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perhaps they were legitimate and not tion accorded him by Festschrift cologists II: Interviews by David Healy (pp. to be feared as symptoms. He hoped to attendees; the crowd of colleagues, 377–407). : Altman. fully embrace and enjoy these feelings, students and friends knew his feel- Myrianthopoulos, N. C., Nichols, P. L., Broman, S. H., & Anderson, V. E. (1972). Intellectual yet the cool hand of caution kept them ings were/are legitimate. development of a prospectively studied popu- in partial check. Additional information about the lation of and comparison with I have known life and work of Professor Irving singletons. In J. de Grouchy, F. J. G. Ebling, for many years. The weight of his and I. W. Henderson (Eds.), Human : Gottesman can be found in the refer- Proceedings of the Fourth International Congress scholarship is evident, perhaps best ences listed at the end of this article of Human Genetics (pp. 243–257). demonstrated by his receipt of the and on his homepage: Newman, H. H., Freeman, F. N., & Holzinger, K. from the J. (1937). Twins: A study of heredity and envi- International Society for Psychiatric References ronment. Chicago: University of Chicago Press. Genetics — the only such honor ever Gottesman, I. I. Biography (unpublished). Price, R. A., & Gottesman, I. I. (1991). Body fat in identical twins reared apart: Roles for genes received by a . Like Gottesman, I. I., & Bertelsen, A. (1989). and environment. Behavior Genetics, 21, 1–8. Confirming unexpressed genotypes for schizo- Gottesman, I would, however, go Segal, N. L. (2000). Entwined lives: Twins and phrenia. Archives of General , 46, beyond the obvious to note that no what they tell us about human behavior. New 867–872. one has grasped the texture of York: Plume. Gottesman, I.I., & Shields, J. (1972). Schizo- Torrey, E. F., Bowler, A. E., Taylor, E. H., & science, the culture of the field or the phrenia and genetics: A study vantage rules of research better than he has – Gottesman, I. I. (1994). and point. New York: Academic Press. manic depressive disorder: The biological roots of he is a master at it. In conclusion, I Healy, D. (1998). Irving Gottesman: Predisposed mental illness as revealed by a landmark study of would urge him to relish the recogni- toward predispositions. The Psychopharma- identical twins. New York: Basic Books. ■

Abstracts from the Festschrift — Foreword

Lisabeth F.DiLalla Southern Illinois University School of Medicine, Carbondale, USA

University of Virginia, Dr. Gottesman Hospital, Germany), Susan Trumbetta The purpose of this Festschrift was to returned to the (Vassar College), and honor the distinguished scientific where he was formerly a Professor of (). The symposia career of Dr. Irving I. Gottesman, . He will have appointments discussants were Drs. Lisabeth DiLalla whose work on schizophrenia and the at the Psychiatry Department at the (Southern Illinois University School of behavior genetics of personality and University of Minnesota School Medicine), Dan Hanson (University of , primarily through of Medicine and at the Veterans Minnesota), William Iacono twin research, has permeated the Administration Hospital in Minn- (University of Minnesota), Sandra Scarr thinking of both the scientific commu- eapolis, where he will continue his (Emerita, University of Virginia), and nity and the public at large. The research and collaborations. S. Charles Schulz (University of Festschrift was held in Minneapolis, The presenters at the Festschrift were Minnesota School of Medicine). Lunch MN, on June 8th and 9th, 2001, and Dr. Gottesman’s students, colleagues, discussion group leaders were Drs. brought together a remarkable group and friends. They included Drs. Aksel Sheri Berenbaum (Southern Illinois of researchers whose work has been Bertelsen (Aarhus Psychiatric Hospital, University School of Medicine), touched, both directly and indirectly, Denmark), Thomas J. Bouchard, Jr. Leonard Heston (Emeritus, Univ. of by Dr. Gottesman over the past 35 (University of Minnesota), Greg Carey Washington School of Medicine), Ann years. The title of the Festschrift (University of Colorado), David Masten (University of Minnesota), reflects the many areas of research in DiLalla (Southern Illinois University), Vishwajit Nimgaonkar (University of which Dr. Gottesman has been actively Niki Erlenmeyer-Kimling (Columbia Pittsburgh), Susan Resnick (National involved. Speakers came from all over University), Anne Farmer (King’s Institutes of Health), and the world to present research and to re- College London), H. Hill Goldsmith (California State University, Fullerton). establish ties with each other and with (University of Wisconsin), Matt Dr. Gottesman is internationally Dr. Gottesman. The conference was McGue (University of Minnesota), renowned for his extensive and held in Minneapolis because, following Peter McGuffin (Kings College innovative work in many areas of his retirement this spring from the London), Hans Moises (Kiel University psychopathology, most notably his twin

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research on schizophrenia. He recently to apply polygenic/threshold models of everyone had a chance to contribute by was awarded the Distinguished Scientific inheritance to the field of psy- either presenting, asking questions, or Contributions Award from APA. Receipt chopathology. Their threshold model interacting one-on-one. This was a of this Award reflects the committee neatly describes the mechanism by chance not only for old friends to meet consensus that he is “at the absolute top which behavior varies from normal to again, but also for students to meet of the field”. His research focuses on abnormal, positing that genetic and some of the people they had only read genetic principles and the many ways environmental risks for psychopathol- about. The gathering mixed scientists that genetic factors interact with and ogy exist, and that an accumulation of from every rank, from students through augment environmental influences that sufficient risks can push an individual emeriti, and provided us with a wonder- lead to psychopathology. His innovative over the threshold from normal behav- ful opportunity to learn, to teach, and work with twin populations, including ior to psychopathology. Fewer risks to think. Further information about the the study of identical twin pairs discor- may result in sub-threshold manifesta- Festschrift can be found on the web dant for schizophrenia and