factors in first birth to those with none; results similar when assessed in any birth). In particular, gestational diabetes was associated with a significantly increased risk of ASD in results of primary and sensitivity analyses (OR in primary analysis = 1.76, 95% CI 1.34, 2.32, P<0.0001); suboptimal parity and suboptimal age-at-first-birth were also individual factors associated with ASD. Associations were similar by diagnostic subgroup, suggesting autism, Asperger syndrome, and other Pervasive Developmental Disorders are all associated with pregnancy complications. Consistent with previous research, the general class of pregnancy complications was associated with ASD as a whole. Additional work will be required to more fully assess the role of gestational diabetes. Autism Res 2012,5:21-30. © 2011 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Several studies support a genetic influence on obsessive-compulsive disorder (OCD) etiology. The role of glutamate as an important neurotransmitter affecting OCD pathophysiology has been supported by neuroimaging, animal model, medication, and initial candidate gene studies. Genes involved in glutamatergic pathways, such as the glutamate receptor, ionotropic, kainate 2 (GRIK2), have been associated with OCD in previous studies. This study examines GRIK2 as a candidate gene for OCD susceptibility in a family-based approach. Probands had full DSM-IV diagnostic criteria for OCD. Forty-seven OCD probands and their parents were recruited from tertiary care OCD specialty clinics from France and USA. Genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes were analyzed using Haploview and FBAT software. The polymorphism at rs1556995 ( P= 0.0027; permuted P-value = 0.03) was significantly associated with the presence of OCD. Also, the two marker haplotype rs1556995/rs1417182, was significantly associated with OCD ( P= 0.0019, permuted P-value = 0.01). This study supports previously reported findings of association between proximal GRIK2 SNPs and OCD in a comprehensive evaluation of the gene. Further study with independent samples and larger sample sizes is required. [ABSTRACT FROM AUTHOR]

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 = .563, p = .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. [ABSTRACT FROM AUTHOR]

The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender, comorbid conditions and familial risk of tics and OCD by studying a population consisting exclusively of patients with early-onset OCD. One hundred and forty-four patients having OCD were recruited in the study (108 early-onset probands and 36 late-onset probands). The early-onset probands and 199 of their first-degree relatives were investigated using structured interviews and questionnaires. This sample of early onset was mainly composed of children and adolescents (74 children and adolescents and 34 adults). The average age of onset of OCD is 9.98 ± 3.2 years. Forty-four per cent of the probands have a comorbid tic disorder. The age-corrected morbid risk among the first-degree relatives is 17% for OCD and 12% for tics. Morbid risk for OCD and tics was independent of the presence of tics in probands. Only 32.6% of the probands have a positive family history of OCD. These findings are consistent with other reports in the literature that the morbid risk of OCD is elevated in relatives of probands with early-onset OCD. However, the majority of cases do not have a positive family history of OCD. This result suggests that early onset is not the only specific clinical marker for familial risk in OCD. Thus more work is needed to clearly elucidate other factors related to increased genetic vulnerability for OCD. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive symptoms (OCS) frequently occur in patients with Tourette syndrome (TS) and autism spectrum disorders (ASD). It has been suggested that genetic factors play a role in the transmission of both TS and ASD and that obsessive-compulsive disorder (OCD) may have some genetic relationship with these disorders. The objective of this study was to explore whether the OCS associated with TS and ASD were found in the parents of TS and ASD probands by comparing them with normal controls. The subjects were parents of 13 TS and 16 ASD probands. All parents underwent an examination for tic symptoms and OCD, and completed the Maudsley Obsessional Compulsive Inventory (MOCI) and State-Trait Anxiety Inventory (STAI). No significant differences were observed in the MOCI and STAI scores among all three groups. However, the MOCI total score was higher in fathers of ASD probands than in male normal controls with a marginal significance. There was a significant tendency for the mean cleaning score of MOCI in fathers of ASD probands to be higher than that in male normal controls, and the mean checking score in fathers of ASD probands was fourfold higher than that in male normal controls, although there was no significant difference. No significant relationship was observed between OCS in TS or ASD probands and OCS of their parents. Further studies on OCD and OCS including a dimensional approach within ASD families are needed. [ABSTRACT FROM AUTHOR]

