Biomedical subjects

Abby J Fyer

Publications and source records attributed to Abby J Fyer.

15 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

A third-pass genome scan in panic disorder: evidence for multiple susceptibility loci.

BACKGROUND: Panic disorder (PD) is a common illness with a definite but "complex" genetic contribution and estimated heritability of 30-46%. METHODS: We report a genome scan in 120 multiplex PD pedigrees consisting of 1591 individuals of whom 992 were genotyped with 371 markers at an average spacing of 9cM. Parametric two-point, multipoint, and nonparametric analyses were performed using three PD models (Broad, Intermediate, Narrow) and allowing for homogeneity or heterogeneity. The two-point analyses were also performed allowing for independent male and female recombination fractions (theta). Genome-wide significance was empirically evaluated using simulations of this dataset. RESULTS: Evidence for linkage reached genome-wide significance in one region on chromosome 15q (near GABA-A receptor subunit genes) and was suggestive at loci on 2p, 2q and 9p using an averaged theta. Analyses allowing for sex-specific theta's were consistent except that support at one locus on 2q increased to genome-wide significance and an additional region of suggestive linkage on 12q was identified. However, differences in male and female recombination fractions predicted by the sex-specific approach were not consistent with current physical maps. CONCLUSIONS: These data provide evidence for chromosomal regions on 15q and 2q that may be important in genetic susceptibility to panic disorder. Although we are encouraged by the findings of analyses using sex-specific recombination fractions, we also note that further understanding of this analytic strategy will be important.

Chromosomes, Human, Pair 15↗

PubMed2006

Hoarding in obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study.

Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study. We found that, compared to non-hoarding individuals, hoarders were more likely to have symmetry obsessions and repeating, counting, and ordering compulsions; poorer insight; more severe illness; difficulty initiating or completing tasks; and indecision. Hoarders had a greater prevalence of social phobia and generalized anxiety disorder. Hoarders also had a greater prevalence of obsessive-compulsive and dependent personality disorders. Five personality traits were independently associated with hoarding: miserliness, preoccupation with details, difficulty making decisions, odd behavior or appearance, and magical thinking. Hoarding and indecision were more prevalent in the relatives of hoarding than of non-hoarding probands. Hoarding in relatives was associated with indecision in probands, independently of proband hoarding status. The findings suggest that hoarding behavior may help differentiate a distinct clinical subgroup of people with OCD and may aggregate in some OCD families. Indecision may be a risk factor for hoarding in these families.

Adolescent↗

PubMed2006

The OCD collaborative genetics study: methods and sample description.

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.

Adolescent↗

PubMed2006

An open pilot study of interpersonal psychotherapy for panic disorder (IPT-PD).

Interpersonal psychotherapy (IPT) is a time-limited psychotherapy initially developed to treat depression. It has yet to be studied systematically for treatment of panic disorder. We modified IPT for the treatment of panic disorder and tested this treatment in an open clinical trial with 12 patients seeking treatment of DSM-IV panic disorder. Patients were assessed before during and after treatment. At completion of treatment, nine patients (75%) were independently categorized as responders (i.e., rated as much improved or very much improved on the Clinical Global Impression-Change Scale). Substantial improvement was found for panic symptoms, associated anxiety and depressive symptoms, and physical and emotional well-being. Degree of change in this sample approximated that obtained in studies using established treatments such as cognitive behavioral therapy. Results, though preliminary, suggest that IPT may have efficacy as a primary treatment of panic disorder. Further study is warranted.

Adolescent↗

PubMed2005

Noncardiac chest pain and psychopathology in children and adolescents.

OBJECTIVE: We sought to examine the prevalence of DSM-IV psychiatric disorders in children and adolescents with complaints of noncardiac chest pain (NCCP). METHOD: We assessed 27 youngsters (ages 8-17 years) referred to a pediatric cardiology practice with complaints of NCCP. Each child and a parent were interviewed using the Anxiety Disorders Interview Schedule for Children. RESULTS: Sixteen youngsters (59%) were diagnosed with a current DSM-IV disorder. Fifteen (56%) had a current anxiety disorder, nine of whom were diagnosed with panic disorder. One participant was diagnosed with a depressive disorder. CONCLUSION: Results of this preliminary study suggest that DSM-IV anxiety disorders may be common in youngsters with NCCP. No evidence was found for high prevalence of depression in this sample. Larger controlled studies are needed to determine the prevalence and impact of psychopathology in youngsters with NCCP.

