This application is for a continuation of my Research Scientist Development Award. During the initial period of this award, all of the major research and educational objectives were achieved. First, as a proposed, extensive data on the premorbid development and adult psychiatric outcome of a sample of 120 subjects were obtained. The data included childhood home-movies which served as the primary source of information on activity level and neuromotor and socioemotional development. Results from analyses of these films indicate that preschizophrenia subjects are characterized by an elevated rate of neuromotor abnormalities, particularly in first two years of life, and higher rates of negative affective displays throughout childhood. Retrospective ratings of childhood behavior indicated that preschizophrenia children had significantly more behavior problems than their healthy siblings. Parental ratings of behavior problems were correlated with both neuromotor abnormalities and negative affect ratings from the films. Integrative papers on the neurodevelopmental implications of these findings have also been published. With respect to the educational goals of the RSDA, the award made it possible for me to gain additional training in basic neuroscience, with specialization in the biological basis of motor functions. This exposure is reflected in the biological emphases of recent papers. The findings of this work, as well as some pilot studies recently conducted in our laboratory, led to the research proposed in the present continuation application. It also led to the proposed educational plan in neurochemistry and neuroendocrinology. The research goals involve the extension of our study of precursors to explore the longitudinal course and the correlates of motor dysfunction in schizophrenia. This research is based on a model which assumes that striatal pathology contributes to both psychotic symptoms and hyperkinetic movement abnormalities. Specifically, we propose that DA activity triggers the behavioral expression of striatal pathology, and that stress exacerbates this process through the effects of the HPA axis on DA release. The educational goals of the application are related to this model. They include further study in the general area of psychoneuroendocrinology and collaborative work on the development of animal models.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research (K02)
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Study Section
Special Emphasis Panel (SRCM (21))
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Heinssen, Robert K
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Emory University
Schools of Arts and Sciences
United States
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Walker, Elaine F; Bonsall, Robert; Walder, Deborah J (2002) Plasma hormones and catecholamine metabolites in monozygotic twins discordant for psychosis. Neuropsychiatry Neuropsychol Behav Neurol 15:10-7
Kestler, L P; Walker, E; Vega, E M (2001) Dopamine receptors in the brains of schizophrenia patients: a meta-analysis of the findings. Behav Pharmacol 12:355-71
Weinstein, D D; Diforio, D; Schiffman, J et al. (1999) Minor physical anomalies, dermatoglyphic asymmetries, and cortisol levels in adolescents with schizotypal personality disorder. Am J Psychiatry 156:617-23
Walker, E; Lewis, N; Loewy, R et al. (1999) Motor dysfunction and risk for schizophrenia. Dev Psychopathol 11:509-23
Walker, E F; Diforio, D (1997) Schizophrenia: a neural diathesis-stress model. Psychol Rev 104:667-85
Walker, E F; Lewine, R R; Neumann, C (1996) Childhood behavioral characteristics and adult brain morphology in schizophrenia. Schizophr Res 22:93-101
Baum, K M; Walker, E F (1995) Childhood behavioral precursors of adult symptom dimensions in schizophrenia. Schizophr Res 16:111-20
Neumann, C S; Grimes, K; Walker, E F et al. (1995) Developmental pathways to schizophrenia: behavioral subtypes. J Abnorm Psychol 104:558-66
Walker, E F (1994) Developmentally moderated expressions of the neuropathology underlying schizophrenia. Schizophr Bull 20:453-80
Grimes, K; Walker, E F (1994) Childhood emotional expressions, educational attainment, and age at onset of illness in schizophrenia. J Abnorm Psychol 103:784-90

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