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Childhood videotaped neuromotor and social precursors of schizophrenia: A prospective investigation

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Childhood videotaped neuromotor and social precursors of schizophrenia: A prospective investigation

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Content CHILDHOOD VIDEOTAPED NEUROMOTOR AND SOCIAL PRECURSORS OF SCHIZOPHRENIA: A PROSPECTIVE INVESTIGATION by Jason Schiffman A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirments for the Degree DOCTOR OF PHILOSOPHY (PSYCHOLOGY) December, 2002 Copyright 2002 Jason Schiffman Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 3093816 Copyright 2002 by Schiffman, Jason Eric All rights reserved. ® UMI UMI Microform 3093816 Copyright 2003 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UNIVERSITY OF SOUTHERN CALIFORNIA THE GRADUATE SCHOOL UNIVERSITY PARK LOS ANGELES, CALIFORNIA 90089-1695 This dissertation, written by Jason Eric Schiffman under the direction o f h_±s__ dissertation committee, and approved by all its members, has been presented to and accepted by the Director o f Graduate and Professional Programs, in partial fulfillment o f the requirements fo r the degree of DOCTOR OF PHILOSOPHY <r\si Director D ate D ecem n er 1 8 , 2 0 0 2 Dissertation Committee Chair (\ , 1 ^ A . Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. DEDICATION For Mom, Dad, Monica, Danielle, Stephanie, and My Friends... my family. ii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGMENTS It’s only right to thank Samoff first and last, after all, he’s orchestrated my graduate school successes from start to finish. So this serves as acknowledgment one for you Samoff; acknowledgment two will follow (ironically, you’ll probably tell me that the way I’ve ordered the ACKNOWLEDGMENTS section doesn’t flow well and ask me to revise it). Thanks to my many close friends who’ve supported me in various aspects of my life. Whether through professional collaborations, or mutual complaining, or working out, or fun adventures, or going to Trader Joe’s, or crying, or watching sports, or just enjoying time together, the well rounded life you gave me was the perfect balance for graduate school. Thanks to Charlie and Sarah. It was a long road, but you both managed to stick it out. It was your dedication to the Herculean effort of coding all the subjects that made this happen. And, thanks to Letty for taking care of all the other details I couldn’t handle. Thanks to my dissertation committee for their help and support: Gayla Margolin, Adrian Raine, John Brekke, and Mitch Earleywine. I’d like to specifically thank Gayla for her role as my Clinical Advisor for five years. Under your protection, I smoothly traveled through what could’ve been choppy waters. Thanks to the Earleywine family: Mitch, Elana, and Dahlia. You’ve become the non-traditional family I can turn to for both academic knowledge and personal iii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. wisdom. And Mitch thanks for helping me learn how to write... that skill came in handy. Thanks to Elaine Walker, my other mentor. If I ever develop half of your integrity, humility, generosity, intelligence, and joi de vie, I’ll feel pretty good about myself. Thanks to my family. You all seem to believe in me even when I don’t. I’ve come to find that that’s not as common in families as I once thought. You’ve bom the burden of my ups and downs more than anyone. You make me feel that even if I weren’t related to you, I’d still benefit from your infinite patience and love. I love all of you very much. And again, thanks to Samoff. From my first day at USC, you welcomed me as a son. You’ve yet to stop watching over me; a comforting feeling. I’m grateful for your patience with my slow learning curve and my occasional mishaps. Your consistent effort, fast turn-around on my work, ever-present encouragement, and willingness to eat Korean food daily, significantly shaped me. Your charm, wit, and desire to learn the expression “Why not!?” in every language kept me entertained and reminded me that research is fun. You’ve become far more than an advisor to me. You are a role model, a very close friend, and a second father. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS Page DEDICATION ..........................................................................................................ii ACKNOWLEDGEMENTS .....................................................................................iii LIST OF TABLES ................................................................................................. vi LIST OF FIGURES .................................................................................................. vii ABSTRACT ............................................................................................................. viii CHAPTER 1: INTRODUCTION............................................................................ 1 CHAPTER 2: STUDY HYPOTHESES ................................................................. 14 CHAPTER 3: METHOD ......................................................................................... 17 CHAPTER 4: RESULTS ......................................................................................... 23 CHAPTER 5: DISCUSSION......................................................................... 45 REFERENCES .......................................................................................................... 63 APPENDIX A .......................................................................................................... 69 APPENDIX B .......................................................................................................... 70 APPENDIX C .......................................................................................................... 71 v Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF TABLES Table 1. Ten continuous variables coded from videotapes................. 21 Table 2. Demographics of videotaped subjects.................................... 24 Table 3. Descriptive statistics of ten variables from videotape coding........................................................................ 25 Table 4. Loading of coding measurements on Sociability (Factor 1), Involuntary Hand Movements (Factor 2), and General Neuromotor (Factor 3).............................................................. 26 Table 5. Demographics of subjects with partners................................. 29 Table 6. Differences between subjects with and without a partner on Sociability, Involuntary Hand Movements, and Neuromotor Scale scores.......................................................... 29 Table 7. Means and standard deviations of Sociability, Involuntary Hand Movements, and General Neuromotor Scale scores for High-Risk and Low Risk, partners only 31 Table 8. Means and standard deviations of Sociability, Involuntary Hand Movements, and General Neuromotor Scale scores, partners only................................................................... 36 Table 9. Means and standard deviations of Sociability, Involuntary Hand Movements, and General Neuromotor Scale scores, with and without partners................................... 41 Table 10. Stepwise likelihood ratio logistic regression analysis showing the impact of different factors on the prediction of schizophrenia........................................................................... 43 Table 11. Classification based on logistic regression............................. 44 vi Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF FIGURES Figure 1. Sociability scale by diagnostic group, partners only 36 Figure 2. Involuntary hand movement scale by diagnostic group, partners only................................................................. 37 Figure 3. General neuromotor scale by diagnostic group, partners only............................................................................ 37 Figure 4. General neuromotor scale by diagnostic group, and by sex, partners only.......................................................... 38 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ABSTRACT Childhood deficits preceding full-blown adult schizophrenia suggest that schizophrenia is a developmental disorder beginning early in life. Research indicates elevated social and neuromotor deficits among children who later develop schizophrenia. This study examines videotaped preadolescent behaviors of future adult-onset schizophrenia patients and control subjects to disclose possible social and neuromotor deficits foreshadowing later development of schizophrenia. In 1972, a sample of 265 11-13 year old children from a Danish birth cohort was intensively examined. The sample consisted of children with a parent with schizophrenia, of children with a parent with a hospitalized non-psychotic psychiatric disorder, and of children with parents who had no record of psychiatric hospitalization. The assessment included videotaping of the children's behavior in a standard context (eating lunch). This study systematically analyzed the videotapes to determine if children who later developed adult schizophrenia evidenced greater social and/or neuromotor deficits compared to children who did not develop a psychiatric disorder, and to children who developed other psychiatric disorders. The findings from this study suggest that the brief videotaped footage of children eating lunch from this study can discriminate between individuals who later develop schizophrenia and individuals who do not. In particular, pre-schizophrenia children evidenced deficits on measures of sociability and general neuromotor viii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. functioning as compared to children who developed other psychiatric disorders, and to children who did not develop a psychiatric disorder. In addition to furthering the understanding of schizophrenia in terms of a developmental disorder, the results from this study may assist in the formation of a detection program for children at risk for schizophrenia. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Chapter 1: Introduction Schizophrenia is perhaps the most devastating psychiatric disorder. Characterized by disorganized thought, hallucinations, delusions, cognitive deficits, and impaired social functioning, schizophrenia gravely impacts the affected individual, as well as friends and family. Its impact is widespread, occurring in nearly 1% of the population. In 1991 alone, schizophrenia cost the United States $70 billion in direct care, aftercare, and lost earnings (Wyatt, Henter, Leary, & Taylor, 1995). Researchers have not yet uncovered the etiology of schizophrenia; however, recent study of early clinical correlates has improved our understanding of schizophrenia’s origins. Two etiologically informative premorbid correlates include poor social functioning and neuromotor abnormality (Walker, Lewis, Loewy, & Palyo, 1999). Better understanding of these premorbid characteristics may offer insight into the pathophysiology of schizophrenia. The majority of individuals with schizophrenia manifest the illness in the second or third decade of life (Torrey, 1989), yet developmental theories of schizophrenia suggest that the disorder begins well before psychotic symptom onset. Researchers offer various theories to account for the onset of schizophrenia in late adolescence or early adulthood. Weinberger (1987) suggests that the clinical manifestations of a neurodevelopmental "lesion" become apparent when the brain areas affected by the lesion reach functional maturity in late adolescence or early adulthood. When the brain matures and calls on the mal-developed regions for more 1 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. complex tasks, severe symptomatology arises. Research suggests that sub-clinical signs of neuropathology are already evident during adolescence (Schultz, Koller, Kishore, Hamer, Gehl, & Friedel, 1983), possibly as early as infancy (Dykes, Mednick, Machon, Praestholm, & Pamas, 1992; Walker, 1994) and birth (Cannon, Mednick, & Pamas, 1989). Associations between markers of early life events such as minor physical anomalies, dermatoglyphic abnormalities, and obstetrical complications, with later schizophrenia support the notion that the development of schizophrenia begins early. Social and neuromotor abnormalities in childhood also correlate with adult schizophrenia, and may reflect developmental precursors to schizophrenia. The study of social and neuromotor abnormalities in childhood may help inform researchers about the etiology of the disorder. Additionally, the identification of neuromotor abnormalities before the