other tions of unusual behavior, but not in page at . , has greatly influenced overt psychopathology. A second much of the behavior genetics literature. model of development is his reaction References Dr. Gottesman’s impact on the field is range concept (Gottesman, 1963), Gottesman, I. I. (1963). The efficiency of several combinations of discrete and continuous vari- evident not only through his own work, more recently elaborated into a reac- ables for the diagnosis of zygosity. Proceedings, but also through the work of the large tion threshold model (Turkheimer, Second International Congress of Human number of students whom he has men- Goldsmith, & Gottesman, 1995). This Genetics (pp 346–347). Rome: G. Mendel tored and who have gone on themselves model elegantly describes the ways that Institute. to make major contributions to the fields genetic and environmental influences Gottesman, I. I., & Moldin, S. O. (1999). Schizophrenia and genetic risks: A guide to of psychology and psychopathology. separately create limits for the expres- genetic counseling for consumers, their families, Included at the Festschrift were both stu- sion of behavior, resulting in behaviors and mental health workers, 2nd ed. Arlington, dents and colleagues who fall into this that are multiply determined, but have VA: NAMI. category, many of whom currently upper and lower limits as a function of Gottesman, I. I., & Shields, J. (1967). A poly- genic theory of schizophrenia. Science, 156, conduct leading edge research on twins both genetic and environmental influ- 537–538. as a direct result of their interactions ences. Dr. Gottesman first introduced Turkheimer, E., Goldsmith, H. H., & with Dr. Gottesman. Drs. Goldsmith, this concept from the genetics litera- Gottesman, I. I. (1995). Commentary — McGue, and Carey were graduate stu- ture into psychology, and now it is Some conceptual deficiencies in ‘developmen- dents of Dr. Gottesman’s at the included in nearly every introductory tal’ behavior genetics. Human Development, 38, 142–153. University of Minnesota in the 1970’s. psychology textbook. Dr. Bouchard is a self-proclaimed Dr. Gottesman’s treatment of his mentee of Dr. Gottesman from their research topics is impressive in its shared faculty time at the University of mixture of science and compassion. He Presentation Abstracts Minnesota. Drs. Farmer and McGuffin has always been sensitive to issues of ■ were post-doctoral fellows at Washington genetic determinism and has been clear Developmental Behavior University in St. Louis when Dr. about the importance of both genetic Genetics Symposium Gottesman was on faculty there, and and environmental influences on behav- TEMPERAMENT AND CHILDHOOD they became students, collaborators, and ior. Even when there is evidence of a BEHAVIORAL DISORDERS friends. Drs. Erlenmeyer-Kimling, genetic effect on a disorder, he is a H. Hill Goldsmith, Ph.D., Leona Tyler Professor, Moises, and Bertelsen met Dr. strong advocate for individual personal Department of Psychology, University of Wisconsin. Gottesman through research avenues rights. For example, in a recent NAMI Research on childhood behavioral dis- and became close collaborators and (The Nation’s Voice on Mental Illness) orders has historically proceeded friends, publishing together over a large pamphlet on Schizophrenia and without sufficient reference to the number of years. Drs. L. DiLalla, D. Genetic Risks (Gottesman & Moldin, growing body of work on the of DiLalla, and Trumbetta were graduate 1999), the authors answer the question typical emotional development and students of Dr. Gottesman’s at the of whether schizophrenics should have temperament. Reviewing data from University of Virginia in the 1980’s and children, with the following statement: several studies, we consider experien- 1990’s. Dr. Turkheimer was recruited by “A simple ‘yes’ or ‘no’ answer cannot do tial, biological and genetic factors as Dr. Gottesman to the University of justice to this very personal and delicate providing causal input to typical devel- Virginia, where they have been compa- question that goes to the heart of per- opmental variation in fearfulness, triots in behavior genetic work in the sonal liberty and civil rights in a pleasure, irritability and other tempera- clinical department of Psychology. democratic society.” Dr. Gottesman’s mental traits during infancy and early Dr. Gottesman is one of the world’s research has combined a compassionate childhood. Longitudinal behavioral leading experts on the genesis of schiz- treatment of the rights of individuals methods, psychophysiological mea- ophrenia. His constructs of the with a rigorous scientific approach to sures, and a behavior-genetic development of psychopathology have psychopathology, resulting in a career framework are used to approach these become accepted models for the ways worthy of commemoration. This issues. Twin study results implicate, for in which genes and environment inter- Festschrift provided the appropriate instance, moderately strong genetic act. For example, Dr. Gottesman (in forum for such a celebration. The influences on different facets of tem- 1967, with James Shields) was the first atmosphere was informal enough that peramental fearfulness as well as

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childhood anxiety symptoms. Then we health risk behaviors, including consis- ■ Genetic Influences on consider the distinction between tency and changes in each over the Psychopathology Symposium normal range temperament and child- period studied. We also examine the GENETIC AND ENVIRONMENTAL hood behavioral symptoms from a degree to which genetic and environ- RISK FACTORS FOR MAJOR quantitative genetic perspective. mental factors implicated in health risk DEPRESSION Biological correlates (cortisol, asym- behaviors may contribute to the heri- Anne Farmer, MD FRCPsych, Professor of Psychiatric metric frontal EEG activation, cardiac Nosology at the Institute of Psychiatry and Director of tability of divorce risk and of risk for Medical Education at the London. reactivity) of inhibited behavior are never marrying. considered as related Major technological advances have ensured that molecular genetics has for anxiety. In a non-genetic analysis, ■ Genetic Influences on dominated research activity in psychi- we report the prediction of internaliz- Personality Symposium ing problems during kindergarten from atric disorders and behavioural traits earlier temperament and earlier basal PERSONALITY AND over the past 