• Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness

      Faraone, Stephen V.; Biederman, Joseph; Mennin, Douglas; Russell, Ronald (Wiley, 1998-02-07)
      Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:108–116, 1998. © 1998 Wiley-Liss, Inc.
    • Effectiveness and Tolerability of Tomoxetine in Adults With Attention Deficit Hyperactivity Disorder

      Spencer, Thomas; Biederman, Joseph; Wilens, Timothy; Prince, Jeffry; Hatch, Mary; Jones, Janice; Harding, Margaret; Faraone, Stephen V.; Seidman, Larry (American Psychiatric Association Publishing, 1998-05)
      Objective: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). Method: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. Results: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. Conclusions: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment.
    • NIMH genetics initiative millennium schizophrenia consortium: Linkage analysis of African-American pedigrees

      Kaufmann, Charles A.; Suarez, Brian; Malaspina, Dolores; Pepple, John; Svrakic, Dragan; Markel, Paul D.; Meyer, Joanne; Zambuto, Christopher T.; Schmitt, Karin; Matise, Tara Cox; et al. (Wiley, 1998-07-10)
      The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article—one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample—presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01–0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:282–289, 1998. © 1998 Wiley-Liss, Inc.
    • Genome-wide search for schizophrenia susceptibility loci: The NIMH genetics initiative and millennium consortium

      Cloninger, C. Robert; Kaufmann, Charles A.; Faraone, Stephen V.; Malaspina, Dolores; Svrakic, Dragan M.; Harkavy-Friedman, Jill; Suarez, Brian K.; Matise, Tara C.; Shore, David; Lee, Hang; et al. (Wiley, 1998-07-10)
      chizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:275–281, 1998. © 1998 Wiley-Liss, Inc.
    • Further investigation of a chromosome 15 locus in schizophrenia: Analysis of affected sibpairs from the NIMH genetics initiative

      Leonard, Sherry; Gault, Judith; Moore, Theodore; Hopkins, Jan; Robinson, Misi; Olincy, Ann; Adler, Lawrence E.; Cloninger, C. Robert; Kaufmann, Charles A.; Tsuang, Ming T.; et al. (Wiley, 1998-07-10)
      Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the α7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:308–312, 1998. © 1998 Wiley-Liss, Inc.
    • The concept of target features in schizophrenia research

      Tsuang, M. T.; Faraone, S. V. (Wiley, 1999-05)
      Target features are clinical or neurobiological characteristics that arc expressions of the underlying predisposition to an illness. They comprise a wide range of phenomena, from thc classic signs and symptoms of psychopathology to sophisticated measures of brain structure and function. For schizophrenia, many target features have been identified. These include eye tracking dysfunction, attentional impairment, allusive thinking, neurological signs, thought disorder, characteristic auditory evoked potentials, neuropsychological impairment, structural brain abnormalities and functional brain abnormalities. In their most pathological forms, thcse features are present among many schizophrenic patients, yet it is their presence among their non-psychotic relatives that shows them to be target features. We discuss the theoretical background for target features, present examples and describe how the discovery of target features has implications I for schizophrenia research.
    • Pediatric mania: a developmental subtype of bipolar disorder?

      Biederman, Joseph; Mick, Eric; Faraone, Stephen V; Spencer, Thomas; Wilens, Timothy E; Wozniak, Janet (Elsevier BV, 2000-09)
      Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards. Biol Psychiatry 2000;48: 458–466 © 2000 Society of Biological Psychiatry.
    • Pediatric mania: a developmental subtype of bipolar disorder?

