bluuebunny/crossref_metadata_2025 huggingface dataset:
Report from the 4th International Meeting of the Attention Deficit Hyperactivity Disorder Molecular Genetics Network
Authors: Faraone Stephen V.
Published: July 2003

Investigators from around the world have convened annually since 1999 to share their work on the molecular genetic basis of attention deficit hyperactivity disorder (ADHD). The 4th meeting of the ADHD Molecular Genetics Network was held in May 2002. This conference began with a discussion of ongoing and proposed collaborative projects. Ongoing collaborations include the International Multi‐Center ADHD Genetics (IMAGE) project, a study of additive and interactive effects of DAT1 and DRD4 on ADHD and a meta‐analysis of association studies of ADHD and the DRD5 gene. A new collaborative project regarding DNA pooling was also proposed. Over 20 investigators presented recent findings from their individual research sites. Participants also broke up into working groups to discuss additional projects and topics of mutual interest, including population genetic studies using dimensional phenotypic data and a QTL approach, endophenotypes for ADHD and the genetics of ADHD in adults. Finally, participant feedback was obtained about the utility of the ADHD Molecular Genetics Network conferences and the e‐mail network. Although technological and statistical advances in the field of molecular genetics have allowed researchers to begin to identify specific genes that are associated with ADHD, continued collaborative efforts are needed to fully elucidate the genetic underpinnings of this complex phenotype. Data collected at the current conference indicate that the ADHD Molecular Genetics Network has facilitated new collaborative as well as single‐site projects among ADHD researchers. © 2003 Wiley‐Liss, Inc.
CAG‐Repeat length in exon 1 of KCNN3 does not influence risk for schizophrenia or bipolar disorder: A meta‐analysis of association studies
Authors: Glatt Stephen J. , Faraone Stephen V. , Tsuang Ming T.
Published: July 2003

Schizophrenia and bipolar disorder both show some evidence for genetic anticipation. In addition, significant expansion of anonymous CAG repeats throughout the genome has been detected in both of these disorders. The gene KCNN3, which codes for a small/intermediate conductance, calcium‐regulated potassium channel, contains a highly polymorphic CAG‐repeat array in exon 1. Initial evidence for association of both schizophrenia and bipolar disorder with increased CAG‐repeat length of KCNN3 has not been consistently replicated. In the present study, we performed several meta‐analyses to evaluate the pooled evidence for association with CAG‐repeat length of KCNN3 derived from case‐control and family‐based studies of both disorders. Each group of studies was analyzed under two models, including a test for direct association with repeat length, and a test for association with dichotomized repeat‐length groups. No evidence for a linear relationship between disease risk and repeat length was observed, as all pooled odds ratios approximated 1.0. Results of dichotomized allele‐group analyses were more variable, especially for schizophrenia, where case‐control studies found a significant association with longer repeats but family‐based studies implicated shorter alleles. The results of these meta‐analyses demonstrate that the risks for both schizophrenia and bipolar disorder are largely, if not entirely, independent of CAG‐repeat length in exon 1 of KCNN3. This study cannot exclude the possibility that some aspect of this polymorphism, such as repeat‐length disparity in heterozygotes, influences risk for these disorders. Further, it remains unknown if this polymorphism, or one in linkage disequilibrium with it, contributes to some distinct feature of the disorder, such as symptom severity or anticipation. © 2003 Wiley‐Liss, Inc.
Analysis of transmission of novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene in patients with autism
Authors: Lauritsen Marlene B. , Nyegaard Mette , Betancur Catalina , Colineaux Catherine , Josiassen Trine L. , Kruse Torben A. , Leboyer Marion , Ewald Henrik
Published: July 2003

Infantile autism is a pervasive developmental disorder with a strong genetic component. The mode of inheritance appears to be complex and no specific susceptibility genes have yet been identified. Chromosome 16p13.3 may contain a susceptibility gene based on findings from genome scans and reports of chromosome abnormalities in individuals with autism. The somatostatin receptor 5 (SSTR5) gene is located on chromosome 16p13.3 and is thus a positional candidate gene for autism. SSTR5 may also be a functional candidate gene for autism because somatostatin inhibits growth hormone secretion, and increased growth hormone response has been reported in some individuals with autism. Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine D2 receptor and the SSTR5 receptor interact to form a receptor complex with enhanced functional activity. In the present study, we tested whether the alleles of twelve new single nucleotide polymorphisms (SNPs) in the SSTR5 gene were preferentially transmitted, using the transmission disequilibrium test (TDT) in a sample of 79 trios with autism (18 from Denmark and 61 from France). Furthermore, we combined four missense SNPs into haplotypes and searched for preferential transmission using the program TRANSMIT. No significant preferential transmission of the alleles and haplotypes of the twelve SNPs was found. Our results do not suggest the SSTR5 gene as a susceptibility gene for autism. © 2003 Wiley‐Liss, Inc.
Genome scan of the fifty‐six bipolar pedigrees from the NIMH genetics initiative replication sample: Chromosomes 4, 7, 9, 18, 19, 20, and 21
Authors: Willour Virginia L. , Zandi Peter P. , Huo Yuqing , Diggs Tyra L. , Chellis Jennifer L. , MacKinnon Dean F. , Simpson Sylvia G. , McMahon Francis J. , Potash James B. , Gershon Elliot S. , Reich Theodore , Foroud Tatiana , Nurnberger John I. , Raymond DePaulo J. , McInnis Melvin G.
Published: July 2003

