Biomedical subjects

David Pauls

Publications and source records attributed to David Pauls.

11 recordsLinked to original sources

PubMed2006

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

BACKGROUND: Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. METHODS: Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. RESULTS: After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). CONCLUSIONS: Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

Comorbidity↗

PubMed2006

Examining the relationship between obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in children and adolescents: a familial risk analysis.

BACKGROUND: To use family study methodology to examine the relationship between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. METHODS: We assessed for ADHD and OCD in the 1533 first-degree relatives of three groups of index children: those with ADHD and OCD, those with ADHD but no OCD, and matched controls with neither disorder. RESULTS: The risk for ADHD was similarly elevated in families of ADHD youth with (18.9%) and without OCD (20.1%; p = .91), and both groups had significantly higher rates of ADHD compared with controls (4.6%; p < or = .001), which was consistent with previous research showing a strong familial risk for ADHD. The risk for OCD was significantly elevated only among relatives of youth with ADHD plus comorbid OCD (13.0%) compared with controls (.5%; p < or = .001) and was consistent with previous research showing a strong familial risk for OCD. Relatives affected with ADHD had a significantly elevated risk for OCD compared with relatives unaffected by ADHD (7.4% vs. 1.3%; p < .001), suggestive of co-segregation between these disorders. There was no evidence of nonrandom mating between ADHD- and OCD-affected spouses. CONCLUSIONS: These results extend previously reported findings regarding the heritability of both ADHD and OCD and provide new evidence of a familial relationship between ADHD and pediatric OCD that best fits the hypothesis of a unique familial subtype.

Adolescent↗

PubMed2005

Three diagnostic approaches to Asperger syndrome: implications for research.

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, HFA) or AS. Diagnoses of AS were established based on three different approaches: DSM-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 HFA (but not from PDD-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 PDD-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 HFA, AS, and PDD-NOS.

Adolescent↗

PubMed2005

Early-onset obsessive-compulsive disorder: a subgroup with a specific clinical and familial pattern?

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

PubMed2004

Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network.

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.

Alleles↗

PubMed2004

The Military Life Scale: a measure of perceived stress and support in the Israeli Defense Force.

GOALS: The purpose of this study was to construct a reliable and valid measure of perceived stress and support by adolescents in the Israeli military, and to explore its structure and psychometric properties. METHOD: A large stratified sample of soldiers, representing different types of units, different lengths of service in the Israel Defense Force, and different ranks, were administered the Military Life Scale. Principal component factor analysis with varimax rotation resulted in a 5-factor structure for the stress scale, and a 5-factor structure for the support scale. RESULTS: All factor-derived scales showed satisfactory scale reliability and discriminant validity. CONCLUSIONS: The Military Life Scale is useful for measuring the stress experienced by individuals and groups within the Israel Defense Force. In addition, the Military Life Scale may be of use in other military environments, and with minor revision, in non-military environments in which the normative passage from late adolescence into adulthood occurs, such as a college setting.

Adolescent↗

PubMed2003

Autism.

Autism is a disorder characterised by severe difficulties in social interaction and communication, and with unusual behaviours. Once thought of as rare, autism is now recognised as being common. The role of CNS factors in pathogenesis is suggested by high rates of seizure disorder; research has highlighted the role of several specific brain regions in syndrome pathogenesis. Autism is a strongly genetic disorder and probably arises because of multiple genes; recurrence rates in families with one child are high. Early intervention with various techniques is helpful in many cases. Some pharmacological agents may help with certain problematic behaviours but do not address the underlying cause of the disorder.

Adult↗

PubMed2003

Continuing the search for dyslexia genes on 6p.

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.

Adolescent↗

PubMed2003

Familial aggregation of delusional proneness in schizophrenia and bipolar pedigrees.

OBJECTIVE: Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder. To identify a potential psychotic dimension common to families of both bipolar and schizophrenia probands, the authors tested if delusional proneness was observed among first-degree relatives of bipolar and schizophrenia probands. METHOD: The authors included 32 schizophrenia probands and 61 bipolar probands and their respective first-degree relatives (N=63 and N=59). They were all interviewed with the Diagnostic Interview for Genetic Studies, and delusional proneness was assessed with a self-report questionnaire, the Peters et al. Delusions Inventory. Schizophrenia and bipolar probands were subdivided into subgroups according to the intensity of delusional symptoms assessed by Peters et al. Delusions Inventory scores, and the authors compared delusional proneness in their respective first-degree relatives. RESULTS: Familial aggregation of delusional proneness was demonstrated, since Peters et al. Delusions Inventory scores were higher among nonschizophrenic first-degree relatives of schizophrenia probands with productive symptoms and among first-degree relatives of bipolar probands with psychotic features during their affective episodes. The authors also found an intrafamilial correlation of delusional proneness scores in nonaffected siblings of schizophrenia and bipolar probands. CONCLUSIONS: Delusional proneness appears to be an inherited predisposition common to both schizophrenia and bipolar disorder. In the future, this dimension might be valuable when used as a quantitative phenotype in linkage and association studies.

Adult↗

PubMed2002

No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network.

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.

Asperger Syndrome↗

PubMed1998

Visual-motor integration functioning in children with Tourette syndrome.

A neuropsychological model of visual-motor integration skill was proposed and tested in 50 children with Tourette syndrome (TS) and 23 unaffected control children matched for age. Children with TS performed significantly worse than control children on the Beery Visual-Motor Integration (VMI) Test. Consistent with the proposed model, visuoperceptual and fine-motor coordination subprocesses were significant predictors of VMI scores. However, the subprocesses did not fully account for the diagnostic group difference on the VMI. These results suggest that the integration of visual inputs and organized motor output is a specific area of neuropsychological weakness among individuals with TS.

Adolescent↗