2 decades. Some PSYCHOPATHOLOGY cortisol measures. Our review high- researchers have focused all their atten- lights connections between behavioral Gregory Carey, Ph.D.,Associate Professor, tions on “genes” and seem to regard Department of Psychology, and Faculty Fellow, Institute indicators and various putative endo- for Behavioral Genetics, University of Colorado. ”the environment” as that proportion phenotypes and the fuzzy boundary David DiLalla, Ph.D., Associate Professor, Department of the variance in liability (to develop a between normal-range temperament of Psychology, Southern Illinois University. particular disorder or trait) that is ”left and childhood behavioral disorders. In this paper, we analyze two models over” in calculations of the contribu- for the genetic association between tion of genetic risk factors, and DEVELOPMENTAL BEHAVIORAL personality and psychopathology. The therefore something that can be GENETIC PERSPECTIVES ON ”ignored”. One reason for this lack of ADOLESCENT SUBSTANCE USE first is a mediation model whereby interest is that for the most part, envi- AND ABUSE genes influence phenotypic personality traits which subsequently influence ronmental risk factors for many Matt McGue, Ph.D., Professor, Department of disorders and traits are unknown. Also, Psychology, University of Minnesota. libility to psychopathology. The second those that are recognised make rela- Behavioral genetic studies of substance model assumes that genes influence tively small contributions to the use and abuse in adult samples impli- common biological pathways for both variance compared to genetic risk cate a strong influence of genetic personality and psychopathology. In factors (Jablensky & Eaton, 1995). In factors. Nonetheless, we know rela- general, mediation models explain contrast to those who ignore the envi- tively little about the how genetic observed twin data more poorly than ronment, Professor Irving Gottesman, influences on substance use disorders do common biological pathway whose life’s work we are celebrating, combine with or are modulated by models. We discuss potential reasons has always emphasised the importance environmental factors. We will for this phenomenon. of environmental risk factors and their describe longitudinal behavioral interaction and co-action with genes in genetic research aimed at identifying GENETIC INFLUENCE ON SOCIAL relation to both disorders and behav- the determinants of initial use of ATTITUDES: ANOTHER CHALLENGE TO ioural traits. (Gottesman, 1991). alcohol and other substances in early FROM BEHAVIOR GENETICS In recognition of Professor Gottes- adolescence, the transition to regular Thomas J. Bouchard, Jr., Ph.D., Professor, Department man’s major contribution to research in patterns of substance use in late ado- of Psychology, and Director of the Minnesota Center this area, I will discuss recent studies lescence, and the progression to for Twin and Adoption Research, University examining both genetic and environ- substance abuse and dependence in of Minnesota. mental risk factors in major depression, early adulthood. There is now a sufficient body of where the causal role of certain types of empirical evidence to support the con- HEALTH HABITS, MARRIAGE, AND life event is well-recognised (Brown & clusion that within modern industrial DIVORCE DURING THE GREATEST Harris, 1978). In particular, I will GENERATION’S MIDDLE AGE societies measures of social attitudes present recent findings from the Susan Trumbetta,Ph.D.,Assistant Professor, manifest significant variance due to Depression Study, a sib-pair study of life Department of Psychology,Vassar College. genetic factors. This genetic variance events and depression in depressed Social causation and social selection cannot be explained by supposed nui- probands, their nearest aged siblings, hypotheses have been offered to sance variables such as general healthy control probands and their sib- explain persistent positive relationships cognitive ability or personality. These lings (Farmer et al., 2000). Unlike some between marriage and physical health findings challenge the belief that twin studies (Kendler et al, 1994) where observed in both clinical and epidemi- family rearing environment and a self- report checklist method has been ological studies. This study evaluates straightforward learning models of used to assess whether particular events the strength of these hypotheses in attitude formation and acquisition have occurred, in the Cardiff study, life light of data from the National found in psychology textbooks are suf- events were recorded following a Academy of Sciences-National ficient to explain kin similarity in detailed interview, the Life Events and Research Council’s World War II attitudes. The evidence in support of Difficulties Schedule (Brown & Harris, Veteran Twin Registry. Using data this conclusion, based on twin, adop- 1978). In addition, measures of person- from the 1972 and 1985 health ques- tion and family studies, will be ality, cognitive and attributional style tionnaires, we examine phenotypic reviewed and its implications for were also administered. The study associations between marital status and future research explicated. design has enabled us to examine the

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relationship between the familiality of psychopathology and early phenotypic well as cognitive and behavioral dys- depression, reporting an excess of indicators of the genetic liability to function which appear long before the certain types of events and aspects of schizophrenia and related disorders. In onset of the illness. Findings of studies personality and cognition. For example, the NYHRP, two samples (N = 324) of will be reviewed suggesting an involve- do individuals with high scores on mea- offspring of schizophrenic, affectively ment of neurodevelopmental genes in sures of sensation seeking have more life ill, and psychiatrically normal parents the susceptibility to schizophrenia. events due to their propensity for have been followed from the age of “hazard prone” behaviour? An alterna- 7–12 years old (in 1971–72 or ■ Molecular Genetics and the tive hypothesis is that those with high 1977–79) to mid-adulthood in search Future of the Field Symposium scores for Aneuroticism@ exaggerate the of this goal. Although all of the off- NULL HYPOTHESIS SIGNIFICANCE impact of life events, and are thereby spring were free of major psychiatric TESTING AND THE MOLECULAR ”threat perceiving”. disorders