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Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether... more
Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an im...
Research Interests: Genetics, Humans, Microglia, Neurons, Astrocytes, and 3 moreTourette Syndrome, Genotype, and Glutamic Acid
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Bipolar disorder is an etiologically complex syndrome that is clearly heritable. Multiple genes, working singly or in concert, are likely to cause susceptibility to bipolar disorder. Bipolar disorder genetics has progressed rapidly in the... more
Bipolar disorder is an etiologically complex syndrome that is clearly heritable. Multiple genes, working singly or in concert, are likely to cause susceptibility to bipolar disorder. Bipolar disorder genetics has progressed rapidly in the last few decades. However, specific causal genetic mutations for bipolar disorder have not been identified. Both candidate gene studies and complete genome screens have been conducted. They have provided compelling evidence for several potential bipolar disorder susceptibility loci in several regions of the genome. The strongest evidence suggests that bipolar disorder susceptibility loci may lie in one or more genomic regions on chromosomes 18, 4, and 21. Other regions of interest, including those on chromosomes 5 and 8, are also under investigation. New approaches, such as the use of genetically isolated populations and the use of endophenotypes for bipolar disorder, hold promise for continued advancement in the search to identify specific bipolar...
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Tourette syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). However, the genetic relations between... more
Tourette syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). However, the genetic relations between these disorders have not been clearly elucidated. This study examined the familial relations among TS, OCD, and ADHD in a large sample of TS families. Parent-offspring concordance of TS, OCD, and ADHD was examined in 952 individuals from 222 TS-affected sib-pair families originally collected for genetic studies using logistic regression with generalized estimating equations to control for correlated data. Variance components methods were used to estimate the heritability and genetic and environmental correlations among TS, OCD, and ADHD. Bilineal families where both parents had TS or OCD were excluded. OCD and ADHD were highly heritable in these TS families. There were significant genetic correlations between TS and OCD and between OCD and ADHD, but not between TS and ADHD. In addition, significant environmental correlations were found between TS and ADHD and between OCD and ADHD. Parental OCD + ADHD was associated with offspring OCD + ADHD. This study provides further evidence for a genetic relation between TS and OCD and suggests that the observed relation between TS and ADHD may due in part be to a genetic association between OCD and ADHD and in part due to shared environmental factors.
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Although susceptibility loci exist for Gilles de la Tourette syndrome (GTS), no causative gene has been identified, perhaps in part because of phenotypic heterogeneity. This study used latent class analyses (LCA) to identify GTS... more
Although susceptibility loci exist for Gilles de la Tourette syndrome (GTS), no causative gene has been identified, perhaps in part because of phenotypic heterogeneity. This study used latent class analyses (LCA) to identify GTS subphenotypes and assess characteristics and heritability of the classes. The study included 952 individuals from 222 GTS families recruited for genetic studies. LCA identified a best-fit model for combinations of the diagnoses of GTS, obsessive-compulsive disorder (OCD), OC symptoms and behaviors (OCS/OCB), and attention-deficit/hyperactivity disorder (ADHD) in a random sample of one sibling from each family (n = 197), a replication sample randomly chosen from the remaining siblings (n = 203), and in the entire sample (all siblings and parents, N = 952). Heritabilities were assessed for all categoric diagnoses and LCA classes using a variance components approach. In this large sample of GTS sib pairs and their parents, three GTS-affected groups were identified-GTS + OCS/OCB (Class III), GTS + OCD (Class IV), and GTS + OCD + ADHD (Class V)-in addition to a minimally affected class (I) and a small chronic tics + OCD class (II). A preponderance of males and younger age at onset was found in more comorbidly affected classes. Only the GTS + OCD + ADHD class was highly heritable. Our data suggest that GTS classes may represent distinct entities, with both shared and unique etiologies. In particular, GTS + OCD + ADHD may represent a separate, heritable phenotype that can be used to further inform genetic studies.
