Biomedical subjects

Gerald Nestadt

Publications and source records attributed to Gerald Nestadt.

At least 19 recordsLinked to original sources

PubMed2007

Factor analysis of the Yale-Brown Obsessive Compulsive Scale in a family study of obsessive-compulsive disorder.

Our objective in this study was to determine whether symptoms of obsessive-compulsive disorder (OCD) cluster into groups that can usefully subclassify OCD. Psychiatrists or psychologists interviewed 221 subjects using the Lifetime Anxiety Version of the Schedule for Affective Disorders and Schizophrenia (SADS-LA) for the diagnosis of DSM-IV disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for OCD symptoms. We analyzed 16 symptom categories from the Y-BOCS using exploratory factor analysis to identify latent symptom dimensions. The relationship between these symptom dimensions and clinical characteristics and familiality was investigated. A four-factor model emerged as the best classification of OCD symptoms in the Y-BOCS. These factors were labeled Pure Obsessions, Contamination, Symmetry/Order, and Hoarding. The contamination factor was least likely to be associated with other Axis I disorders. Whereas no significant relationship was found between the factor scores of probands and the presence of OCD in their first-degree relatives, the Symmetry/Order and Hoarding factors did breed true. Hoarding was found to predict poorer treatment response. A four-factor classification of OCD features best describes the symptom patterns of a sample of patients with OCD. There were specific clinical correlates for these factors, and significant intrafamilial sib-sib correlations were found for the Symmetry/Order and Hoarding factors.

Adult↗

PubMed2007

Utility of the Leyton Obsessional Inventory to distinguish OCD and OCPD.

The Leyton Obsessional Inventory (LOI) is a self-report questionnaire that assesses obsessional symptoms. The ability of the LOI to distinguish between obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD) has not been adequately addressed. Our purpose is to identify dimensions of obsessional symptoms from the LOI and determine how well they distinguish between OCD and OCPD. The LOI was completed by 488 participants diagnosed by trained clinicians. Factor analysis was performed on responses to the interference items of the LOI. The relationship between the factors, OCD and OCPD was evaluated using logistic regression. Five factors underlying the LOI were identified: (I) obsessional ruminations and compulsions, (II) ordering and arranging, (III) organizing activities, (IV) contamination, and (V) parsimony. Factors I, III, and IV were strongly associated with OCD. Only Factor II was associated with OCPD. Factor IV was negatively associated with obsessive-compulsive personality traits. LOI factors are useful in discriminating between OCD and OCPD. Obsessional ruminations and compulsions, organizing activities, and contamination fears may indicate OCD, and ordering and arranging symptoms may indicate OCPD rather than OCD. Parsimony may indicate neither disorder, and contamination, the absence of OCPD traits compared with the other LOI factors. These findings may contribute to effective diagnosis and treatment by allowing the LOI to screen for OCD and OCPD in a population exhibiting obsessional symptoms and traits.

Adolescent↗

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

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

Relationship between cortisol responses to stress and personality.

Although there is growing evidence of links between the cortisol stress response and personality, the nature of the relationships and the underlying mechanisms require further clarification. The purpose of this study was to examine associations between personality traits and cortisol responses to stress using the Revised NEO Personality Inventory five-factor model of personality. In total, 68 healthy adults, aged 18-30 years, completed the personality assessment and underwent a laboratory psychological stress test that consisted of a 5 min speech and 5-min of mental arithmetic. Findings showed that in the sample as a whole, less Openness was associated with lower cortisol responses to the challenge. Cortisol responses also corresponded to certain personality dimensions in a gender-specific manner. Blunted cortisol responses were associated with higher Neuroticism in women and with lower Extraversion in men. These findings suggest that personality traits that have been traditionally associated with greater psychopathology were also associated with blunted HPA axis responses to stress.

Adolescent↗

PubMed2006

Agoraphobia in adults: incidence and longitudinal relationship with panic.