      Biederman, Joseph; Mick, Eric; Faraone, Stephen V; Spencer, Thomas; Wilens, Timothy E; Wozniak, Janet (Elsevier BV, 2000-09)
    • Report from the second international meeting of the attention deficit hyperactivity disorder Molecular Genetics Network

      Faraone, Stephen V. (Wiley, 2001)
      Given evidence from twin, family, and adoption studies of genetic influence on attention deficit hyperactivity disorder (ADHD), a growing number of researchers have initiated molecular genetics studies to explore the influence of specific genes on this condition. In 1999, these investigators convened to discuss ways of sharing information and facilitating collaborations across research sites. Enthusiastic response to this first conference prompted an even larger group of investigators to come together this year. This recent meeting, held in London, began with a presentation of Hypescheme, an operational criteria checklist developed in an effort to promote the reliable communication of diagnostic and other relevant clinical information related to ADHD. The benefits and limitations of Hypescheme, as well as the continued challenges to collaboration, were discussed. A new ADHD-specific rating scale, developed to be of use in genetic analyses, was also presented. Focus then turned to collaborative projects proposed by investigators and practical suggestions regarding joint data analyses projects. Finally, new data from individual sites were presented. Because the mode of inheritance of ADHD is likely to be complex, efforts to collaborate and cross-validate findings remain an important priority for researchers studying the molecular genetics of this disorder. © 2001 Wiley-Liss, Inc.
    • Further Evidence of Association Between Behavioral Inhibition and Social Anxiety in Children

      Biederman, Joseph; Hirshfeld-Becker, Dina R.; Rosenbaum, Jerrold F.; Hérot, Christine; Friedman, Deborah; Snidman, Nancy; Kagan, Jerome; Faraone, Stephen V. (American Psychiatric Association Publishing, 2001-10)
      Objective: The authors sought to examine psychopathological correlates of behavioral inhibition in young offspring of parents with panic disorder and/or major depression. Method: Behavioral inhibition, determined by using standard laboratory observations, was assessed in four groups of children (age 2–6 years): 129 children of parents with both panic disorder and major depression, 22 children of parents with panic disorder alone, 49 children of parents with major depression alone, and 84 comparison children of parents with neither panic disorder nor major depression. Psychopathology in children ≥5 years was compared between children with behavioral inhibition (N=64) and without (N=152). Results: Social anxiety disorder (social phobia or avoidant disorder) was significantly more likely to be found in the children with behavioral inhibition (17%) than in those without (5%). Noninhibited children were significantly more likely than inhibited children to have disruptive behavior disorders (20% versus 6%, respectively) and had higher scores on the attention problems scale of the Child Behavior Checklist (mean=52.1 versus 50.8). Conclusions: This study adds to the growing literature suggesting an association between behavioral inhibition and social anxiety disorder and an inverse relationship between inhibition and disruptive behavior disorders.
    • Lack of Association Between Parental Alcohol or Drug Addiction and Behavioral Inhibition in Children

      Biederman, Joseph; Hirshfeld-Becker, Dina R.; Rosenbaum, Jerrold F.; Perenick, Sarah G.; Wood, Julia; Faraone, Stephen V. (American Psychiatric Association Publishing, 2001-10)
      Objective: “Behavioral inhibition to the unfamiliar” has been proposed as a precursor to anxiety. A recent study proposed that it may also be a precursor to alcoholism. The authors sought to replicate the latter finding through a secondary analysis of data from a large study of young children (age 2–6 years)—offspring of parents with panic and depressive disorders—who had been assessed for behavioral inhibition through laboratory-based observations. Method: The offspring were stratified on the basis of presence or absence of parental lifetime history of DSM-III-R alcohol dependence (N=115 versus N=166, respectively) or drug dependence (N=78 versus N=203). The rates of behavioral inhibition were then compared between groups. Results: Despite adequate power to detect associations, neither parental alcohol dependence nor drug dependence was associated with a higher risk for behavioral inhibition in the offspring. Conclusions: These results are not consistent with the hypothesis linking behavioral inhibition to addictions
    • Influence of Gender on Attention Deficit Hyperactivity Disorder in Children Referred to a Psychiatric Clinic