Research Interests: Genetics, Attention-Deficit/Hyperactivity Disorder, Adolescent, Comorbidity, Biological Sciences, and 14 moreBiological Psychiatry, Humans, Child, Female, Male, Obsessive Compulsive Disorder, Phenotype, Genetic linkage analysis, Tourette Syndrome, Family Health, Latent Class Analysis, Compulsive behavior, Age of Onset, and Random Allocation
Assortative mating, or the tendency for individuals with similar phenotypes to mate more frequently than expected by chance, has been reported for a variety of complex traits, including many neuropsychiatric disorders. Although... more
Assortative mating, or the tendency for individuals with similar phenotypes to mate more frequently than expected by chance, has been reported for a variety of complex traits, including many neuropsychiatric disorders. Although assortative mating has been reported in affective disorders, the studies done to date have been inconclusive. This study attempts to assess the degree of assortative mating in individuals
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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... more
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.
Hikikomori, a form of social withdrawal first reported in Japan, may exist globally but cross-national studies of cases of hikikomori are lacking. To identify individuals with hikikomori in multiple countries and describe features of the... more
Hikikomori, a form of social withdrawal first reported in Japan, may exist globally but cross-national studies of cases of hikikomori are lacking. To identify individuals with hikikomori in multiple countries and describe features of the condition. Participants were recruited from sites in India, Japan, Korea and the United States. Hikikomori was defined as a 6-month or longer period of spending almost all time at home and avoiding social situations and social relationships, associated with significant distress/impairment. Additional measures included the University of California, Los Angeles (UCLA) Loneliness Scale, Lubben Social Network Scale (LSNS-6), Sheehan Disability Scale (SDS) and modified Cornell Treatment Preferences Index. A total of 36 participants with hikikomori were identified, with cases detected in all four countries. These individuals had high levels of loneliness (UCLA Loneliness Scale M = 55.4, SD = 10.5), limited social networks (LSNS-6 M = 9.7, SD = 5.5) and mo...
Research Interests: Psychology, Demography, Psychotherapy, Treatment Outcome, Japan, and 19 moreAdolescent, Multivariate Analysis, India, Humans, United States, Female, Male, Regression Analysis, Young Adult, Social Isolation, Social Psychiatry, Mental Disorders, Clinical Sciences, Republic of Korea, Middle Aged, Questionnaires, Adult, Drug Therapy, and Self report
Obsessive compulsive disorder (OCD) has a complex etiology that encompasses both genetic and environmental factors. However, to date, despite the identification of several promising candidate genes and linkage regions, the genetic causes... more
Obsessive compulsive disorder (OCD) has a complex etiology that encompasses both genetic and environmental factors. However, to date, despite the identification of several promising candidate genes and linkage regions, the genetic causes of OCD are largely unknown. The objective of this study was to conduct linkage studies of childhood-onset OCD, which is thought to have the strongest genetic etiology, in
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The aim of this study was to refine the population prevalence estimate of Tourette Syndrome (TS) in children and to investigate potential sources of heterogeneity in previously published studies. A systematic review was conducted and all... more
The aim of this study was to refine the population prevalence estimate of Tourette Syndrome (TS) in children and to investigate potential sources of heterogeneity in previously published studies. A systematic review was conducted and all qualifying published studies of TS prevalence were examined. Extracted data were subjected to a random-effects meta-analysis weighted by sample size; meta-regressions were performed to examine covariates that have previously been proposed as potential sources of heterogeneity. Twenty-six articles met study inclusion criteria. Studies derived from clinically referred cases had prevalence estimates that were significantly lower than those derived from population-based samples (P = 0.004). Among the 21 population-based prevalence studies, the pooled TS population prevalence estimate was 0.52% (95% confidence interval CI: 0.32-0.85). In univariable meta-regression analysis, study sample size (P = 0.002) and study date (P = 0.03) were significant predictors of TS prevalence. In the final multivariable model including sample size, study date, age, and diagnostic criteria, only sample size (P < 0.001) and diagnostic criteria (omnibus P = 0.003; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR]: P = 0.005) were independently associated with variation in TS population prevalence across studies. This study refines the population prevalence estimate of TS in children to be 0.3% to 0.9%. Study sample size, which is likely a proxy for case assessment method, and the use of DSM-IV-TR diagnostic criteria are the major sources of heterogeneity across studies. The true TS population prevalence rate is likely at the higher end of these estimates, given the methodological limitations of most studies. Further studies in large, well-characterized samples will be helpful to determine the burden of disease in the general population. © 2014 International Parkinson and Movement Disorder Society.