in childhood, 14%, 5% and GENETICS OF COMPLEX 0.6% of the three parental diagnostic BEHAVIOR CONTRIBUTIONS OF THE DANISH TWIN REGISTER TO groups, respectively, have later devel- Eric Turkheimer, Ph.D., Associate Professor and UNDERSTANDING oped adulthood schizophrenia or Director of Graduate Studies, Psychology Department, University of Virginia. PSYCHOPATHOLOGY related psychoses (SRP). Aksel Bertelsen, M.D., Institute of Psychiatric In a childhood test-battery, deficits This paper examines an ironic contrast Demography,Aarhus Psychiatric Hospital, Risskov, in three neurobehavioral measures — between two of the most important Denmark assessing global attention, gross motor trends in contemporary social science. Denmark has been an eldorado for skills, and short-term verbal memory— On the one hand, after 75 years of research in psychiatric epidemiology and emerge as moderate to strong predic- domination by ritualistic null hypoth- genetics due to its thoroughly registered tors, respectively, of adulthood SRP, but esis significance testing (NHST), the population. The nation-wide population not other psychiatric disorders, in the field has at last begun to question the register (the Central Person Number group with schizophrenic parents. utility of its reliance on p <.05 Register), the Central Psychiatric These deficits, however, were rare or methodology, and begun to turn in Register, and the twin, adoption, and absent in the offspring of affectively ill the direction of effect size estimation, criminal registers together with an until and normal parents, thus suggesting careful consideration of statistical recently homogenous and easily accessi- that they may be expressions of specific power, Bayesian approaches, and ble population have allowed and at the schizophrenia-susceptibility genes. The meta-analysis. On the other hand, same time been an obligation to do extensive data bank of the NYHRP is exponential advances in molecular extensive research in psychiatric genetics. under analysis to identify other neu- genetic technology has made it possi- During the last 30 years, Irving robehavioral, social, clinical, ble to conduct ever-widening scans of Gottesman has been our initiator, collab- environmental and family variables, the genome in a search for associations orator, and mentor in a number of collected over the longitudinal course between specific alleles and complex studies: A twin study on criminality, a of the project, that may be potentiators behavior. And at the bottom of the twin study of schizophrenia and particu- interacting to enhance the effect of statistical methodology on which this larly in its extension in a study on the such susceptibility genes. Different pat- new technology is based, we findY. offspring of discordant monozygotic terns of variables are also under NHST, complete with familiar discus- schizophrenic twins, a twin study on investigation in offspring who have sions of appropriate p values, Type-I manic-depressive disorder, and most developed affective, rather than schizo- error corrections, appropriate levels of lately, a dual mating study on the off- phrenia-related, psychoses. statistical power, and the relative spring of two psychiatric in patients. The advantages of parametric and nonpara- GENES AND survey of the results from these studies metric approaches. will be mentioned in their contributions NEURODEVELOPMENT IN SCHIZOPHRENIA There are only two ways to resolve to psychopathology and psychiatric this apparent paradox. Either the mole- genetics will be discussed. Hans W.Moises, Ph.D., Director, Molecular Genetics Laboratory, Department of Psychiatry, Kiel University cular genetics of complex behavior is Hospital, Kiel, Germany. better suited to NHST than routine ■ Genetic Influences on Genetic and neurodevelopmental social science, or it is following a Schizophrenia Symposium hypotheses are currently the two most methodological blind alley already thor- LONGITUDINAL PREDICTION OF widely accepted models to explain the oughly explored by several generations SCHIZOPHRENIA IN A distal etiology of schizophrenia. The of social scientists. Choosing between PROSPECTIVE HIGH-RISK STUDY polygenic model of schizophrenia by these alternatives requires an explana- Niki Erlenmeyer-Kimling, Ph.D., Chief of Medical Gottesman and Shields (1967) has tion of an aspect of the NHST problem Genetics, New York State Psychiatric Institute, and Professor, Departments of Psychiatry and Genetics and been confirmed by numerous family, that remains poorly understood: why Development, College of Physicians and Surgeons, twin, adoption, and linkage studies has the practice of NHST hung on so Columbia University. while the developmental hypothesis of long (and it’s not dead yet) despite A goal of high-risk research studies, the disorder is able to explain such almost universal opposition to it on the- such as the New York High-Risk divergent findings as obstretic compli- oretical grounds? The answer, I will Project (NYHRP), has been the identi- cations, congenital dermatoglyphic suggest, is that although NHST was fication of neurobiological variables abnormalities, neurological soft signs, designed as a method for distinguishing that may be both predictors of future and structural brain abnormalities, as true scientific signals from sampling

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error, sampling error has turned out not In other childhood or developmental psychiatric disorder comprised the to be the most important source of disorders such as ADHD and reading groups in this study. T scores for each noise in social science. Instead, noise in disability there are also promising find- scale were entered into a discriminant social science arises from the ineluctable ings. Current molecular genetic studies function analysis (DFA) in which diag- contextual embedding of behavior. in behaviour focus not just on disor- nosis served as the grouping variable. What we learn about a complex psycho- ders but on traits that showed DFA correctly placed in diagnostic logical phenomenon in one setting does continuous variation in the popula- groups 19 future schizophrenics and 18 not, in general, apply to the same phe- tion, such as personality and cognitive non-schizophrenics; overall accuracy of nomenon in a different setting. The ability. Discovering genes involved in the function was 80.4% (χ2 ‘ 18.8, df ‘ persistence of NHST is explained by normal and abnormal behaviour and 6, p < .005). PPP for group placement the fact