BACKGROUND: Theories regarding how spontaneous panic and agoraphobia relate are based mostly on cross-sectional and/or clinic data. AIMS: To determine how spontaneous panic and agoraphobia relate longitudinally, and to estimate the incidence rate of and other possible risk factors for first-onset agoraphobia, using a general population cohort. METHOD: A sample of 1920 adults in east Baltimore were assessed in 1981-1982 and the mid-1990s with the Diagnostic Interview Schedule (DIS). Psychiatrist diagnoses were made in a subset of the sample at follow-up (n = 816). RESULTS: Forty-one new cases of DIS/DSM-III-R agoraphobia were identified (about 2 per 1000 person-years at risk). As expected, baseline DIS/DSM-III panic disorder predicted first incidence of agoraphobia (OR = 12, 95% CI 3.2-45), as did younger age, female gender and other age, female gender and other phobias. Importantly, baseline agoraphobia without spontaneous panic attacks also predicted first incidence of panic disorder (OR=3.9, 95% CI1.8-8.4). Longitudinal relationships between panic disorder and psychiatrist-confirmed agoraphobia were strong (panic before agoraphobia OR=20, 95% CI 2.3-180; agoraphobia before panic OR=16, 95% CI 3.2-78). CONCLUSIONS: The implied one-way causal relationship between spontaneous panic attacks and agoraphobia in DSM-IV appears incorrect.

Adolescent↗

PubMed2006

Serotonin-norepinephrine reuptake inhibitors in the treatment of obsessive-compulsive disorder: A critical review.

OBJECTIVE: To critically review the antiobsessional properties of serotonin-norepinephrine reuptake inhibitors (SNRIs) (venlafaxine and clomipramine) in the treatment of obsessive-compulsive disorder (OCD) as an alternative to selective serotonin reuptake inhibitors (SSRIs), which are currently considered the first-line treatment of OCD. DATA SOURCES: A MEDLINE search was performed to identify clinical trials with the SNRIs venlafaxine and clomipramine published from 1996 to 2004 (keywords: SNRIs, venlafaxine, duloxetine, and clomipramine, each matched individually with the term OCD), focusing on the best-designed studies for inclusion. DATA SYNTHESIS: Much of the literature about SNRIs in OCD supports the efficacy of these compounds in the treatment of OCD. However, double-blind, placebo-controlled studies with venlafaxine are lacking, and the most relevant studies consist of active comparison trials between SNRIs and SSRIs. In these studies, SNRIs seem to be as effective as SSRIs in OCD; SNRIs might be preferred for patients with certain types of treatment-resistant OCD or those with particular comorbid conditions. A large number of placebo-controlled and active comparison trials with clomipramine document efficacy in OCD, and meta-analytic studies suggest a small superiority over SSRIs. Compared with clomipramine, the SNRI venlafaxine showed fewer side effects and better tolerability. CONCLUSION: The SNRIs may represent a valid alternative to the SSRIs, particularly in specific cases. Double-blind, placebo-controlled studies are, however, needed to confirm the positive findings reported by several studies with venlafaxine.

Adrenergic Uptake Inhibitors↗

PubMed2005

Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios.

Bipolar, schizophrenia, and schizoaffective disorders are common, highly heritable psychiatric disorders, for which familial coaggregation, as well as epidemiological and genetic evidence, suggests overlapping etiologies. No definitive susceptibility genes have yet been identified for any of these disorders. Genetic heterogeneity, combined with phenotypic imprecision and poor marker coverage, has contributed to the difficulty in defining risk variants. We focused on families of Ashkenazi Jewish descent, to reduce genetic heterogeneity, and, as a precursor to genomewide association studies, we undertook a single-nucleotide polymorphism (SNP) genotyping screen of 64 candidate genes (440 SNPs) chosen on the basis of previous linkage or of association and/or biological relevance. We genotyped an average of 6.9 SNPs per gene, with an average density of 1 SNP per 11.9 kb in 323 bipolar I disorder and 274 schizophrenia or schizoaffective Ashkenazi case-parent trios. Using single-SNP and haplotype-based transmission/disequilibrium tests, we ranked genes on the basis of strength of association (P<.01). Six genes (DAO, GRM3, GRM4, GRIN2B, IL2RB, and TUBA8) met this criterion for bipolar I disorder; only DAO has been previously associated with bipolar disorder. Six genes (RGS4, SCA1, GRM4, DPYSL2, NOS1, and GRID1) met this criterion for schizophrenia or schizoaffective disorder; five replicate previous associations, and one, GRID1, shows a novel association with schizophrenia. In addition, six genes (DPYSL2, DTNBP1, G30/G72, GRID1, GRM4, and NOS1) showed overlapping suggestive evidence of association in both disorders. These results may help to prioritize candidate genes for future study from among the many suspected/proposed for schizophrenia and bipolar disorders. They provide further support for shared genetic susceptibility between these two disorders that involve glutamate-signaling pathways.