This study examined social-emotional functioning in children with Gilles de la Tourette's syndrome (TS) alone and children with TS and Attention Deficit Hyperactivity Disorder (ADHD). In addition, the contribution of family functioning to social competence was examined. Children with a clinical diagnosis of TS were recruited from the Yale Child Study Center TS specialty clinic. Unaffected control children were recruited through newspaper advertisements and announcements within the university and at area schools. The final sample consisted of 72 children (45 boys and 27 girls) between the ages of 8 and 14. Sixteen children met DMS-III-R criteria for TS, 33 children met criteria for TS and ADHD, and 23 children had no psychiatric diagnoses. Children with TS and ADHD evidenced more externalizing and internalizing behavior problems and poorer social adaptation than children with TS only or unaffected controls. Children with TS only were not significantly different from unaffected controls on most measures of externalizing behaviors and social adaptation but did exhibit more internalizing symptoms. Tic symptom severity was not associated with social, behavioral, or emotional functioning among children with TS, even after stratifying by medication status. However, ADHD diagnosis, obsessional symptom severity, and family functioning were significantly associated with social and emotional adjustment among TS children. Moreover, family functioning was associated with social and emotional adjustment even after controlling for TS and ADHD diagnostic status. These findings demonstrate that much of the social and behavioral dysfunction in children with TS is ADHD-specific and children with TS alone have a very different social-emotional profile than do those with TS plus ADHD. Finally, social-emotional adjustment in children with TS is best understood within the family context. [ABSTRACT FROM AUTHOR]

This review presents a model of disease pathogenesis in the context of CNS development M begins with an exploration of the clinical features and natural history of Tourette's syndrome. This is followed by a consideration of the role of genetic and non gene tic factors. An effort is then made to review the anatomical organization of the basal ganglia and related cortical sites. These circuits are intimately involved in (he normal processing of sensorimotor, cognitive, and emotionally laden information. Evidence implicating these circuits in the pathobiology of Tourette's syndrome is then considered. The review closes with the prospects for advances in interdisciplinary research and therapeutics using this model as a guide. [ABSTRACT FROM AUTHOR]

Tourette's disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). While the relationship between TD and OCD suggests that they share etiological factors, the exact relationship between TD and ADHD is less clear. The goal of the current analyses was to understand better the familial relationship between DSM-IV ADHD and TD. Direct interview diagnostic data from a case-control study of 692 relatives of 75 comorbid TD and ADHD (TD + ADHD), 74 TD without ADHD (TD Only), 41 ADHD without TD (ADHD Only), and 49 control probands were analyzed. Hierarchical loglinear modeling was used to explore association patterns between TD, ADHD, and OCD or sub-clinical OCD (OCD/OCDsub) diagnoses among the 190 affected probands and their 538 relatives. The presence of OCD or OCDsub diagnosis in a proband was associated with a significantly increased risk of comorbid TD + ADHD in his/her relatives. The finding of an association between TD, ADHD and a proband OCD/OCDsub diagnosis was unexpected. The current results suggest that TD, ADHD, and OCD symptoms have overlapping neurobiology when occurring in families of TD and/or ADHD probands., (Copyright © 2011 Wiley-Liss, Inc.)

SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessive-compulsive disorder (OCD). Several independent research groups have reported significant associations between OCD and single nucleotide polymorphisms (SNPs) in this gene. Previously, we evaluated 13 SNPs in, or near, SLC1A1 and reported a strong association signal with rs301443, a SNP 7.5 kb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886–892]. The aims of the current study were first, to further investigate this finding by saturating the region around rs301443; and second, to explore the entire gene more thoroughly with a dense panel of SNP markers. We genotyped an additional 111 SNPs in or near SLC1A1, covering from 9 kb upstream to 84 kb downstream of the gene at average spacing of 1.7 kb per SNP, and conducted family-based association analyses in 1,576 participants in 377 families.We found that none of the surrounding markers were in linkage disequilibrium with rs301443, nor were any associated with OCD. We also found that SNP rs4740788, located about 8.8 kb upstream of the gene, was associated with OCD in all families (P = 0.003) and in families with male affecteds (P = 0.002). A three-SNP haplotype (rs4740788–rs10491734–rs10491733) was associated with OCD in the total sample (P = 0.00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD.