full onset of schizophrenia may provide researchers and practitioners a practical tool in identifying at-risk individuals who may benefit from early intervention. Sociability Deficits and Schizophrenia Sociability Deficits: Historical Context Disturbances in affective expression and sociability have historically characterized the schizophrenic process. Both Kraepelin (1919) and Bleuler (1950) described “negative symptoms” (e.g., alogia, avolition, anhedonia, and affective 2 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. blunting) as the fundamental symptoms of the disorder (as cited in Andreasen, 1997). Bleuler contended that negative symptoms were pathognomonic to schizophrenia; Kraeplin argued that negative symptoms were the most debilitating symptoms of the disease. Kraeplin and Bleuler both perceived delusions and hallucinations (currently the main symptoms used to identify schizophrenia) as auxiliary to symptoms such as emotional dullness, loss of affective responsiveness, and avolition (Andreasen, 1997). In the 1960’s and 1970’s emphasis in schizophrenia theory and research shifted from attention to negative symptoms to “positive symptoms” (e.g., delusions and hallucinations). Mostly for diagnostic purposes, “psychotic” components of the disorder, such as hallucination and delusions, became defining qualities of schizophrenia. More recently, the field has begun a renewed recognition of negative symptoms as essential characteristics of schizophrenia. Modem research investigating negative symptoms uncovers a host of affective and social deficits in patients. For example, studies of the facial expressions of adult schizophrenia patients find a significantly reduced amount of positive emotions, as well as a general impairment in facial emotion expression (Krause, Steimer, Sanger-Alt, & Wagner, 1989; Kring, 1999; Mandal, Pandey, & Akhouri, 1998). In addition to impaired affective expression, social skills deficits are a hallmark of schizophrenia (DSMIV, American Psychiatric Association, 1994). Nisenson and Berenbaum (1998), for instance, observed schizophrenia patients 3 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. interacting with college students. The patients demonstrated less smiles and eye contact, qualities related to perceived levels of “strangeness.” Sociability Deficits Before the Onset of Schizophrenia: Follow-back Studies Social deficits exhibited before the onset of schizophrenia suggest that difficulties in affective expression precede recognizable psychotic symptoms and are an important part of the life-course of schizophrenia. In a retrospective study of teachers' comments from school records, Watt (1978) found that pre-schizophrenia girls were socially withdrawn and passive during adolescence, while the pre schizophrenia boys were aggressive and disturbing to the class. In another retrospective study, Goldberg and Schmidt (2001) reported greater shyness and social dysfunction among schizophrenia patients in childhood as compared to controls. Based on maternal recall, Cannon and colleagues (1997) reported that schizophrenia subjects had poorer pre-morbid social adjustment compared to patients with bipolar disorder. Collectively, these retrospective studies provide support for the link between pre-morbid social deficits in patients later developing schizophrenia. Retrospective studies, although informative, suffer from methodological weaknesses, including systematic bias and inaccurate reporting (Voldsgaard et al., in press). A unique study by Walker and colleagues overcame certain limitations of traditional retrospective studies (Walker, Grimes, Davis, & Smith, 1993). The study evaluated childhood home movies of schizophrenia patients, their healthy siblings, 4 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. subjects with affective disorders, their healthy siblings, and normal controls. Subjects were recruited through community announcements soliciting individuals with schizophrenia or a major mood disorder and having childhood home-videos. The authors examined facial expressions of emotion, coded from the childhood home-movies. Pre-schizophrenia females showed reduced expressions of joy when compared to same-sex controls from infancy through adolescence; pre-schizophrenia males showed a trend for greater negative expressions in pre-adolescence and early adolescence. Due to the unique nature of this research, the authors presented several limitations of this study. First, because of the need for home movies, the sample of subjects was not representative. Most subjects came from middle to upper-middle- class families and had good medical care. Secondly, the social and physical context of the movies varied considerably across subject groups, but not as much between siblings. Therefore, sibling-patient differences may have been more obvious. Finally, because the amount of data varied among subjects, the authors could not use their findings to estimate the proportion of patients with abnormalities. Sociability Deficits Before the Onset of Schizophrenia: High-Risk Studies Longitudinal study of “high-risk” (at least one parent with schizophrenia) individuals provides an alternative opportunity to view the developmental course of schizophrenia. In the high-risk method, researchers identify offspring of parents with schizophrenia, as these offspring are more likely to develop schizophrenia than Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. offspring of non-psychotic parents (one parent with schizophrenia, -16% vs. general population, ~1%). Researchers assess various aspects of functioning in high-risk children, and follow their diagnostic status through adulthood. Full-blown schizophrenia rarely manifests itself until early adulthood; therefore, high-risk designs can identify clues to the development of schizophrenia before full onset. High-risk projects offer the potential to uncover important antecedents of schizophrenia. Several major high-risk projects have investigated social functioning in children followed longitudinally (e.g., Copenhagen High-Risk Study, Cannon et al. 1990; New York High-Risk Project, Erlenmeyer-Kimling et al., 2000; Jerusalem Infant Development Study, Hans et al., 2000). Unfortunately, at this time, not all of these studies have followed subjects through the major risk period for schizophrenia. Studies of high-risk children not yet through the age of risk for schizophrenia provide limited information regarding social functioning and full schizophrenia. These studies, do, however, offer insight into the course of genetically at-risk individuals at increased risk to develop schizophrenia. The New York High-Risk Study found that the offspring of schizophrenia patients had poorer social competence in adolescence than low-risk subjects and children at risk for affective disorder (Dworkin et al., 1990). High-risk children in this study exhibited poorer peer relationships and fewer interests. From this same project, Erlenmeyer-Kimling and colleagues reported an indirect link between high- risk children and physical anhedonia, mediated through attention deviance. The 6 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. relationship between high-risk status and anhedonia was not found in children at risk for affective disorders. Similarly, in the Jerusalem Infant Development Study, Hans and colleagues reported that high-risk children (-1 5 years of age) showed poorer peer engagement and social problems characterized by immaturity compared to controls (Hans, Auerbach, Asamow, Styr, & Marcus, 2000). These finding collaborate previous reports from this sample (e.g., Hans, Marcus, Henson, Auerbach, & Mirsky, 1992). Sociability Deficits in High-Risk Studies with Adult Diagnostic Outcome Several high-risk investigations have followed subjects through the age o f risk and provide information regarding pre-morbid functioning and adult diagnostic outcome. In a report from the Copenhagen High-Risk Study (Cannon, Mednick, & Pamas, 1990), teachers noted more negative-type behavior (e.g., difficulty making friends, passive, socially unresponsive to peers, unresponsive to praise or punishment from the teacher) among high-risk subjects who later succumbed to predominately negative symptom schizophrenia compared to those who developed predominately positive symptom schizophrenia. In a recent study from the New York High-Risk Project incorporating adult diagnostic information, Amminger and colleagues (1999) reported more childhood behavior problems in adults with a schizophrenia-related psychosis as compared to adults with anxiety or affective disorders, and adults with substance abuse or no disorders. Although limited in number, these high-risk studies Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. following subjects through adulthood provide compelling evidence for the developmental nature of social deficits in schizophrenia. Neuromotor Deficits and Schizophrenia Neuromotor Deficits: Historical Context In addition to social deficits, early investigators of schizophrenia cited neuromotor disturbances as common symptoms among patients. First Kalhbaum, followed by Kraeplin and Bleuler, described unusual neuromotor functioning in psychiatric patients (Bleuler 1950; Kahlbaum, 1973; Kraepelin, 1971). Kalhbaum attributed motor disturbances to a brain disease. With the advent of neuroleptics, however, the majority of mental health professionals ascribed neuromotor abnormalities in schizophrenia to neuroleptic side effects (Ismail, Cantor-Graae, Cardenal, & McNeil, 1997). More recently, theorists have revisited neural explanations of motor abnormalities in schizophrenia. Recent research suggests that motor deviations correlate with schizophrenia, even in non-medicated patients (e.g., Owens, Johnson, & Frith, 1982). Findings of motor disturbances in non-medicated schizophrenia patients implicate neuromotor abnormalities as a true part of the disease process. McNeil and Cantor-Graae (2000) defined neuromotor abnormalities as one or more of the following: motor coordination difficulties, involuntary movements, mirror movements, and deviations in muscle power and tone. Researchers 8 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. commonly identify these abnormalities through brief, in-person, neurological examinations. Interest in neuromotor abnormalities increases, as researchers contend that neuromotor abnormalities may: 1) inform a “neurodevelopmental hypothesis” of schizophrenia; and, 2) provide a method for early detection of high-risk individuals likely to develop schizophrenia. Neuromotor Abnormalities before the Onset of Schizophrenia: Follow-back Studies In addition to the 1993 report of social deficits observed in the childhood home-movies of pre-schizophrenia patients mentioned above, Walker, Savoie, and Davis (1994) published an article investigating neuromotor development in these subjects. The study evaluated neuromotor functioning of pre-schizophrenia patients through the naturalistic observation of the home-movies filmed by parents through patients’ childhood. Results suggested more neurological soft-signs (abnormalities without a known area of localization in the brain) and poorer motor skills compared to the control groups. As mentioned earlier, videotapes had the advantage of recording behaviors occurring in the child’s natural environment before illness onset. The films, however, were non-standard across subjects and were not of a representative sample. In a study of adolescents diagnosed with schizotypal personality disorder, Walker and colleagues (1999) reported an increase of involuntary movements compared to adolescents with other diagnoses and normal controls. The study sample consisted of adolescents with schizotypal personality disorder, other axis II 9 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. disordered subjects, and normal controls, averaging 15 years of age. The investigators conducted SCIDII interviews for the assessment of personality disorders that were videotaped. These videos were coded for neuromotor abnormalities in the form of involuntary movements. Results suggested that schizotypal adolescents (adolescents possibly on a trajectory towards full-blown schizophrenia) showed significantly more involuntary movements than subjects with other disorders, and the normal control comparison groups. Neuromotor Abnormalities Before the Onset of Schizophrenia: High-Risk Studies A number of researchers report that the children of mothers with schizophrenia evidence more neuro-developmental abnormalities than the children of normal, healthy parents (Erlenmyer-Kimling, Golden, & Comblatt, 1989; Sameroff, Barocas, & Seifer, 1984; Rolf, Crowther, Teri, & Bond, 1984). In an early study of high-risk children