The NIMH genetics initiative on bipolar disorder was established to collect uniformly ascertained bipolar pedigrees for genetic studies. In 1997, the four participating sites published a genome scan on the initial set of 97 bipolar pedigrees. Fifty‐six additional bipolar pedigrees have now been ascertained and evaluated. This replication pedigree set contains 354 genotyped subjects, including 139 bipolar I (BPI) subjects, five schizoaffective bipolar type SA/BP subjects, 41 bipolar II (BPII) subjects, and 43 recurrent unipolar (RUP) depression subjects. Our site has recently genotyped the replication study bipolar pedigrees using 107 microsatellite markers from chromosomes 4, 7, 9, 18, 19, 20, and 21. We are now reporting parametric and nonparametric linkage results from this effort. Multipoint nonparametric linkage analysis produced three candidate regions with allele sharing LOD scores ≥ 1.0. The linkage signal on 4q35 peaked between markers D4S3335 and D4S2390 with an allele sharing LOD score of 2.49. This finding exceeds standard criteria for suggestive linkage. Two additional loci approach suggestive linkage levels: the 4q32 finding had its maximum near marker D4S1629 with an allele sharing LOD score of 2.16, and the 20p12 finding peaked at D20S162 with an allele sharing LOD score of 1.82. Multipoint parametric linkage analysis produced similar findings. When we combined the genotype data from the original and the replication pedigree sets, 20p12 yielded a nonparametric LOD score of 2.38, which exceeds standard criteria for suggestive linkage, and a corresponding parametric HLOD score of 2.98. The combined analysis did not provide further support for linkage to 4q32 and 4q35. © 2003 Wiley‐Liss, Inc.
Genetic dissection of psychopathological symptoms: Insomnia in mood disorders and CLOCK gene polymorphism
Authors: Serretti Alessandro , Benedetti Francesco , Mandelli Laura , Lorenzi Cristina , Pirovano Adele , Colombo Cristina , Smeraldi Enrico
Published: July 2003

We investigated the possible effect of the 3111T/C CLOCK gene polymorphism on sleep disorders in a sample of 620 patients affected by major depressive disorder (MDD) and bipolar disorder (BP). We detected a significantly higher recurrence of initial (P = 0.0001), middle (P = 0.0009), and early (P = 0.0008) insomnia in homozygotes for the C variant and a similar trend concerning decreased need of sleep in BP (P = 0.0074). Other demographic and clinical features were found not related with CLOCK polymorphisms. This preliminary observation leads to hypothesize a possible involvement of the CLOCK gene polymorphism in the sleep disregulations in MDD and BP. Copyright © 2003 Wiley‐Liss, Inc.
D2 and D4 dopamine receptor gene polymorphisms and personality traits in a young Korean population
Authors: Lee Heon‐Jeong , Lee Hong‐Seock , Kim Yong‐Ku , Kim Leen , Lee Min Soo , Jung In‐Kwa , Suh Kwang‐Yoon , Kim Sangduk
Published: July 2003

The correlation between the D4 dopamine receptor gene (DRD4) and the D2 dopamine receptor gene (DRD2) polymorphisms was investigated with personality traits. For this study, homogeneous population consisting of 243 young alcohol‐ and drug‐naive Koreans who were blood‐unrelated with a mean age (±SD) of 13.87 (±0.30) years old was analyzed for the DRD4 and the DRD2 polymorphisms with their personality trait by Temperament and character inventory (TCI). The association between Novelty seeking (NS) score and DRD4 long alleles was only observed among the female subjects (t = 2.11, P = 0.037), but not in the male counter part. Female subjects who carried the DRD2 less frequent alleles (TaqI A1, TaqI B1, and Intron6 1) showed higher RD4 scores (dependence vs. independence) of Reward dependence (RD) than those without these alleles (P < 0.05). There was no interaction between DRD4 and DRD2 on the personality traits. These results, thus, confirmed the previous findings in which the long repeats of the DRD4‐exon III polymorphism are related to NS personality trait, and also suggested that the DRD2 less frequent alleles were also associated with the reward‐dependent trait. © 2003 Wiley‐Liss, Inc.
Association between human μ‐opioid receptor gene polymorphism, pain tolerance, and opioid addiction
Authors: Compton Peggy , Geschwind Daniel H. , Alarcón Maricela
Published: July 2003

Central to both pain responses and opioid addiction is activity at the μ‐opioid receptor. To explore the role of the μ‐opioid receptor gene (OPRM) in human pain tolerance and opioid addiction, we examined the relationships among OPRM genotype and experimental pain tolerance in opioid addicts in methadone treatment (n = 50) and healthy normal controls (n = 59). Pain phenotype (pain tolerant vs. pain intolerant) was operationalized as tolerance to a standardized noxious stimulus (either thermal or mechanical), and dichotomized based on distribution. One microsatellite and two single nucleotide polymorphisms, A118G and C17T, in exon 1 were typed to study the OPRM gene. Although the established relationship between the phenotypes of opioid addiction and pain intolerance was validated (P = 0.02), genotype differed neither between addict‐affected vs. control, nor pain tolerant vs. intolerant subjects. The variant A118G was absent in all individuals and the C17T polymorphism appeared in only three African‐American individuals (two addicts and one control). The absence of this polymorphism, the small sample size and the heterogeneous ethnic backgrounds of participants in the pilot study allow only tentative conclusions based on the results, thus the role of the opioid receptor in pain and opioid reward response remains uncertain. © 2003 Wiley‐Liss, Inc.
Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia‐Pacific region
Authors: Handoko Herlina Y. , Nancarrow Derek J. , Hayward Nicholas K. , Ohaeri Jude U. , Aghanwa Henry , McGrath John J. , Levinson Douglas F. , Johns Christopher , Walters Marilyn K. , Nertney Deborah A. , Srinivasan T.N. , Thara R. , Mowry Bryan J.
Published: July 2003