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Background and ObjectivesTourette syndrome (TS) is a neuropsychiatric disorder in which the pattern of symptom presentation can vary greatly between individuals. Although globally described, TS has not been well characterized in many... more
Background and ObjectivesTourette syndrome (TS) is a neuropsychiatric disorder in which the pattern of symptom presentation can vary greatly between individuals. Although globally described, TS has not been well characterized in many parts of the world. Differences in individual and cultural perceptions of TS may impact its expression and recognition in some countries, confounding the identification of affected individuals. This
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The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We... more
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for ...
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Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare... more
Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis…
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BackgroundWhile genetic epidemiological studies demonstrate a substantial degree of genetic predisposition for attention-deficit/hyperactivity disorder (ADHD), they also suggest that the genetics are complex and may differ between... more
BackgroundWhile genetic epidemiological studies demonstrate a substantial degree of genetic predisposition for attention-deficit/hyperactivity disorder (ADHD), they also suggest that the genetics are complex and may differ between populations or ethnic groups.
Research Interests: Genetics, Attention-Deficit/Hyperactivity Disorder, Costa Rica, Adolescent, Comorbidity, and 15 moreHumans, Child, Female, Male, Siblings, Mental Disorders, Clinical Sciences, Prevalence, Comprehensive, Adult, Ethnic Group, Genetic Predisposition, Epidemiologic Studies, Age of Onset, and Severity of Illness Index
The authors examined whether assigning patients from three ethnic groups-blacks, Latinos, and Asians-to three psychiatric inpatient units that provided culturally appropriate treatment to those groups would affect rates of diagnosis of... more
The authors examined whether assigning patients from three ethnic groups-blacks, Latinos, and Asians-to three psychiatric inpatient units that provided culturally appropriate treatment to those groups would affect rates of diagnosis of various psychiatric disorders. Retrospective administrative data for 5,983 inpatients at a large urban community hospital with several ethnically focused units were examined. The data represented 10,645 admissions between 1989 and 1996. Chi square analyses and Stuart-Maxwell tests of symmetry and homogeneity were used to assess the relationship between matching patients to ethnically focused units and the rates of major psychiatric illnesses among Asian, black, and Latino patients compared with whites. Ethnic differences in diagnostic rates were consistent with the results of previous studies. Black patients had more diagnoses of psychotic disorders and fewer diagnoses of affective disorders than other ethnic minorities or whites, and Latino patients had more nonspecific diagnoses. Matching inpatients to ethnically focused units did not have a marked effect on patterns of diagnoses among black patients, but an association was observed for Latino patients, particularly those who had only one admission. No significant diagnostic differences were found between Asian patients and whites, irrespective of whether the Asian patients had been ethnically matched to a specialty focus unit. The effect of referring inpatients with serious mental illnesses to an ethnically focused psychiatric unit varied by ethnic group, probably because each specialty unit functioned differently, depending on the needs of its particular patient population.
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The authors examined whether assigning patients from three ethnic groups-blacks, Latinos, and Asians-to three ethnically focused psychiatric inpatient units would affect treatment outcome. Retrospective administrative data for 5,983... more
The authors examined whether assigning patients from three ethnic groups-blacks, Latinos, and Asians-to three ethnically focused psychiatric inpatient units would affect treatment outcome. Retrospective administrative data for 5,983 inpatients at a large urban community hospital with several ethnically focused units were examined. The data represented 10,645 admissions between 1989 and 1996. Cox proportional-hazards models, logistic and multinomial regressions, and chi square analyses were used to assess the relationship between matching patients to ethnically focused units and time to rehospitalization, referral destination on discharge, and length of stay for Asian, black, and Latino patients. Ethnic matching status was strongly associated with referral destination for Asian and Latino patients but not for black patients. Asian and Latino patients who had been treated on the appropriate ethnically focused units were more frequently sent to outpatient or residential treatment (71 to 73 percent of discharges) than unmatched patients, black patients, and white patients (44 to 49 percent of discharges), who more frequently refused follow-up or were sent to locked facilities. No association was found between matching status and time to rehospitalization or length of stay for any ethnic group. Matching inpatients to ethnically focused psychiatric units was related to referral destination at discharge. Matched patients were more likely than unmatched patients to accept referral to postdischarge treatment, which has been shown previously to reduce readmission rates. Among persons with serious mental illness, matching patients to ethnically focused units may be important for enhancing communication and trust as a means of improving participation in ongoing treatment programs.
