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Biomedical subjects

D L Pauls

Publications and source records attributed to D L Pauls.

At least 19 recordsLinked to original sources
PubMed1995

Complex segregation analyses of old order Amish families ascertained through bipolar I individuals.

Specific genetic hypotheses about the mode of transmission of bipolar affective disorders were examined by performing complex segregation analyses of Old Order Amish families. The analyses were performed on 1) the total set of 42 families including 689 relatives, 2) a subset of 19 families consisting of those kindreds sharing common ancestors within three generations that contained 333 relatives, and 3) a subset of 23 more distantly related families with 356 relatives. When all 42 families were included in the analyses, the specific mode of transmission that could be distinguished was dependent upon the diagnostic scheme used in the analysis. An autosomal dominant mode of inheritance could be rejected when relatives with bipolar I, atypical bipolar, major depressive disorder, and hypomania were included as affected. When analyses included only the subset of families more closely related, an autosomal dominant inheritance model was found to be consistent with transmission of BP I disorder. It was not possible to distinguish between other transmission models with broader diagnostic schemes in this subset of families. Finally, results of analyses on the subset of more distantly related families suggest that there is a significant proportion of Old Order Amish families in which the genetic factors contributing to the expression of bipolar illness are either polygenic or oligogenic.

Adolescent↗
PubMed1995

Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome.

A novel serotonin receptor designated 5HT7 (genetic locus HTR7) was cloned in 1993. This receptor has interesting properties related to ligand affinity and CNS distribution that render HTR7 a very interesting candidate gene for neuropsychiatric disorders. We mapped this gene, first by physical methods and then by genetic linkage. First, we made a tentative assignment to chromosome 10, based on hybridization of an HTR7 probe to a Southern blot of DNA from somatic cell hybrids. We then identified a genetic polymorphism at the HTR7 locus. We identified one extended pedigree where the polymorphism segregated. Using the LIPED computer program for pairwise linkage analysis, we confirmed the assignment of the gene to chromosome 10, specifically 10q21-q24, based on a lod score of 5.37 at 0% recombination between HTR7 and D10S20 (a chromosome 10 reference marker). Finally, we excluded genetic linkage between this locus and Tourette syndrome under a reasonable set of assumptions.

Blotting, Southern↗
PubMed1995

An epidemiological study of trichotillomania in Israeli adolescents.

OBJECTIVE: To determine the prevalence of trichotillomania and comorbid psychopathology in nonreferred adolescents. METHOD: Using a questionnaire and interview, 794 Israeli 17-year-olds were screened for current and past hair-pulling and comorbid psychopathology. RESULTS: Eight current or past hair-pullers (5 male, 3 female) were identified, yielding a lifetime prevalence of hair-pulling of 1%. Four subjects reported current hair-pulling (point prevalence of 0.5%). None of these reported alopecia, distress, or tension before pulling; only two reported relief after pulling. Thus, none met the full DSM-III-R criteria for trichotillomania. Four subjects reported past but not current hair-pulling, with bald spots in two cases. Three of the four current hair-pullers had significant obsessive-compulsive symptoms, a significantly elevated rate compared to the entire screened population. Two subjects with obsessive-compulsive disorder also had generalized anxiety disorder and, in one case, chronic simple vocal tics. Hair-pullers did not differ significantly from non-hair-pullers in IQ, physical fitness, and overall competency, or prevalence of other comorbid disorders. CONCLUSIONS: In a community adolescent sample, only 25% of hair-pullers reported resulting bare spots and none endorsed both rising tension and subsequent relief. The prevalence of obsessive-compulsive symptoms was significantly elevated in these nonreferred hair-pullers.

Adolescent↗
PubMed1995

Linkage analyses of chromosome 18 markers do not identify a major susceptibility locus for bipolar affective disorder in the Old Order Amish.

Previously reported linkage of bipolar affective disorder to DNA markers in the pericentromeric region of chromosome 18 was reexamined in a larger homogeneous sample of Old Order Amish families. Four markers (D18S21, D18S53, D18S44, and D18S40) were examined in three kindreds containing 31 bipolar I (BP I) individuals. Although linkage findings were replicated in the one previously studied Amish pedigree containing four BP I individuals, linkage to this region was excluded in the larger sample. If a susceptibility locus for bipolar disorder is located in this region of chromosome 18, it is of minor significance in this population.