      Biederman, Joseph; Mick, Eric; Faraone, Stephen V.; Braaten, Ellen; Doyle, Alysa; Spencer, Thomas; Wilens, Timothy E.; Frazier, Elizabeth; Johnson, Mary Ann (American Psychiatric Association Publishing, 2002-01)
      Objective: The substantial discrepancy in the male-to-female ratio between clinic-referred (10 to 1) and community (3 to 1) samples of children with attention deficit hyperactivity disorder (ADHD) suggests that gender differences may be operant in the phenotypic expression of ADHD. In this study the authors systematically examined the impact of gender on the clinical features of ADHD in a group of children referred to a clinic. Method: The study included 140 boys and 140 girls with ADHD and 120 boys and 122 girls without ADHD as comparison subjects. All subjects were systematically assessed with structured diagnostic interviews and neuropsychological batteries for subtypes of ADHD as well as emotional, school, intellectual, interpersonal, and family functioning. Results: Girls with ADHD were more likely than boys to have the predominantly inattentive type of ADHD, less likely to have a learning disability, and less likely to manifest problems in school or in their spare time. In addition, girls with ADHD were at less risk for comorbid major depression, conduct disorder, and oppositional defiant disorder than boys with ADHD. A statistically significant gender-by-ADHD interaction was identified for comorbid substance use disorders as well. Conclusions: The lower likelihood for girls to manifest psychiatric, cognitive, and functional impairment than boys could result in gender-based referral bias unfavorable to girls with ADHD
    • Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample

      Faraone, Stephen V.; Skol, Andrew D.; Tsuang, Debby W.; Bingham, Stephen; Young, Keith A.; Prabhudesai, Sarita; Haverstock, Susan L.; Mena, Felicitas; Menon, Aerath Sri Kumar; Bisset, Darren; et al. (Wiley, 2002-07-29)
      Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semi-parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al.
    • Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample

      Faraone, Stephen V.; Skol, Andrew D.; Tsuang, Debby W.; Bingham, Stephen; Young, Keith A.; Prabhudesai, Sarita; Haverstock, Susan L.; Mena, Felicitas; Menon, Aerath Sri Kumar; Bisset, Darren; et al. (Wiley, 2002-07-29)
      Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n¼62, 37%), but a substantial proportion were African- American kindreds (n¼60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10cMover the entire chromosome and 2–5 cM for the 13q32 region were genotyped and the data analyzed using semiparametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P¼0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cMof the peak reported by Brzustowicz et al. [1999: Am J Hum Genet 65:1096–1103].
    • Evidence for the multigenic inheritance of schizophrenia

      Freedman, Robert; Leonard, Sherry; Olincy, Ann; Kaufmann, Charles A.; Malaspina, Dolores; Cloninger, C. Robert; Svrakic, Dragan; Faraone, Stephen V.; Tsuang, Ming T. (Wiley, 2002-08-21)
      Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these ®endings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z ¼ 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the a7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z ¼ 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci.
    • Differential Effect of Environmental Adversity by Gender: Rutter’s Index of Adversity in a Group of Boys and Girls With and Without ADHD

      Biederman, Joseph; Faraone, Stephen V.; Monuteaux, Michael C. (American Psychiatric Association Publishing, 2002-09)
      Objective: This study examined the effect of gender in mediating the association between environmental adversity and the risk of attention deficit hyperactivity disorder (ADHD) and associated impairments. Method: The authors studied 280 ADHD and 242 healthy comparison probands of both genders who were between the ages of 6 and 17 years. They tested the association between Rutter’s indicators of adversity (including family conflict, social class, family size, maternal psychopathology, and paternal criminality) and ADHD, comorbidity, and functioning. Results: Greater levels of environmental adversity were associated with a greater risk for ADHD and other comorbidity in both genders in a dose-dependent fashion. However, learning disability and global functioning were modified by gender, with more detrimental effects observed in boys than in girls. Low social class, maternal psychopathology, and family conflict were significantly associated with psychopathology and functional impairment in the probands, with control for gender, parental ADHD, proband ADHD status, and maternal smoking during pregnancy. Conclusions: Psychosocial adversity in general and low social class, maternal psychopathology, and family conflict in particular increased the risk for ADHD and associated morbidity independently of gender and other risk factors, but gender modified the risk for adverse cognitive and interpersonal outcomes; boys were more vulnerable to the disorder than girls. Because of the difficulties in separating the effects of genetics from environment, these results must be interpreted as provisional until confirmation from twin and adoption studies.
    • Treatment of nonpsychotic relatives of patients with schizophrenia: Six case studies

