Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients

Seidman, Larry J.; Faraone, S.V.; Goldstein, J.M.; Goodman, Julie M.; Matsuda, Genichi; Kremen, W.S.; Kennedy, David N.; Makris, Nikos; Caviness, Verne S.; Tsuang, M.T.

doi:10.1016/0006-3223(96)84292-2

Cited by 17 publications

(15 citation statements)

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“…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].…”

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confidence: 72%

Defining alternative phenotypes for genetic studies: What can we learn from studies of schizophrenia?

Tsuang

2001

Am. J. Med. Genet.

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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...

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supporting

confidence: 72%

Defining alternative phenotypes for genetic studies: What can we learn from studies of schizophrenia?

Tsuang

2001

Am. J. Med. Genet.

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“…Using high-resolution magnetic resonance imaging, we showed structural abnormalities among adult siblings of schizophrenic patients (92). Greymatter volumes of subcortical structures were consistently smaller and ventricular volumes were larger among relatives than in controls.…”

Section: Target Features In Adult Relatives Of Schizophrenic Patientsmentioning

confidence: 90%

The concept of target features in schizophrenia research

Tsuang

Faraone

1999

Acta Psychiatr Scand

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Target features are clinical or neurobiological characteristics that are expressions of the underlying predisposition to an illness. They comprise a wide range of phenomena, from the classic signs and symptoms of psychopathology to sophisticated measures of brain structure and function. For schizophrenia, many target features have been identified. These include eye tracking dysfunction, attentional impairment, allusive thinking, neurological signs, thought disorder, characteristic auditory evoked potentials, neuropsychological impairment, structural brain abnormalities and functional brain abnormalities. In their most pathological forms, thcse features are present among many schizophrenic patients, yet it is their presence among their non‐psychotic relatives that shows them to be target features. We discuss the theoretical background for target features, present examples and describe how the discovery of target features has implications for schizophrenia research.

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“…In a pilot study [36], the authors compared six female siblings of schizophrenia patients with 11 female control individuals, and found that gray matter volumes of subcortical structures were smaller among the relatives. In a subsequent, larger sample, 28 nonpsychotic relatives from simplex families had significant reductions bilaterally in the amygdala-hippocampus and thalamus compared with 26 control individuals; marginal differences were noted in the pallidum, putamen, and cerebellum [37,38].…”

Section: Neuroanatomic Abnormalitiesmentioning

confidence: 98%