Adolescent↗

PubMed2005

A direct interview family study of obsessive-compulsive disorder. II. Contribution of proband informant information.

BACKGROUND: Overall findings of our first direct interview family study of obsessive-compulsive disorder (OCD) indicated that OCD is familial. In this replication study, we carefully examined the role of informant data in ascertaining OCD in relatives. METHOD: We interviewed 112 relatives of 57 OCD patients and 115 relatives of 41 not ill controls predominantly by telephone. Additional analyses included a combined sample of relatives about whom any diagnostic information was available (228 OCD and 239 controls). To examine the contribution of proband information about relatives, we considered two sets of best-estimate diagnoses. First, we ascertained best-estimate diagnoses for relatives using information from direct interviews and from all informants except the proband. Then, we re-diagnosed relatives based on all available information, including reports from the proband about their relatives. RESULTS: When relative diagnoses were derived without the benefit of proband informant reports, no evidence of familial OCD transmission was found. When diagnoses were made including information from the proband about the relative, evidence of familial OCD was found, but only when the diagnostic threshold was lowered to include cases with probable OCD or OCD symptoms. Other diagnoses (generalized anxiety disorder, social phobia, drug use disorder) were also higher among OCD relatives. CONCLUSIONS: This second study provides less robust support for familial transmission of OCD. Evidence for familial transmission of OCD was found only when diagnoses were made using information from the affected proband about their relatives. Taken in context of past findings, our own inconsistent results suggest that OCD may be heterogeneous with regard to familial transmission. Also, more careful attention should be paid to the contribution of informant reports, especially from relatives affected by the same disorder.

Adult↗

PubMed2005

A direct interview family study of obsessive-compulsive disorder. I.

BACKGROUND: This and the companion paper present two sequential family studies of obsessive-compulsive disorder (OCD) conducted by the same research group, but with different sampling and best-estimate procedures. In addition to providing further data on familial transmission of OCD, we used comparison of disparate findings (moderate, specific familial aggregation in this first study versus a stronger effect for other anxiety disorders than for OCD alone in the second) to examine possible effects of proband characteristics and informant data on outcome. METHOD: In this initial study we interviewed 179 first-degree relatives of 72 OCD probands and 112 relatives of 32 never mentally ill (NMI) controls. Informant data were obtained on an additional 126 relatives (total "combined" samples of 263 and 154 respectively). Analyses used best-estimate diagnoses made by consensus of two "blinded" senior clinicians who reviewed all diagnostic materials including proband informant data about relatives. RESULTS: Significantly higher risk for OCD but not other anxiety disorders was found in relatives of OCD probands compared to relatives of controls in both the directly interviewed and combined samples. There was no relationship between proband age at onset of OCD and strength of familial aggregation. CONCLUSIONS: These data indicate moderate familial aggregation of OCD, but do not support increased transmission by early onset probands, or a familial relationship between OCD and other anxiety disorders with the possible exception of generalized anxiety disorder.

Adult↗

PubMed2004

Investigation of polymorphisms in the CREM gene in panic disorder.

Clinical and animal studies suggest a role for pathways regulated by cyclic-AMP in anxiety. Mouse gene deletion studies, our own linkage findings on chromosome 10, and a recently published genetic association study by Domschke et al. [2003: Am J Med Genet 117B:70-78] suggest that the cAMP responsive element modulator (CREM) may be involved in panic disorder. We have employed a family-based design to investigate the role of DNA sequence variations in the gene for CREM in panic disorder. We have genotyped 613 individuals in 70 panic disorder pedigrees, as well as 42 parent/offspring triads. Subjects were genotyped at two informative single nucleotide polymorphisms (SNPs) and three polymorphic microsatellites in the CREM genomic region; and the data were analyzed for genetic association and linkage. Linkage analysis employing several diagnostic/genetic models produced a maximum lod score of 0.63 for SNP-1, located in the 5' UTR of CREM, under a dominant model with a broad diagnostic definition of panic disorder. Non-parametric analysis, using the NPL statistic or FBAT, also did not support any linkage or association between the markers and panic disorder. All five markers (spanning 77 kb) used in the study showed modest, but significant linkage disequilibrium. Analysis of 2-, 3-, 4-, or 5-marker haplotypes using TRANSMIT failed to find any globally significant results; however, individual haplotypes containing a single allele of MS-3 were nominally associated with panic disorder. These findings provide little additional evidence for a susceptibility locus for panic disorder either within the CREM gene or in a nearby region of chromosome 10p11 in our sample.