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The importance of genetics in understanding the etiology of mental illness has become increasingly clear in recent years, as more evidence has mounted that almost all neuropsychiatric disorders have a genetic component. It has also become... more
The importance of genetics in understanding the etiology of mental illness has become increasingly clear in recent years, as more evidence has mounted that almost all neuropsychiatric disorders have a genetic component. It has also become clear, however, that these disorders are etiologically complex, and multiple genetic and environmental factors contribute to their makeup. So far, traditional linkage mapping studies have not definitively identified specific disease genes for neuropsychiatric disorders, although some potential candidates have been identified via these methods (e.g. the dysbindin gene in schizophrenia; Straub et al., 2002; Schwab et al., 2003). For this reason, alternative approaches are being attempted, including studies in genetically isolated populations. Because isolated populations have a high degree of genetic homogeneity, their use may simplify the process of identifying disease genes in disorders where multiple genes may play a role. Several areas of Latin America contain genetically isolated populations that are well suited for the study of neuropsychiatric disorders. Genetic studies of several major psychiatric illnesses, including bipolar disorder, major depression, schizophrenia, Tourette Syndrome, alcohol dependence, attention deficit hyperactivity disorder, and obsessive-compulsive disorder, are currently underway in these regions. In this paper we highlight the studies currently being conducted by our groups in the Central Valley of Costa Rica to illustrate the potential advantages of this population for genetic studies.
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We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica... more
We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders.
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Research Interests: Cognitive Science, Neurology, Psychiatry, Bipolar Disorder, Costa Rica, and 20 moreFinland, Biological Sciences, Humans, Haplotypes, Female, Male, Apolipoprotein E, Pedigree, Clinical Sciences, Aged, Human Genome, Linkage Disequilibrium, Neurobiology of Aging, Alzheimer Disease, Genetic Markers, Neurosciences, Logistic Models, Age of Onset, Founder Effect, and The American
Research Interests: Genetics, Attention-Deficit/Hyperactivity Disorder, Obsessive-Compulsive Disorder, Serotonin, Glutamate, and 10 moreTICS, Humans, Obsessive Compulsive Disorder, Pervasive Developmental Disorder, Tourette Syndrome, Psychosomatic, Anxiety Disorder, Neurodevelopmental Disorder Autism, Mood Disorder, and Data Reduction Techniques
Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of... more
Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS.
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Research Interests: Genetics, Psychiatry, Mental Health, Bipolar Disorder, Costa Rica, and 19 moreComorbidity, Humans, Affective Disorders, Substance Abuse, Female, Male, Population based study, Substance Dependence, Pedigree, Risk factors, Prevalence, Middle Aged, Alcohol dependence, Affective, Sex Factors, Risk Factors, Substance-Related Disorders, Age of Onset, and Substance Use Disorder
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Research Interests: Housing, Adolescent, Humans, Child, Female, and 14 moreMale, Risk factors, Tourette Syndrome, Great Britain, Longitudinal Studies, Odds ratio, Educational Status, Risk Factors, Cross Sectional Studies, Cohort Studies, Socioeconomic Factors, Psychosocial deprivation, Statistics as Topic, and Neurologic Examination
Research Interests: Psychology, Depression, Attention, Performance, Adolescent, and 20 moreAnxiety, California, Factor analysis, Medical Students, Humans, Personality Assessment Inventory, Female, Male, Obsessive Compulsive Disorder, Clinical Sciences, Anxiety and Depression, Self Concept, Questionnaires, Adult, Sex Factors, Age Factors, Educational Status, ANXIETY, Clinical Competence, and Cross Sectional Studies
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Research Interests: Psychology, Psychometrics, Depression, Personality Assessment, Culture, and 17 moreCosta Rica, Adolescent, Cross-Cultural Comparison, Humans, Child, United States, Female, Male, Obsessive Compulsive Disorder, Phenotype, Clinical Sciences, Anxiety and Depression, Aged, Middle Aged, Adult, European Continental Ancestry Group, and Cross Sectional Studies
Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. To examine the association between... more
Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort. Relationships between exposures and Tourette syndrome/chronic tic disorder were examined in 6090 children using logistic regression. Maternal alcohol and cannabis use, inadequate maternal weight gain and parity were associated with Tourette syndrome or Tourette syndrome/chronic tic disorder. Other previously reported exposures, including birth weight and prenatal maternal smoking, were not associated with Tourette syndrome/chronic tic disorder. This study supports previously reported relationships between Tourette syndrome/chronic tic disorder and prenatal alcohol exposure, and identifies additional previously unexplored potential prenatal risk factors.
