Arpana Agrawal1,3, Michael C. Neale1,2,3, Carol A. Prescott2,3, and Kenneth S. Kendler1,2,3.  The influence of early onset cannabis use on use and abuse/dependence of other illicit drugs: discordant twin design versus a model-fitting method.

1Department of Human Genetics, Virginia Commonwealth University, Richmond, VA, 2Department of Psychiatry, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, 3Virginia Institute of Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA

Address:  Virginia Institute of Psychiatric and Behavior Genetics, Virginia Commonwealth University, Box# 980003, 800 E. Leigh Street, Richmond, VA 23298 Phone:  804-828-8157 Fax:  804-828-1471 Email:  aagrawa@mail2.vcu.edu

 

Following-up a recent report (M. T. Lynskey, A.C. Heath, K.K. Bucholz, W.S. Slutske, P.A. Madden, E.C. Nelson, D.J. Statham, and N.G. Martin, 2003, JAMA, 289(4), 427-33), we used the discordant twin design to analyze the influence of early onset of cannabis use on use and abuse/dependence of other illicit drugs. Twins who used cannabis before the age of 18 years versus non-user co-twins had odds ratios of 2.0-7.5 for using other illicit drugs.  However, the discordant twin design does not utilize all the available data and has limited ability to examine the genetic etiology of the relationship between cannabis and other illicit drug use. Using 1191 male and 934 female same sex twin pairs from the Mid-Atlantic Twin Registry (K.S. Kendler and, C.A. Prescott, 1999, Arch. Gen. Psychiatry, 56, 39-44), we fit three models to our data (M.C. Neale and, Kenneth S. Kendler, 1995, Am. J. Hum. Genet., 57, 935-953). The correlated liabilities model most suitably explained the data with a very high correlation of 0.91 between the genetic factors influencing early use of cannabis and other illicit drug use. A model that only allowed for specific environmental influences to be correlated (re=0.87) fit poorly. Also, a genetic model of the gateway hypothesis was not supported. The relationship between early cannabis and other illicit drug use does not appear to be due to causation at the phenotypic level (A. Golub and, B.D. Johnson, 1994, J. Stud. Alcohol, 55(5), 607-14) but due to correlations between factors that influence the individual liabilities. Thus, prevention of cannabis use may not be successful in curbing use of other illicit drugs.


Maricela Alarcón1, Rita M. Cantor2, Jussi Niemi3, Mari Qvarnstrom4, Markku Ryynanen5, Taisto Leppasaari4, Aarno Palotie2, and Daniel H. Geschwind1.  Genomewide scan in Finnish families with dyslexia/dysphasia.

1Department of Neurology, University of California, Los Angeles CA, 2Department of Human Genetics, University of California, Los Angeles CA, 3Department of Linguistics, University of Joensuu, Joensuu, Finland, 4Department of Otolaryngology, Kuopio University Hospital, Kuopio, Finland, 5Department of Obstetrics and Gynecology, University of Oulu, Oulu, Finland

Address:  UCLA Department of Neurology, 710 Westwood Plaza 1-145, Los Angeles, CA 90095 Phone:  310 794 4090  Fax:  310 267 2401  Email:  malarcon@ucla.edu

 

Dyslexia affects approximately 5 to 10% of the population in the United States, making this disorder an important public health problem (G. R. Lyon, D. Alexander, and S. Yaffe, 1997, Learning disabilities:  a multidisciplinary perspective, 8, 1-6).  Although the genetic etiology of the disorder is well established, phenotypic and genetic heterogeneity have impeded the identification of susceptibility genes for dyslexia.  To circumvent these problems, our project aims to identify loci responsible for dyslexia in families from a genetic isolate in Central Finland.  The genetic homogeneity and phonetic language of the Finnish families makes them ideally suited for the identification of genes involved in dyslexia.  Linguists and neuropsychologists easily recognize the phonological deficit in Finnish children with dyslexia or dysphasia.  Thus, disagreements regarding diagnostic criteria are uncommon and clinical diagnosis of the disorder is highly consistent.  Three large and 7 nuclear families have been ascertained from phoniatric clinics in Finland.  The families were required to have at least two children and one parent with reading performance two or more levels below grade, and difficulty with phonological processing tasks.  Results of preliminary analyses suggest that candidate regions in chromosomes 6, 15 and 18 may not contain major dyslexia genes in these families.  Thus, a whole genome scan analysis is currently underway to identify novel regions of interest in the affected families.  The single- and multi-point analyses are based on the dyslexia and dysphasia diagnosis provided by the expert phoniatrists. Since the mode of inheritance for most of the families appears to be autosomal dominant with reduced penetrance and variable expressivity, we are using parametric as well as nonparametric approaches for the analysis.  We will also attempt to construct haplotypes linked to the disorder and, subsequently, we will conduct nonparametric linkage analyses.  Complete results of the genome scan will be presented at the Behavior Genetics Association meeting.