5' Untranslated Regions↗

PubMed2004

Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder.

Data from clinical and behavioral pharmacological studies have implicated adenosine in anxiety behaviors, while genetic studies have suggested that adenosine receptors may be associated with panic disorder. We have undertaken an analysis of several DNA sequence variations in the adenosine 2A receptor (ADORA2A) in a large sample of panic disorder pedigrees. Individuals from 70 panic disorder pedigrees, and 83 child-parent 'trios', were genotyped at five single-nucleotide polymorphisms (SNPs) in and near the ADORA2A gene and were analyzed for genetic linkage and association. Linkage analysis revealed elevated LOD scores for a silent substitution (1083C/T, SNP-4) in the second coding exon. This SNP has been previously reported to be associated with panic disorder. We observed a maximal heterogeneity LOD score of 2.98 (theta=0) under a recessive genetic model and narrow diagnostic model. Other SNPs showed no evidence for linkage. Association tests were not significant for any of the five ADORA2A SNPs. When SNP haplotypes were assessed in the triads with TRANSMIT, one 3-marker haplotype (SNPs 1, 4, 5) was nominally significantly associated with panic disorder (p=0.029). Pairwise estimations of linkage disequilibrium between the SNPs showed strong patterns of linkage disequilibrium across the ADORA2A locus. Analyses carried out by broadening the panic disorder phenotype to include agoraphobia continued to support linkage to ADORA2A. Our findings provide evidence for a susceptibility locus for panic disorder, and possibly including agoraphobia, either within the ADORA2A gene or in a nearby region of chromosome 22, and serves as the first successful candidate gene replication study in panic disorder.

Female↗

PubMed2004

Anxiety and depressive symptoms and anxiety sensitivity in youngsters with noncardiac chest pain and benign heart murmurs.

OBJECTIVE: Chest pain in children and adolescents is rarely associated with cardiac disease. We sought to examine psychological symptoms in youngsters with medically unexplained chest pain. We hypothesized that children and adolescents with medically unexplained chest pain would have high rates of anxiety and depressive symptoms. METHODS: We assessed 65 youngsters with noncardiac chest pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self-report measures of anxiety and depressive symptoms and anxiety sensitivity. RESULTS: Compared with the asymptomatic benign-murmur group, youngsters with NCCP had higher levels of some anxiety symptoms and anxiety sensitivity. Differences on depressive symptoms were not significant. CONCLUSIONS: Though preliminary, results suggest that youngsters with chest pain may experience increased levels of some psychological symptoms. Future studies of noncardiac chest pain in youngsters should include larger samples and comprehensive diagnostic assessments as well as long-term follow-up evaluations.

Adolescent↗

PubMed2003

Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q.

Substantial evidence supports that there is a genetic component to panic disorder (PD). Until recently, attempts at localizing genes for PD by using standard phenotypic data have not proven successful. Previous work suggests that a potential subtype of PD called the panic syndrome exists, and it is characterized by a number of medical conditions, most notably bladder/renal disorders. In the current study, a genome scan with 384 microsatellite markers was performed on 587 individuals in 60 multiplex pedigrees segregating PD and bladder/kidney conditions. Using both single-locus and multipoint analytic methods, we found significant linkage on chromosome 22 (maximum heterogeneity logarithm of odds score = 4.11 at D22S445) and on chromosome 13q (heterogeneity logarithm of odds score = 3.57 at D13S793) under a dominant-genetic model and a broad phenotypic definition. Multipoint analyses did not support the observation on chromosome 22. The chromosome 13 findings were corroborated by multipoint findings, and extend our previous findings from 19 of the 60 families. Several other regions showed elevated scores by using when one analytic method was used, but not the other. These results suggest that there are genes on chromosome 13q, and possibly on chromosome 22 as well, that influence the susceptibility toward a pleiotropic syndrome that includes PD, bladder problems, severe headaches, mitral valve prolapse, and thyroid conditions.