Biological and positional evidence supports the involvement of the GAD1 and distal-less homeobox genes (DLXs) in the etiology of autism. We investigated 42 single nucleotide polymorphisms in these genes as risk factors for autism spectrum disorders (ASD) in a large family-based association study of 715 nuclear families. No single marker showed significant association after correction for multiple testing. A rare haplotype in the DLX1 promoter was associated with ASD (P-value = 0.001). Given the importance of rare variants to the etiology of autism revealed in recent studies, the observed rare haplotype may be relevant to future investigations. Our observations, when taken together with previous findings, suggest that common genetic variation in the GAD1 and DLX genes is unlikely to play a critical role in ASD susceptibility., (Copyright © 2010 Wiley-Liss, Inc.)

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is familial and highly heritable. Although genetic influences are thought to play a significant role in the development of TS, no definite TS susceptibility genes have been identified to date. TS is believed to be genetically related to both obsessive-compulsive disorder (OCD) and grooming disorders (GD) such as trichotillomania (TTM). SAP90/PSD95-associated protein 3 (SAPAP3/DLGAP3) is a post-synaptic scaffolding protein that is highly expressed in glutamatergic synapses in the striatum and has recently been investigated as a candidate gene in both OCD and GD studies. Given the shared familial relationship between TS, OCD and TTM, DLGAP3 was evaluated as a candidate TS susceptibility gene. In a family-based sample of 289 TS trios, 22 common single nucleotide polymorphisms (SNPs) in the DLGAP3 region were analyzed. Nominally significant associations were identified between TS and rs11264126 and two haplotypes containing rs11264126 and rs12141243. Secondary analyses demonstrated that these results cannot be explained by the presence of comorbid OCD or TTM in the sample. Although none of these results remained significant after correction for multiple hypothesis testing, DLGAP3 remains a promising candidate gene for TS., (Copyright © 2010 Wiley-Liss, Inc.)

Trichotillomania (TTM) is a disorder with putative genetic underpinnings. Family studies report higher than expected rates of TTM among relatives of affected individuals, but no twin concordance studies have been completed to estimate heritability rates. Same-sex twin pairs with hair pulling in at least one co-twin were included. Subjects were recruited following phone screens and questionnaire completion for zygosity and hair pulling variables. Three sets of criteria were used to define hair pulling and TTM. Two other sets of criteria were widened to include skin picking and bothersome hair manipulation. Fisher exact tests assessed pairwise concordance rates for monozygotic and dizygotic twin pairs and heritability estimates were calculated where significant differences existed. Among 34 identified twin pairs, 24 were monozygotic (MZ) and 10 were dizygotic (DZ). Respective concordance rates for MZ and DZ twin pairs were significantly different at 38.1% and 0% for DSM-IV TTM criteria, 39.1% and 0% using modified DSM criteria, and 58.3% and 20% for noticeable non-cosmetic hair pulling (heritability estimates 76.2%). MZ and DZ concordance rates were not significantly different when broadening hair pulling criteria to include skin picking or when including bothersome hair manipulation. Concordance rates from this study suggest that genetic factors play a significant role in the etiology of TTM. Given the reported discordance rates among the MZ twins, further research is required to fully understand contributory non-genetic factors., ((c) 2009 Wiley-Liss, Inc.)