      Tsuang, Ming T.; Stone, William S.; Tarbox, Sarah I.; Faraone, Stephen V. (Wiley, 2002-11-27)
      There is growing support for the notion that the genetic liability for schizophrenia could be manifested in brain dysfunction, even without the full manifestations of schizophrenia [Meehl, 1962, 1989; Seidman, 1997; Faraone et al., 2001]. This liability is characterized clinically by neurologic, neurobiological, psychiatric, neuropsychological, and psychosocial impairments in nonpsychotic, first-degree relatives of people with schizophrenia and includes eye tracking dysfunction [Levy et al., 1994], allusive thinking [Catts et al., 1993], neurologic signs [Erlenmeyer-Kimling et al., 1982], biochemical abnormalities [Callicott et al., 1998], char acteristic auditory evoked potentials [Friedman and Squires-Wheeler, 1994], neuroimaging assessed brain abnormalities [Seidman et al., 1997], and neuropsycho logical impairment [Kremen et al., 1994]. Paul Meehl introduced the term ‘‘schizotaxia’’ in 1962 to describe the genetic predisposition to schizophrenia [Meehl, 1962], and we have modified the concept to take account of subsequent research [Faraone et al., 2000]. The concept of schizotaxia raises at least three fundamental issues: 1) What is the conceptual basis of schizotaxia? 2) Is it a valid syndrome? and 3) perhaps most importantly from the point of view of the eventual prevention of schizo phrenia, is it treatable? In this paper, we review the model of schizotaxia by focusing first on its nature and extent. We then describe preliminary research criteria for its diagnosis in nonpsychotic relatives of schizo phrenic patients, followed by a presentation of our initial attempts to treat schizotaxia. Finally, prospects for the future focus on the need to validate the proposed syndrome further and on the clinical implications of treating schizotaxia.
    • Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism

      Qian, Qiujin; Wang, Yufeng; Zhou, Rulun; Li, Jun; Wang, Bing; Glatt, Stephen; Faraone, Stephen V. (Wiley, 2003-03-04)
      Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral disorder. Boys are more often affected than girls. Family, twin, and adoption studies have supported a strong genetic basis. Some studies show that a catechol-O-methyltransferase (COMT) polymorphism affecting enzyme activity was associated with personality characteristics and diseases, such as novelty-seeking personality, substance abuse, and heroin addiction, whose features are similar to ADHD or are associated with ADHD. These findings suggest that the COMT gene may be a candidate gene for ADHD. TDT, HHRR, and case-control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM-IV criteria using American Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme-activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, χ2 = 3.858, P = 0.05, df = 1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: χ2 = 5.128, P = 0.024, df = 1; TDT: χ2 = 4.558, P = 0.033, df = 1), especially the ADHD-I subtype (32 trios, HHRR: χ2 = 5.792, P = 0.016, df = 1; TDT: χ2 = 5.333, P = 0.021, df = 1). The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSM-IV criteria for ADHD than in female controls (86 and 79.5%, respectively, χ2 = 4.059, P = 0.044, df = 1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions. © 2003 Wiley-Liss, Inc.
    • Family-based association study of markers on chromosome 22 in schizophrenia using African-American, European-American, and Chinese families

      Takahashi, Sakae; Cui, Yu-hu; Kojima, Takuya; Han, Yong-hua; Zhou, Ru-lum; Kamioka, Masashi; Yu, Shun-ying; Matsuura, Masato; Matsushima, Eisuyke; Wilcox, Marsha; et al. (Wiley, 2003-06-13)
      Several studies suggest that loci at chromosome 22q11.2-q13 might be linked to susceptibility to schizophrenia. Here we performed family-based association studies on chromosome 22q using 12 DNA microsatellite markers in African-American, European-American, and Chinese pedigrees. The marker D22S683 showed significant linkage and association with schizophrenia in not only the European-American sample but also in a combined sample (European-American and Chinese samples). Notably, D22S683 is located nearby and between D22S278 and D22S283, which have shown linkage and association to schizophrenia in prior reports. However, we found no significant association for the African-American sample. In conclusion, our data provide further support for the idea that the region around D22S683 contains a susceptibility gene for schizophrenia. © 2003 Wiley-Liss, Inc.