Adolescent↗

PubMed2005

The longitudinal relationship between personality disorder dimensions and global functioning in a community-residing population.

BACKGROUND: Little is known about the long-term outcome of personality disorder traits. The purpose of this study was to investigate, in a community-residing population, the longitudinal relationship between psychiatrist-assessed personality disorder scores and global functioning 13-18 years later. METHOD: A stratified random sample of residents of east Baltimore were examined by psychiatrists in 1981 and asssessed for DSM-III personality disorders using a semi-structured instrument, the Standardized Psychiatric Examination. A total of 292 persons were re-examined by different psychiatrists during 1994-1999 using the Schedules for the Assessment of Neuropsychiatry (SCAN). After completion of the SCAN, the subjects' functional status was evaluated using the Global Assessment of Functioning (GAF). The relationships between personality dimensions and follow-up GAF scores were evaluated using linear regression models. RESULTS: All of the personality disorder scales measured in 1981 were inversely related to functioning 13-18 years later, with the exception of narcissistic and compulsive scales. After controlling for Axis I disorders diagnosed contemporaneously with GAF assessment, schizoid, antisocial, borderline, histrionic, and avoidant personality disorder scores significantly predicted GAF scores. CONCLUSIONS: Most dimensions of DSM-III personality disorder traits were significantly associated with global functioning after an interval of 15 years. However, only schizoid, antisocial, borderline, histrionic, and avoidant personality disorder traits had long-term effects on functioning when Axis I disorders at follow-up were controlled. This suggests that the functional effect of the other personality disorder traits may be mediated through their relationship with Axis I disorders. Future research is needed using more specific and sensitive outcome measures.

Adolescent↗

PubMed2004

Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by intrusive and senseless thoughts and impulses (obsessions) and by repetitive behaviors (compulsions). Family, twin, and segregation studies support the presence of both genetic and environmental susceptibility factors, and the only published genome scan for OCD identified a candidate region on 9p24 at marker D9S288 that met criteria for suggestive significance (Hanna et al. 2002). In an attempt to replicate this finding, we genotyped 50 pedigrees with OCD, using microsatellite markers spanning the 9p24 candidate region, and analyzed the data, using parametric and nonparametric linkage analyses under both a narrow phenotype model (DSM-IV OCD definite; 41 affected sib pairs) and a broad phenotype model (DSM-IV OCD definite and probable; 50 affected sib pairs). Similar to what was described by Hanna et al. (2002), our strongest findings came with the dominant parameters and the narrow phenotype model: the parametric signal peaked at marker D9S1792 with an HLOD of 2.26 ( alpha =0.59), and the nonparametric linkage signal (NPL) peaked at marker D9S1813 with an NPL of 2.52 (P=.006). These findings are striking in that D9S1813 and D9S1792 lie within 0.5 cM (<350 kb) of the original 9p24 linkage signal at D9S288; furthermore, pedigree-based association analyses also implicated the 9p24 candidate region by identifying two markers (D9S288 and GATA62F03) with modest evidence (P=.046 and .02, respectively) for association.

Chromosome Mapping↗

PubMed2004

Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families.