Juko Ando1 and Yutaka Ono2.  Genetic structure of Cloninger's seven factor model revisited.3

1Faculty of Letters, Keio University, Mita Tokyo, 2Health Center, Keio University, Yokohama Kanagawa, 3Supported by a Grant-in Aid for Scientific Research(A)from the Ministry of Education, Science, Sports and Culture

Address:  Faculty of Letters, Keio University, 2-15-45, Mita, Minatoku, Tokyo, 108-8345, Japan Phone: 81 3 3453 4511 Fax: 81 3 5427 1578 Email: juko@msa.biglobe.ne.jp

 

Ando et al. (2001, Journal of Personality, 70,584-609) investigated the genetic structure of R. Cloninger's seven factor model of personality with 296 pairs of Japanese twins with TCI (Cloninger et al. 1993) and revealed that three temperamental dimensions (novelty seeking: NS, harm avoidance: HA, reward dependence; RD) are genetiucally independent.  The current study is its replication with larger sample (513 pairs : 330 pairs of MZs , 116 pairs of same sex DZ, 67 pairs of opposite sex twins).  Univariate analysis shows that AE model is the best fir for all the dimensions but self-directedness(SD) and additive genetic contributions are 21% for NS, 45% for HA, 39% for RD, 34% for PS (persistence) 46% for CO (cooperativeness) and 48% for ST (self-transcendence ). SD can be explained either AE or CE model. Multivariate analyis by Cholesky decomposition indicates again that genetic latent factors for three temperamental dimentions are independent.


Andrey P. Anokhin1, Angela Ralano1, and Erin Myers1.  Heritability of prepulse inhibition of startle reflex in humans.2

1Department of Psychiatry , Washington University School of Medicine, St.Louis, MO, 2Supported by grants DA00421-02 from the NIH and CRTG-00-300-01-PBP from the American Cancer society

Address:  Washington University School of Medicine, 18 South Kingshighway, Suite 2T, St. Louis, MO 63108

 

Prepulse inhibition (PPI) is a suppression of the startle reflex that occurs when intense startle startling stimulus is preceded by a weaker “prepulse” stimulus. PPI is viewed as an index of sensorimotor gating, a fundamental process of sensory input regulation. PPI deficits have been implicated in the biological bases of schizophrenia and some other neuropsychiatric conditions including substance use disorders and proposed as a possible biological marker ("endophenotype") for genetic studies. However, little is known about the genetic determination of PPI in humans. Accordingly, the purpose of this study was to estimate heritability of PPI in normal human subjects. PPI of acoustic eyeblink startle reflex was assessed in 170 young adult female twins (49 MZ and 36 DZ pairs). Response magnitude was measured as square root of the area under the curve of a rectified, averaged, and smoothed orbicularis oculi EMG signal in the time window of 20-120 ms after stimulus onset. Twin intrapair correlations were significant in MZ (r=0.52, P<0.01), but not in DZ twins (r=0.14, n.s.). Genetic analysis using structural equation modeling showed significant heritability of PPI, suggesting that about 50% of the PPI variance is determined by genetic factors.


Andrey Anokhin1 and Angela Ralano1.  Wisconsin Card Sorting Test performance in female twins.2

1Department of Psychiatry, Washington University School of Medicine, St.Louis, MO, 2Supported by grants DA00421-02 and 5P50 AA11998-03 from the NIH

Address:  Washington University School of Medicine, 18 South Kingshighway, Suite 2T,

St.Louis, MO 63108

 

Wisconsin Card Sorting Test (WCST) is one of the most widely used assessments of executive functioning related to prefrontal cortex.  Performance on the WCST has been suggested to indicate familial vulnerability to psychiatric disorders characterized by executive deficits, such as schizophrenia. However, little is known about genetic and environmental determinants of individual differences in WCST performance in the general population. A previous study based on a very small twin sample did not find significant genetic influences (A. Campana, F. Macciardi, O. Gambini, S. Scarone S., 1996, Neuropsychobiology 34, 14-17).  The present study assessed heritability of standard WCST scores in a sample of 166 young female twins including 58 MZ and 25 DZ pairs. A computer-administered version of WCST was used. Several WSCT indices including total number and percent of errors, and the number of perseverative responses showed modest, but significant heritability ranging from 37 to 46 %, whereas other indices such as the number of categories completed and failure to maintain set did not show evidence for genetic influences. The results suggest that selected aspects of executive functioning measured by the WCST are moderately influenced by genetic factors.
Jessica H. Baker1, Kyle L. Gobrogge2, and Kelly L. Klump.  A Twin Study of Similarities in Self and Co-twin Reports of Personality.

1Department of Psychology, Michigan State University, East Lansing, MI, 2Supported by NIH Grant MH 65447

Address:  129 Psychology Research Building East Lansing, MI 48824 Phone:517 432 9861  Email: klump@msu.edu

 

Objective:  Several studies have examined the agreement between self and informant ratings of personality (Ready 2002; Ready & Clark 2002; Hill et al., 1995; Harkness et al., 1995).  However, few studies have examined the relative influence of genetic factors on similarities of self and informant reports of personality.  Thus, the purpose of the current study was to examine genetic and environmental influences on these reports in male and female twins.  Method:  Subjects included 228 MZ and 58 DZ male and female twins participating in the Michigan State Twin Study.  Personality was measured with the Neuroticism, Extraversion, and Openness to Experience Personality Inventory Revised (NEO-PI-R) (Costa & McCrae, 1985).  Twins completed two versions of this instrument, the first asking them to rate themselves, and the second asking them to rate their co-twin. Biometric model fitting analyses were used to examine genetic and environmental influences on similarities between self and informant reports.  Results:  Model-fitting analyses indicated significant additive genetic and non-shared environmental influences on most of the NEO-PI-R subscales.  Discussion:  Findings suggest greater similarity between self and co-twin reports of personality in MZ relative to DZ twin pairs that can be accounted for by genetic and nonshared environmental factors.


