Premorbid indicators and risk for schizophrenia: A selective review and update

Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 4201 St Antoine, Suite 9B, Detroit, MI 48201, USA.
Schizophrenia Research (Impact Factor: 3.92). 12/2005; 79(1):45-57. DOI: 10.1016/j.schres.2005.07.004
Source: PubMed


Prospective studies of young relatives at risk for schizophrenia (high-risk studies, HR) can shed light on premorbid precursors of schizophrenia. Early HR studies pointed to a wide prevalence of schizophrenia spectrum psychopathology among young relatives at increased genetic risk. Recent studies suggest that young HR relatives have neurobehavioral deficits and structural, physiological, and neurochemical brain abnormalities that may date back to childhood or earlier. In this paper, we provide a selected overview of the lessons and limitations of early "first generation" studies and the beginning insights from recent "second generation" studies. We also provide an interim summary of data from the ongoing studies of young relatives at risk for schizophrenia in Pittsburgh. Collectively, such data may help us to predict the eventual emergence of schizophrenia, and schizophrenia spectrum or non-spectrum psychopathology.

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Available from: John A Sweeney, Jan 08, 2014
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    • "Over the past 50 years, significant research effort has focused on the early detection of emerging psychosis in order to facilitate the identification of etiological mechanisms and earlier intervention. The examination of familial risk, based on presumed genetic contribution to psychotic disorders and accompanying neurodevelopmental markers, has made important progress (Keshavan et al., 2005). In recent years, efforts have expanded to consider clinical and behavioral high risk as well as familial risk, determined through symptom-based screening instruments such as the Structured Interview for Prodromal Syndromes (SIPS, Miller et al., 1999; McGlashan et al., 2001). "
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    ABSTRACT: Background Psychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal-level symptoms in those with schizophrenia or related psychoses is largely unknown. Methods This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at “clinical high risk” (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13–17), or adulthood (18 +). Results Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset. Conclusion Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories.
    Schizophrenia Research 09/2014; 158(1-3). DOI:10.1016/j.schres.2014.05.017 · 3.92 Impact Factor
    • "nclusiones en torno al conocimiento que actualmente se tiene sobre la relación personalidad - esquizofrenia . La impresión clínica , sin embargo , parece indicar que las características premórbidas de la personalidad o precursores etiológicos de la esquizofrenia estarían relacionadas con los rasgos negativos observados en la investigación familiar Keshavan et al . 40 ( 2005 ) Estudiar una visión general de teorías y las limitaciones de los estudios sobre familiares de jóvenes con UHR . Se ofrece un resumen de los datos de los estudios en curso de familiares jóvenes en situación de riesgo para la esquizofrenia en Pittsburgh Revisión Estos datos pueden ayudarnos a predecir la posible aparición de la esquizof"
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    ABSTRACT: This paper reviews and discusses the published information on stressful life events and their influence on the onset of a first psychotic episode. The aim is to update and promote further investigation into these events in the context of a stress-vulnerability model. Milestone studies that referred to the key thematic stressful life events, such as adolescence, coping, resilience, and ethnic differences. A search was conducted using PsycINFO, MEDLINE and PSICODOC between 1980 and 2013 using the following terms: Stressful life events, adolescence, coping, resilience, schizophrenia, stress, first psychotic episode, and vulnerability. A total of 289 studies were found, of which 59 were selected for review. The integrated assessment of stressful life events, along with other individual and contextual variables, allow an approach for an early detection and a prevention tool. The results suggest the need for a multiple and integrated approach, since there are several factors that are involved in the whole network which forms a first psychotic episode.
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    • "In fact, epigenetics may provide a more proximate mediator of neuronal and behavioral effects than changes in the DNA sequence, and in turn these neuronal alterations may predispose individuals to schizophrenia, a question that has received comprehensive coverage in a recent canonical review (11). Moreover, the proposed additions also provide a prospective research impetus for studying particular sub-groups such as children of schizophrenia patients, a group that provides a particularly unique intersection of genetic risk, altered neurodevelopment, and environmental contributions (12–14). Finally, the notion of stress reactivity impacting brain network function is a particular extension of the seminal concept of “allostatic load” (15, 16), morphologic degeneration as a response to repeated adaptive responses to stress. "
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    ABSTRACT: The recent sociodevelopmental cognitive model of schizophrenia/psychosis is a highly influential and compelling compendium of research findings. Here, we present logical extensions to this model incorporating ideas drawn from epigenetic mediation of psychiatric disease, and the plausible effects of epigenetics on the emergence of brain network function and dysfunction in adolescence. We discuss how gene-environment interactions, effected by epigenetic mechanisms, might in particular mediate the stress response (itself heavily implicated in the emergence of schizophrenia). Next, we discuss the plausible relevance of this framework for adolescent genetic risk populations, a risk group characterized by vexing and difficult-to-explain heterogeneity. We then discuss how exploring relationships between epigenetics and brain network dysfunction (a strongly validated finding in risk populations) can enhance understanding of the relationship between stress, epigenetics, and functional neurobiology, and the relevance of this relationship for the eventual emergence of schizophrenia/psychosis. We suggest that these considerations can expand the impact of models such as the sociodevelopmental cognitive model, increasing their explanatory reach. Ultimately, integration of these lines of research may enhance efforts of early identification, intervention, and treatment in adolescents at-risk for schizophrenia.
    Frontiers in Psychiatry 06/2014; 5:71. DOI:10.3389/fpsyt.2014.00071
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