The relatively short history of linkage studies in bipolar disorders (BPs) has produced inconsistent findings. Implicated regions have been large, with reduced levels of significance and modest effect sizes. Both phenotypic and genetic heterogeneity may have contributed to the failure to define risk loci. BP is part of a spectrum of apparently familial affective disorders, which have been organized by severity. Heterogeneity may arise because of insufficient data to define the spectrum boundaries, and, in general, the less-severe disorders are more difficult to diagnose reliably. To address the inherent complexities in detecting BP susceptibility loci, we have used restricted diagnostic classifications and a genetically more homogeneous (Ashkenazi Jewish) family collection to perform a 9-cM autosomal genomewide linkage scan. Although they are genetically more homogeneous, there are no data to suggest that the rate of illness in the Ashkenazim differs from that in other populations. In a genome scan of 41 Ashkenazi pedigrees with a proband affected with bipolar I disorder (BPI) and at least one other member affected with BPI or bipolar II disorder (BPII), we identified four regions suggestive of linkage on chromosomes 1, 3, 11, and 18. Follow-up genotyping showed that the regions on chromosomes 1, 3, and 18 are also suggestive of linkage in a subset of pedigrees limited to relative pairs affected with BPI. Furthermore, our chromosome 18q22 signal (D18S541 and D18S477) overlaps with previous BP findings. This research is being conducted in parallel with our companion study of schizophrenia, in which, by use of an identical approach, we recently reported significant evidence for a schizophrenia susceptibility locus in the Ashkenazim on chromosome 10q22.

Bipolar Disorder↗

PubMed2004

An indirect test of the new mutation hypothesis associating advanced paternal age with the etiology of schizophrenia.

Two studies by Malaspina et al. [2001: Arch Gen Psychiatr 58:361-367]; [2002: Am J Med Genet 114:299-303] have put forward the hypothesis that advanced paternal age with concomitant mutations in the male germ line is associated with sporadic schizophrenia in offspring. The hypothesis was supported by an observation of a monotonic increase in the risk for schizophrenia with increased paternal age, and a second observation in a separate sample of greater paternal mean age at birth among cases of apparent sporadic schizophrenia. The present study did not test the association of the risk of schizophrenia with advanced paternal age, but repeated the test of paternal age at birth among sporadic versus familial schizophrenic probands. We also examined the risk of schizophrenia, psychosis, and broad psychosis among paternal 1st and 2nd degree relatives of schizophrenic probands as a function of paternal age at birth of the proband, reasoning that if probands born to older fathers are more likely to be sporadic cases, the risk of schizophrenia (or psychosis) should be lower on the paternal side of the family. Results indicate a lack of support for the previous finding that sporadic probands tend to have older fathers at birth than familial probands. Results also failed to support the related hypothesis that increased paternal age is associated with the lower risk of schizophrenia (or psychosis) in the relatives of schizophrenic probands. The failure to support the paternal age hypothesis may be a function of heterogeneous samples, but calls for further research in the context of family studies.

Family Health↗

PubMed2004

Clinical correlates of recurrent major depression in obsessive-compulsive disorder.

Major depressive disorder is the most frequent comorbid condition in obsessive-compulsive disorder (OCD). This study investigated factors associated with the development of recurrent major depressive disorder (RDD) in patients with OCD. Eighty OCD cases and 73 control probands were examined by psychiatrists or clinical psychologists using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials and made final consensus diagnoses using DSM-IV criteria. Family history of OCD and RDD, additional comorbid disorders, OCD symptoms and illness severity were compared between persons with OCD alone (n = 21) and OCD with RDD (n = 41). Compared to OCD probands without RDD, OCD probands with RDD had earlier age at first diagnosis, more severe obsessive-compulsive symptoms, and were more likely to have a family history of RDD. Social phobia, separation anxiety disorder, and body dysmorphic disorder occurred more frequently in the comorbid group. In a multiple logistic regression model, only early age of OCD diagnosis was significantly associated with RDD. Early age at onset of OCD increases the risk of depressive disorder in individuals with OCD.

Adult↗

PubMed2004

Anxiety and depressive disorders and the five-factor model of personality: a higher- and lower-order personality trait investigation in a community sample.

We describe in detail normal personality traits in persons with psychiatrist-ascertained anxiety and depressive disorders in a general population sample. We investigated Revised NEO Personality Inventory traits in 731 community subjects examined by psychiatrists with the Schedules for Clinical Assessment in Neuropsychiatry. All of the lifetime disorders of interest (simple phobia, social phobia, agoraphobia, panic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder, major depressive disorder (MDD), and dysthymia) were associated with high neuroticism. Social phobia, agoraphobia, and dysthymia were associated with low extraversion, and OCD was associated with high openness to experience. In addition, lower-order facets of extraversion (E), openness (O), agreeableness (A), and conscientiousness (C) were associated with certain disorders (specifically, low assertiveness (E) and high openness to feelings (O) with MDD, low trust (A) with social phobia and agoraphobia, low self-discipline (C) with several of the disorders, and low competence and achievement striving (C) with social phobia). Neuroticism in particular was related to acuity of disorder. Longitudinal study is necessary to differentiate state versus pathoplastic effects.