Bojan Basrak.  Copulas in QTL mapping.

Eurandom, Eindhoven, The Netherlands

Address:  Eurandom (TUE), P.O.Box 513, 5600 MB Eindhoven, The Netherlands Phone: +31 40 2478123 Fax: +31 40 2478190 Email: basrak@eurandom.tue.nl

 

Detecting linkage of a marker to a quantitative trait locus (QTL) in human genetics essentially means detecting a connection between genetic similarity and similarity of phenotypes. The first similarity is typically measured using the identity by descent (IBD) status and the second one by the notion of linear correlation. This also holds for the two most popular methods--the Haseman-Elston regression method and the variance components likelihood-ratio test. It is well known that the correlation coefficient is the most natural measure of stochastic dependence (similarity) in the world of multivariate normal distributions, but it can be less suitable when the normality assumption is not met. In practical linkage analysis this means that the methods that are derived on the basis of normality have to be used with a great care when this assumption is violated. Not surprisingly, this problem has attracted a lot of attention recently, see for instance J. Blangero, J.T. Williams, and L. Almasy, 2000, Genet. Epidemiol. 19, S8-S14 or P.C. Sham, J.H. Zhao, S.S. Cherny, and J.K. Hewitt, 2000, Genet. Epidemiol. 19, S22-S28.  The most general way of expressing statistical dependence between variables is via copulas. We show how this well established statistical tool can be applied in QTL linkage analysis with a little extra effort and potentially many benefits. One particular copula, namely the bivariate normal copula is discussed in more detail. In particular, we demonstrate how a statistical analysis based on the normal copula model deals with problems of non-normality that appear in many practical studies. Finally we demonstrate applicability and usefulness of this approach by simulation studies.


Daniel M. Blonigen1, Brian M. Hicks1, Robert F. Krueger1, Christopher J. Patrick1, William G. Iacono1, and Matt McGue1.  Psychopathic Personality Traits & Externalizing Psychopathology: Etiologic Connections.

1Department of Psychology, University of Minnesota, Minneapolis, MN, 2The Minnesota Twin Family Study is supported in part by U.S. Public Health Service Grants AA00175, & AA09367, & DA05147, & MH65137

Address:  Department of Psychology 75 East River Rd. University of Minnesota, Minneapolis, MN 55455 Phone: 612-624-0499   Fax: 612-626-2079  Email: bloni001@umn.edu

 

Psychopathic Personality (psychopathy) is defined as a constellation of interpersonal, affective, and behavioral features. Our recent factor analytic work with the Psychopathic Personality Inventory (PPI), a self-report psychopathy measure for non-incarcerated populations, has shown that it is represented by two orthogonal factors. The first factor (PPI-I) is related to social dominance and stress immunity, core features of the affective/interpersonal dimension of psychopathy. The second factor (PPI-II) is marked by negative emotionality and low constraint, and is strongly related to a dimension of externalizing psychopathology, defined as the covariance among child and adult antisocial behavior symptoms, alcohol and drug dependence, and disinhibitory personality traits (R. F. Krueger, B. M. Hicks, C. J. Patrick, S. R. Carlson, W.G. Iacono, and M. McGue, 2002, Journal of Abnormal Psychology 111, 411 - 424).  Although the two factors exhibit distinct relations with personality and behavioral measures, it is not clear if they are etiologically distinct as well. In this study we conducted a biometric analysis of the relationship between psychopathy and externalizing in a sample of male and female twins from the Minnesota Twin Family Study. The Multidimensional Personality Questionnaire was used to index the two PPI factors, and an externalizing factor was derived from a principal components analysis of symptom counts of child and adult antisocial behavior, and alcohol, drug, and nicotine dependence. We performed a Cholesky decomposition of the PPI factor scores and externalizing to index the amount of shared variance among the observed phenotypes that is determined by genetic or environmental contributions.  Ultimately, the results will address the question of whether or not the two phenotypically distinct dimensions of psychopathy are preferentially linked to the externalizing dimension at an etiologic level.


Stefan M. Brudzynski.  Quantitative parameters of the ultrasonic communication in rats.1

Department of Psychology and Centre for Neuroscience, Brock University, St. Catharines, ON, Canada, 1Supported by the Natural Sciences and Engineering Research Council of Canada

Address:  Department of Psychology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario, L2S 3A1 Canada, Email: sbrudzyn@spartan.ac.brocku.ca

 