The genetic basis of reading disability (RD) has long been established through family and twin studies. More recently genetic linkage studies have identified genomic regions that appear to harbor susceptibility genes for RD. Association studies have been shown to have greater power for detecting genes of modest effect, particularly in genetically isolated populations. Hence, a case control study of RD was undertaken in the Afrikaner population in South Africa. Sixty-eight microsatellite markers in regions where linkages had been reported in previous studies were genotyped on 122 children with reading disability and 112 typically reading controls drawn from the same school population. A single allele of marker D6S299 showed a highly significant association with the RD phenotype (D6S299[229], P-value 0.000014). Other markers on other chromosomes also showed suggestive associations. Of particular interest were markers on chromosomes 1 and 15. These two regions have been implicated in studies of populations that formed the founding population in the Afrikaner population.

Obsessive-compulsive disorder (OCD) is likely a disorder involving complex genetic transmission. This suggests that multiple genetic and environmental factors are involved in its etiology. This is complicated further by the probability of genetic heterogeneity for this phenotype. In this report, we describe a preliminary approach to deal with both complexities. SLC1A1, a glutamate transporter gene on chromosome 9p, was originally proposed to be related to OCD based on two linkage studies, and subsequently association of OCD to the gene has been replicated. Additionally, genetic linkage to a subtype of OCD, compulsive hoarding, has been reported on chromosome 14q. We hypothesized that both genomic regions contribute to OCD in some instances. Using the analytic program GENEFINDER we found that conditioning linkage on chromosome 14q to a marker adjacent to SLC1A1, reduced the size of the linkage region on chromosome 14q and provided evidence for interaction between the regions on chromosomes 9p and 14q., (2008 Wiley-Liss, Inc.)

Obsessive compulsive disorder (OCD) is a common psychiatric disorder that can have disabling effects on both adults and children. Twin, family, segregation, and linkage studies have demonstrated that OCD is familial, that the familiality is due in part to genetic factors and there are regions of the genome which very likely harbor susceptibility loci for OCD. Over 60 candidate gene studies have been conducted. Most studies have focused on genes in the serotonergic and dopaminergic pathways. Unfortunately, none have achieved genome-wide significance and with the exception of the glutamate transporter gene, none have been reliably replicated. Future research will requite much larger samples and the collaboration of researchers to be able to identify susceptibility loci for OCD., (Copyright 2008 Wiley-Liss, Inc.)

In this study, we attempted to confirm genetic linkage to developmental dyslexia and reading-related quantitative traits of loci that have been shown to be associated with dyslexia in previous studies. In our sample of 108 Dutch nuclear families, the categorical trait showed strongest linkage to 1p36 (NPL-LOD = 2.1). LOD scores for quantitative traits word-reading, non-word reading, and rapid naming peaked near the same location as the categorical trait, as well as on chromosome 2. Non-word repetition showed little phenotypic correlation with dyslexia or with the other quantitative traits, and this trait showed linkage peaks on 11p and 15q. No evidence for linkage to 6p22-23 was found for this set of families. Comparison of our results and literature data shows that loci link to different phenotypes in different samples. The mutual connections of these traits and their relation to developmental dyslexia remain elusive., (Copyright 2007 Wiley-Liss, Inc.)

Context: Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required., Objectives: This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females., Design: Family-based association candidate gene study., Setting: Participants were recruited from tertiary care OCD specialty clinics., Participants: OCD probands and their first degree relatives., Main Outcomes Measures: Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes., Results: Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045)., Conclusions: This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported., (2007 Wiley-Liss, Inc.)