and neuromotor deficits, Mednick, Mura, Schulsinger, and Mednick (1971) reported that both the high-risk and other-psychiatric-risk groups showed significantly more neo-natal abnormalities than the normal control group. Further, the abnormalities in the other-psychiatric-risk group dissipated after five days, whereas abnormalities observed in the high-risk subjects persisted at the five day examination. Marcus and colleagues, in separate reports from the NIMH Israeli Kibbutz-City High-Risk Study (Marcus, Hans, Lewow, Wilkinson, & Burack, 1984), the Jerusalem Infant Development Study (JIDS) (Marcus, Auerbach, Wilkinson, & 10 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Burack, 1981), and the Danish Perinatal Project (Marcus, Hans, Mednick, Schulsinger, & Michelsen, 1985), reported impairments in fine motor performance, motor coordination, and sensory integration among children with a parent with schizophrenia. Similarly, McNeil, Harty, Blennow and Cantor-Graae (1993) reported that neuromotor deficits during the first year of life, and at age six, related to parental diagnosis of schizophrenia. In a report from the New York Infant Study, Erlenmyer-Kimling and colleagues identified a pattern of erratic neuromotor dysfunction in the offspring of mothers with schizophrenia (Erlenmeyer-Kimling, Golden, & Comblatt, 1989). Two studies identified more neuromotor abnormalities specifically in high- risk boys (Marcus, Hans, Auerbach, & Auerbach, 1993; Reider & Nichols, 1979). High-risk girls did not demonstrate significantly elevated neuromotor abnormities as compared to low-risk girls. Sex differences in neural function or structure may leave males more vulnerable to neuromotor dysfunction than females. Neuromotor Deficits in High-Risk Studies with Adult Diagnostic Outcome Several high-risk studies have followed subjects from childhood through the age of risk. Rosso and colleagues (2000) found neuromotor deficits in children ages four and seven who later developed schizophrenia. More recent follow-up studies from the New York sample report that neuromotor deficits predicted to schizophrenia-spectrum disorders in adulthood (Erlenmeyer-Kimling, et al., 2000). 11 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Working with data from the sample used in the current investigation, La Fosse (1994) reported increased deficits in coordination in childhood among subjects who later developed schizophrenia. On the same days of the neurological examinations assessing coordination, investigators videotaped the 11-13 year old subjects for this study. A part of that examination involved an investigation of motor coordination. La Fosse (1994) found that adult-diagnosed schizophrenia patients evidenced significantly elevated levels of motor coordination difficulties on the day of videotaping in 1972. Present Investigation Collectively, the studies reviewed suggest that schizophrenia is a longitudinal syndrome, with premorbid signs of social and neuromotor deficits already present during childhood. Many of these studies, however, lack adult psychiatric outcome data and depend on data not collected for research purposes. The proposed study overcomes these limitations by examining observable behavior from childhood, using a sample followed since 1972, who have passed through a considerable part of the risk period for schizophrenia. We now have DSM-III-R adult outcome data for these subjects based on structured psychiatric interviews and psychiatric hospital records. Videotape records, the primary source of data in this study, were uniformly and systematically obtained in 1972 during pre-adolescence (ages 11-13 years of age), before any of the subjects developed a psychiatric disorder. This observational 12 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. method allows for the direct assessment of behaviors without relying on accounts of others or self reports (Margolin et al., 1998). The identification of predictive childhood characteristics in subjects who eventually develop schizophrenia has at least two significant implications. First, it improves our understanding of the disorder in terms of its longitudinal development, assisting in the development of more accurate etiological models. Second, the observed characteristics may contribute to the development of unobtrusive assessment procedures identifying children at risk for schizophrenia. The identification of at-risk children would permit intervention research at an age when primary prevention may be effective. Rating Scales Used for Hypotheses The videotapes yielded ten observable continuous variables. The selection of these variables will be thoroughly discussed in the Methods section. Further, as discussed in the Results sections, we performed a principal components analysis that yielded three factors: Sociability Scale, Involuntary Hand Movements Scale, and General Neuromotor Scale. We mention these scales now so that we may present our hypotheses considering each of these scales. 13 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Chapter 2: Study Hypotheses Hypotheses 1: Psychiatric Risk Status Given the literature supporting social and neuromotor deficits among children with a parent with schizophrenia, we predicted that: High-Risk vs. Low-Risk 1) Children of a parent with schizophrenia have deficits on the Sociability Scale compared to the children of parents without a psychiatric diagnosis. 2) Children of a parent with schizophrenia have deficits on the Involuntary Hand Movement Scale compared to the children of parents without a psychiatric diagnosis. 3) Children of a parent with schizophrenia have deficits on the General Neuromotor Scale compared to the children of parents without a psychiatric diagnosis. Specificity: High-Risk vs. Psychiatric Control Risk 4) Children of a parent with schizophrenia have deficits on the Sociability Scale compared to the children of a parent with a non-psychotic psychiatric diagnosis. 14 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 5) Children of a parent with schizophrenia have deficits on the Involuntary Hand Movement Scale compared to the children of a parent with a non- psychotic psychiatric diagnosis. 6) Children of a parent with schizophrenia have deficits on the General Neuromotor Scale compared to the children of a parent with a non-psychotic psychiatric diagnosis. Hypotheses 2: Adult Diagnostic Outcome Given the literature suggesting social and neuromotor deficits among children who later develop schizophrenia, we predicted that: 1) Children who later develop schizophrenia have deficits on the Sociability Scale compared to children who do not develop a mental illness. 2) Children who later develop schizophrenia have deficits on the Involuntary Hand Movement Scale compared to children who do not develop a mental illness. 3) Children who later develop schizophrenia have deficits on the General Neuromotor Scale compared to children who do not develop a mental illness. 15 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Specificity: Schizophrenia vs. Other Non-Psychotie Psychiatric Outcomes 4) Children who later develop schizophrenia have deficits on the Sociability Scale compared to children who develop a non-psychotic psychiatric condition. 5) Children who later develop schizophrenia have deficits on the Involuntary Hand Movement Scale compared to children who develop a non-psychotic psychiatric condition. 6) Children who later develop schizophrenia have deficits on the General Neuromotor Scale compared to children who develop a non-psychotic psychiatric condition. Hypotheses 3: Predicting Schizophrenia 1) The Sociability Scale, the Involuntary Hand Movements Scale, and the General Neuromotor Scale will be useful in predicting individuals at increased risk for developing schizophrenia. 16 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Chapter 3: Method Diagnosis of the Subjects: The Parents The present study investigates high-risk children in a major perinatal cohort of 9,182 deliveries bom in Copenhagen, 1959-1961. In order to identify high-risk children and controls, in 1969, the lifetime record of psychiatric admissions was checked through the Danish psychiatric record for the 18,012 parents of the birth cohort. At that time the parents averaged 32 years of age. Subjects were drawn from a Danish birth cohort consisting of all children bom between September 1, 1959, and December 31, 1961, at Rigshospitalet in Copenhagen (Zachau-Christiansen & Ross, 1975). In 1972, a sample of 265 11-13 year old children from this cohort was intensively examined (Mednick, Mura, Schulsigner, & Mednick, 1971). Two-hundred-forty-two were available for follow- up examinations at age 31-33. All children whose mothers or fathers had a psychiatric hospital diagnosis of schizophrenia comprised the first group (N=81). A group of controls consisted of 87 children who had parents with psychiatric records other than schizophrenia. The remaining 74 subjects were controls with no parental records of psychiatric hospitalization. Diagnostic Methods: The Offspring In 1992, when the subjects were between 31-33 years of age, their psychiatric status was ascertained. A psychiatrist administered two structured clinical psychiatric interviews, the Structured Clinical Interview for DSM-III-R (SCID; Spitzer, Williams, & 17 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Gibbons, 1990) and the psychosis section of the Present State Examination (PSE; Wing, Cooper, & Sartorious, 1974). These interviews yielded DSM-III-R diagnoses. In addition, Danish psychiatric hospital records of subjects were examined. A detailed coding scheme yielded DSM-III-R diagnoses. Based on interview and/or hospital records, we obtained adult diagnostic outcomes for 242 of the 265 subjects (91% successful follow-up after 20 years; 23 subjects had neither an interview nor hospital records). A senior Danish psychiatrist (Professor Fini Schulsinger) supervised all the interviews and diagnoses. After complete description of the study to the subjects, written informed consent was obtained. Sixteen schizophrenia patients have been identified on the basis of the above diagnostic procedures, and 10 others have been diagnosed with a schizophrenia- spectrum disorder (5-Any Psychosis or Delusional Disorder, 3-Schizotypal Personality Disorder, 2-Paranoid Personality Disorder). No subject had a diagnosis of affective psychosis. Of the 26 subjects with a schizophrenia-spectrum disorder, 13 were diagnosed through interview only, 7 through hospital records only, and 6 both hospital and interview. Seven subjects with a hospital diagnosis did not have SCID interviews. Seventy subjects were diagnosed with a non-psychotic disorder (Other Disorder; “OPD”): 19 Non-Psychotic Mood or Anxiety Disorder, 33 Non-Psychotic Alcohol/Drug Abuse, 1 non-hospitalized Minor Axis I Disorder, 4 Personality Disorder NOS, 6 Other Personality Disorder, 5 Borderline Personality Disorder, 1 Schizoid Personality Disorder, and 1 Antisocial Personality Disorder); 146 subjects were judged to have no mental illness (“NMI”). Of the 70 Other Disorder subjects, only 2 had hospital diagnoses (one drag abuse, one alcohol abuse). 18 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1972 Videotaping Procedures In 1972, when the subjects were 11-13 years of age, they came to a laboratory at Kommunehospitalet in Copenhagen for a one-day assessment. At noon on the day of the assessment, researchers provided the subjects with a lunchtime meal in a specially designated room. The videotaping took place under highly standard conditions, blind to psychiatric risk status, and to diagnostic outcome 20 years later. Generally, two randomly paired children were examined each day. In the case of 41 subjects, lunch partners were not available. When two children were present, each sat on either side of the comer of a table facing the tri-pod mounted video camera. The children, of the same age level, did not know each other before entering this situation. Some pairs of children began a conversation during their meal. The meal consisted of Danish open-face sandwiches. These sandwiches are constructed in layers and require some motor skills. The camera and tape recorder were an Akai VT-100R, black and white, 1/4 inch, reel-to-reel video and audio recorder new to the market that year (1972). The lighting, distance of the camera from the subjects, and sound recording level, were not altered during the course of the study. The camera angle was changed from, 1) initial focus on both children (three-minutes) to, 2) a close-up of the subject sitting to the left (one-minute) and, 3) a close-up on the subject sitting to the right (one- minute). For the final part of the taping the focus was again on both children (one- minute). These changes were done with the same timing for all of the subject dyads. 