Bipolar Disorder↗
PubMed1994

Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison with Tourette's syndrome and healthy controls.

BACKGROUND: Limited neurobiological data have implicated central arginine vasopressin in the pathobiology of obsessive-compulsive disorder (OCD). Based on twin, family genetic, and pharmacological studies, some forms of OCD are etiologically related to Tourette's syndrome. The role of arginine vasopressin and related compounds such as oxytocin in Tourette's syndrome has not been previously explored. METHODS: To compare cerebrospinal fluid (CSF) levels of arginine vasopressin and oxytocin, we collected CSF at midday in a standardized fashion from a total of 83 individuals (29 patients with OCD, 23 patients with Tourette's syndrome, and 31 normal controls). We also collected family study data on each subject to determine which subjects had a family history positive for Tourette's syndrome, OCD, or related syndromes. RESULTS: In contrast to previous reports, we report similar concentrations of arginine vasopressin for all three groups but increased oxytocin levels in patients with OCD. Remarkably, this increase was observed only in a subset of patients with OCD (n = 22) independently identified as being without a personal or family history of tic disorders (P = .0003). In this subgroup of patients, the CSF oxytocin level was correlated with current severity of OCD (n = 19, r = .47, P < .05). CONCLUSIONS: A possible role for oxytocin in the neurobiology of a subtype of OCD is suggested by the elevated CSF levels of oxytocin and by the correlation between CSF oxytocin levels and OCD severity. These findings reinforce the value of family genetic data in identifying biologically homogeneous (and perhaps more etiologically homogeneous) groups of patients with OCD. Together with emerging pharmacological data showing differential responsiveness to treatment of tic-related OCD vs non-tic-related OCD, these data also argue strongly for the incorporation of tic-relatedness as a variable in biological and behavioral studies of patients with OCD.

Adolescent↗
PubMed1994

Genetic mechanisms in childhood psychiatric disorders.

OBJECTIVE: This review summarizes research findings on the genetics of several childhood psychiatric disorders. METHOD: One hundred fifty papers were reviewed from the past several decades and were selected because they have suggested that genetic factors may play a role in the etiology of certain childhood disorders. This review is not meant to be exhaustive but rather has emphasized those disorders for which a genetic etiology has been proposed by different research groups. RESULTS: The more classical approaches to genetic research are reviewed and critiqued. The status of research for a number of childhood disorders is summarized. The molecular basis for several developmental disorders is presented and the prospects for arriving at a similar molecular understanding for other childhood psychiatric illnesses are discussed. CONCLUSIONS: Genetic factors play a determining role for certain developmental disorders. However, the molecular basis for other psychiatric disorders has yet to be elucidated and there are complicating factors that bear on genetic research of complex behavioral disorders.

Adoption↗
PubMed1992

Risks of affective illness among first-degree relatives of bipolar I old-order Amish probands.

Data from bipolar I old-order Amish families suggest that the morbid risk of illness is not significantly different in this population when compared with estimates of risk from previous studies. The age-corrected rates of bipolar I, bipolar II, and major depressive disorder among first-degree relatives are 8.7, 3.7, and 11.6, respectively. Risk of illness is not significantly different among male and female relatives and among relatives of male and female probands. Consistent with other reports, the rate of illness is higher among relatives of probands with early-onset disease. In contrast with previous reports, there does not appear to be a cohort effect in this population.

Adolescent↗
PubMed1992

Update on the search for DNA markers linked to manic-depressive illness in the Old Order Amish.

In this report we describe our efforts to identify a gene involved in bipolar illness using a large, multigenerational Old Order Amish pedigree with many affected individuals. The original collection of cell lines from Amish pedigree 110 has been extended to include 169 individuals. We have used over 250 markers spaced at approximately 20 centiMorgans that detect restriction length fragment polymorphisms, but no LOD scores greater than 3 have been obtained from pairwise linkage analyses. We are expanding our collection of cell lines from both normal and affected family members and updating our diagnostic data as we continue our systematic screening of the genome for a gene involved in bipolar illness.

Bipolar Disorder↗
PubMed1992

An epidemiological study of obsessive-compulsive disorder and related disorders in Israeli adolescents.