A single nucleotide polymorphism (TNF−308A) within the promoter region of the gene encoding tumor necrosis factor (TNF), has been significantly associated with schizophrenia in a study of Italian patients and control subjects Boin et al. [2001: Mol Psychiatry 6:79–82]. We have applied case‐control analyses to examineTNFpromoter haplotypes (containingTNF−308and two additional promoter variants:TNF−376andTNF−238) in four schizophrenia cohorts drawn from Australian, Indian Fijian, Indigenous Fijian, and Brahmin populations. In addition, we have applied the sibling transmission disequilibrium (STD) test to promoter haplotypes within 81 trios drawn from Australian Caucasian pedigrees with multiple schizophrenia cases, and 86 trios drawn from the Brahmin population of Tamil Nadu province in Southern India. Within each of these cohorts, we found no evidence of recombination between these tightly linked promoter variants, supporting previous studies which demonstrated that only a subset of the eight possible haplotypes exist. Of the four observed haplotypes, we and others have observed only one carries theTNF−308Avariant allele. We report no significant differences inTNFpromoter haplotype frequencies between the patient and control groups within each population, although the Indian Fijian cohort showed a trend towards reducedTNF−308Aalleles amongst schizophrenia cases (P = 0.07). We found no evidence of bias inTNFpromoter haplotype transmission to schizophrenia probands. Very similar results were obtained when only theTNF−308polymorphism was considered. Taken together, these data provide no support for the involvement ofTNFpromoter variantsTNF−308,TNF−376, andTNF−238in schizophrenia susceptibility within four ethnically distinct cohorts. © 2003 Wiley‐Liss, Inc.
Association of a haplotype in the serotonin 5‐HT4 receptor gene (HTR4) with Japanese schizophrenia
Authors: Suzuki T. , Iwata N. , Kitamura Y. , Kitajima T. , Yamanouchi Y. , Ikeda M. , Nishiyama T. , Kamatani N. , Ozaki N.
Published: July 2003

The serotonin 5‐HT4 receptor (5‐HT4) is implicated in cognitive function, of which impairment is hypothesized as one of the core disturbances of schizophrenia. Linkage analysis shows that 5q33.2, in which HTR4 is located, is schizophrenia‐susceptibility loci. We therefore hypothesized that variation in the 5‐HT4 receptor gene (HTR4) modifies genetic susceptibility to schizophrenia. HTR4 coding regions and introns that include the branch sites of HTR4 were investigated in 96 unrelated Japanese schizophrenics using denaturing high‐performance liquid chromatography analysis. One silent single nucleotide polymorphism (SNP) within the coding region and six intronic SNPs were detected. 353 + 6G > A was located in the branch site that could be effect to RNA splicing. None of the four SNPs, in which rare‐allele frequencies were more than 10% was associated with 189 schizophrenics, in comparison to 299 controls. However, a highly significant association between schizophrenia and haplotype A‐T (OR = 0.13 [0.03–0.58]) was detected. These findings suggest that haplotype A‐T itself may inhibit the occurrence of schizophrenia, or that another susceptible genetic variants may exist within linkage disequilibrium. © 2003 Wiley‐Liss, Inc.
The association of the D2S2944 124 bp allele with recurrent early onset major depressive disorder in women
Authors: Philibert Robert , Caspers Kristin , Langbehn Douglas , Troughton Edward P. , Yucuis Rebecca , Sandhu Harinder K. , Cadoret Remi J.
Published: July 2003

Major depressive disorder (MDD) and substance use disorders (SUD) are complex behavioral disorders with 40–50% heritability. Recently, Zubenko and colleagues reported that the 124 bp allele of D2S2944, a tetranucleotide repeat marker on 2q35, is strongly associated with recurrent, early onset MDD (RE‐MDD) and alcohol use disorders in women. To test this hypothesis, we examined the association of the 124 bp allele in a subset of 171 adoptees from the Iowa Adoption Studies, a population with high rates of MDD and SUD. We report that in our population, the 124 bp allele significantly associated with RE‐MDD in women. There was slight evidence of an increased of SUD in women with the 124 bp allele with the rate of cannabis use disorders reaching statistical significance (P < 0.04) before correction for multiple comparisons. Given the history of prior studies implicating 2q35 as a locus encoding vulnerability to co‐morbid alcoholism and depression, these findings strongly suggest that sequence variation conveying increased susceptibility to MDD and possibly SUD is in close proximity to D2S2944. © 2003 Wiley‐Liss, Inc.
A psychometrically derived impulsive trait related to a polymorphism in the serotonin transporter gene‐linked polymorphic region (5‐HTTLPR) in a japanese nonclinical population: Assessment by the barratt impulsiveness scale (BIS)
Authors: Sakado Kaoru , Sakado Miwako , Muratake Tatsuyuki , Mundt Christoph , Someya Toshiyuki
Published: July 2003