19 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The camera operator made an effort to ensure that variations in the subjects' videotaped behavior were not partly ascribable to variations in situational factors. These videotapes have been transcribed onto videocassettes. Training of Coding Procedures In order to be useful as a source of data on behavioral precursors of schizophrenia, the videotapes must meet two criteria; 1) they must feature behavioral phenomena that can be reliably coded, and 2) the characteristics of the behavior must show adequate inter-individual variability. Dr. Elaine Walker and the Principal Investigator established a coding scheme for the videos meeting these criteria. The coding scheme yielded ten continuous variables similar to variables established in previous video studies investigating early signs of schizophrenia (Walker et al., 1993,1994). The number of instances of each behavior was noted. (See Appendices A and B; Coding Form and Coding Instructions). 20 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1. Ten continuous variables coded from videotapes. Number of smiles Number of laughs Number of vocalizations initiated by subject to lunch partner Number of vocalizations responding to lunch partner Number of nystagmus-like eye movements Number of raised elbows Number of involuntary facial movements Number of involuntary movements of the right hand Number of involuntary movements of the left hand Number of other abnormal movements The principal investigator trained an undergraduate research assistant. Together, this research assistant and the principal investigator trained another undergraduate research assistant. Training involved specific instructions, followed by independent work. Questions from the raters regarding independent coding were addressed in regular training meetings to avoid drift; however, all coding decisions were made independently. Communication between the principal investigator and raters continued throughout the coding process to ensure consistency. While coding a subject with a partner, raters focused on only one subject at a time. Raters watched each subject three times to assess all codes. The first viewing focused on smiles, laughs, vocalizations initiated by subject, and vocalizations responding to lunch partner. The second viewing concentrated on nystagmus-like eye movements, involuntary facial movements, and other abnormal movements. The final viewing focused on involuntary movements of the right hand, involuntary movements of the left hand, and raised elbows. 21 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. All raters, including the principal investigator, were completely blind to adult diagnostic outcome. Data regarding the 1992 adult psychiatric assessment were kept in Denmark until the completion of video coding. Data Entry At the completion of data collection, an experienced undergraduate research assistant entered the data twice into two independent Microsoft Excel spreadsheets. The spreadsheets were compared to identify entry discrepancies. The original coding forms were consulted in the event of a discrepancy between the first and second entry. 22 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Chapter 4: Results Missing Data Of the 265 original 1972 subjects, 23 either died or refused to participate. Additionally, 48 subjects did not have videotapes. As mentioned, the camcorder used was among the first personal video recording devices, using reel-to-reel technology. When the tapes were converted to modem standards at the Akai facility in London, a reel may have been missing, accounting for the 48 subjects without footage. The subjects without videos, however, do not systematically differ from the subjects with videos in terms of diagnostic outcome, sex, or psychiatric risk status (Adult Diagnostic Outcome: Schizophrenia vs. NMI, x2 (1, N=162) = .77, p = NS; Schizophrenia vs. OPD, y2 (1, N=86) = .48, p = NS; Schizophrenia vs. Spectrum, % 2 (1, N=26) = 1.35, p = NS; NMI vs. OPD, % 2 (1, N-216) - .77, p - NS; NMI vs. Spectrum, % 2 (1, N=156) = 2.76, p = NS; OPD vs. Spectrum, % 2 (1, N=80) = 2.42, p = NS. Psychiatric Risk Status: High-Genetic-Risk vs. Psychiatric-Control-Risk, % (1, N-168) - 3.64, p = NS; High-Genetic-Risk vs. Low-Genetic-Risk, x2(l, N=155) = 3.64, p = NS; Psychiatric-Control-Risk vs. Low-Genetic-Risk, x2(l, N=161) = 1.24, p = NS. Gender: Male vs. Female, % 2 (1, N=242) = 1.35, p = NS). (See Table 2). Due to equipment failure, one subject who was rated for elbows, nystagmus-like eyes, involuntary facial movements, involuntary hand movements, and other abnormalities, was not rated for smiles, laughs, vocalization responses, and initiated vocalizations. 23 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 2. Demographics of videotaped subjects. Taped Not Taped Percent Taped Adult Diagnostic Outcome Schizophrenia 14 2 87.5% (14/16) NMI 114 32 78.1% (114/146) OPD 56 14 80.0% (56/70) Spectrum 10 0 100% (10/10) Psychiatric Risk Status Hi Genetic Risk 70 11 86.4% (70/81) Psychiatric Cntrl 65 22 74.7% (65/87) Low Genetic Risk 59 15 79.7% (59/74) Gender Male 99 20 83.2% (99/119) Female 95 28 77.2% (95/123) Data Reduction Coding of the videos resulted in ten continuous measures of behavior. (See Table 3 for descriptive statistics of variables. See Appendix C for histograms of variables). We analyzed the dimensionality of the ten coding scores using a principal components factor analysis. The factor analysis yielded three factors with an eigenvalue greater than one. Consequently, we rotated the three factors using a Varimax rotation procedure. The rotated solution, as shown in Table 4, yielded three interpretable factors: Sociability, Involuntary Hand Movements, General Neuromotor signs. The Sociability factor accounted for 26.8% of the item variance, the Involuntary Hand Movements accounted for 18.1%, and the General Neuromotor accounted for 15.7% of the item variance. One item, Involuntary Facial Movements, 24 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. loaded on both the Involuntary Hand Movements factor and the General Neuromotor factor at a value above .400, but did not differ by more than .100 in magnitude between scales. It did, however, load more strongly on the General Neuromotor factor. We assigned Involuntary Facial Movements to the General Neuromotor factor, leaving the second factor purely Involuntary Hand Movements. Table 3. Descriptive statistics of ten variables from videotape coding N Min Max Mean Std Dev Variance Skewness (Std. Error) Kurtosis (Std. Error) Smiles 193 0 10 1.83 2.35 5.52 1.49 .17 1.74 .35 Laughs 193 0 10 .96 2.61 6.83 3.69 .17 15.03 .35 Vocal Initiated 193 0 17 .98 2.86 8.20 3.36 .17 11.06 .35 Vocal Responded 193 0 17 .71 2.26 5.11 4.15 .17 19.60 .35 Nystgms-Like Eye 191 0 5 .32 .79 .62 3.30 .18 13.49 .35 Elbows 194 0 22 1.88 3.77 14.19 2.65 .17 7.48 .35 Invol Face 193 0 26 2.31 3.69 13.62 2.99 .17 11.81 .35 Invol Rt Hand 194 0 25 3.07 3.94 15.51 2.47 .17 8.00 .35 Invol Lft Hand 194 0 26 3.63 4.73 22.34 2.21 .17 5.80 .35 Other Abnorm 193 0 19 2.05 2.70 7.27 2.65 .17 10.02 .35 To create the scales, we first standardized the variables, setting them to equal means and standard deviations. We then summed each variable according to the factor to which it loaded. To account for missing data, we divided the summed scores by the number of variables each particular subject had per factor. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 4. Loading of coding measurements on Sociability (Factorl), Involuntary Hand Movements (Factor2), and General Neuromotor (Factor3). Coding Variable Factor 1 Sociability Factor 2 Involuntary Hand Movements Factor 3 General Neuromotor Elbows .217 -.098 .661 Invol Right Hand -.044 .865 -.020 Invol Left Hand .098 .821 .233 Nystagmus-like Eyes -.190 .110 .585 Invol Face .017 .429 .486 Other Abnrml Moves -.066 .414 .628 Smiles .719 -.067 .215 Subject Vocals .867 .035 -.043 Vocal Responses .733 .025 -.239 Laughs .880 .039 .023 Reliability Two raters were involved in the coding process. One rater was trained by the principal investigator and coded all taped subjects. This rater trained the secondary rater who coded 95% of all taped subjects and whose ratings were only used for reliability determination. In an effort to identify discrepancies between raters, we calculated the difference between Rater 1 and Rater 2 on each scale. We considered differences greater than two standard deviations outliers (Wilcox, 2001). Of the 193 subjects coded on the Sociability Scale, seven differed by two standard deviations. Of the 194 subjects coded on the Involuntary Hand Movement Scale, 14 differed by two standard deviations. Of the 194 subjects coded on the General Neuromotor Scale, four differed by two standard deviations. Outliers were excluded from all further analyses. 26 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Intraclass Correlation Coeffiencts. Based on the scales of Rater 1 compared to Rater 2, two-way random, absolute agreement intraclass correlation coefficients for the three scales were : Sociability = .95, Involuntary Hand Movements = .68, General Neuromotor = .69. We deemed the primary rater as the expert coder and only used his scores for all subsequent analyses. Internal Consistency. We computed coefficient alpha for each scale to estimate reliability of the three scales through internal consistency. Cronbach’s Alpha for each scale was: Sociability = .82, Involuntary Hand Movements = .67, General Neuromotor = .46. Explanation of Scales Scores As described above, we derived each scale by summing the standardized scores of a particular factor then dividing the sum by the number of items the particular subject had. This method results in scores with a mean of zero and results in positive and negative directions. Social Scale. A positive score on the Social Scale indicates more positive social interactions. A negative score indicates reduced social interaction. Involuntary Hand Movements Scale. A positive score on the Involuntary Hand Movements Scale indicates more involuntary movements. A negative score indicates less involuntary movements. 27 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. General Neuromotor Scale. A positive score on the General Neuromotor Scale indicates more neuromotor signs. A negative score indicates less neuromotor signs. Covariates/Data Screen We tested for potential confounding effects of socio-economic status (SES) and gender on all three scales. SES at rearing did not significantly correlate with any of the three scales. Similarly, males and females did not significantly differ on the Sociability or the Involuntary Hand Movements Scales. Males did, however, show elevated General Neuromotor Scale scores as compared to females, t( 169) = 3.56, p < .000 (males, N = 97, M = .09, SQ = .64; females, N = 93, M = -.19, £D = .44). We therefore report all General Neuromotor analyses for males and females separately. As discussed in the Methods section, the original investigators went to great lengths to standardize the conditions of the videotaping. However, not every subject had a lunch partner (subjects without a partner, N = 41). Although two subjects were invited for testing every day, occasionally only one came. The subjects without partners did not systematically differ from the subjects with partners in terms of diagnostic outcome, psychiatric risk status, or sex (Adult Diagnostic Outcome: Schizophrenia vs. NMI, % 2 (1, N=128) - .53, p = NS; Schizophrenia vs. OPD, % 2 (1, N=70) = .32, p = NS; Schizophrenia vs. Spectrum, % 2 (1, N=24) = .23, p = NS; NMI vs. OPD, x2 (1, N-170) = .04, p = NS; NMI vs. Spectrum, x2 (1, N=124) - .00, p = NS; OPD vs. Spectrum, % 2 (1, N=66) = .01, p = NS. Psychiatric Risk Status: High 28 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Genetic Risk vs. Psychiatric Control Risk, % 2(1, N=135) = .21, p = NS; High Genetic Risk vs. Low Genetic Risk, % 2 (1, N=129) = .91, p = NS; Psychiatric Control Risk vs. Low Genetic Risk, % 2 (1, N=124) = 1.89, p = NS. Gender: Male vs. Female, X2 (1, N-144) = 1.06, p - NS). (See Table 5). Table 5. Demographics of subjects with partners. Partner No Partner Percent Partnered Adult Diagnostic Outcome Schizophrenia 10 4 71.4% (10/14) NMI 91 23 79.8% (91/114) OPD 44 12 78.6% (44/56) Spectrum 8 2 80.0% (8/10) Psychiatric Risk Status Hi Genetic Risk 56 14 88.9% (56/70) Psychiatric Cntrl 54 11 83.1% (54/65) Low Genetic Risk 43 16 72.9% (43/59) Gender Male 81 18 81.8% (81/99) Female 72 23 75.8% (72/95) Table 6. Differences between subjects with and without a partner on Sociability, Involuntary Hand Movements, and Neuromotor Scale scores Partner Mean (SD) No Partner Mean (SD) df t P Sociability .03 (.79) N = 145 -.27 (.31) N = 41 166.8 -3.66 <.000 Involuntary -.11 (.77) M= 149 .08 (.63) N = 34 178 1.32 .189 Neuromotor -.13 (.41) N = 151 .31 (.41) N = 39 42.5 3.05 .004 29 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. T-tests, however, revealed significant differences between those with and without partners on the Sociability and General Neuromotor Scales (see Table 6). Due to the differences between partnered and non-partnered subjects, we first report analyses using only those subjects with a partner. For completeness, we follow these analyses looking at all videotaped subjects with outcome data, with and without partners. Hypotheses 1: Psychiatric Risk Status High-Risk vs. Control Risk. For these analyses, we looked at subjects with partners only.1 Comparison of means failed to reveal significant differences between offspring of a parent with schizophrenia and offspring of parents without a diagnosed psychiatric condition on any of the three scales (See Table 7). As mentioned, analyses revealed significant differences between males and females on the General Neuromotor Scale. Therefore, among the General Neuromotor Scale, we repeated analyses for males and females separately. High-risk and low-risk males did not significantly differ on the General Neuromotor Scale. High-risk females, however, showed deficits on the General Neuromotor Scale compared to female children of a parent without a diagnosed psychiatric disorder. 