that it seems to offer the frus- following through with functional was 79% and NPP was 82%. These trated social scientist a statistical and studies of the effects of molecular vari- results, considered along with other methodological remedy for the context- ation is likely to have a profound recent evidence, support the notion dependent variability of behavior, but influence on psychiatry and psychol- that there are premorbid processes that unfortunately it doesn’t work. The final ogy. First, there are implications for a differentiate schizophrenics from question is whether linkage and associa- better understanding of the neurobio- non-schizophrenics, and, further, that tion studies of complex behavior are as logical underpinning of disorders such the MMPI is effective in measuring context-dependent as traditional social as schizophrenia and normal traits such those processes. science. Consideration of this question as personality and . Second, leads to conclusions about the possibili- behavioural will drive the last THE MULTIPLE DIMENSIONS nails into the coffins of those seem- OF SCHIZOTYPY IN THE FIRST ties and limitations of genetic DEGREE BIOLOGICAL RELATIVES explanation in psychology. ingly everlasting old phonies: “nature OF SCHIZOPHRENIA PATIENTS versus nurture” and “mind versus BEHAVIOURAL GENOMICS: Monica E. Calkins, Clayton E. Curtis,William M. body”. With this should come a third Grove, & William G. Iacono, University of Minnesota, WHERE MOLECULAR GENETICS IS result, a change in attitude towards Minneapolis, MN. TAKING PSYCHIATRY AND mental illness, not, as has sometimes PSYCHOLOGY There has been considerable research been suggested, in the direction of Peter McGuffin, M.D., Ph.D., Director of the Social, aimed at identifying individuals who Genetic, and Developmental Psychiatry Research increasing its stigma, but rather in the carry the latent predisposition for schiz- Centre, Institute of Psychiatry, King’s College London. direction of reducing it. Fourth, there ophrenia, with much effort devoted to Both the promise and the frustrations will be important spin-offs for drug the characterization of the personality of applying molecular genetic methods discoveries in that molecular genetics characteristics of the biological relatives in the study of behaviour are well will identify targets for new and more of schizophrenia patients. Although exemplified by schizophrenia. effective compounds, ultimately resource consuming interview methods Although it is clear from twin and improving the lives of those with of assessing schizotypal features in adoption studies that schizophrenia is mental health problems. schizophrenia relatives have yielded highly heritable (with most estimates promising results, investigators have suggesting that genetic factors account long sought self-report measures that for about 80% of variance), linkage Poster Abstracts index genetic risk for schizophrenia. studies have produced conflicting and, The Schizotypal Personality Question- at times, confusing results. This almost CAN THE MMPI AT AGE 15 naire (SPQ) is a self-report measure PREDICT -TO- certainly reflects on the fact that schiz- BE? REVISITING THE QUESTION that assesses the 9 major features of ophrenia, as predicted by Gottesman schizotypy as defined by the DSM. P.Kevin Bolinskey, Irving I. Gottesman, and Daniel and Shields (1967), is a polygenic dis- R. Hanson, University of Virginia,Charlottesville,VA, and Previous work has indicated that three order where many genes of small effect University of Minnesota, Minneapolis, MN. factors (social-interpersonal, cognitive- combine to produce a liability. For Recent research has found evidence for perceptual and disorganization) example, a systematic scan using nearly a group of selected clinical and supple- underlie the SPQ. The SPQ, modified 200 families containing affected sib mentary MMPI scales to differentiate to include validity scales, was adminis- pairs (Williams et al., 1999) excluded a premorbid schizophrenics from com- tered to 135 non-psychotic first-degree gene, conferring a relative risk of three parison groups. This research has relatives of schizophrenia patients and from over 80% of the whole genome. focused on a group of scales comprising 112 healthy controls. Social interper- However, some chromosomal regions the Moldin-Gottesman Psychometric sonal deficits best differentiated have been replicated in more than one Index. The current study examined the relatives from controls and thus may be study and it seems likely that a combi- validity of an index of six scales to the most important features associated nation of linkage and association predict future schizophrenia onset in with genetic vulnerability. Principal approaches will identify at least some the Hathaway-Monachesi ninth-grade components analysis yielded three of the genes involved in the foreseeable normative participants who later devel- factors that correlated highly with pre- future. Meanwhile, recent linkage oped the disorder. Twenty-three viously reported factors. Inconsistent studies have produced replication in participants (14 males, 9 females) with with the hypothesis that schizophrenia disorders where the genetic basis has, valid MMPIs who later developed relatives are more defensive in respond- in the past, been disputed, such as schizophrenia and their classroom- ing to schizotypy questionnaires, autism (Hanson & Gottesman, 1982). matched controls who developed no relatives were significantly less defensive

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than controls. The results demonstrate recognition memory for faces. However, schizophrenia patients consistently that a multidimensional paper-and- studies have not examined the specificity demonstrated impaired performance pencil measure can characterize of this deficit relative to other cognitive across working memory measures, their schizotypal features in schizophrenia functions nor the relationship between first-degree nonpsychotic relatives relatives and, as such, will be useful for this deficit and particular schizophrenia demonstrated impairment only on a the further delineation of the heritable symptoms. In addition, no studies have subset of measures. It may be that schizophrenia spectrum phenotype. examined recognition memory for faces working memory impairment in these in unaffected biological relatives of schiz- relatives is directly related to the degree INTERNALIZING AND ophrenia patients who likely share some EXTERNALIZING AS A