There is ample evidence that ultrasonic calls emitted by rats are used for intraspecies communication, which plays an adaptive role in improving  chances of individual and group survival.    Ultrasonic calls are emitted in biologically significant situations and they have acoustic features, which are not only specifically recognized by the recipients but also contain a quantitative dimension reflecting the magnitude of the emitter's response. The goal of the presentation is to review the features of the ultrasonic calls in search of the acoustic parameters, which could reflect the quantitative aspect of the rat vocal communication in addition to the commonly recorded rate of calling. Isolation calls of rat pups have a variable sound frequency and call duration, and have changing sonographic structure over time. It has been concluded that the "message" is encoded in one or more of the alternative sweeps of frequency, which facilitate attending and retrieval of the pup by the dam. Isolation calls are replaced with age by two other ultrasonic call patterns. The, so called 22-kHz calls, or alarm calls, are emitted predominantly in agonistic and other aversive situations. They are characterized by a relatively constant sound frequency, and remarkable variability in the duration of single calls. This variability and the results of pharmacological studies suggest that the quantitative aspect in the vocal expression of these calls seems to be encoded in the length of individual calls. Finally, the 50-kHz calls have

been reported in positive, non-agonistic behavioural situations. They are characterized by a very short and relatively constant single call duration, and by a variable sound frequency. Results of the pharmacological studies and the variability of sound frequency suggest that the peak sound frequency is likely to reflect the quantitative aspect in the vocal expression in this type of calls.


Susan A. Brunelli.  Selective breeding for an infantile phenotype (rat pup ultrasonic vocalizations): A window on developmental processes.1,2

Department of Developmental Psychobiology, New York State Psychiatric Institute & Columbia University, New York NY, 1Supported by NIMH Grant MH40430, 2Supported by NIMH Grant MH54027

Address:  New York State Psychiatric Institute Box 40 Room 4917, 1051 Riverside Drive, New York NY 10032 Phone: 212 543 5711 Fax: 212 543 5467 Email: sab9@columbia.edu

 

A series of studies posed two questions: (1) How generations of selective breeding of rats for high (High USV line) or low (Low USV line) levels of USV responses at 10 days of age may affect the time course of USV response development over the postnatal period; and (2) How the development of other behavioral and psychological traits may have been altered over the same period in association with changes in the selected trait.  Longitudinal and cross-sectional studies of rat pups from litters of High, Low and Random lines were conducted in which two cohorts of litters were tested:  one at 3, 10 and 18 days postnatal age, and the second at 7, 14 and 21 days.  In addition to the USV response to two minute isolation tests, other isolation-induced behaviors, physical markers of maturation and measures of thermoregulation were studied. The results support the idea that the developmental trajectories of High and Low lines have been altered differently, i.e., the two lines are not mirror images, and developmental paths are independent of each other.


Tanya Button1, Anita Thapar2, and Peter McGuffin1.  Maternal smoking during pregnancy and antisocial outcomes in young people.3

1Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, 2Department of Psychological Medicine, University of Wales College of Medicine, 3Supported by MRC PhD Scholarship

Address:  PO 80, Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF Phone: +44 (0) 20 7848 0629 Fax: +44 (0) 20 7848 0575 Email:  t.button@iop.kcl.ac.uk

 

Maternal smoking during pregnancy is associated with conduct problems in young people. One possible explanation for this association is the effects of the cigarettes on the brain of the developing fetus, and there is evidence that nicotine exposure affects brain development. An alternative explanation is that smoking during pregnancy is an index of maternal antisocial behavior, and offspring conduct problems may result from genetic transmission for the propensity to antisocial behavior.  This study examines the relationship between maternal prenatal smoking and antisocial behavior using data from 1896 twins pairs from the Greater Manchester and Lancashire Twin Registry. Twins behavior and mothers prenatal smoking habits were analysed using structural equation modelling.  Two models were fitted. In the first it was assumed that maternal smoking had a direct environmental effect (the environmental mediation model), whilst in the second it was assumed that the correlation between conduct disorder and maternal smoking was mediated via the mothers' genotype (the genetic mediation model).  The results confirmed that adolescents whose mother smoked during pregnancy scored significantly higher for antisocial behavior than those whose mothers were non-smokers. This increased with the number of cigarettes smoked daily. The genetic mediation model was a slightly better fit than the environmental model calling into question the frequent assumption that the effects of maternal smoking on later antisocial behavior in offspring result from direct toxic effects on the developing fetus.


Michèle Carlier1,2, Charles Cohen-Salmon1,3, Chabane Chérif1, Fatima Marouf Verray1, Paricia Arechi1, Fabienne Godin1, Franz Sluyter1,4, Brice Marcet5, Bernard Verrier5, and Pierre L. Roubertoux1,6.  Development of congenic strains for mitochondrial DNA in mice.  Implication of mtDNA in pre-weaning development and motor behavior.

1CNRS Génétique Neurogénétique Comportement, France, 2Present address: PsyCLÉ (EA3273), Université de Provence, France, 3Present address: UMR 7593 CNRS and Université Paris VI, Paris, France, 4Present address: SGDP Centre, Institute of Psychiatry, London, UK, 5INPC CNRS 31, Marseille, France, 6Present address: INPC CNRS 31, Marseille, France.  Supported by the CNRS to Génétique Neurogénétique Comportement and to Institut des Neurosciences Physiologiques et Cognitives. F. Sluyter received a fellowship from the Fondation Fysen and Cohen Salmon a financial support from Laboratoire Ipsen.