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Tourette Syndrome (TS) has a complex etiology and wide variability in phenotypic expression. Identifying underlying symptom patterns may be useful for etiological and outcome studies of TS. Lifetime tic and related symptom data were... more
Tourette Syndrome (TS) has a complex etiology and wide variability in phenotypic expression. Identifying underlying symptom patterns may be useful for etiological and outcome studies of TS. Lifetime tic and related symptom data were collected between 1996 and 2001 in 121 TS subjects from the Central Valley of Costa Rica and 133 TS subjects from the Ashkenazi Jewish (AS) population in the US. Subjects were grouped by tic symptoms using an agglomerative hierarchical cluster analysis. Cluster membership was tested for association with available ancillary information (age of onset, tic severity, comorbid disorders, medication treatment and family history). Cluster analysis identified two distinct groups in each sample, those with predominantly simple tics (cluster 1), and those with multiple complex tics (cluster 2). Membership in cluster 2 was correlated with increased tic severity, global impairment, medication treatment, and presence of comorbid obsessive-compulsive symptoms in both samples, and with family history of tics, lower verbal IQ, earlier age of onset, and comorbid obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in the AS sample. This study provides evidence for consistent and reproducible symptom profiles in two independent TS study samples. These findings have implications for etiological studies of TS.
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Research Interests: Genetics, Psychology, Algorithms, Psychometrics, Principal Component Analysis, and 14 moreFamily, Behavior Genetics, Obsessive-Compulsive Disorder, Factor analysis, Humans, Female, Male, Obsessive Compulsive Disorder, Phenotype, Genotype, Five Factor Model, Psychological Models, Neurosciences, and Cohort Studies
Substantial evidence suggests that both environmental and genetic factors contribute to the development and clinical expression of... more
Substantial evidence suggests that both environmental and genetic factors contribute to the development and clinical expression of Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. Although genetic studies of Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome are common, studies of environmental factors are relatively few and have not identified consistent risk factors across studies. This study examines in a large cohort of subjects (N=180) the relationship between prenatal/perinatal adverse events with Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome severity as determined by tic severity and rates of commonly comorbid disorders such as obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and self-injurious behavior. Tic severity, OCD, ADHD, self-injurious behavior, and exposure to a variety of prenatal/perinatal events were systematically assessed in all subjects enrolled in three genetic studies of Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. Using linear and logistic regression, a best-fit model was determined for each outcome of interest. Prenatal maternal smoking was strongly correlated with increased tic severity and with the presence of comorbid OCD in these Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome subjects. Other variables, such as paternal age and subject&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s birth weight, were significantly but less strongly associated with increased symptom severity. The authors found no association between symptom severity and hypoxia, forceps delivery, or hyperemesis during pregnancy, which have been previously identified as risk factors. This study identifies prenatal maternal smoking as a strong risk factor for increased symptom severity in Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome.
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To date, only one complete genome screen for obsessive-compulsive disorder (OCD) has been published. That study identified a region of suggestive linkage (maximum lod score of 2.25) with a relatively small sample size (N = 56; 27 with... more
To date, only one complete genome screen for obsessive-compulsive disorder (OCD) has been published. That study identified a region of suggestive linkage (maximum lod score of 2.25) with a relatively small sample size (N = 56; 27 with OCD). Additional complete genome screens are needed to confirm this finding and identify other regions of linkage. We present the clinical characteristics and power to detect linkage of 11 multigenerational families with OCD and hoarding (N = 92; 44 with OCD), as well as heritability estimates for several quantitative traits. Families with at least two individuals with OCD were identified through probands with childhood-onset OCD. Expected lod scores were calculated for simulated genetic marker data under an additive and two dominant models assuming a dense SNP marker map. All affected individuals had an early age of onset (18 or younger). Hoarding was present in 46% of subjects. Obsessive-compulsive symptoms and hoarding were highly heritable. The maximum mean expected lod score was 3.31 for OCD and 1.39 for hoarding. We found reasonable power to detect regions of interest (lod = 2) for OCD in these families, but will need to expand our family collection to have adequate power to detect regions of interest for hoarding.