Adult↗

PubMed2004

Five latent factors underlying schizophrenia: analysis and relationship to illnesses in relatives.

Clinical signs and symptoms in a sample of 1,043 individuals with schizophrenia or schizoaffective disorder were subjected to latent class factor analysis. Positive, negative, disorganized, and affective factors were similar in content to factors described in a number of other studies, while a fifth factor representing early onset/developmental signs provided a new area for investigation. The five sets of factor scores were logistically regressed on psychiatric illness indicators in first and second degree relatives. Relatives of probands with higher positive or negative symptom factor scores had a lower risk of depressive illness. Higher affective factor scores in probands predicted more mania and depression in relatives. Both the disorganized and the early onset/developmental factors were related to increased risk of psychiatric hospitalization in relatives, as well as increased risk of psychosis (marginally so for the disorganization factor). Increased early onset/developmental signs in the proband were also associated with increased risk for depression in relatives. These findings suggest a possible endophenotypic role for the factor scores in future studies.

Adult↗

PubMed2004

Lifetime and 1-month prevalence rates of intermittent explosive disorder in a community sample.

OBJECTIVE: To determine the lifetime and 1-month prevalence of intermittent explosive disorder (IED) by both DSM-IV and research criteria in a community sample. METHOD: The final 253 (34.1%) of individuals who were entered into the Hopkins Epidemiology Study of Personality Disorder and sampled in the context of a follow-up study of participants from the Baltimore Epidemiologic Catchment Area (ECA) study completed a supplemental interview that allowed for the determination of IED by DSM-IV and/or research criteria. RESULTS: The mean +/- SE percentage of subjects who met inclusion criteria was 11.07% +/- 1.97%, and 6.32% +/- 1.53% met full criteria, for lifetime IED by either diagnostic criteria set; 2.37% +/- 0.96% met full criteria for IED within the previous 1 month. Adjusting the prevalence rates to account for differential sampling from the original ECA study did not substantially affect these results. Onset of problematic aggressive behavior in IED subjects (described as lifelong in most subjects) began as early as childhood, peaked in the third decade, and declined steadily after the fifth decade. While distress and/or impairment due to aggressive behavior was documented in 87.5% of IED subjects, only 12.5% of IED subjects reported seeking help for this problem. CONCLUSIONS: Intermittent problematic aggressive behavior in the community, as defined by IED, may be far more common than previously thought. Conservatively estimated, the number of individuals in the United States with IED, based on these data, may be no lower than 1.4 million for current IED or nearly 10 million for lifetime IED.

Age Factors↗

PubMed2003

Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22.

Previous linkage studies in schizophrenia have been discouraging due to inconsistent findings and weak signals. Genetic heterogeneity has been cited as one of the primary culprits for such inconsistencies. We have performed a 10-cM autosomal genomewide linkage scan for schizophrenia susceptibility regions, using 29 multiplex families of Ashkenazi Jewish descent. Although there is no evidence that the rate of schizophrenia among the Ashkenazim differs from that in other populations, we have focused on this population in hopes of reducing genetic heterogeneity among families and increasing the detectable effects of any particular locus. We pursued both allele-sharing and parametric linkage analyses as implemented in Genehunter, version 2.0. Our strongest signal was achieved at chromosome 10q22.3 (D10S1686), with a nonparametric linkage score (NPL) of 3.35 (genomewide empirical P=.035) and a dominant heterogeneity LOD score (HLOD) of 3.14. Six other regions gave NPL scores >2.00 (on chromosomes 1p32.2, 4q34.3, 6p21.31, 7p15.2, 15q11.2, and 21q21.2). Upon follow-up with an additional 23 markers in the chromosome 10q region, our peak NPL score increased to 4.27 (D10S1774; empirical P=.00002), with a 95% confidence interval of 12.2 Mb for the location of the trait locus (D10S1677 to D10S1753). We find these results encouraging for the study of schizophrenia among Ashkenazi families and suggest further linkage and association studies in this chromosome 10q region.

Adolescent↗