Although a number of studies have shown that human impulsive traits are associated with indices of central serotonin function, few researchers have investigated the relationship between a polymorphism in the serotonin transporter gene‐linked region (5‐HTTLPR) and a psychometrically derived impulsive trait. We determined the 5‐HTTLPR polymorphism in 123 employed Japanese male adults using the polymerase chain reaction. The distribution of allelic frequency was determined and also investigated the relationship of the 5‐HTTLPR polymorphism to a impulsive trait as measured by the Barratt Impulsiveness Scale, 11th version (BIS‐11). The distribution of allelic frequency was found to be almost identical to that previously reported in Japanese (the frequency for the long (L)/L, L/short (S), and S/S genotypes was: 3, 28, and 68%, respectively). In a comparison between the genotype groups, the S/S genotype group significantly higher scored for the total BIS‐11 and the subscale attentional impulsiveness than the L/S + L/L genotype group. These findings suggest that individuals with a homozygous S‐allele may be more impulsive than those with the other genotype. © 2003 Wiley‐Liss, Inc.
Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism
Authors: Sinha Rashmi , Cloninger C. Robert , Parsian Abbas
Published: July 2003

A number of studies have reported a possible association between serotonergic pathway genes and alcoholism. A silent polymorphism (G to C substitution) in the gene encoding the autoreceptor 5‐HT1B was linked to antisocial alcoholism in Finnish and an American Indian populations [Lappalainen et al., 1998: Arch Gen Psychiatry 55:989–994]. Several other polymorphisms of this gene have been investigated for their association with neuropsychiatric disorders. In the present study, a sample of 133 alcoholics without and 39 alcoholics with medical complications, and 88 normal controls was screened for three single nucleotide polymorphisms (SNPs), G861C, G261T, and C129T, in the 5‐HT1B gene. The goal was to investigate their association with the disease, to measure the strength of linkage disequilibrium (LD) between the SNPs, and to compare haplotype frequencies between alcoholic groups and normal controls. Data was also analyzed on the basis of Type I (n = 47) and Type II (n = 85) alcoholism. There was no significant difference in the allele frequencies or the genotype distribution between any alcoholic groups, alcoholic subgroups, and controls for any polymorphism. G861C and C129T polymorphisms were in complete LD. The pattern of distribution of haplotypes was similar in patients and controls. It is concluded that these SNPs are not playing any direct role in the development of susceptibility to alcoholism in our patient sample. © 2003 Wiley‐Liss, Inc.
Children at familial risk for Tourette's disorder: Child and parent diagnoses
Authors: McMahon William M. , Carter Alice S. , Fredine Nancy , Pauls David L.
Published: July 2003

Tourette's disorder (TD) is a neuropsychiatric disorder that onsets in childhood and appears to result from an interaction of genetic and environmental factors. The goal of the current prospective longitudinal study is to examine the onset of TD in offspring of parents with TD. At‐risk children and control children were enrolled between the ages of 3 and 6 years and prospectively studied with yearly structured assessments over intervals of 2–5 years. Of 34 at‐risk children free of tics at baseline, 10 (29%) subsequently developed a tic disorder, including 3 with TD. None of the 13 control children developed a tic disorder (P = 0.045). OCD or subclinical OCD emerged in 11 cases but no controls (P = 0.021). Finally, ADHD occurred in 14 at‐risk children but no controls (P = 0.005). When at‐risk families were dichotomized into bilineal or unilineal categories, rates of TD in children with two affected parents were three times the rate observed for children with one affected parent. These findings support the hypothesis that at least some cases of TD result from a complex genetic etiology. TD, OCD, and ADHD are significantly increased in children with TD parents. Furthermore, the risk is even greater when both parents are affected. Finally, our diagnosis of tic disorders in 21% of subjects initially reported by parents to be unaffected affirms the value of structured clinical assessments. © 2003 Wiley‐Liss, Inc.
Extended investigation of tau and mutation screening of other candidate genes on chromosome 17q21 in a Swedish FTDP‐17 family
Authors: Froelich Fabre Susanne , Axelman Pia , Almkvist Åsa , Basun Hans , Lannfelt Lars
Published: July 2003

Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP‐17) is an autosomal dominant condition clinically characterized by behavioral, cognitive and motor disturbances. It was recently discovered that the majority of the FTDP‐17 families carry missense or 5′ splice mutations in the exons coding for the microtubule‐binding domains of the tau protein. However, in at least five FTDP‐17 families, no such mutations could be identified. In the present study, we aimed at further investigate abnormalities in the tau gene in a Swedish FTDP‐17 family, where no mutations in the tau gene previously have been identified. Initially, we searched for larger deletions by Southern blot hybridization. Furthermore, possible abnormal splicing events was investigated by RT‐PCR from brain tissue of affected individuals. In addition, we investigated the presence of mutations in other genes in the FTDP‐17 candidate region on chromosome 17q21; Gamma‐tubulin, Glial Fibrillary Acid Protein (GFAP), Human dual specificity phosphatase tyrosine/serine (VHR), Rap‐interacting protein 8 (RPIP8), P35, and the recently identified FTDCG1. In conclusion, no pathological changes in the tau gene were observed, neither was any mutations segregating with the disease detected in the investigated candidate genes. Further investigation of extended intron sequences or promoter regions of the tau gene and additional candidate genes on chromosome 17q21, therefore seems to be necessary in order to identify the additional causes of FTDP‐17. © 2003 Wiley‐Liss, Inc.
Segregation analysis of phenotypic components of learning disabilities. II. Phonological decoding
Authors: Chapman Nicola H. , Raskind Wendy H. , Thomson Jennifer B. , Berninger Virginia W. , Wijsman Ellen M.
Published: July 2003