Address:  Centre de recherche en Psychologie de la Cognition, du Langage et de l’Émotion (PsyCLÉ EA 3273), Université de Provence, 29 avenue Robert Schuman, 13624 Aix en Provence cedex 1, France Phone: 33 (0) 442933999 Fax: 33 (0) 442389170 Email:  mcarlier@up.univ-aix.fr

 

Mammalian mitochondrial (mt) genome that encodes 13 subunits and specifies 22 tRNAs and 2 rRNAs is exclusively maternally transmitted. The implication of the 13 proteins in respiratory chain and ATP synthase has been demonstrated. Their possible impact on cognitive or other behavioral processes has been previously suspected. As the number of mtDNA molecules is large per one somatic cell (more than 1,000) the gene targeting strategy cannot be used to address the implication of mtDNA genes in cognition. For this reason, we developed congenic strains for mtDNA. We selected NZB/BlN and CBA/H mice that carry mtDNA from different origins. We present here the development of this quartet of congenic strains, controls for mtDNA cross-transfer and for the isogenicity of the nuclear background.  mtDNA modulates motor development as soon as the pre-weaning period in interaction with nuclear DNA. This effect persist in adults and an interaction between mtDNA, nuclear DNA and age is observed for a wide set of motor measurements.


Penny L. Biersach Clark, Carol A. Van Hulle, Erri Hewitt, and H. Hill

Goldsmith1.  Exploring the genetic architecture of social and non-social fear in infancy.2

1Department of Psychology, University of Wisconsin, Madison, WI, 2Supported by NIH Grant MH-50560

Address:  Department of Psychology, 1202 W. Johnson St., Madison, WI 53706 Phone: 608-263-4735 Fax: 608-265-3649 Email: plclark@wisc.edu

 

Many researchers have examined the development of fear in infancy. The majority of this research has focused on social fear, which has been shown to be moderately heritable. Additionally, genetic influences account for the largest portion of the covariation in parent-report and observed measures of social fear (Goldsmith et al., 1999, Developmental Psychology 35(4), 972-985). Fewer studies have examined the development of non-social fear in infancy. Recent research suggests social and non-social fear are differentially related to vulnerabilities for disruption in emotion regulation (Locke& Goldsmith, 2002, poster presented at ICIS, Toronto, Canada) highlighting the importance of considering different aspects of fear in infancy.  The current study examines social and non-social fear in 150 6 and 12 month-old twin pairs participating in an ongoing longitudinal study of emotional development. Non-social fear was assessed via observation of infants' reactions to four novel masks. Social fear was assessed via maternal report as well as observation of infants' reactions to a stranger approach. At 6 months, the three measures were not significantly correlated. At 12 months, however, observed social fear correlated with maternal report of social fear (r=.261, p<.05) and observed non-social fear (r=.231, p<.05). All measures exhibited moderate stability over time (r=.248 to .341, p<.05). A bivariate Cholesky model was fit to the data on maternal report of social fear and observed non-social fear for each age.  At 6 months, there was complete overlap in additive genetic and shared environmental influence on social and non-social fear, but non-shared environmental effects were independent. At 12 months, there was no overlap in additive genetic influence, a slight overlap in non-shared environment (re=.15), and a single shared environment factor influenced both measures.  Future analyses will include a larger sample size and multivariate analyses with multi-method assessments of social and non-social fear.


R. P. Corley1, S. E. Young1, M. C. Stallings1, J. K. Hewitt1, A. Smolen1, and D. Huizinga2.  Sibling resemblance for adolescent problem behavior: National Youth Survey and CADD.3

1Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 2Institute of Behavioral Science, University of Colorado, Boulder, CO, 3Supported by grants DA-05131 and DA-11015, HD-10333, MH-43899, and AA-11949

Address:  Institute for Behavioral Genetics, Campus Box 447, University of Colorado,

Boulder, CO 80309-0447 Phone: 303 492 5189   Fax: 303 492 8063  Email: Robin.Corley@colorado.EDU

 

The National Youth Survey (D. S. Elliott, D. Huizinga, and S. Menard, 1989, Multiple Problem Youth: Delinquency, Drugs and Mental Health Problems. New York, NY: Springer, 1989) is a longitudinal study of adolescent problem behavior and its sequelae.  The foundation sample of the National Youth Survey (NYS) consisted of 1725 individuals drawn from a national probability sample of 1044 households, with 574 households represented by only a single adolescent between the ages of 11 and 17, and the remaining 470 households represented by at least two such individuals, when initially recruited in 1976.  Ten waves of assessment on the original respondents have been completed through 2002. The sibling relationships in the NYS sample have been used previously by David Rowe and colleagues (e.g., Rowe & Britt, 1991, Journal of Quantitative Criminology, 7:315-331), but are central to the extension of the NYS into a three-generation family study of problem behavior, a collaborative research effort between the Institutes of Behavioral Science and for Behavioral Genetics at the University of Colorado.  We review the pedigree structures of NYS households and estimate sibling resemblance for indicators of problem use of substances and other problem behaviors, and compare them with estimates from data collected beginning in 1993 from genetically informative adolescent and young adult siblings (twins, adoptive siblings, and full siblings) assessed as part of the Colorado Center for the Genetics and Treatment of Antisocial Drug Dependence (CADD).


Danielle M. Dick1, Richard J. Viken1, Jaakko Kaprio2, Lea Pulkkinen3, & Richard J. Rose1.  Parents: The Anti-Drug?  Clarifying the role of parental influence on adolescent smoking and drinking using data from FinnTwin12.4

1Department of Psychology, Indiana University, Bloomington IN, 2Department of Public Health, University of Helsinki, FINLAND, 3Department of Psychology, University of Jyvaskyla, FINLAND, 4FinnTwin12 is supported by NIH (AA 12502), and by the Academy of Finland.