Obsessive-compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. Phenotypic studies of affected sib-pairs (SPs) may help to characterize familial components of the phenotype. To determine whether SPs affected with OCD are similar in age at onset of obsessive-compulsive symptoms (OCS), symptom dimensions and presence of tic disorders (TDs). Forty OCD siblings ranging from 13 to 59 years old were evaluated by expert psychiatrists or psychologists. Families with two or more siblings affected with OCD were recruited from several OCD clinics in Brazil. The Yale Brown Obsessive-Compulsive Scale Checklist was used to assess OCS and the severity of OCD. The OCD diagnoses were made according to the DSM-IV. The chi-square test was used to assess concordance of TD presence within SPs based on the TD frequency reported in the literature (30%). There were significantly more siblings with early-onset OCS than with late-onset OCS (P = 0.002). Age at onset of OCS correlated positively and significantly between the two members of each SP (P = 0.005). Fourteen patients (35%) were diagnosed with TDs. There was no concordance of the TD presence within the SPs. When both were male, there was a significant sibling correlation in the contamination obsessions/cleaning compulsions dimension (ICC = 0.74; P = 0.002). Similarly, when both siblings were female, they were comparable in the hoarding obsessions/compulsions dimension (ICC = 0.76; P = 0.01). Familial factors seem to contribute to specific OCD phenotypic components such as age at onset of OCS and specific dimensions. The obvious influence of gender is as yet unexplained., ((c) 2007 Wiley-Liss, Inc.)

Results from twin and family studies suggest that obsessive-compulsive disorder (OCD) may be transmitted in families but, to date, genes for the disorder have not been identified. The OCD Collaborative Genetics Study (OCGS) is a six-site collaborative genetic linkage study of OCD. Specimens and blinded clinical data will be made available through the National Institute of Mental Health (NIMH) cell repository. In this initial report, we describe the methods of the study and present clinical characteristics of affected individuals for researchers interested in this valuable resource for genetic studies of OCD. The project clinically evaluated and collected blood specimens from 238 families containing 299 OCD-affected sibling pairs and their parents, and additional affected relative pairs, for a genome-wide linkage study. Of the 999 individuals interviewed to date, 624 were diagnosed with "definite" OCD. The mean age of subjects was 36 years (range 7-95). The majority of affected individuals (66%) were female. The mean age at onset of obsessive-compulsive symptoms was 9.5 years. Specific mood disorders, anxiety disorders, eating disorders, and skin picking were more prevalent in female cases, whereas tics, Tourette disorder, and alcohol dependence were more prevalent in male cases. Compared to "definite" cases of OCD, "probable" cases (n = 82) had, on average, later age at onset of obsessive-compulsive symptoms, lower severity score, and fewer numbers of different categories of obsessions and compulsions, and they were less likely to have received treatment for their symptoms., (Copyright 2006 Wiley-Liss, Inc.)

Results from family studies have suggested that obsessive-compulsive disorder (OCD) is a genetically heterogeneous disorder and have emphasized the importance of identifying valid subgroups of patients. The current study focused on early-onset OCD probands and examined the recurrence risks of OCD and tics among first-degree family members. One hundred six children and adolescents with OCD were recruited from a specialty clinic for OCD and 44 control individuals without OCD were identified by random-digit dialing. These 150 probands and their 465 first-degree relatives were assessed by trained interviewers, using standardized semi-structured interviews. Diagnoses were assigned according to DSM-IV criteria by two experts blind to the proband's diagnosis, through the best-estimate process. These data were analyzed using chi(2) tests, t-tests, logistic regression, and generalized estimating equations (GEE). Case probands had a mean age of onset of OC symptoms of 6.7 years (SD = 2.8), and high comorbid rates with Tourette syndrome (33%) and chronic tics (13.2%). Compared to control relatives, case relatives had higher age-corrected recurrence risks of OCD (22.7% vs. 0.9%, odds ratio (OR) = 32.5, 95% confidence interval (CI) = 4.5-230.8, P = 0.0005), and chronic tics (11.6% vs. 1.7%, OR = 7.9, 95% CI = 1.9-33.1, P = 0.005). A comorbid diagnosis of tics in the relatives was the best predictor of their diagnosis of OCD (OR = 7.35, 95% CI = 3.79-14.25, P < 0.0001). There was a significant correlation between the ages of onset of OCD in probands and their affected relatives. Childhood onset OCD is a highly familial disorder. Some early-onset cases may represent a valid subgroup, with higher genetic loading and shared vulnerability with chronic tic disorders., (Copyright 2005 Wiley-Liss, Inc.)

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., (Published 2004 Wiley-Liss, Inc.)