Dyslexia is a common, complex disorder, which is thought to have a genetic component. The study of the genetics of dyslexia is complicated by a lack of consensus on diagnostic criteria, and the probability of genetic heterogeneity—it is possible that deficits in different language processes are caused by different underlying genes. In order to address these difficulties, we study continuous phenotypes that are part of the psychometric test batteries often used to diagnose dyslexia. Prior to embarking on a linkage study, it is helpful to employ segregation analysis, both to identify phenotypes that may be amenable to mapping by linkage analysis, and to determine the best models to use for model based analyses. We study 409 people in 102 nuclear families, and employ (1) oligogenic segregation analysis to estimate the number of quantitative trait loci (QTLs) contributing to each phenotype, and (2) complex segregation analysis in order to identify the most parsimonious inheritance model. In this paper, we consider two measures of phonological decoding ability—word attack and phonemic decoding efficiency. We find evidence for one or two genes of at least modest effect contributing to phonemic decoding efficiency, and the best fitting model is a dominant major gene model with residual familial correlations. For word attack, we find evidence for one or two genes of at least modest effect, and the variation in the trait is best explained by a polygenic model. © 2003 Wiley‐Liss, Inc.
Multipoint and single point non‐parametric linkage analysis with imperfect data
Authors: Sullivan Patrick F. , Neale Benjamin M. , Neale Michael C. , van den Oord Edwin , Kendler Kenneth S.
Published: July 2003

We used simulation to explore the impact of common data imperfections (i.e., missing parents, genotyping error, map error, and missing genotypes) upon the performance of multipoint and single point linkage analysis in the analyses of linkage data from pairs of siblings affected with an idealized complex trait. The performance of single point and multipoint linkage was similar under an unrealistic best case scenario; however, when four data imperfections were combined, the performance of single point linkage analysis appeared to be superior to multipoint. The absence of parental genotypes in the presence of 1% genotype error led to marked degradation of linkage signal, particularly for multipoint analyses. © 2003 Wiley‐Liss, Inc.
Linkage and association between serotonin 2A receptor gene polymorphisms and bipolar I disorder
Authors: Ranade Swati S. , Mansour Hader , Wood Joel , Chowdari Kodavali V. , Brar Laurie K. , Kupfer David J. , Nimgaonkar Vishwajit L.
Published: July 2003

Several inconsistent associations between bipolar I disorder (BD1) and polymorphisms of the genes encoding the serotonin 2A receptor (HTR2A) have been published. We conducted the Transmission Disequilibrium Test (TDT) and case‐control comparisons involving nine single nucleotide polymorphisms at the serotonin 2A receptor gene (four SNPs of HTR2A exons and five flanking SNPs). Comparison of BD1 cases (n = 93) with a group of unrelated population based controls (n = 92) revealed associations with SNPs on exons 2 and 3 (516C/T and 1354C/T, respectively), consistent with haplotype‐based differences. Analysis of the cases and their available parents using the TDT suggested significant linkage and associations with 1354C/T, as well as haplotypes bearing this SNP. Our results support an etiological role for HTR2A in BD1. In view of the relatively small sample, replicate studies using large samples are needed. © 2003 Wiley‐Liss, Inc.
Association of the 480 bp DAT1 allele with methylphenidate response in a sample of Irish children with ADHD
Authors: Kirley Aiveen , Lowe Naomi , Hawi Ziarih , Mullins Celine , Daly Grainne , Waldman Irwin , McCarron Mary , O'Donnell Deirdre , Fitzgerald Michael , Gill Michael
Published: July 2003

Several studies have implicated the dopamine transporter gene (DAT1) as conferring susceptibility to attention deficit hyperactivity disorder (ADHD), in particular, a VNTR situated at the 3′ end of the gene. In addition, the 10‐repeat VNTR allele associated with ADHD has been reported to be associated with an over‐active transporter protein (DAT). Thus children possessing this variant might be particularly responsive to methylphenidate, a drug known to act by blocking DAT. We have examined this hypothesis and now report an association between the 10‐repeat VNTR DAT1 polymorphism and retrospectively rated methylphenidate response in a sample of 119 Irish children with ADHD (χ2 = 7.918, df = 1, P = 0.005). Our findings suggest a role for the 10‐repeat DAT1 risk allele in medication response and may help to predict positive clinical outcome in ADHD. © 2003 Wiley‐Liss, Inc.
Bayesian analysis of a previously published genome screen for panic disorder reveals new and compelling evidence for linkage to chromosome 7
Authors: Logue Mark W. , Vieland Veronica J. , Goedken Rhinda J. , Crowe Raymond R.
Published: July 2003