Address:  Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut St., IB-130, Indianapolis, IN  46202-5251 Phone: 317-274-2218 Fax: 317-274-2387 E-mail: ddick@indiana.edu

 

In 1998, the White House Office of National Drug Control Policy launched the National Youth Anti-Drug Media Campaign, an initiative that has emphasized the role parents can play in preventing their adolescents from using drugs.  We sought to better clarify the influence of parents on their adolescents' substance use using data from a longitudinal twin-family study on the development of smoking and drinking patterns across adolescence.  The sample for this study, FinnTwin12, consists of five consecutive birth cohorts of Finnish twins, born 1983-1987.  Twins were assessed with questionnaires at ages 11-12 and reported on several aspects of their relationship with their parents, such as the amount of time spent engaged in activities with their parents, and the degree to which their parents monitor their behavior.  The twins were reassessed at age 14, at which time they reported on their use of cigarettes and alcohol.  Nearly all measures of parental relations at age 12 predicted smoking and drinking behavior at age 14:  children who spent more time with their parents, reported more parental monitoring and a better home atmosphere were less likely to be smoking or drinking at age 14.  However, twins' reports of parenting were under a modest degree of genetic influence, as were their substance use patterns at age 14.  Therefore, to clarify the role of genetic and environmental influences on the relationship between parenting and substance use, we fit bivariate models to reported parental supervision and smoking/alcohol use.  For all measures of parenting and substance use, shared genetic influence could be dropped from the model.  This suggests that the association between perceived parenting and substance use is not confounded by a shared genetic liability.  Genetically informative twin designs provide a useful method for differentiating these developmental influences.


Brian D_Onofrio1, Eric Turkheimer1, Robert Emery1, Jane Mendle1, Stacy Lynch1,

Wendy Slutske2, Andrew Heath3, Nick Martin4.  Association Between Parental Divorce and Offspring Life Transitions:  Selection or Causation?

1Department of Psychology, University of Virginia, Charlottesville, VA, 2Department of Psychological Science, University of Missouri, Columbia, MO, 3Department of Psychiatry, Washington University, St. Louis, MO, 4Genetic Epidemiology Section, Queensland Institute of

Medical Research, Brisbane, QLD, Australia

Address:  Psychology Department, University of Virginia, 102 Gilmer Hall, PO Box 400400, Charlottesville, VA 22904-4400, Phone: 804-982-4750, Email:  briand@virginia.edu

 

Previous research has shown that children of divorced parents are more likely to initiate harmful behaviors at younger ages and engage in untraditional family transitions than children from intact households.  However, the causes underlying these associations are unclear.  Genetically informed designs, including the Children of Twins design, help delineate the possible genetic and environmental processes that account for the association between parental characteristics and child outcomes. In order to disentangle the relation between parental divorce and life transitions in the offspring, a longitudinal study of twins and their adult children was utilized. The sample included 2,554 offspring from 889 twin pairs from the Australian Twin Registry. Results indicated that children from divorced families started to use alcohol, drink heavily, smoke cigarettes, try marijuana, and engage in sexual intercourse at earlier ages than children from intact families. They were also more likely to have a child before they were 18, live with a cohabiting partner, and experience marital separation themselves.  Genetically informed analyses revealed that environmental processes within nuclear families that are associated with parental divorce accounted for the relations. Shared genetic factors and environmental factors which influence twin families could did not mediate the intergenerational associations.


Cathy Fernandes1, Jose Paya-Cano1, Frans Sluyter1, Ursula D'Souza1, Robert Plomin1, and Leonard C. Schalkwyk1.  The power of gene expression profiling and mouse models to unravel  behaviour.

1Social, Genetic and Developmental Psychiatry Research Centre,Institute of Psychiatry, King's College London

Address:  Social, Genetic and Developmental Psychiatry Research Centre, PO 82, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, U.K. Tel: +44(0)207 848 0279 Fax: +44(0)207 848 0801 Email spjgcaf@iop.kcl.ac.uk

 

Understanding the genetic component of complex traits such as behaviour has long been a formidable task as it has been difficult to study multiple genes and their products in a single system.  Gene expression profiling using microarrays is an exciting new technology that can take a snapshot of the simultaneous gene expression across thousands of genes.  The mouse is an excellent model for such functional genomics research as there is considerable genetic overlap with humans, behavioural phenotypes have been well characterized and a great deal of genomic information is available. Moreover, both genes and environment can be manipulated or controlled in mice, which makes it possible to study the relationship between genes and environment at the level of gene expression.  I will present data on a study comparing hippocampal gene expression profiles across eight different inbred mouse strains (A/J, C3H/HeJ, FVB/NJ, DBA/2J, C57BL/6J, Balb/cByJ, 129S1/SvImJ and SJL/J) using the Affymetrix GeneChip system.  I will focus on the ways in which the microarray data can be analysed to identify novel candidate genes and potential gene interactions, using examples of gene expression profiles that replicate previous findings and those that nominate novel candidate genes in this study.  The potential of using a range of inbred strains of mice for quantitative  analysis of genetic and environmental influences on gene expression profiles will be considered.


