Early and Late Neurodevelopmental Influences in the Prodrome to Schizophrenia: Contributions of Genes, Environment, and Their Interactions (original) (raw)

Journal Article

,

Tyrone D. Cannon, Ph.D.

Staglin Family Professor of Psychology, Psychiatry, and Human Genetics

University of California

Los Angeles

Send reprint requests to Dr. T.D. Cannon, Department of Psychology, University of California, Los Angeles. 1285 Franz Hall, Los Angeles, CA 90095; e-mail: cannon@psych.ucla.edu

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Theo G. M. van Erp, M.A., Ph.D.

candidate

University Utrecht, University of California

Los Angeles

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Carrie E. Bearden, Ph.D.

Assistant Professor of Psychiatry and Biobehavioral Sciences

University of California

Los Angeles

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Rachel Loewy, M.A., Ph.D.

candidate

University of California

Los Angeles

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Paul Thompson, Ph.D.

Assistant Professor of Neurology

Department of Neurology, UCLA School of Medicine

Los Angeles, CA

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Arthur W. Toga, Ph.D.

Professor of Neurology and Director of the Laboratory of Neuroimaging

UCLA School of Medicine

Los Angeles, CA

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Matti O. Huttunnen, M.D.

Dr.Med., Professor of Psychiatry

Department of Mental Health, National Public Health Institute of Finland

Helsinki, Finland

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Matcheri S. Keshavan, M.D.

Professor of Psychiatry

Department of Psychiatry, Western Psychiatric Institute and Clinic and University of Pittsburgh School of Medicine

Pittsburgh, PA

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Larry J. Seidman, Ph.D.

Professor of Psychology

Harvard Medical School, Massachusetts Mental Health Center, Harvard Institute of Psychiatric Epidemiology and Genetics, Neuropsychology Laboratory

Boston, MA

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Ming T. Tsuang, M.D.

Professor of Epidemiology, Director

Harvard Medical School Department of Psychiatric Epidemiology and Genetics, Harvard Medical School Departments of Psychiatry at Massachusetts Mental Health Center and Massachusetts General Hospital

Boston, MA

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Published:

01 January 2003

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Tyrone D. Cannon, Theo G. M. van Erp, Carrie E. Bearden, Rachel Loewy, Paul Thompson, Arthur W. Toga, Matti O. Huttunnen, Matcheri S. Keshavan, Larry J. Seidman, Ming T. Tsuang, Early and Late Neurodevelopmental Influences in the Prodrome to Schizophrenia: Contributions of Genes, Environment, and Their Interactions, Schizophrenia Bulletin, Volume 29, Issue 4, 2003, Pages 653–669, https://doi.org/10.1093/oxfordjournals.schbul.a007037
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Abstract

Both early (i.e., pre- and perinatal periods) and late (i.e., adolescent period) neurodevelopmental processes are thought to participate in the etiology and pathophysiology of schizophrenia. However, whether markers of these processes would be expected to predict an imminent onset of psychosis, as is hoped in the current generation of prodromal research programs, depends on whether their disruptions result from genetic factors shared by patients and some of their unaffected relatives, nongenetic factors specific to those who manifest the illness phenotype, or combinations of these sets of influences. Here we present recent work deriving primarily from high-risk and family-study (i.e., “genetic high-risk”) designs, which provide a frame-work for investigating the neural changes that may occur proximally to the initial onset of psychosis. This work indicates that some of the alterations in brain function and structure in schizophrenia are primarily genetically mediated and also appear in some of patients' unaffected first degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk (Cannon et al. 2002_a_, 2002_c_; Van Erp et al. 2002). Whereas the primarily genetically mediated deficits shared by at-risk but nonsymptomatic relatives are not likely to show differential change in the premorbid period and may be necessary but clearly not sufficient for the development of psychotic symptoms, the deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodromal (i.e., “clinical high-risk”) state appear to be interpretable within this framework.

A number of questions arising from this line of inquiry need to be addressed in the current generation of pro dromal research programs: To what extent do the neural systems affected by early and late neurodevelopmental influences overlap? Is there likely to be a schizophrenia-related disturbance in the processes associated with adolescent brain maturation, or are these maturational processes themselves intact, partic ipating in psychosis onset only indirectly, by promot ing a neurobiological context in which the early neu rodevelopmental disturbances can be expressed in psychotic symptoms? What pattern of changes observable from in vivo imaging studies is consistent with a reduction in neuropil volume? We develop a frame work for addressing these questions and evaluating their implications for understanding the roles of early and late neurodevelopmental influences in the etiology and pathophysiology of schizophrenia.

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Topic:

• phenotype
• adolescent
• genes
• neuropil
• psychotic disorders
• schizophrenia
• brain
• diagnostic imaging
• genetics
• genetic aspects
• family studies
• psychotic symptom
• perinatal period
• brain function
• genetic risk
• prodrome
• causality
• symptom onset
• first degree relative

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