More clues on "latent" schizophrenia point to developmental origins
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Cited by 15 publications
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Schizophrenia is a highly heritable disorder, even though most relatives of patients with schizophrenia will not develop schizophrenia. What, then, are the effects of the schizophrenia genes that are carried by the relatives? In fact, many such effects have been identified, including attentional impairments, eye-tracking dysfunction, allusive thinking, neurological signs, thought disorder, characteristic auditory-evoked potentials, neuropsychological impairments, and structural brain abnormalities. The question then becomes: How can these deficits be integrated into useful phenotypes for genetic studies, especially when any given one of the effects only appears in a portion of the affected relatives? This article describes a model for exploring alternative phenotypes that derived originally from a concept ("schizotaxia") proposed by Paul Meehl [1962] that we have reformulated to account for more recent research findings . After a brief description of the concept, the bases of the model are described, with its structure and implications.Meehl [1962] introduced the term "schizotaxia" to describe the genetic predisposition to schizophrenia. Schizotaxic individuals, he surmised, would develop either schizotypy or schizophrenia, depending on environmental circumstances. For the past 15 years, we have been testing hypotheses about neurobiologic manifestations of schizotaxia among the nonpsychotic adult relatives of schizophrenic patients. Our workshowing that schizotaxia is associated with negative symptoms [Tsuang et al., 1991], neuropsychological dysfunction [Faraone et al., 1995a], and structural brain abnormalities [Seidman et al., 1997]-converges with data from other centers to show that schizotaxia is a subtle brain disorder affecting about 20-50% of the nonpsychotic relatives of schizophrenic patients [Faraone et al., 1995a,b].From studies of children at risk for schizophrenia we know that schizotaxia emerges early in childhood. It predicts affective flattening in adolescence [Rinaldi et al., 1991], behavioral problems known to be precursors of schizophrenia [Cornblatt and Erlenmeyer-Kimling, 1985], anhedonia, social isolation, and-possiblynonparanoid psychosis in adolescence and adulthood [Erlenmeyer-Kimling and Cornblatt, 1992;Erlenmeyer-Kimling et al., 1995]. From studies of adult relatives we know that some cases of schizotaxia continue into adulthood without decompensating into psychosis. These adults manifest clinically significant functional deficits, but often do not meet criteria for specific psychiatric disorders.Any discussion of alternative phenotypes must consider two important features of schizophrenia theory: its multifactorial etiology, and its neurodevelopmental origins. DIATHESIS-STRESS THEORYOF SCHIZOPHRENIA The diathesis-stress, or vulnerability, model of schizophrenia has been advocated by Meehl [1962], Gottesman [1991], and many other investigators. This model views schizophrenia as arising from the impact of the environment on the genetic predisposition to the disorder. Twin and adoption...
Schizophrenia is a highly heritable disorder, even though most relatives of patients with schizophrenia will not develop schizophrenia. What, then, are the effects of the schizophrenia genes that are carried by the relatives? In fact, many such effects have been identified, including attentional impairments, eye-tracking dysfunction, allusive thinking, neurological signs, thought disorder, characteristic auditory-evoked potentials, neuropsychological impairments, and structural brain abnormalities. The question then becomes: How can these deficits be integrated into useful phenotypes for genetic studies, especially when any given one of the effects only appears in a portion of the affected relatives? This article describes a model for exploring alternative phenotypes that derived originally from a concept ("schizotaxia") proposed by Paul Meehl [1962] that we have reformulated to account for more recent research findings . After a brief description of the concept, the bases of the model are described, with its structure and implications.Meehl [1962] introduced the term "schizotaxia" to describe the genetic predisposition to schizophrenia. Schizotaxic individuals, he surmised, would develop either schizotypy or schizophrenia, depending on environmental circumstances. For the past 15 years, we have been testing hypotheses about neurobiologic manifestations of schizotaxia among the nonpsychotic adult relatives of schizophrenic patients. Our workshowing that schizotaxia is associated with negative symptoms [Tsuang et al., 1991], neuropsychological dysfunction [Faraone et al., 1995a], and structural brain abnormalities [Seidman et al., 1997]-converges with data from other centers to show that schizotaxia is a subtle brain disorder affecting about 20-50% of the nonpsychotic relatives of schizophrenic patients [Faraone et al., 1995a,b].From studies of children at risk for schizophrenia we know that schizotaxia emerges early in childhood. It predicts affective flattening in adolescence [Rinaldi et al., 1991], behavioral problems known to be precursors of schizophrenia [Cornblatt and Erlenmeyer-Kimling, 1985], anhedonia, social isolation, and-possiblynonparanoid psychosis in adolescence and adulthood [Erlenmeyer-Kimling and Cornblatt, 1992;Erlenmeyer-Kimling et al., 1995]. From studies of adult relatives we know that some cases of schizotaxia continue into adulthood without decompensating into psychosis. These adults manifest clinically significant functional deficits, but often do not meet criteria for specific psychiatric disorders.Any discussion of alternative phenotypes must consider two important features of schizophrenia theory: its multifactorial etiology, and its neurodevelopmental origins. DIATHESIS-STRESS THEORYOF SCHIZOPHRENIA The diathesis-stress, or vulnerability, model of schizophrenia has been advocated by Meehl [1962], Gottesman [1991], and many other investigators. This model views schizophrenia as arising from the impact of the environment on the genetic predisposition to the disorder. Twin and adoption...
In an effort to identify the developing abnormalities preceding psychosis, Dr. Ming T. Tsuang and colleagues at Harvard expanded Meehl's concept of "schizotaxia," and examined brain structure and function in families affected by schizophrenia (SZ). Here, we systematically review genetic (familial) highrisk (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings inform models of SZ etiology, and suggest directions for future research. Neuroimaging studies of youth at HR for SZ through the age of 30 were identified through a MEDLINE (PubMed) search. There is substantial evidence of gray matter volume abnormalities in youth at HR compared to controls, with an accelerated volume reduction over time in association with symptoms and cognitive deficits. In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the most consistently reported finding in HR. There was also consistent evidence of smaller hippocampal volume. In functional studies, hyperactivity of the right PFC during performance of diverse tasks with common executive demands was consistently reported. The only longitudinal fMRI study to date revealed increasing left middle temporal activity in association with the emergence of psychotic symptoms. There was preliminary evidence of cerebellar and default mode network alterations in association with symptoms. Brain abnormalities in structure, function and neurochemistry are observed in the premorbid period in youth at HR for SZ. Future research should focus on the genetic and environmental contributions to these alterations, determine how early they emerge, and determine whether they can be partially or fully remediated by innovative treatments.
In this paper, we discuss the conceptual background for including a dimensional component to the DSM V diagnoses for psychoses. We review the evidence for a continuous distribution of psychosis like symptoms in the general population and summarise the research validating the clinical usefulness of psychopathological dimensions. We conclude that diagnostic models using both categorical and dimensional representations of psychosis have better predictive validity than either model independently. Dimensions do not appear to be diagnosis specific so a flexible scoring of dimensions across all psychotic and major affective disorders may be potentially more informative than a system where categorical diagnoses are kept artificially dimension-specific.
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