Tourette's disorder (TD) is a neuropsychiatric disorder that onsets in childhood and appears to result from an interaction of genetic and environmental factors. The goal of the current prospective longitudinal study is to examine the onset of TD in offspring of parents with TD. At-risk children and control children were enrolled between the ages of 3 and 6 years and prospectively studied with yearly structured assessments over intervals of 2-5 years. Of 34 at-risk children free of tics at baseline, 10 (29%) subsequently developed a tic disorder, including 3 with TD. None of the 13 control children developed a tic disorder (P = 0.045). OCD or subclinical OCD emerged in 11 cases but no controls (P = 0.021). Finally, ADHD occurred in 14 at-risk children but no controls (P = 0.005). When at-risk families were dichotomized into bilineal or unilineal categories, rates of TD in children with two affected parents were three times the rate observed for children with one affected parent. These findings support the hypothesis that at least some cases of TD result from a complex genetic etiology. TD, OCD, and ADHD are significantly increased in children with TD parents. Furthermore, the risk is even greater when both parents are affected. Finally, our diagnosis of tic disorders in 21% of subjects initially reported by parents to be unaffected affirms the value of structured clinical assessments., (Copyright 2003 Wiley-Liss, Inc.)

This study is a continuation and extension of the work with Orton Developmental Dyslexia (DD) pedigrees [Grigorenko et al., 1997; 2000, Grigorenko et al., 2001]. This study utilized an extended sample (N = 176) and a well-saturated map of chromosome 6p (30 markers). Six phenotypes were constructed to span a range of dyslexia-related cognitive processes. These phenotypes were: (1) Phonemic Awareness (of spoken words); (2) Phonological Decoding (of printed nonwords); (3) Rapid Automatized Naming (of colored squares or object drawings); (4) Single Word Reading (orally, of printed real words); (5) Phonemic Awareness/Decoding/Single-Word Reading pathway; and (6) Phonemic Awareness/Rapid Naming/Single-Word Reading pathway. The study resulted in two major findings. First, considering the distributions of the genetic linkage indicators across all phenotypes examined, there appear to be three regions of interest (around markers D6S109, D6S1261, and in the D6S105-D6S265 region). Any of these regions could serve as a starting point in the search for specific gene candidates contributing to the manifestation of DD, yet they all might be echo peaks of a single peak, the boundary of which is difficult to establish due to the limited power of this sample. Second, the DD-related linkage in 6p21.3 appears to be most closely related to the manifestations of DD through phonemic awareness and single-word reading deficits., (Copyright 2003 Wiley-Liss, Inc.)

Obsessive-compulsive disorder (OCD) is an etiologically heterogeneous disorder. Recent factor analyses have consistently identified several symptom dimensions, two of which are associated with increased familial risk for OCD; aggressive, sexual, and religious obsessions and checking compulsions (FACTOR 1) and symmetry and ordering obsessions and compulsions (FACTOR 2). Both of these symptom dimensions are also frequently seen in association with Gilles de la Tourette syndrome (GTS). The purpose of this study was to determine whether these obsessive-compulsive (OC) symptom dimensions are correlated within families (between sibs and between parent-child pairs). Using data collected by the Tourette Syndrome Association International Consortium for Genetics Affected Sibling Pair Study, the authors selected all available GTS sib pairs and their parents for which these OC symptom dimensions (factor scores) could be generated. This group included 128 full sibs and their mothers (54) and fathers (54). Four OC symptom dimension scores were computed for each family member using an algorithm derived from item endorsements from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) symptom checklist. In addition to a series of univariate analyses, complex segregation analyses were also completed using these quantitative OC symptom dimension scores. FACTOR 1 and FACTOR 2 scores were significantly correlated in sib pairs concordant for GTS. The mother-child correlations, but not father-child correlations, were also significant for these two factors. Segregation analyses were consistent with dominant major gene effects for both FACTOR 1 and FACTOR 2. We conclude that familial factors contribute significantly to OC symptom dimension phenotypes in GTS families. This familial contribution could be genetic or environmental., (Copyright 2003 Wiley-Liss, Inc.)