Five hundred and sixty-two, 16- to 17-year-old consecutive inductees into the Israeli Army, constituting a random sample of their cohort, were screened for obsessive-compulsive disorder (OCD), Tourette's syndrome, transient tics (TT), chronic multiple tics (CMT), and attention-deficit hyperactive disorder (ADHD). Two child psychiatrists interviewed the subjects, using screening items from structured interviews that implement DSM-III-R diagnostic criteria. For OCD, a point prevalence of 3.6% was found, 3.9% for ADHD, 1.8% for CMT, and 1.6% for TT. For ADHD, TT, and CMT, but not for OCD, there was a significantly higher prevalence for males than for females. Among the OCD individuals, there was an elevation of TT, CMT, and Tourette's syndrome relative to the population rates.

Adolescent↗
PubMed1992

The genetics of obsessive compulsive disorder and Gilles de la Tourette's syndrome.

This article reviews the evidence that obsessive compulsive disorder (OCD) and Gilles de la Tourette's syndrome (GTS) are both familial and genetic. Studies are summarized that suggest that (1) some forms of OCD are related to GTS, (2) some forms of OCD are familial and may not be related to GTS, and (3) the patterns of inheritance of GTS and OCD within the same families are consistent with the transmission of an autosomal dominant genetic locus.

Diseases in Twins↗
PubMed1991

Linkage of bipolar affective disorders to markers on chromosome 11p is excluded in a second lateral extension of Amish pedigree 110.

Linkage between markers on chromosome 11p and bipolar affective disorders can be excluded in a second large lateral extension of the original Amish Pedigree 110. These results, together with previous negative linkage findings, suggest that there is not one single gene on 11p conferring susceptibility for bipolar affective disorders among the Old Order Amish.

Adult↗
PubMed1991

A family study of Gilles de la Tourette syndrome.

Previous studies have demonstrated that Gilles de la Tourette syndrome (TS) is a familial disorder and that chronic tics (CT) and obsessive compulsive disorder (OCD) appear to be etiologically related to the syndrome. In the present study we report the results from a study of 338 biological relatives of 86 TS probands, 21 biologically unrelated relatives of adopted TS probands, and 22 relatives of normal subjects. The 43 first-degree relatives of the adopted TS and normal probands constituted a control sample. The rates of TS, CT, and OCD in the total sample of biological relatives of TS probands were significantly greater than in the relatives of controls. In addition, the morbid risks of TS, OCD, and CT were not significantly different in families of probands with OCD when compared to relatives of probands without OCD. These findings provide further evidence that OCD is etiologically related to TS.

Humans↗
PubMed1991

Progress in the search for genetic linkage with Tourette syndrome: an exclusion map covering more than 50% of the autosomal genome.

Gilles de la Tourette syndrome is a neuropsychiatric disorder with an autosomal dominant mode of inheritance and reduced penetrance at a single genetic locus. Several research groups have genetic linkage studies underway to detect the chromosomal location of the gene that predisposes for this disorder. Strong and clear evidence of linkage has not yet been produced for Tourette syndrome. This paper presents an overview of the methods and progress of the groups centered at Yale University and Erasmus University in excluding linkage from a large portion of the genome. Our labs have screened 228 genetic marker loci for linkage with a gene for this disorder in a series of affected families in the United States, Canada, The Netherlands, and Norway. More than 50% (and perhaps as much as 66%) of the autosomal genome has now been excluded on the assumption that genetic heterogeneity is not an important factor in the Tourette syndrome pedigrees pooled for this summary.

Chromosome Mapping↗
PubMed1990

Gilles de la Tourette syndrome is not linked to D2-dopamine receptor.

Gilles de la Tourette syndrome has an important genetic component; the pathophysiology of this disorder may involve the dopamine system. We tested a D2-dopamine receptor (locus DRD2, recognized by probe hD2G1) for genetic linkage with Gilles de la Tourette syndrome. Using a genetic linkage map of the region of DRD2 on the long arm of chromosome 11 and restriction fragment length polymorphism data from a total of four markers (DRD2 itself, D11S84, D11S29, and PBGD), we were able to exclude linkage of this candidate gene and Gilles de la Tourette syndrome in two extended kindreds segregating for Gilles de la Tourette syndrome. This rules out causation of Gilles de la Tourette syndrome by mutation in DRD2 in the kindreds studied under the genetic assumptions we employed; use of the map and multipoint linkage analyses also allowed us to exclude a Gilles de la Tourette syndrome susceptibility locus from a larger genetic region.

Chromosome Mapping↗