FUNCTION to which executive processes are evoked, OF RELATIONSHIP IN PRESCHOOL of the genetic diathesis for this disorder such that only tasks that require substan- TWINS AND SIBLINGS without presenting the potential con- tial manipulation of material within Rebecca A. Caraway & Lisabeth F.DiLalla, Southern founds of mentally ill study samples. The working memory or its protection from Illinois Univ. School of Medicine, Carbondale, IL. Faces subtests from the Wechsler interference reveal impaired perfor- Identical (MZ) twins, who spend much Memory Scale -Third Edition were used mance. These findings may begin to time with each other and are very much to evaluate recognition memory for faces suggest which components of working alike, may experience less diversity in in 39 schizophrenia patients, 33 of their memory are most effective at identifying their playmates than do fraternal (DZ) first-degree relatives and 56 normal con- individuals with genetic risk for schizo- twins, who may experience less diversity trols. Both schizophrenia patients and phrenia and the corresponding candidate than do other-age siblings. Therefore, their relatives were impaired, relative to sites of neuropathology. developmental social genetics theory control participants, in recognition SACCADIC DISINHIBITION IN might predict that MZ twins will be memory for faces after controlling for group differences in simple attention or SCHIZOPHRENIA PATIENTS more socially withdrawn than DZ twins, AND THEIR FIRST-DEGREE who will be more withdrawn than non- verbal memory. Further, recognition BIOLOGICAL RELATIVES: twin siblings. Conversely, MZ twins memory for faces was associated with A PARAMETRIC STUDY OF might be either more aggressive because positive symptoms in the schizophrenia THE EFFECTS OF INCREASING of less experience with others or less group and schizotypal personality traits INHIBITORY LOAD aggressive because they are more inhib- in the relative group. These findings may Clayton E. Curtis, Monica E. Calkins, & William G. Iacono, University of Minnesota, Minneapolis, MN. ited. These hypotheses were assessed have important implications for reduc- using the Child Behavior Checklist ing etiological heterogeneity among Several studies have reported that (CBCL) scales of withdrawn, aggressive, schizophrenia populations, identifying patients with schizophrenia and their rel- internalizing, and externalizing. Parents disorder susceptibility among their rela- atives perform poorly on antisaccade of 5-year-old twins and 5-year-old non- tives and furthering understanding of tasks and have suggested that this deficit twin sibling pairs completed a packet of disorder etiology. represents saccadic disinhibition. If this proposition is so, then varying task para- questionnaires, among them the CBCL. WORKING MEMORY IMPAIRMENT Thirty-two MZ twins, 68 DZ twins, and IN SCHIZOPHRENIA PATIENTS meters that specifically increase the 51 siblings were rated on the CBCL. A AND THEIR FIRST-DEGREE difficulty with which unwanted saccades MANOVA was performed on with- RELATIVES can be inhibited should exacerbate drawn, aggressive, internalizing, and Heather M. Conklin, Clayton E. Curtis & William deficits. Forty-two schizophrenia externalizing scores, with zygosity group G. Iacono, University of Minnesota, Minneapolis, MN. patients, 42 of their first-degree biologi- (MZ, DZ, or siblings) as the indepen- There is accumulating evidence for the cal relatives, 21 psychotic affective dent factor. There were significant group involvement of the prefrontal cortex in disorder patients, and 38 non-psychiatric effects on the withdrawn scale (F(2,151) the genetic diathesis for schizophrenia. comparison subjects were administered = 2.64, p < .08) and internalizing A primary function supported by the fixation and antisaccade tasks. The intro- (F(2,151) = 4.88, p < .01), but not on prefrontal cortex is working memory. duction of distractors and the presence aggression or externalizing. Siblings’ studies increasingly of visible fixation stimuli were parame- withdrawn and internalizing scores were suggest that working memory task char- ters used to vary the difficulty in significantly higher than MZ scores. acteristics, including stimuli type (e.g., suppressing unwanted saccades This does not support the developmental verbal, spatial or object), as well as pro- (inhibitory load). It is known that the social genetics theory that experience cessing demands (e.g., storage, presence of a fixation stimulus at the with dissimilar peers may be important rehearsal/maintenance or executive time when a saccade must be inhibited for reducing withdrawn behaviors in processes such as task management) acti- results in fewer reflexive errors on anti- preschool children. vate distinct neural regions thought to saccade tasks. Performance on fixation mediate performance. Given these find- tasks without (low load) vs. with distrac- RECOGNITION MEMORY FOR tors (high load) and antisaccade tasks FACES IN SCHIZOPHRENIA ings, we evaluated the performance of PATIENTS AND THEIR FIRST- schizophrenia patients, their first-degree that had fixation stimuli still visible (low DEGREE RELATIVES relatives and nonpsychiatric controls on load) vs. already extinguished (high load) Heather M. Conklin, Monica E. Calkins, Charles W. a battery of working memory tasks that at the time when the reflexive saccade Anderson III,Thomas J. Dinzeo & William G. varied in stimuli type and processing must be inhibited was compared. The Iacono, University of Minnesota, Minneapolis, MN. demands (digit span, letter-number schizophrenia patients and their first- It has consistently been shown that sequencing, delayed response and self- degree biological relatives showed schizophrenia patients are impaired in ordered pointing tasks). Whereas evidence of increased saccadic disinhibi-