This article presents a Bayesian re‐analysis of a linkage study of panic disorder Crowe et al. [2001: Am J Med Genet (Neuropsychiatr Genet) 105:105–109]. In the initial analysis Crowe et al. failed to find compelling evidence for linkage based on either LOD scores or NPL scores anywhere in the genome. The maximum LOD score was 2.23 on chromosome 7 at marker D7S2846 (57.79 cM according to Marshfield). Over the past several years we have been developing a Bayesian alternative approach to linkage analysis, based on direct measurement of the posterior probability of linkage (PPL), and have shown elsewhere that this approach has several advantages over the available alternatives for mapping complex‐disease genes Vieland [1998: Am J Med Genet 63:947–954]; Wang et al. [1999: Genet Epidemiol 17(Suppl 1):S749–S754]; Wang et al. [2000: Ann Hum Genet 64:533–553]; and Vieland et al. [2001: Hum Hered 51:199–208]. One limitation of this approach in previous applications has been that it required the investigator to specify a fixed genetic model for the trait. We employ a new implementation of the PPL that treats the unknown trait model as a vector of nuisance parameters, which is integrated out of the PPL equation. When we apply this new model‐integrated version of the PPL to the data of Crowe et al. [2001: Am J Med Genet (Neuropsychiatr Genet) 105:105–109] we obtain much clearer evidence than previously reported for a locus on chromosome 7, with an 80% probability of linkage to marker D7S521. A second location is also identified on chromosome 16 near marker D16S749 (PPL = 24%). The results for the remainder of the genome are consistently low. The two loci identified here are also supported by independent evidence from other studies. © 2003 Wiley‐Liss, Inc.
Does fear of coercion keep people away from mental health treatment? Evidence from a survey of persons with schizophrenia and mental health professionals
Authors: Swartz Marvin S. , Swanson Jeffrey W. , Hannon Michael J.
Published: July 2003

Mental health consumer advocates have long argued that involuntary treatment frightens persons with mental disorder and thus deters them from voluntarily seeking help. We surveyed 85 mental health professionals and 104 individuals with schizophrenia spectrum conditions to assess their experience with and perceptions of involuntary treatment and other treatment mandates. Of the clinicians, 78% reported that overall they thought legal pressures made their patients with schizophrenia more likely to stay in treatment. Regarding involuntary outpatient commitment, 81% of clinicians disagreed with the premise that mandated community treatment deters persons with schizophrenia from seeking voluntary treatment in the future. Of the consumer sample, 63% reported a lifetime history of involuntary hospitalization, while 36% reported fear of coerced treatment as a barrier to seeking help for a mental health problem—termed here “mandated treatment‐related barriers to care.” In bivariate analyses, reluctance to seek outpatient treatment associated with fear of coerced treatment (mandated treatment‐related barriers to care) was significantly more likely in subjects with a lifetime history of involuntary hospitalization, criminal court mandates to seek treatment, and representative payeeship. However, experience with involuntary outpatient commitment was not associated with barriers to seeking treatment. Recent reminders or warnings about potential consequences of treatment nonadherence, recent hospitalization, and high levels of perceived coercion generally were also associated with mandated treatment‐related barriers to care. In multivariable analyses, only involuntary hospitalization and recent warnings about treatment nonadherence were found to be significantly associated with these barriers. These results suggest that mandated treatment may serve as a barrier to treatment, but that ongoing informal pressures to adhere to treatment may also be important barriers to treatment. Copyright © 2003 John Wiley & Sons, Ltd.
The antecedents of aggressive behavior among men with schizophrenia: a prospective investigation of patients in community treatment
Authors: Hodgins Sheilagh , Hiscoke Ulrika L. , Freese Roland
Published: July 2003

The association between psychotic symptoms and violence is unclear, due in part to methodological features of investigations that have examined this question, and in part to the fact that the association likely differs by disorder and treatment conditions. Using data from The Comparative Study of the Prevention of Crime and Violence by Mentally Ill Persons, we examined 128 men with schizophrenia or schizoaffective disorder discharged from general and forensic psychiatric hospitals in Canada, Finland, Germany, and Sweden. The association between symptoms and aggressive behavior was studied during two 6 month periods when the patients lived in the community. Severe positive and negative symptoms of psychosis, depression, and anxiety were measured at the beginning of each of the 6 month periods. In addition, at the beginning of the second 6 month period changes in symptoms in the previous period were indexed. Aggressive behavior was measured in each 6 month period by reports from patients and from collaterals. During the first 6 months post‐discharge, after controlling for the presence of antisocial personality disorder or PCL score and past diagnoses of alcohol/drug abuse/dependence, the presence of a severe positive symptom significantly increased the risk of aggressive behavior. During the second 6 month period, after controlling for antisocial personality disorder or PCL score and self‐reported alcohol/drug use, the presence of a severe positive symptom, a TCO symptom, and an increase in TCO symptoms significantly increased the risk of aggressive behavior. Neither depot medications nor obligatory community treatment reduced the risk of aggressive behavior after controlling for the presence of a severe positive symptom and/or TCO symptoms. These findings suggest that, among men with schizophrenia being treated in the community, the presence of severe psychotic symptoms and the development of TCO symptoms are antecedents of aggressive behavior. Copyright © 2003 John Wiley & Sons, Ltd.
Waking Rip van Winkle: why developments in the last 20 years should teach the mental health system not to use housing as a tool of coercion
Authors: Allen Michael
Published: July 2003