1 Analyzing subjects with and without partners revealed the same pattern of findings. 30 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 7. Means and standard deviations of Sociability, Involuntary Hand Movements, and General Neuromotor Scale scores for High-Risk and Low Risk, partners only. High-Risk Low-Risk t (df) E Sociability -.03 (.69) N = 51 .04 (.81) N = 41 .40 (90) .688 Involuntary -.09 (.84) N = 55 -.18 (.68) N = 42 .52 (93) .604 Neuromotor -.09 (.41) N = 55 -.20 (.39) N = 42 1.30(95) .198 Neuromotor (males only) -.06 (.41) N = 33 -.05 (.48) N = 22 .10(53) .919 Neuromotor (females only) -.14 (.40) N = 22 -.36 (.16) N = 20 2.42 (28.0) .022 Specificity: High-Risk vs. Psychiatric-Control-Risk. Comparison of means failed to reveal significant differences between offspring of a parent with schizophrenia and offspring of a parent with a non-psychotic psychiatric condition on any of the three scales (Sociability Scale, psychiatric-control-risk, N = 53, t(102) - .67, p = .505; Involuntary Hand Scale, psychiatric-control-risk, N = 52, t(103) = .14, p = .892; General Neuromotor Scale, psychiatric-control-risk, N = 54,1(107) = .45, p = .653). These findings remained for the General Neuromotor Scale when separated by sex (General Neuromotor Scale, psychiatric-control-risk, males only, N - 25,1(56) = .58, p = .562; General Neuromotor Scale, psychiatric-control-risk, females only, N = 29,1(49) = 1.02, p = .315). 31 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Summary: Psychiatric Risk Status Children of parents with schizophrenia did not have deficits on the Sociability Scale, the Involuntary Hand Movement Scale, or the General Neuromotor Scale compared to children of parents without a psychiatric history. Female high- risk subjects did, however, show deficits on the General Neuromotor Scale compared to female offspring of parents without a psychiatric diagnosis. The high-risk group did not significantly differ on any of the three scales when compared to the psychiatric-control-risk group. Hypotheses 2: Adult Diagnostic Outcome Partners Only Schizophrenia vs. No Mental Illness Outcome. Comparisons of means revealed that children who later developed schizophrenia had impaired scores compared to children with a non-psychiatric outcome (NMI) on the Sociability Scale, t(67.4) = 3.99, p < .000, and the General Neuromotor Scale, 1(98) = 2.07, p = .042. Analyzing males and females separately for the General Neuromotor Scale, results revealed significantly higher scores on the General Neuromotor Scale for males in the schizophrenia group compared to the NMI group, 1(48) = 2.07, p = .044, but not for females, 1(48) = .85, p = .403. Pre-schizophrenia and pre-NMI children did not significantly differ on the Involuntary Hand Movement Scale, 1(95) = -.73, p = .470. 32 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Specificity: Schizophrenia vs. Other Psychiatric Outcomes In addition to the main hypotheses regarding the behavior of the schizophrenia patients compared to the normal controls, we were also interested in the specificity of these effects to pre-schizophrenia children as compared to children who later developed other psychiatric disorders. We repeated the above analyses comparing the pre-schizophrenia patients to the pre-other-disordered patients on all three scales. For completeness, we also compared the pre-schizophrenia patients to the pre-schizophrenia spectrum patients (similar in nature to schizophrenia, lesser in severity) on all three scales. No strong conclusions, however, can be drawn from the analyses comparing schizophrenia patients to spectrum patients, as sample sizes are very small. Schizophrenia vs. Non-Psvchotic Psychiatric Disorders. Pre-schizophrenia patients had significantly lower Sociability Scale scores, t(50.8) = 2.38, p = .021 compared to children who later developed other psychiatric conditions. The pre schizophrenia patients also showed a trend towards elevated General Neuromotor Scale scores as compared to the pre-other-disordered group, 1(10.3) = 2.05, p = .066. The General Neuromotor Scale significantly differed between the schizophrenia patients and the other disordered patients among males only, t(30) = 3.36, p = .002. No significant difference was found between the schizophrenia group and the OPD group on the Involuntary Hand Movements Scale, 1(49) = -.93, p = .355, nor the General Neuromotor Scale among females only, 1(30) = 1.19, p = .247. 33 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Schizophrenia vs. Spectrum. We repeated the analyses comparing pre schizophrenia subjects to pre-spectrum disordered subjects. These tests did not yield statistically significant differences; however the N ’s for these analyses limited power (Schizophrenia, N = 10 [5 male, 5 female] for General Neuromotor and Involuntary Hand Movements Scales; Schizophrenia, N = 9 for Sociability; Spectrum, N = 7 [3 male, 4 female] for General Neuromotor and Sociability Sclaes; Spectrum, N = 8 for Involuntary Hand Movements). (Sociability Scale, 1(7.90) = 1.23, p = .255; Involuntary Hand Movements Scale, 1(16) - -.90, p = .380; General Neuromotor Scale, 1(15) = 1.21, p = .246; General Neuromotor Scale (males only), 1(6) = 1.88, p = .110; General Neuromotor Scale (females only), t(7) = .551, p = .599. Non-Psvchotic Psychiatric Disorders vs. No Mental Illness Outcome. We did not hypothesize differences between the NMI and OPD group, however, we report these analyses for completeness. NMI and OPD subjects did not significantly differ on any of the three scales (Sociability Scale, 1(127) = .80, p = .424; Involuntary Hand Movements Scale, 1(126) = -.27, p = .791; General Neuromotor Scale, 1(132) = .91 p = .364; General Neuromotor Scale (males only), 1(70) = 1.29, p = .200; General Neuromotor Scale (females only), 1(60) = .35, p = .724). Summary: Partners Only Children who later develop schizophrenia have significantly lower Sociability Scale scores as compared to children who do not develop a psychiatric condition. Additionally, children who later develop schizophrenia have significantly 34 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. lower Sociability Scale scores as compared to children who develop other non- psychotic psychiatric conditions. Furthermore, male pre-schizophrenia patients have higher General Neuromotor Scale scores as compared to males who do not develop a psychiatric condition and males who develop a non-psychotic disorder. No mental illness subjects and other non-psychotic psychiatric subjects did not significantly differ when compared to one another on the Sociability, the Involuntary Hand Movement Scale, and the General Neuromotor Scales. No significant differences were detected between any diagnostic group on the Involuntary Hand Movement Scale; nor were any significant differences detected among females between any diagnostic group on the General Neuromotor Scale. The mean scale scores, by diagnostic group, are presented in Table 8. For illustrative purposes, the mean rates of the three scales by diagnostic group are presented in Figures 1-4. Figures 1-4 do not include Spectrum subjects, as low group size prevent meaningful interpretation. 35 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 8. Means and standard deviations of Sociability, Involuntary Hand Movements, and General Neuromotor Scale scores, partners only. Schizophrenia NMI OPD Spectrum MEANS (SD) Sociability -.32 (.16) N=9 .10 (.86) N=85 -.02 (.77) N=44 -.14 (.36) N=7 Involuntary -.30 (.44) N=10 -.04 (.79) N=87 -.07 (.75) N=44 -.09 (.59) N=8 Neuromotor .17 (.57) N=10 -.14 (.44) N=90 -.20 (.31) N=44 -.11 (.28) N=7 Neuromotor (boys only) .47 (.61) N = 5 -.01 (.48) N = 45 -.15 (.32) N = 27 -.25 (.26) N = =3 Neuromotor (girls only) -.12 (.36) N=5 -.26 (.36) N=45 -.30 (.28) N=17 .00 (.27) N=4 Figure 1. Sociability Scale by Diagnostic Group, Partners Only • f ' Schizophrenia Diagnostic Group 36 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2. Involuntary Hand Movement Scale by Diagnostic Group, Partners Only Schizophrenia Diagnostic Group No SPD Figure 3. General Neuromotor Scale by Diagnostic Group, Partners Only £ i I U © 0.25 r ..... — ..r ........ i.. Schizophrenia OPD NMI Diagnostic Group Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 4. General Neuromotor Scale by Diagnostic Group, and by Sex, Partners Only ■3 - Sex H Male LI Female Schizophrenia Diagnostic Group With and Without Partners Schizophrenia vs. No Mental Illness Outcome: With and Without Partners. Examining all subjects, regardless of whether they were partnered, revealed that children who later developed schizophrenia had deficits compared to children with a non-psychiatric outcome on the Sociability Scale, t(58.1) = 3.24, p = .002, and the General Neuromotor Scale, 1(125) = 2.15, p = .033. Separating by sex, analyses revealed significantly higher scores on the General Neuromotor Scale for males, 1(58) = 2.51, p = .015, but no significant differences for females, 1(65) = .327, p = .745. Pre-schizophrenia and pre-normal children did not significantly differ on the Involuntary Hand Movement Scale 1(118) = -.66, p = .512. 38 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Specificity We repeated the above analyses comparing the pre-schizophrenia patients to the pre-other-disordered patients and the pre-schizophrenia-spectrum patients on all three scales, regardless of whether subjects were partnered. Schizophrenia vs. Non-Psvchotic Psychiatric Disorders: With and Without Partners. Among partnered and non-partnered subjects, the schizophrenia group showed a trend toward higher General Neuromotor Scale scores as compared to the OPD group among males only, 1(39) = 1.98, p = .055. No significant difference was found between the schizophrenia group and the other disordered group on the Sociability Scale, 1(67) = .97, p = .338, the Involuntary Hand Movements Scale, 1(61) = 1.12, p = .267, the General Neuromotor Scale among all subjects, 1(67) =1.52, p = .133, or the General Neuromotor Scale among females, 1(26) -.27, p = .790. Schizophrenia vs. Spectrum: With and Without Partners. We repeated the analyses comparing pre-schizophrenia subjects to pre-schizotypal personality disordered subjects. These tests did not yield statistically significant differences; however the N ’s for these analyses limited power (Schizophrenia, N = 14 [7 males, 7 females] for General Neuromotor; Schizophrenia, N = 13 for Sociability and Involuntary Hand Movements; Spectrum, N = 8 [5 males, 3 females] for General Neuromotor; Spectrum, N = 9 for Sociability; Spectrum, N = 10 Involuntary Hand Movements Scales). (Sociability Scale, 1(20) = 1.70, p = .104; Involuntary Hand 39 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Movements Scale, 1(12.6) = -.94, g = .363; General Neuromotor Scale (males only), t(20) = 1.42, g = .170; General Neuromotor Scale (males only), 1(8) = 1.69, p = .129; General Neuromotor Scale (females only), t(8) = .38, g = .711). Non-Psvchotic Psychiatric Disorders vs. No Mental Illness Outcome: With and Without Partners. No mental illness and other psychiatric disorders subjects did not significantly differ on any of the three scales. (Sociability Scale, 1(162) = 1.02, g - .309; Involuntary Hand Movements Scale, 1(158) = .95, g = .343; General Neuromotor Scale, 1(166) = .54, g = .592; General Neuromotor Scale (males only), 1(85) = .04, g = .970; General Neuromotor Scale (females only), 1(79) = .76, g = .451). Summary: With and Without Partners Similar to analyses limited to subjects with partners only, children with or without partners who later develop schizophrenia have significantly lower Sociability Scale scores as compared to children who do not develop a psychiatric condition. Among subjects with and without partners, the schizophrenia group did not significantly differ from the other non-psychotic psychiatric disorders group on the Sociability Scale. Male pre-schizophrenia patients have higher General Neuromotor Scale scores as compared to males who do not develop a psychiatric condition. Additionally, pre-schizophrenia males show a trend towards higher General Neuromotor Scale scores as compared to males who develop other non- psychotic psychiatric conditions. No mental illness and other non-psychotic 40 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. psychiatric disorders subjects did not significantly differ when compared to one another on the Sociability or the General Neuromotor Scales (male or females). No significant differences were detected between any comparison group on the Involuntary Hand Movement Scale. The mean scale scores, by diagnostic group, are presented in Table 9. Table 9. Means and standard deviations of Sociability, Involuntary Hand Movements, and General Neuromotor Scale scores, with and without partners. Schizophrenia NMI OPD Spectrum MEANS (SD) Sociability -.29 (.23) N=13 .03 (.79) N=108 -.10 (.70) N=56 -.09 (.34) N=9 Involuntary -.48 (.81) N=13 -.20(1.55) N=107 .00(1.50) N=50 .04(1.60) N=10 Neuromotor .25 (.76) N=14 -.08 (.53) N=H3 -.03 (.61) N=55 -.14 (.28) N=8 Neuromotor (males only) .66 (.89) N=7 .06 (.56) N=53 .06 (.70) N=34 -.25 (.26) N=3 Neuromotor (females only) -.14 (.30) N=7 -.20 (.48) N=60 -.19 (.38) N=21 -.08 (.29) N=5 Hypotheses 3: Predicting Schizophrenia We performed a sequential logistic regression analysis to assess prediction of schizophrenia or no mental illness, first on the basis of genetic risk, then after addition of the General Neuromotor Scales and the Sociability Scale. We do not report analyses including the Involuntary Movements Scale because this scale failed 41 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. to significantly distinguish any of the outcome groups.2 We included genetic risk because of the established link between schizophrenia and genetic predisposition. Including genetic risk allows us to assess whether the scales from the videotapes contribute to the prediction of schizophrenia above the contributions of genetic risk alone. For this analysis, we excluded subjects in the psychiatric-control-risk group (having a parent with a non-psychotic disorder). Additionally, following the practices of Carter and Mednick (2001), we excluded subjects who developed a non- psychotic disorder in adulthood. Thus, this analysis predicted an outcome of schizophrenia or no mental illness among high and low genetic risk subjects from the factors genetic risk, the Sociability Scale, and the General Neuromotor Scale. Data from 78 subjects were available for analysis: 11 subjects with an adult outcome of schizophrenia and 67 subjects with a normal adult outcome. There was a good model fit (discrimination among groups) on the basis of genetic risk and the Neuromotor Scale and the Sociability Scale, % 2 (8, N = 78) = 1.76, p = .988, Cox and Snell R2 = .240. Comparison of the log-likelihood ratios for models with and without the Neuromotor and Sociability Scales showed reliable improvement with the addition of these scales (p = .004) indicating that they contributed to the model above and beyond genetic risk. Table 10 presents results for each factor. Because the Wald statistic has poor properties when used for hypothesis testing, Tabachnic and Fidell (2001) suggest comparing the log-likelihood ratios for models with and without each variable individually. The difference between a model containing all 2 In unreported analyses, as expected, the Involuntary Movements Scale did not significantly contribute to the logistic regression. 42 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. predictors and a model without one predictor provides the contribution of the excluded predictor. Comparisons of the log-likelihood ratios with and without both the Neuromotor and the Sociability Scales suggest that both scales independently and significantly contribute to the model (Neuromotor, p = .004; Sociability, p = .008). Table 10. Stepwise likelihood ratio logistic regression analysis showing the impact of different factors on the prediction of schizophrenia. (N = 78). Factor Change in Model If Removed df P Genetic Risk 10.81 1 .001 Neuromotor & Sociability 11.07 2 .004 Neuromotor 8.32 1 .004 Sociability 6.94 1 .008 In addition to assessing contribution to a prediction model, logistic regression also offers the opportunity to predict outcome group based on predictor variables. Based on a cut-off criterion of .75, the model provided 82% correct classification of schizophrenia subjects, 85% correct classification of normal subjects, and an overall correct classification of 85%. See Table 11. 43 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 11. Classification based on logistic regression Predicted Schizophrenia No Mental Illness Observed Schizophrenia 9(81.8%) 2(18.2%) No Mental Illness 10 (14.9%) 57 (85.1%) 44 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Chapter 5: Discussion Summary of Findings Overall, observation from these standardized videotapes suggests differences between children who do and do not develop schizophrenia in adulthood. Specifically, the results of this study support the hypotheses that children who later develop schizophrenia evidence social deficits as compared to children who do not develop a psychiatric disorder and to children who develop a non-psychotic disorder. Additionally, boys who later develop schizophrenia evidence general neuromotor deficits as compared to boys who do not develop a psychiatric disorder, and to boys who develop a non-psychotic disorder. The data failed to support hypothesized differences in the Involuntary Hand Movement Scale between the pre-schizophrenia group and the other outcome groups. We also hypothesized social and neuromotor differences between subjects with varying levels of genetic risk for psychiatric conditions. Contrary to hypothesized deficits among children with high genetic risk for schizophrenia compared to children with risk for other psychiatric conditions or no identifiable genetic risk, most analyses failed to detect significant differences. Girls with a mother diagnosed with schizophrenia did, however, show deficits on the General Neuromotor Scale compared to children of parents without a psychiatric diagnosis. 45 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Covariates Social Class and Gender. We considered social class and gender as potential covariates in our analyses. Analyses did not suggest a relation between SES and any of the three scales. Similarly, gender did not significantly relate to the Sociability Scale or the Involuntary Hand Movements Scale. Boys, however, did show deficits on the General Neuromotor Scale compared to girls. Similarly, Reider and Nichols (1979) as well as Marcus and colleagues (1993) found more neuromotor impairment among high-risk boys than high-risk girls. Genetic Risk Status and Sociability and Neuromotor Deficits: Hypotheses The below hypotheses predict that high-risk subjects (having a parent with schizophrenia) will evidence childhood differences on the Sociability Scale, the Involuntary Hand Movements Scale, and the General Neuromotor Scale compared to subjects without a parent with schizophrenia. 1. Children o f a parent with schizophrenia have deficits on the Sociability Scale compared to the children o f parents without a psychiatric diagnosis. 2. Children o f a parent with schizophrenia have deficits on the Involuntary Hand Movement Scale compared to the children o f parents without a psychiatric diagnosis. 3. Children o f a parent with schizophrenia have deficits on the General Neuromotor Scale compared to the children o f parents without a psychiatric diagnosis. 46 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Specificity: High-Risk vs. Psychiatric Control Risk 4. Children o f a parent with schizophrenia have deficits on the Sociability Scale compared to the children o f a parent with a non-psychotic psychiatric diagnosis. 5. Children o f a parent with schizophrenia have deficits on the Involuntary Hand Movement Scale compared to the children o f a parent with a non- psychotic psychiatric diagnosis. 6. Children o f a parent with schizophrenia have deficits on the General Neuromotor Scale compared to the children o f a parent with a non-psychotic psychiatric diagnosis. Previous longitudinal high-risk studies have uncovered social and neuromotor deficits in children at high-risk for schizophrenia compared to other children (e.g., Erlenmeyer-Kimling, Golden, & Comblatt, 1989; Hans et al., 2000). Contrary to previous literature, the three scales from this study did not significantly differ by genetic risk status. Neither social nor neuromotor deficits appear more common among subjects at high genetic risk for schizophrenia compared to subjects at risk for other disorders and normal controls. These findings suggest that risk status may not be a controlling factor for the three scales in this study. One previous high-risk project reported non-significant differences in neuromotor function between high-risk and non-high-risk subjects. Bergman, 47 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Wolfson, and Walker (1997) failed to detect significant differences between children with varying risk for psychopathology based on parental diagnosis. The children in the Bergman and colleagues study were of similar age to the children in our study. Researchers contend that age of neuromotor assessment may mediate findings (McNeil, Harty, Blennow, & Canto-Graae, 1993). McNeil and colleagues (1993) suggested that neuromotor dysfunction, especially in HR subjects, “unfolds differently at different ages....” (pg. 52). Another possible explanation for our non-significant results is that our measures of sociability and neuromotor dysfunction differ from measures used in previous research. We used the actual behaviors of children interacting while eating lunch. Although we have the advantage of standardized observation of behavior, our measures may not have been sensitive enough to detect differences between risk status. All previous high-risk research investigating neuromotor behavior evaluated dysfunction through a neurological examination. These one-on-one, structured exams may be more sensitive to differences between risk status groups than our observation of the videotapes. Previous high-risk studies examining social function are not observational in nature. Generally, past high-risk studies used self-report, parent-report, and teacher-report to measure sociability. These methods may more sensitively assess sociability as compared to our in vivo observation. An alternative explanation for the lack of significant differences between high and low-risk children is that the observable effects from this study may result from findings specifically relating to pre-schizophrenia, not risk status. From this 48 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. perspective, future diagnostic outcome, not risk status, may relate to observable deviations in children. Theoretically, only 16% of high-risk children develop schizophrenia. If observable deviant behavior relates to pre-schizophrenia subjects only, and we are assessing a high-risk sample, we would expect non-deviant behavior from the high-risk subjects who do not develop schizophrenia (84%). Perhaps the non-pre-schizophrenia high-risk subjects dilute the effect. We attempted to test this hypothesis by analyzing high-risk subjects only', comparing high-risk schizophrenia subjects to high-risk normal subjects. We predicted that among the high-risk group, pre-schizophrenia subjects would evidence more deviant behavior than pre-normal subjects. Unfortunately, our analyses lacked sufficient power to detect significant differences. The findings, however, were in the predicted direction. We did find a significant difference between high and low genetic risk and the General Neuromotor Scale among girls. Although previous research suggests a difference in neuromotor functioning between high and low-risk children, no study points to a specific effect found in girls but not boys. Adult Diagnostic Outcome and Scale Scores: Hypotheses The next set of hypotheses predicted childhood deficits among children who developed schizophrenia compared to children who did not develop an adult mental illness and to children who developed a non-psychiatric diagnosis. These comparisons are regardless of genetic psychiatric risk status. 