Tom A Fowler1, Jane Scourfield1, Anita Thapar1, and Anne Farmer2.  Does Disabling Fatigue in Children & Adolescents Share Common Genes with Depression?

1Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, Wales, 2Social, Genetic & Developmental Research Centre, Institute of Psychiatry, London, England, 3Supported by PPP Healthcare Medical Trust Grant 1206/192

Address:  Department of Psychological Medicine, University of Wales College of

Medicine, Cardiff, Wales, CF14 4XN Phone: 44 (0)29 20742201 Fax :44 (0)29 20747839 Email:

fowlerta@cf.ac.uk

 

INTRODUCTION:  Due to the overlap of symptomology between chronic disabling fatigue and depression it has been suggested that Chronic Fatigue Syndrome (K. Fukuda, S.E. Straus, I. Hickie, et al. 1994, Annals of Internal Medicine, 121, 953-9) is simply a form of depression. A twin method has been employed to examine whether chronic fatigue and depression in adolescence overlap in terms of genetic aetiology.  METHOD:  A screening questionnaire for lifetime ever disabling fatigue was completed by the parents of 1457 twins, aged 8-17 years, identified from the UK population based twin register CASTANET (Cardiff Study of All Wales & Northwest England Twins). Parents and children over 11 were also asked to complete the Mood and Feelings Questionnaire (E.J. Costello and A. Angold, 1988, Journal of the American Academy of Child and Adolescent Psychiatry, 27, 726-37). To examine whether the co-morbidity between disabling fatigue and  depression is due to shared aetiology, a multivariate twin analysis, including a Cholesky decomposition, was undertaken.  RESULTS:  The study showed that fatigue lasting at least one month was familial and had a substantial genetic aetiology. While there were some risk factors that were shared with depression, nonetheless, most of the genetic and environmental risk factors for chronic fatigue were specific and different to those for depression.  CONCLUSION:  Chronic disabling fatigue in adolescents is partly genetically influenced and this genetic aetiological component is largely independent of the genetic risk factors for depression.


Amber L. Gahagan1 and Irwin D. Waldman1.  Pubertal Maturation differences in Genetic and Environmental Influences on Conduct Disorder.

1Department of Psychology, 532 N. Kilgo Circle, Emory University, Atlanta, GA  30322.

Address:  Department of Psychology, 532 N. Kilgo Circle, Emory University, Atlanta, GA  30322 phone:  (770) 986-7715 fax:  (404) 727-0372 e-mail:  agahaga@emory.edu

 

Theories of the development of antisocial behavior have posited greater genetic influences and lesser environmental influences on early- as compared with late-onset antisocial behavior.  In this study, we examine the effects of pubertal maturation (PM) on the genetic and environmental influences on Conduct Disorder (CD) in children and adolescents.  The participants were twin pairs from the Georgia Twin Registry, a registry of all multiple births recorded in the state birth records of Georgia from 1973 to 1991.  In the present study, questionnaire data were available for ~500 twin pairs.  Parent-report questionnaire measures assessed symptoms of DSM-IV childhood disorders, including the symptoms of CD.  For each CD symptom, the parent indicated on a 0 to 4 scale how frequently the child exhibited the symptom during the past year.  A CD symptom scale score was calculated for each child by summing their scores for each of the symptoms that constituted CD.  The questionnaire also contained a set of sex-appropriate items regarding the Tanner stages of PM.  We addressed a number of hypotheses regarding pubertal differences on genetic and environmental influences on CD.  First, univariate behavior genetic analyses were conducted in order to explore the genetic and environmental influences on PM and CD, respectively.  Second, we conducted univariate behavior genetic analyses of CD separately for pre- and post-pubertal children in order to test whether the genetic and environmental influences on CD differed as a function of PM.  Third, we repeated these analyses separately for boys and girls to see whether any PM differences in the genetic and environmental influences on CD differed by sex.  Finally, we conducted bivariate behavior genetic analyses to estimate common and unique genetic and environmental influences on PM and CD.  In this final set of analyses, we explored to what extent the genetic and environmental influences on PM also underlie the etiology of CD.


Jody M. Ganiban1.  Mothering  and Adolescent Externalizing Behavior: A Behavioral Genetic Exploration.2

1Department of Psychology, The George Washington University, Washington, DC, 2The Swedish Twin Mothers Project was supported by a grant from the NIMH (R01 MH54610, PI: Dr. David Reiss)

Address:  Department of Psychology, The George Washington University, Washington, DC

20052. Telephone: (202) 994-7571 Fax: (202) 994-1602 Email: ganiban@gwu.edu

 