Many housing programs for people with mental illnesses rely on models that require the person to adhere to treatment as a condition of continuing access to housing. These models that ‘bundle’ housing and treatment are relics of a past in which persons with mental illnesses were afforded little real choice in treatment, housing and other social supports. Conditioning access to housing in this manner is coercive and at odds with current thinking regarding treatment, as well as legal principles that shape the environment in which treatment is provided. This article summarizes the reasons why housing for people with mental illnesses should be provided free of the use of coercion. Copyright © 2003 John Wiley & Sons, Ltd.
Evaluation of a mental health treatment court with assertive community treatment
Authors: Cosden Merith , Ellens Jeffrey K. , Schnell Jeffrey L. , Yamini‐Diouf Yasmeen , Wolfe Maren M.
Published: July 2003

Without active engagement, many adults with serious mental illnesses remain untreated in the community and commit criminal offenses, resulting in their placement in the jails rather than mental health facilities. A mental health treatment court (MHTC) with an assertive community treatment (ACT) model of case management was developed through the cooperative efforts of the criminal justice and mental health systems. Participants were 235 adults with a serious mental illness who were booked into the county jail, and who volunteered for the study. An experimental design was used, with participants randomly assigned to MHTC or treatment as usual (TAU), consisting of adversarial criminal processing and less intensive mental health treatment. Results were reported for 6 and 12 month follow‐up periods. Clients in both conditions improved in life satisfaction, distress, and independent living, while participants in the MHTC also showed reductions in substance abuse and new criminal activity. Outcomes are interpreted within the context of changes brought about in the community subsequent to implementation of the MHTC. Copyright © 2003 John Wiley & Sons, Ltd.
Perspectives on probation and mandated mental health treatment in specialized and traditional probation departments
Authors: Skeem Jennifer L. , Encandela John , Louden Jennifer Eno
Published: July 2003

Despite the prevalence of mentally ill probationers, and probation officers' (POs') central role in their supervision, this is the first reported study to investigate how POs implement mandates to participate in psychiatric treatment. Five focus groups were conducted in major cities with 32 POs and 20 probationers representing a mix of traditional and “specialty” probation agencies. Three key findings resulted. First, there were considerable differences between POs in specialty and traditional agencies in the nature, range, and timing of strategies applied to monitor and enforce treatment compliance. Second, the quality of PO–probationer relationships colored POs' use of these strategies and was perceived as central to probationer outcomes. Relationships characterized by a respectful, personal, approach were perceived as more effective in achieving desired outcomes than those that were more authoritarian. Third, specialty agencies strongly emphasized offender rehabilitation whereas traditional agencies focused more exclusively on community safety. These agencies differed in how well probationers with mental illness “fit” their standard operating procedure. Implications for future research and directions for probation practice are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of involuntary outpatient commitment on subjective quality of life in persons with severe mental illness
Authors: Swanson Jeffrey W. , Swartz Marvin S. , Elbogen Eric B. , Wagner H. Ryan , Burns Barbara J.
Published: July 2003

Recent evidence suggests that involuntary outpatient commitment (OPC), when appropriately applied, can improve adherence with psychiatric treatment, decrease hospital recidivism and arrests, and lower the risk of violent behavior in persons with severe mental illness. Presumably these are benefits that improve quality of life (QOL); however, insofar as OPC involves legal coercion, the undesirable aspects of OPC could also exert a negative effect on quality of life, thus offsetting clinical benefits.

Involuntarily hospitalized subjects, awaiting discharge under outpatient commitment, were randomly assigned to be released or continue under outpatient commitment in the community after hospital discharge, and were followed for one year. Quality of life was measured at baseline and 12 months follow‐up. Treatment characteristics and clinical outcomes were also measured.

Subjects who underwent longer periods of outpatient commitment had significantly greater quality of life as measured at the end of the 1 year study. Multivariable analysis showed that the effect of OPC on QOL was mediated by greater treatment adherence and lower symptom scores. However, perceived coercion moderated the effect of OPC on QOL.

Involuntary outpatient commitment, when sustained over time, indirectly exerts a positive effect on subjective quality of life for persons with SMI, at least in part by improving treatment adherence and lowering symptomatology. Copyright © 2003 John Wiley & Sons, Ltd.
The reported prevalence of mandated community treatment in two Florida samples
Authors: Christy Annette , Boothroyd Roger A. , Petrila John , Poythress Norman
Published: July 2003

Questions on multiple modes of mandated community treatment (e.g. outpatient commitment, advance directive, representative payee, and special housing) were included in two studies of persons with mental illness, using a mail survey of Medicaid enrollees receiving SSI and interviews conducted as part of an evaluation of a specialty mental health court. Results indicate that the majority of individuals reported no experience with any forms of mandated community treatment. However, respondents from the two samples who had been subject to community mandates reported comparatively similar experiences. Additional studies of the prevalence of mandated community treatment are necessary to garner expanded information regarding the use of such mandates. In addition, future studies must assure that the language employed to query individuals regarding such mandates is clearly understood by respondents, as certain terms (e.g. “outpatient commitment”) may mean different things to different respondents. Copyright © 2003 John Wiley & Sons, Ltd.
Gender‐ and age‐related differences in the morphology of the corpus callosum
Authors: Suganthy J. , Raghuram L. , Antonisamy B. , Vettivel S. , Madhavi C. , Koshi Rachel
Published: August 2003