49 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 7. Children who later develop schizophrenia have deficits on the Sociability Scale compared to children who do not develop a mental illness. 8. Children who later develop schizophrenia have deficits on the Involuntary Hand Movement Scale compared to children who do not develop a mental illness. 9. Children who later develop schizophrenia have deficits on the General Neuromotor Scale compared to children who do not develop a mental illness. Specificity: Schizophrenia vs. Other Non-Psvchotic Psychiatric Outcomes 10. Children who later develop schizophrenia have deficits on the Sociability Scale compared to children who develop a non-psychotic psychiatric condition. 11. Children who later develop schizophrenia have deficits on the Involuntary Hand Movement Scale compared to children who develop a non-psychotic psychiatric condition. 12. Children who later develop schizophrenia have deficits on the General Neuromotor Scale compared to children who develop a non-psychotic psychiatric condition. As hypothesized, schizophrenia patients showed pre-morbid social deficits and neuromotor deficits, as measured by the General Neuromotor Scale (but not the Involuntary Hand Movement Scale). Pre-schizophrenia patients showed impaired 50 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. sociability compared to normal controls and psychiatric controls. These findings suggest impairment unique to pre-morbid schizophrenia, not observed in children who later develop other disorders. Similarly, male children (but not females) who later developed schizophrenia showed impaired neuromotor functioning as assessed by the General Neuromotor Scale compared to normal controls. The impairment seemed specific to schizophrenia patients, as these subjects showed deficits compared to children who developed other psychiatric conditions in childhood as well. We did not detect significant differences between pre-schizophrenia patients, pre-other-psychiatric controls, and pre-normal controls on the Involuntary Hand Movement Scale. The above findings suggest observable differences in individuals who later develop schizophrenia. The course of schizophrenia begins early, and group differences evidence themselves in childhood prior to overt clinical symptoms. Origins of Neuromotor Deficits Neuromotor deficits as assessed through neurological examinations often imply brain abnormalities, particularly among the basal ganglia and dopaminergic functioning. Keshavan and colleagues (1998) suggest that the basal ganglia (a subcortical structure comprised of the caudate nucleus, putamen, and the globus pallidus) play important roles in both higher cognitive functioning and motor functioning. Flashman, Flaum, Gupta, and Andreasen (1996) attributed increased 51 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. soft signs, poor motor speed, and poor coordination to compromised basal ganglia functioning leading to poor frontal/subcortical circuitry. Walker (1994) implicates the dopaminergic system, interacting with sub- cortical CNS regions, as contributing to the etiology of neuromotor signs. High levels of dopamine, a neurotransmitter associated with schizophrenia, input to the caudate nucleus, putamen, and the nucleus accumben, a sub-cortical region. Excess dopamine may interact with impairments in neural circuitry linking the dorsal basal ganglia with the motor cortex (Alexander, Crutcher, & DeLong, 1990). Over-activity in dopamine neurotransmission, specifically in sub-cortical regions, may contribute to the neuropathophysiology of movement abnormalities and of psychotic symptoms (Walker, Lewis, Loewy, & Palyo, 1999). Lang and Weiner (1992) also suggested that excess dopamine activity contributed to excess involuntary movements seen in psychiatric populations. Additionally, dopamine plays important roles in Parkinson’s and Huntington’s disease that resemble schizophrenia in terms of motor dysfunction. Regardless of the exact location of brain morphology related to schizophrenia, researchers generally find neuroanatomical abnormalities rather than neurodegenerative defects. Arnold and Trojanowski (1996) observed that postmortem studies conducted with the brain tissue of schizophrenia patients did not show neurodegenerative processes such as senile plaques and neurofibrillary tangles observed in Alzheimer’s’ patients. Consistent with these findings, studies of high- risk infants and children reported neuromotor dysfunction early in life (e.g., Mednick 52 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. et al., 1971; Marcus et al., 1981). These findings lend support to the early (perhaps prenatal) presence of static neural lesions resulting in neuromotor disturbances. Despite evidence linking neuromotor dysfunction to neuropathology, the observable behaviors from these videotapes do not lend themselves to accurate speculations about neuromotor underpinnings associated with the General Neuromotor Scale. Brain scans or functional MRIs linking brain morphology to the General Neuromotor Scale would provide a clearer link between behavior and the brain. Currently, we do not have structural or functional brain imaging data for the subjects in this sample. Potential future follow-up with this sample may include measurement of brain morphology. We would expect that childhood neuromotor deficits as identified through the videotapes would relate to adult neuropathology. Origins of Sociability Deficits Early social deficits seem to portend adult schizophrenia. In high-risk children, however, research has yet to effectively uncover conclusive links between early social function and neuropathology among schizophrenia patients. Studies examining the relation between brain morphology and pre-morbid social functioning have the potential of informing the etiology of both sociability deficits and schizophrenia itself. Future follow-up of this sample may address this question. Possible Environmental Contributors to Deficits: Future Study. We found no significant differences between psychiatric risk groups on the three scales. The pre schizophrenia subjects, however, did evidence deficits on the Sociability Scale and 53 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. the General Neuromotor Scale (for boys only). This combination of findings suggests the possibility that the differences we observed on the scales between pre schizophrenia subjects and pre-normal subjects may not be genetically influenced. Rather, differences between diagnostic groups may result from environmental factors. Several childhood environmental factors with established links to adult schizophrenia may contribute to the development of the observed deficits. Possible factors include obstetrical complications (e.g., McNeil, Cantor-Graae, & Ismail, 2000), early separation from family (Schiffman et al., 2000 unpublished manuscript), and poor family rearing circumstances (Schiffman et al., 2002; Tienari, 1991). The current study is part of a larger project assessing pre-morbid functioning in high-risk and control subjects. The project included collection of information regarding birth complications, social functioning as assessed by the mother, cognitive functioning, and family rearing circumstances. Future studies investigating the link between these factors and the Sociability Scale and the General Neuromotor Scale may offer insight into possible correlates of, or perhaps etiologic contributors to, the scales. Prediction of Schizophrenia: Hypothesis We used logistic regression analyses to predict schizophrenia among high and low genetic risk subjects. 54 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 13. The Sociability Scale, the Involuntary Hand Movements Scale, and the General Neuromotor Scale will be useful in predicting individuals at increased risk for developing schizophrenia. The above findings have implications for primary prevention. Identification of individuals likely to develop schizophrenia is critical for preventions targeting early childhood experiences. A reliable method of identifying some individuals at risk for schizophrenia is to assess parents for a history of schizophrenia. Not every high-risk child, however, receives a genetic disruption of fetal neural development possibly contributing to later schizophrenia. Observable behaviors such as neuromotor dysfunction and lack of sociability, however, may help identify those high-risk subjects at increased risk for schizophrenia. Previous longitudinal high-risk research using neuromotor dysfunction as obtained through childhood neurological examinations predicted approximately one third of high-risk children who later develop schizophrenia or schizophrenia-like conditions (e.g., LaFosse, 1994; Erlenmyer-Kimling et al., 2000). Due to limited sample sizes and the use of only 3 predicting variables, our prediction model offers only a tentative glimpse into the possibility of a more accurate predicting protocol. Using a restricted sample, we accurately predicted nine of the 11 (82%) schizophrenia patients from genetic risk and the Sociability and Neuromotor Scales. In addition to a high rate of correct classification, our model generated a modest rate of false positives. Only 10 of the 67 (15%) children who did 55 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. not develop an adult psychiatric diagnosis were predicted to develop schizophrenia. An intervention guided by this model would correctly treat 82% of the pre schizophrenia patients and incorrectly treat 15% of normal outcome children. Incorporating additional pre-morbid correlates of schizophrenia into a prediction model may increase accuracy. Study Strengths Prospective Data Collection. All measures for this study were prospective; data were gathered 20 to 33 years before diagnosis. This method of data collection greatly reduces the likelihood of the adult clinical picture influencing measurement of prenatal and early childhood events. We assessed subjects at age 11-13, before any major signs of mental illness, and well before the critical age of risk. In 1972, when the tapes were created, researchers were blind to psychiatric risk status, and obviously blind to diagnostic outcome. Additionally, all current research team members (raters, data entry assistants, PI) were blind to adult diagnostic outcome until after the coding of all videotapes. In fact, all identifying information remained in Denmark until the completion of coding. Consecutive Birth Cohort. The high-risk subjects from this study were selected from a Danish birth cohort consisting of all children bom between September 1, 1959, and December 31, 1961, at Rigshospitalet in Copenhagen. Every child having a parent diagnosed with schizophrenia was included in our sample. Thus, rather than being selected through various means, the 90 identified high-risk 56 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. subjects are truly representative of high-risk children in Denmark. Therefore, the 16 diagnosed schizophrenia patients in this sample are representative of genetically at risk Danish children who develop schizophrenia. First Use of Videotaping Technology. The Akai video camera used in this study was new to the market in 1972. Portable, personal video recording units were very uncommon. Dr. Mednick’s demonstrated outstanding foresight in purchasing this equipment. Today, almost every aspect of a research protocol is videotaped. This study may be the first to utilize video camera technology to capture invaluable data. Standardized Videotaping Procedures. Previous work discerning social and neuromotor deficits in pre-morbid schizophrenia suffers from lack of standardization (Walker et al., 1994). The protocol for this project, however, dictated strict standardization. All subjects were given the same meal (Danish smorrebrod), at the same time of day, in the same chairs, for the same length of time, by the same photographer. Even the table and camera tri-pod were nailed to the floor to ensure consistent conditions. The attention to uniform and systematic protocol limited measurement error. Prediction. The Sociability Scale and the General Neuromotor Scale assessed in childhood significantly predict adult schizophrenia. The observation of sociability and neuromotor deficits may be a valuable tool (along with other measures) for recognizing individuals at elevated risk for