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tion that was most pronounced during correlations between the theoretically these findings for understanding the high inhibitory load conditions. These interesting Stroop Interference Score symptomalogy of depression in the data indicate that dysfunctional and the eleven Multidimensional second half of life are discussed. inhibitory processes, at least in the Personality Questionnaire Scales nor oculomotor domain, are associated with with Full Scale WAIS IQ. Correlations DEVELOPMENTAL INSTABILITY IN MZ TWINS CONCORDANT AND the liability for schizophrenia. Results with the reading tests were statistically DISCORDANT FOR SCHIZOPHRENIA also suggest that this genetic liability may significant but much lower than James L. Reilly & Irving I. Gottesman, University of be related to dysfunctional prefrontal expected (.15 and .19). The correlation Virginia, Charlottesville,VA. cortical areas that provide top-down with spelling was not significant (.11). Although a major genetic component inhibitory control over reflexive saccade Various special mental ability tests underlying the complex etiology of generation. (Pedigrees, a memory composite, Flexibility of Closure and Speed of schizophrenia has been substantiated, RHEUMATIC DISEASES AND Closure) correlated with the interfer- concordance rates slightly less than 50% SCHIZOPHRENIA: AN AUTOPSY- ence score to about the same extent as among monozygotic (MZ) twin pairs BASED INVESTIGATION the reading tests (.21, .20, .17, .29). highlight the importance of epigenetic Daniel R. Hanson, Chang-Jiang Zheng, & June These findings suggest that the Stroop and environmental factors in etiology. White, Departments of Psychiatry & Occupational Developmental instability represents the Medicine, Regions Hospital, St. Paul, MN. Interference Score is to a considerable degree independent of reading ability degree to which an individual’s onto- The neuropsychiatric consequences of genic program is perturbed by streptococcal rheumatic disease have as well as mental ability and personal- ity. The intraclass correlations for the environmental and non-heritable been well established for Sydenham genetic factors over time. Develop- Chorea and Obsessive-Compulsive dis- MZA twins was .43, suggesting signifi- cant for this trait. mental instability is indexed by order (PANDA syndrome). We revisit an fluctuating asymmetry (FA) of bilater- older hypothesis that streptococcal HERITABLILITY OF DEPRESSION ally symmetrical morphometric traits, rheumatic disease plays a role in psy- SYMPTOMATOLOGY IN THE such as dermatoglyphics, and by minor choses including schizophrenia. We SECOND HALF OF LIFE: EVIDENCE FROM DANISH TWINS OVER 45 physical anomalies, all of which reflect describe a collection of consecutive developmental integrity over the pre- autopsies from Minnesota State Wendy Johnson, Matt McGue, David Gaist, James W.Vaupel, & Kaare Christensen, University of and early post-natal periods. The Hospitals and present preliminary statis- Minneapolis, Minneapolis, MN, and Department of present study examined levels of devel- tical findings. Among a population of Psychology, Odense University, Odense, Denmark. opmental instability, measured by a 392 patients with psychoses, 14% had The heritability of depression symp- composite of dermatoglyphic FA and histories of streptococcal rheumatic toms was investigated in a sample of minor physical anomaly measures, in disease. Clinical, epidemiologic, and 2,169 pairs of Danish twins (1,033 the Torrey, Gottesman and colleagues’ neuropathological findings are discussed. MZ and 1,136 same sex DZ) ranging sample of MZ twin pairs concordant (n In addition, we consider a simple in age from 45 to over 95. Twins com- = 20) and discordant (n = 23) for schiz- rheumatic-epidemic model and propose pleted an interview assessment that ophrenia and spectrum disorders. While a few conceptual issues or predictions identified symptoms of depression, there was no difference in the level of that may be pertinent to future investi- which were scored on Affective, developmental instability between dis- gations. The tentative conclusion drawn Somatic, and Total scales. For the full cordant and concordant pairs, affected from the current study implies that sample, heritability estimates (h2) for members of discordant pairs had sub- 2 2 streptococcal infection may play a larger the Affective (h = .27), Somatic (h = stantially greater instability relative to 2 role in the genesis of schizophrenia than .26), and Total (h = .29) scales were their unaffected co-twins. These find- what has been generally appreciated. all moderate, statistically significant, ings will be discussed in the context of and similar to results from other THE STROOP INTERFERENCE developmental instability as an impor- EFFECT: READING, MENTAL studies (e.g. McGue & Christiansen, tant framework from which to consider ABILITY, AND PERSONALITY 1997). To assess possible variations in epigenetic processes in schizophrenia. CORRELATES IN THE MINNESOTA heritability across the wide age span, STUDY OF TWINS REARED APART the sample was stratified into age REUNITED TWINS VS. THEIR Wendy Johnson,Thomas J. Bouchard, Jr., Nancy L. groups in increments of five years. The ADOPTIVE SIBLINGS: WHO DO Segal, Margaret Keyes, & Jay Samuels, University of magnitude of heritable influence did THEY FAVOR? Minnesota, Minneapolis, MN. not vary significantly with age or sex, Nancy L. Segal & Sara Arad, California State The Stroop Color-Word Test was though there was some tendency for University, Fullerton, CA. administered to 50 pairs of monozy- Affective scale heritability to increase of social closeness and famil- gotic twins reared apart (MZA) and 37 with age and for Somatic scale heri- iarity between reunited monozygotic pairs of dizygotic twins reared apart tability to decrease with age. In (MZA) and dizygotic (DZA) twins were (DZA) in the Minnesota Study of addition, Somatic scale heritability compared via a detailed Twin Relation- Twins Reared Apart (MISTRA) as well tended to be greater for females than ship Survey. This study is the first to as some spouses and other participants for males. Bivariate model fitting pro- systematically assess social relatedness in (N = 97). These individuals also com- duced a genetic correlation of .71 and this special twin sample. Participants pleted personality and special mental a non-shared environmental correla- included 44 MZA and 33 DZA twin ability tests, two reading tests and one tion of .43 for the Affective and pairs, and several individual twins and spelling test. There were no significant Somatic scales. The implications of triplets from the Minnesota Study of