The size and shape of the adult corpus callosum may vary with gender and age. There is, however, little data on the morphology of the corpus callosum in the Indian population. The purpose of this study was to measure the size of the corpus callosum in normal adult Indian males and females, and to identify gender‐ and age‐related differences. The size of the corpus callosum on midsagittal section was measured in 100 (50 males, 50 females) normal adult Indians using magnetic resonance imaging. The length of the corpus callosum, the width of the genu, trunk, and splenium, the area of the splenium, and the total area of the corpus callosum were measured. The length of the brain also was measured. Means were compared for significant difference by gender using the Student's unpaired t‐test and by age using ANOVA followed by Duncan's multiple range test. Gender was estimated by discriminant function analysis and age was estimated by regression analysis from significant parameters. The corpus callosum was longer in males and the discriminant score to differentiate gender was determined with an accuracy of 66%. The length of the corpus callosum increased with age and regression equations for predicting age was derived from the length of the corpus callosum. The width of the trunk and genu decreased with age in males but not in females. Clin. Anat. 16:396–403, 2003. © 2003 Wiley‐Liss, Inc.
Intramuscular innervation of the human soleus muscle: A 3D model
Authors: Loh Eldon Y. , Agur Anne M. , McKee Nancy Hunt
Published: August 2003

The purpose of this study was to document the neural distribution patterns within the human soleus muscle using 3D computer modelling. Through serial dissection, pinning, and digitization, nerve distribution and muscle volume of a human cadaveric soleus muscle were documented and a detailed 3D computer model of neural distribution within the muscle volume was generated. Branching patterns demonstrated divisions that parallel architectural partitions within the soleus; that is, into anterior, posterior, and marginal soleus. Additionally, branching patterns demonstrated further partitioning of the posterior soleus into five distinct regions and the anterior soleus into two regions. Communication between nerve branches of the five regions of posterior soleus and between the anterior and posterior soleus were recorded. Knowledge of these anatomical partitions and their interaction is important as it will aid in the development of functional muscle models and in the understanding of normal and pathological muscle function. Clin. Anat. 16:378–382, 2003. © 2003 Wiley‐Liss, Inc.
Unusual extended fibular origin of the human soleus muscle: Possible morpho‐physiologic significance based on comparative anatomy
Authors: Barberini F. , Bucciarelli‐Ducci C. , Zani A. , Cerasoli D.
Published: August 2003

A bilateral anomalous extended origin of the soleus muscle was observed in a 73‐year‐old female cadaver. It arose from the head, neck, and proximal two‐thirds of the medial crest of the fibula and ran through the posterior intermuscular septum of the leg, from the lateral border of the fibula. The soleus muscle formed the vault of a muscular tunnel, overcoming the deep flexor muscles of the leg that was about 15 cm in length and directed inferiorly and laterally. The extended fibular origin delimited a blind recess lateral to the muscular tunnel and parallel to the posterior surface of the fibula. This recess measured 6.5 cm in length and extended 3.5 cm above the inferior opening of the muscular tunnel; the superior portion of the flexor hallucis longus was housed within it between the portions of the extended origin from the medial crest of the fibula and posterior intermuscular septum. The neurovascular bundle of the posterior leg coursed in the muscular tunnel. The tibial origin and calcaneal insertion of the soleus muscle were normal. Phylogenetic studies of the muscles of the lower limbs in mammals indicate that the fibular origin of soleus is more constant than the tibial origin and, in primates, the fibular origin is the only one observed in most monkeys. The case reported might be considered a conspicuous enlargement of the fibular origin observed in primates. This large fibular origin of the soleus muscle may prove to be a difficulty during surgery when accessing the proximal two‐thirds of the fibula for ligation of the peroneal artery. Clin. Anat. 16:383–388, 2003. © 2003 Wiley‐Liss, Inc.
Branches of the splenic artery and splenic arterial segments
Authors: Daisy Sahni A. , Indar Jit B. , Gupta C.N.M. , Gupta D. Madhur , Harjeet E.
Published: August 2003

In 200 adult autopsy specimens, the arterial supply to the pancreas and spleen was studied radiologically and by manual dissection. The splenic artery divided into two or three lobar arteries, which supplied its corresponding lobe; each lobar artery subsequently divided into two to four lobular branches. Six to twelve lobular branches were observed entering the splenic substance at the hilum. Lobar arteries did not anastomose with each other, hence, the lobes of the spleen are also termed segments. The lobules, however, were not found to be independent segments and the arteries of one lobule anastomosed with those of other lobules. The branching pattern of the splenic artery varied from one specimen to another, so much so that a prevailing pattern could not be identified. Polar arteries, particularly to the superior pole, arose quite proximal to the hilum in 51% of cases and were occasionally missed. In 45% of males and 40% of females, the posterior gastric artery arose from about the middle of the splenic artery. The splenic artery was not found to be tortuous in fetuses, newborns, and young children. Tortuosity was seen in only 10% of adults; thus, the characteristic tortuosity of the splenic artery appears to develop with age. Clin. Anat. 16:371–377, 2003. © 2003 Wiley‐Liss, Inc.