Previous research indicates that distal family-level factors such as marital dissatisfaction and parents’ mental health are related to adolescents’ behavior problems, and that these associations are mediated by parenting style. Although these findings are well-established, the mechanisms that account for them are less clear. This paper will examine the degree to which associations between distal family factors and maternal negativity are explained by genetic and environmental factors. Additionally, exploratory analyses will examine whether associations between family factors and adolescents’ externalizing behaviors are best explained by passive genetic transmission or by evocative gene-environment processes.  Data from the Swedish Twin Mothers Project will be presented (Reiss, D., Cederblad, M., Pedersen, N., et al, 2001, Family Process, 8, 40, 261-272). This study included female twins, their partners, and their children. The sample consisted of 150 MZ and 176 DZ female twin pairs (mean age = 44 + 4.5 years), and 552 children (322 male cousins, and 330 female cousins; average age = 15 + 2.2 years). Self-report measures were used to assess the women’s depressive symptoms, marital dissatisfaction, and parenting style. Mothers also rated their adolescents’ externalizing behaviors. Factor analyses were used to create composite scores for marital dissatisfaction and maternal negativity towards her child.  Preliminary analyses indicate that maternal depressive symptoms and marital dissatisfaction contribute to maternal negativity through different channels:  while genetic factors primarily explained associations between depressive symptoms and maternal negativity, associations between marital dissatisfaction and maternal negativity were explained by nonshared environment factors.  Exploratory analyses will capitalize upon the inclusion of adolescent cousins who vary in genetic relatedness in this study, and estimate the degree to which associations between maternal negativity and adolescents’ externalizing behaviors are explained by the passive transmission of genes from mother to child, or by the adolescents’ unique genetic makeup.


Heather L. Gelhorn1, Michael C. Stallings1, Susan E. Young1, Robin P. Corley1, John K. Hewitt1, Thomas J. Crowley2.  A Detailed Investigation of DSM-IV Conduct Disorder Symptoms: Heritability of Individual Items and a Comparison of Selected and Unselected

Samples.3

1Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 2Dept. of Psychiatry, U. of Colorado Health Sciences Center, Denver, CO, 3Supported by NIDA grants DA-05131, DA-11015, DA-12845

Address:  Institute for Behavioral Genetics, Campus Box 447 University of Colorado, Boulder, CO 80309-0447 Phone: (303) 735-2428 Fax: (303) 492-8063 Email: gelhorn@colorado.edu

 

Research on antisocial traits from twin and adoption studies has consistently implicated genetic factors in the etiology of conduct disorder (CD). However few studies have looked at individual symptoms to determine the extent to which these behavioral problems may be genetically or environmentally influenced.  Additionally, researchers frequently employ case-control designs where CD symptoms are compared between selected samples and unselected controls. Such strategies assume that the selected cases simply represent the extremes of an underlying distribution that is shared with the controls.  There has been very little research to directly support this assumption.  The current study uses both patient and community-based adolescents participating in the Center for Antisocial Drug Dependence at the University of Colorado.  The aim of the investigation is to characterize individual DSM-IV CD symptoms in terms of heritability, age trends, severity, and the underlying factor structure of the disorder.  Twin analyses were conducted to estimate heritability at the item level, yielding a wide range of estimates (.00 - .80). Guttman scaling was carried out to examine possible heterogeneity in the relative severity of symptoms between the selected and community samples.  Binary factor analyses were used to explore factor structures for the two groups.  Results indicate that selected and control samples likely share a single underlying distribution for CD symptoms.  In general the single distribution appears to be a robust assumption and there are few items that show important variation between clinical and control adolescents in our sample.  The results of this study will be useful for future studies aimed at finding genetic variants that contribute to risk for CD.


Kyle L. Gobrogge1 and Kelly L. Klump1.  Homosexual Mating Preferences from an Evolutionary Perspective.2

1Department of Psychology, Michigan State University, East Lansing, MI, 2Supported by the Michigan State University Dean’s Assistantship Undergraduate Grant

Address:  5400 Mall Drive West Apt. 3111, MI 48917 Phone:  517/881 3776 Email: gobrogge@msu.edu

 

Objective:  Several studies have examined mating behavior from an evolutionary perspective in both heterosexual and homosexual male populations (Silverthorne & Quinsey, 2000; Bailey et al., 1994; Jankowiak et al., 1992; Freund et al., 1973).  These investigations have shown that both heterosexual and homosexual men prefer younger partners compared to heterosexual women.  However, most studies relied on laboratory-based assessments that required subjects to hypothesize about their preferences and did not specify what types of relationships were desired for each preference.  The purpose of the present study was to examine these issues naturalistically by comparing partner preferences of homosexual and heterosexual men who placed internet personal advertisements.  Method:  Subjects included 338 homosexual and 265 heterosexual men placing internet personal ads on lavalife.com in each of the 50 states in the U.S.  Only subjects who mentioned a preferred age of partner were included.  Ads were coded for the subject’s age, the relationship type they were seeking (i.e., sexual encounter versus longer-term relationship), and their partner age preferences.  Chi-square analyses and ANOVAs with Tukey’s post hoc t-tests were used to analyze differences in general preferred age (i.e., younger, older, same, or open), mean preferred age of partner, and relative difference in age between ad placer and partner sought.  Results:  Heterosexual and homosexual men seeking sexual encounters only sought significantly older partners and a wider age range of partners compared to men seeking longer-term relationships.  Discussion:  These findings indicate that both heterosexual and homosexual men are less selective about their partner’s age when seeking a sexual encounter.  These results suggest that sex, age, and relationship type preferences may develop independently.  Additional research examining a range of mating preferences and relationship types sought in heterosexual and homosexual men and women is needed in order

to replicate the current findings.


Detre A. Godinez1, Michael C. Stallings1, Susan E. Young1, Robin P. Corley1, John K. Hewitt1.  Investigating Genetic and Environmental Influences on Age at Onset of Alcohol Use and the Latency from First Use to Regular Use in the Colorado Adolescent Twin Sample.2

1Institute for Behavioral Genetics, University