Chromosome Mapping↗

PubMed2002

Evidence for a susceptibility locus for panic disorder near the catechol-O-methyltransferase gene on chromosome 22.

BACKGROUND: A well-characterized single nucleotide polymorphism (472G/A-Val/Met-SNP8) in the coding sequence of the catechol-O-methyltransferase (COMT) gene leads to a three- to fourfold difference in enzymatic activity and clinical and animal studies suggest a role in anxiety states like panic disorder. METHODS: Subjects from 70 panic disorder pedigrees, and 83 "triads", were genotyped at seven single nucleotide polymorphisms (SNPs), polymorphic microsatellites in the first intron of COMT and approximately 339kb upstream of COMT (D22S944) and analyzed for genetic association and linkage. RESULTS: Linkage analysis showed elevated LOD scores for 472G/A (SNP 8), silent exon 3 substitution (186C/T-SNP 5), and the marker D22S944 (2.88, 2.62, and 2.93, respectively), using a variety of diagnostic and genetic models. Association tests were not significant for the SNPs, but were highly significant for D22S944 (p =.0001-.0003). One three-marker haplotype formed from the above three polymorphisms was significantly associated with panic disorder (p =.0001), as was the "global" p value for this combination (p =.005). In addition, numerous haplotypes with combinations of D22S944 and COMT SNPs were found to be significantly associated with panic disorder. CONCLUSIONS: Our findings provide strong evidence for a susceptibility locus for panic disorder either within the COMT gene or in a nearby region of chromosome 22.

Adult↗

PubMed2002

Clinical features of four DSM-IV-specific phobia subtypes.

Seventy-three patients (ages 18 to 66) with specific phobias from one of four DSM-IV subtypes (animal, situational, blood-injection-injury, and natural environment) were assessed by experienced clinicians using a semistructured diagnostic interview. All patients were free of lifetime anxiety comorbidity. Subtype groups were compared on age of onset, mode of onset, presence of unexpected panic attacks, and focus of fear. Consistent with earlier findings, participants with situational phobia had a later age of onset and more unexpected panic attacks. No differences were found across subtypes in mode of onset. Contrary to previous findings, natural environment and situational phobias were most frequently associated with a focus on danger or harm rather than other foci such as internal sensations associated with panic attacks. Implications for the usefulness of current subtype categories are discussed.

Adolescent↗

PubMedDate not supplied

Alcohol use disorders in relatives of patients with panic disorder.

OBJECTIVE: The aim of this study was to use data from a family study of anxiety disorders to examine the familial association between alcohol use disorders and panic disorder (PD), controlling for alcohol use disorders in the proband. METHOD: Data from a family study of anxiety disorders were used to compare rates of alcohol use disorders in the relatives of 3 proband groups (PD with lifetime alcohol use disorders, PD without lifetime alcohol use disorders, and not-ill controls). RESULTS: There was a significantly higher rate (12%) of alcohol use disorders among the relatives of PD probands compared with relatives of controls (5%), even in the absence of alcohol use disorders in the proband and after adjusting for differences in sociodemographic characteristics and lifetime drug use disorders (chi2 = 5.4; df = 1; P = .02). Anxiety symptoms were more frequent among the male relatives of panic probands who received an alcohol diagnosis, compared with those who did not have alcohol use disorders (10/25 vs 22/111; chi2 = 4.6; df = 1; P = .03). A similar pattern was found in women (8/11 vs 63/156; chi2 = 4.4; df = 1; P = .036). CONCLUSIONS: These findings suggest a familial association between PD and alcohol use disorders. Future studies with more refined alcohol diagnoses are needed to replicate and investigate the mechanism of this association.

Alcoholism↗