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Twins Reared Apart. A repeated mea- posterior brain regions, diminished P2 order to examine performance variabil- sures ANOVA showed significantly and late positive complex (LPC) compo- ity schizophrenia patients were divided greater closeness and familiarity among nents over prefrontal and frontal regions, into high and low scoring groups. The MZA and DZA twin pairs. In addition, and diminished P3 amplitudes over high scoring group performed as well as MZA intraclass correlations significantly frontal, central, and parietal regions. normal controls and appeared to have exceeded DZA correlations for current Next, we examined ERPs associated with similar P3 amplitudes. Results support closeness and current familiarity ratings. recall deficits. For control subjects failure the contention that schizophrenia Most revealing, twins’ current closeness to recall words was associated with patients fail to exhibit greater perfor- and familiarity scores for their newly diminished P2 and P3 components over mance decrement over the course of a found co-twins exceeded those for the frontal and central scalp regions during degraded-stimulus CPT than control unrelated siblings with whom they were encoding. In contrast, schizophrenia subjects. ERP analyses suggest that low- raised. Other analyses showed that corre- patients failure to recall words was asso- scoring schizophrenia patients may lations between twins’ perceptions of ciated with diminished early negative engage anomalous brain processes (as their current physical resemblance and components (80 to 250 msec after stim- reflected by P3 amplitude) when per- current social closeness and familiarity ulus onset) over the posterior-temporal forming visual target detection. This were positive and statistically significant. brain regions and diminished P2 ampli- may differentiate them from high- However, most correlations between tudes over the left frontal-temporal brain scoring schizophrenia patients. social relatedness ratings and contact region during encoding. These findings time measures were non-significant. are consistent with schizophrenia THE SIGNIFICANCE OF patients having encoding abnormalities PROVERB INTERPRETATION Some exploratory studies of associations IN SCHIZOPHRENIA between twins’ social relatedness and during early processing by posterior-tem- poral brain regions and later processing Scott R. Sponheim, Christa Surerus-Johnson, similarities in personality traits, interests, Jennie Leskela, & Michael E. Dieperink, Minneapolis values, and educational background were by left frontal-temporal brain regions. VA Medical Center and University of Minnesota, Minneapolis, MN. also conducted. The findings support ATTENTION OR SUSTAINED various theoretical perspectives anticipat- ATTENTION DEFICIT? EVENT- In order to determine which phenomena ing greater cooperation and affiliation RELATED POTENTIALS OVER THE in schizophrenia are closely tied to among close relatives, compared to COURSE OF A CONTINUOUS proverb interpretation, we examined the distant relatives and non-relatives. PERFORMANCE TASK IN associations of proverb interpretation SCHIZOPHRENIA with domains of symptomatology and DEFICIENT RECALL, INTACT Scott R. Sponheim & Kathryn A. McGuire, cognition in schizophrenia patients. RECOGNITION: ERP EVIDENCE Minneapolis VA Medical Center and University of REGARDING THE NATURE OF Minnesota, Minneapolis, MN. Interpretations of proverbs by schizo- phrenia and comparison subjects were VERBAL MEMORY DEFICITS IN It is unclear whether poor performance SCHIZOPHRENIA rated for abstraction, concreteness, and by schizophrenia patients on continu- Scott R. Sponheim, Minneapolis VA Medical Center, ous performance tasks (CPT) is bizarre-idiosyncratic quality. Subjects University of Minnesota, Minneapolis, MN. attributable to a specific deficit in sus- also completed structured interviews and Although studies have consistently tained attention or an overall attentional tests of cognition. Results showed schizo- shown schizophrenia patients to manifest impairment. In an attempt to identify phrenia subjects showed less abstract, verbal memory deficits extending functional brain abnormality associated more concrete and bizarre-idiosyncratic beyond a generalized cognitive dysfunc- with impaired sustained attention, we interpretation of proverbs than compari- tion, the nature of these deficits remains examined event-related potentials son subjects. For schizophrenia subjects unclear. In order to explore the basis for (ERPs) of schizophrenia and nonpsychi- abstraction in proverb interpretation was verbal memory dysfunction in schizo- atric control subjects while they positively associated with overall intelli- phrenia we examined the behavioral performed a degraded-stimulus CPT. gence, but no symptom measures. responses and brain electrical activity During correct responses to target Concreteness in proverb interpretations (event-related potentials [ERPs]) of stimuli schizophrenia patients exhibited by schizophrenia patients was negatively schizophrenia and control subjects com- smaller P3 amplitudes than control sub- associated with overall intelligence, exec- pleting verbal memory tasks. Across tasks jects. Additionally, the P3 amplitudes utive functioning, attention, and schizophrenia patients performed worse for target and non-target stimuli were memory. Concreteness was also associ- than control subjects in recalling verbal less differentiated for schizophrenia ated with bizarre behavior in material, but they performed similarly to patients than for control subjects. To schizophrenia patients. Finally, bizarre- control subjects in recognizing verbal examine sustained-attention processes idiosyncratic responses by schizophrenia material. Both schizophrenia patients trials were divided into three time patients during proverb interpretation and control subjects exhibited repetition blocks (first third, middle third, last failed to be associated with any cognitive priming effects on their reaction times. third) of 160 trials each. Across the functions; however, these responses were Analyses of ERPs to visually presented three time blocks P3 amplitudes to associated with positive formal thought words revealed similar functional brain target stimuli failed to decrement in disorder. The conclusion was that con- abnormalities during encoding, identifi- either the schizophrenia or control sub- creteness in proverb interpretation may cation, and recognition in schizophrenia jects in the mid-parietal region. reflect cognitive dysfunction in schizo- patients. Compared to control subjects, Amplitude differences between normal phrenia while bizarre-idiosyncratic schizophrenia patients, exhibited dimin- controls and schizophrenia patients aspects of interpretation may reflect posi- ished C1 and N1 amplitudes over decreased in the mid-central region. In tive formal thought disorder. ■

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