schizophrenia. Additionally, data were derived from children performing a very natural event: eating lunch. Future 57 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. investigations similar to the current project may eventually contribute to a readily accessible lunch eating protocol for early detection of those at risk greater for schizophrenia. As discussed above, early identification of vulnerable individuals may be invaluable in targeting those who may benefit from primary prevention programs. Study Limitations Reliability of Seales. The ten variables measuring the observed behaviors from the videotapes yielded three scales (see Tables 1 and 2). Agreement between raters ranged from very high for the Sociability Scale (ICC of .95), to moderate for the Involuntary Hand Movements Scale (ICC of .68) and for the General Neuromotor Scale (ICC of .69). The Sociability Scale consisted of easily recognizable items including smiles, laughs, and vocalization, resulting in reliable coding between raters. More ambiguous items composed the two neuromotor scales. Nystagmus-like eye movements, for example, were difficult to discern from the videos. Similarly, the difference between an involuntary movement of the hand and a voluntary re-gripping of the silverware was difficult to determine. These subtle distinctions resulted in less agreement between raters. Overall, the intraclass correlations for the three scales suggest, to varying degrees, that raters coded the subjects with adequate agreement. Our rating system was only one of many possible ways to code these tapes. Other coding systems may more accurately discern social and neuromotor 58 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. differences than our system. Our codes, however, were created in conjunction with Elaine Walker and colleagues, who successfully created coding schemes assessing the childhood home-movies of schizophrenia patients. Despite other possible coding schemes, our Sociability Scale and General Neuromotor Scale significantly discriminated the pre-schizophrenia patients from controls. Measurement of internal consistency varied across the scales as well. The Sociability Scale showed very high internal consistency (a - .82). The items in this scale strongly relate to one another. The Involuntary Hand Movements showed moderate internal consistency {a = .67). The General Neuromotor Scales showed only modest internal consistency (a = .48). Low internal consistency may result from low number of items in the scales, and low behavioral frequencies of each item. Modest reliability suggests that scales may not measure a single factor. The non-consistent nature of these scales dictates caution when interpreting results. Poorer reliability in the Involuntary Hand Movements and the General Neuromotor Scales may contribute to failures to reject null hypotheses, in particular when sample sizes are small. Despite these limitations, however, we still found hypothesized significant effects on the General Neuromotor Scale. Missing Videotape Footage. This study suffers from sizable missing data. Of the 242 subjects with adult follow-up information, 48 subjects did not have videotapes. Data for these 48 subjects would have increased power and confidence in our findings. Fortunately, the subjects with and without tapes do not systematically differ in terms of adult diagnostic outcome, sex, or psychiatric risk 59 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. status. We therefore assume that the subjects we do have are a representative sample of the original study sample. Partners vs. No Partners. Subjects without partners had lower Sociability Scales scores and elevated General Neuromotor Scale scores compared to subjects with partners. Two of the codes comprising the Sociability Scale completely depend on the presence of a partner (Vocalizations initiated by subject to the lunch partner and Vocalizations responding to lunch partner). The other two codes in the factor (Smiles and Laughs) are also impacted by a lunch partner. Accordingly, subjects with partners had significantly higher Sociability Scale scores. Additionally, subjects with partners were coded as having significantly fewer general neuromotor signs. In cases with only one subject, the camera focused directly on the subject; whereas subjects with partners were filmed at an angle allowing both children to fit in the frame. The additional focus on the non-partnered subjects may account for higher General Neuromotor Scale scores. While partnered and non-partnered subjects differed on the Sociability and General Neuromotor Scales, they did not significantly differ in terms of demographics. Partnered and non-partnered subjects were similar in terms of diagnostic outcome, psychiatric risk status, and sex. Most importantly, findings analyzing partnered-only subjects were similar to results considering subjects with- and-without-partners. Limited Number of Schizophrenia Patients. We based our results on a relatively small number of schizophrenia patients (N = 16). The number of 60 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. schizophrenia patients becomes even less when we only consider subjects with partners. Additionally, because the General Neuromotor Scale differed by sex, we ran boys and girls separately. This further reduced our sample of patients. Due to a small number of schizophrenia patients, our analyses may lack power to detect significant differences and impact our confidence in interpreting null findings as evidence that significant differences do not exist. Given the small number of subjects with schizophrenia, however, significant differences we did obtain seem all the more impressive. Possible Type I Error. Given the limited number of schizophrenia subjects and the uniqueness of these data, we were concerned with Type II Error (not detecting a significant difference when a difference exists). Consequently, rather than employing omnibus tests to assess for overall group differences, and rather than correcting significance levels to reflect multiple tests, we used uncorrected-planned- comparison t-tests as the primary statistical analyses assessing group differences on the Sociability Scale, Involuntary Hand Movement Scale, and General Neuromotor Scale. While these practices minimize the chances of Type II Error, they increase the risk for Type I Error (detecting a significant difference when one does not exist). Given the concern for Type II Error with these data, and our specific a priori hypotheses, we contend that our method of analysis most accurately captures the true meaning of the data. 61 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Summary and Implications Results from this study suggest that brief videotaped footage of children eating lunch can discriminate between individuals who later develop schizophrenia and individuals who do not. In particular, pre-schizophrenia children show deficits on measures of sociability and general neuromotor abnormalities as compared to children who develop other disorders and to children who do not develop psychiatric disorders. In addition to furthering understanding of schizophrenia in terms of a developmental disorder, the results from this study may assist in the formation of an accurate detection program for children at risk for schizophrenia. Future work investigating the neuropathological substrates associated with the behavioral deficits observed in this study may contribute to the understanding of schizophrenia as a neural-developmental disease. Additionally, research incorporating a variety of known pre-morbid correlates of schizophrenia, including observable social and neuromotor deficits as revealed in this study, may contribute to effective screening measures used to identify children likely to develop schizophrenia. Ultimately, it is our hope that effective primary interventions targeting these identified children may prevent some cases of schizophrenia. 62 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. References Alexander, G.E., Crutcher, M.D., & DeLong, M.R. (1990). Basal ganglia- thalamocortical circuits: Parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Progress in Brain Research. 85. 119-145. 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Appendix A Coding Form Coder ___ Subject name/ID Subject Sex _ Subject Age _ Date of film ___ Partners Name Partners Sex _ Partners Age _ Time Start 1. # of involuntary arm or hand movements (Right): yes _______________________ no if yes, describe 2. # of involuntary arm or hand movements (Left): yes _______________________ no if yes, describe 3. # of smiles: _______________________________ _ 4. # of laughs:_________________________________ 5. # of vocalizations to other child initiated by subject. 6. # of vocalizations to other child initiated by other child. 7. # of raised elbows:_______________ N o____ 8. # of nystagmus-like eye movements________________No 9. # of involuntary facial movements:____________ 10. # of other abnormal movements:____________ Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Appendix B Coding Instructions 1. # of involuntary arm or hand movements (Right): yes _________________________ no if yes, describe E.G., TICS, TREMOR, DYSKINESIAS 2. # of involuntary arm or hand movements (Left): yes _________________________ no if yes, describe E.G., TICS, TREMOR, DYSKINESIAS 3. # of smiles:___________________ NO VOCALIZATION OF LAUGHTER. TEETH OR CLEARLY DEFINED CHEEK SMILE. 4. # of laughs_____________________________________________ MUST BE ACCOMPANIED BY VOCALIZATION OF LAUGHTER. 5. # of vocalizations to other child initiated by subject. WHEN ONE KID RESPONDS, THEN QUICKLY INITIATES A NEW DIALOGUE, THE BEGINNING OF THE NEW DIALOGUE IS NEW INITIATION. HIGH PITCHES MAY CUE NEW INITIATION. 6. # of vocalizations to other child initiated by other child. 7. # of raised elbows: No ELBOW RAISED ABOVE PARALLEL 8. # of nystagmus-like eye movements________________ No SHIFTS EYES AROUND 3 PLACES RAPIDLY. 9. # of involuntary facial movements:____________ TICS, OROFACIAL DYSKINESIA 10. # of other abnormal movements: E.G., AVOLITIONAL TORSO MOVEMENTS, JERKY WHOLE HEAD MOVEMENTS 70 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Appendix C Histograms of Ten Variables from Videotape Coding 100 n Std. Dev = 2.35 Mean - 1.8 N = 193.00 0.0 2.0 4.0 6.0 8.0 10.0 Smiles 200 Std. Dev = 2.61 M ean= 1.0 N = 193.00 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 Laughs Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 Vocalizations Initiated by Subject 200 Std. Dev = 2.26 Mean - .7 N = 193.00 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 Vocalizations Responding to Lunch Partner 72 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 200 100 Std. Dev = .79 Mean = .3 N = 191.00 3.0 0.0 1.0 2.0 4.0 5.0 Nystagmus-like Eye Movements 160 140 120 100 Std. D ev-3 .7 7 Mean - 1.9 N = 194.00 2 0 - 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 Elbows 73 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 140 1 2 0 - 100 - Std. Dev = 3.69 Mean = 2.3 N = 193.00 25.0 5.0 10.0 15.0 20.0 0.0 2.5 7.5 12.5 17.5 22.5 Involuntary Face Movements Std. Dev = 3.94 Mean = 3.1 N = 194.00 0,0 ' 51) ' 10.0 15.0 20.0 25.0 2.5 7.5 12.5 17.5 22.5 Involuntary Right Hand 74 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 100 Std. Dev = 4.73 Mean = 3.6 N = 194.00 10.0 15.0 20.0 25.0 0.0 5.0 2.5 7.5 12.5 17.5 22.5 Involuntary Left Hand 120 100 Std. Dev = 2.70 Mean = 2.1 N = 193.00 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 Other Abnormal Movements 75 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.

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Creator Schiffman, Jason Eric (author)

Core Title Childhood videotaped neuromotor and social precursors of schizophrenia: A prospective investigation

School Graduate School

Degree Doctor of Philosophy

Degree Program Psychology

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag health sciences, mental health,OAI-PMH Harvest,psychology, behavioral,Psychology, clinical

Language English

Contributor Digitized by ProQuest (provenance)

Advisor Margolin, Gayla (committee chair), Brekke, John (committee member), Earleywine, Mitchell (committee member), Raine, Adrian (committee member)

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c16-267404

Unique identifier UC11334944

Identifier 3093816.pdf (filename),usctheses-c16-267404 (legacy record id)

Legacy Identifier 3093816.pdf

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Document Type Dissertation

Rights Schiffman, Jason Eric

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Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the au...

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