Understanding Predisposition to Schizophrenia: Toward Intervention and Prevention

Abstract

Objective: Early intervention to prevent schizophrenia is one of the most important goals of schizophrenia research. However, the field is not yet ready to initiate trials to prevent prodromal or psychotic symptoms in people who are at risk for developing the disorder. In this paper, we consider some of the major obstacles that must be studied before prevention strategies become feasible. Method and Results:One of the most important hurdles is the identification of a syndrome or set of traits that reflects a predisposition to schizophrenia and that might provide potential targets for intervention. In a recent reformulation of Paul Meehl's concept of schizotaxia, we integrate research findings obtained over the last 4 decades to propose a syndrome with meaningful clinical manifestations. We review the conceptualization of this syndrome and consider its multidimensional clinical expression. We then describe preliminary research diagnostic criteria for use in adult, nonpsychotic, first-degree relatives of patients diagnosed with schizophrenia, based on negative symptoms and neuropsychological deficits. We follow this with evidence supporting the validity of the proposed syndrome, which mainly includes social dysfunction and response to a low dosage of one of the newer antipsychotic medications. Conclusions:Continued progress toward the eventual initiation of prevention strategies for schizophrenia will include sustained efforts to validate the traits reflecting a predisposition to develop the disorder (for example, schizotaxia), follow-up studies to confirm initial findings, and the identification of potentially useful preventive interventions. (Can J Psychiatry 2002;47:518-526) See page 524 for research funding and support and page 525 for author affiliations.Clinical Implications · The predisposition to develop schizophrenia in nonprodromal, nonpsychotic adult relatives of patients with schizophrenia may be expressed as a meaningful, diagnosable, clinical syndrome or set of traits, called schizotaxia. · In adults, at least some schizotaxia symptoms may be attenuated with interventions. · Interventions that attenuate schizotaxia symptoms in adults may eventually be useful in strategies aimed at preventing schizophrenia.Limitations · Double-blind intervention studies of schizotaxia are needed. · Longitudinal neuroimaging data are needed for children at high risk for developing schizophrenia. · Molecular-genetic studies of schizotaxia are needed to extend and validate the syndrome.

Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

“…For example, PhysAn scores are elevated in the relatives of schizophrenic patients while PerAb scores are not (Katsanis et al, 1990;Clementz et al, 1991) and lifetime risk of schizophrenia-spectrum disorders is higher in relatives of anhedonic schizophrenia probands than in nonanhedonic probands (Schurhoff et al, 2003). Negative, but not positive, symptoms are also elevated in schizophrenia families (Tsuang et al, 1991), and PhysAn is a major component of the stable familial set of traits referred to as 'schizotaxia', which is observed in a subset of relatives (Tsuang et al, 2002). That PhysAn but not PerAb subjects showed an elevated DA response to stress is consistent with Stress-induced dopamine release in schizotypy A Soliman et al the idea that positive and negative schizotypy represent different forms of risk that may follow divergent paths to symptom development (Fanous et al, 2001).…”

Comparison Groups in Autism Family Research: Down Syndrome, Fragile X Syndrome, and Schizophrenia

“…Although the three groups were similar in the marital status of the mother, they differed in the age, gender, and health status of the adult, the mother's age, education, and whether she co-resided with her son or daughter with disabilities. Controlling for these background variables (child age (Asarnow et al, 2001;Krabbendam, Marcelis, Delespaul, Joiles, & Van Os, 2001;Tsuang, Stone, & Faraone, 2002). Such elevated risks are not present in families whose child has Down syndrome nor systematically in heterogeneous comparison groups of families of children with mental retardation due to unknown causes.…”

Review paper. Neuropsychological dimension of schizophrenia - evaluation possibilities and therapeutic implications

“…The researchers also propose the introduction of a new term for diseases of the schizophrenia group-schizotaxis [34]. This term describes the susceptibility or predisposition to schizophrenia and includes a large group of environmental, biological and neuropsychological factors [34,35].…”

“…This term describes the susceptibility or predisposition to schizophrenia and includes a large group of environmental, biological and neuropsychological factors [34,35]. According Tsuang, schizophrenia is a combination of schizotaxis with psychosis, which is the final stage of the disease.…”

“…Badacze proponują także wprowadzenie nowego pojęcia dla chorób z grupy schizofrenii -schizotaksji [34]. Pojęcie to oznacza podatność czy pewną predyspozycję do wystąpienia zachorowania na schizofrenię i obejmuje szeroką grupę czynników środowiskowych, biologicznych i neuropsychologicznych [34,35].…”