Article

Brain maturational processes and delayed onset in schizophrenia. Development and Psychopathology, 11, 525-543

Department of Psychiatry, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA.
Development and Psychopathology (Impact Factor: 4.89). 02/1999; 11(3):525-43. DOI: 10.1017/S0954579499002199
Source: PubMed

ABSTRACT The central feature of schizophrenia is its onset in adolescence. Although this clinical observation is consistent with the view that schizophrenia may be a neurodevelopmental disorder, debate has focused on when the proposed brain maturational deviations may begin and what might be the nature of such defective development. Conflicting models of this illness (e.g., the early and late neurodevelopmental models) have been proposed. In this paper, we will first review concepts from basic developmental neurobiology pertinent to these issues; we then summarize aspects of the neurobiology of schizophrenia that have a particular bearing on the adolescent onset of this illness. We propose that the schizophrenic syndrome may result from early brain adversity and late maturational processes of brain development interacting with adverse humoral, biochemical, and psychosocial factors during adolescence and early adulthood. The onset of schizophrenia in adolescence may be related to the "plasticity switch" secondary to the peripubertal brain maturational changes, perhaps involving an alteration in glutamate receptor function. This loss of plasticity could result in social and nonsocial cognitive deficits that are central to the pathophysiology of schizophrenia; the vulnerable person may therefore utilize prepubertal processing styles that are insufficient to the adaptive and "gistful" abstraction requirements of adult cognition. Schizophrenia onset might occur in the context of psychosocial developmental challenges to a delayed social cognitive capacity among neurodevelopmentally compromised individuals. We review therapeutic implications as well as testable predictions generated by this model, and discuss research strategies that might further our understanding of the brain maturational abnormalities in schizophrenia.

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    • "Premorbid motor and cognitive impairments in schizophrenia have been reported in children (Fish, 1957; Jones et al., 1994; Walker et al., 1994) and young adults (Reichenberg et al., 2005) who later developed schizophrenia (Fuller et al., 2002; MacCabe et al., 2008) and in children who are genetically at high-risk for schizophrenia (Gunnell et al., 2002; Maccabe, 2008; Ozan et al., 2010; Koenen et al., 2009; Woodberry et al., 2008), supporting the idea that schizophrenia is a neurodevelopmental disorder that involves alterations in brain circuits (Insel, 2010; Lewis and Levitt, 2002; Weinberger, 1996). We examined whether adolescence, characterized by substantial neuroplastic maturation (Keshavan and Hogarty, 1999; Shen et al., 2010; Uhlhaas et al., 2009; Yurgelun-Todd, 2007), is an opportune window for prophylactic cognitive therapy. We found that cognitive training in adolescence prevents the onset of adult cognitive deficits in neonatal ventral hippocampal lesion (NVHL) rats, an established neurodevelopmental animal model of schizophrenia (Lipska, 2004; Lipska and Weinberger, 2002; McDannald et al., 2011; Tseng et al., 2009). "
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    ABSTRACT: Brain abnormalities acquired early in life may cause schizophrenia, characterized by adulthood onset of psychosis, affective flattening, and cognitive impairments. Cognitive symptoms, like impaired cognitive control, are now recognized to be important treatment targets but cognition-promoting treatments are ineffective. We hypothesized that cognitive training during the adolescent period of neuroplastic development can tune compromised neural circuits to develop in the service of adult cognition and attenuate schizophrenia-related cognitive impairments that manifest in adulthood. We report, using neonatal ventral hippocampus lesion rats (NVHL), an established neurodevelopmental model of schizophrenia, that adolescent cognitive training prevented the adult cognitive control impairment in NVHL rats. The early intervention also normalized brain function, enhancing cognition-associated synchrony of neural oscillations between the hippocampi, a measure of brain function that indexed cognitive ability. Adolescence appears to be a critical window during which prophylactic cognitive therapy may benefit people at risk of schizophrenia.
    Neuron 08/2012; 75(4):714-24. DOI:10.1016/j.neuron.2012.06.016 · 15.98 Impact Factor
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    • "The growing amount of data on cognitive impairment and cognitive remediation refers mostly to adult and chronic patients with schizophrenia, but less is known about the effectiveness of cognitive remediation in the early course of the disease, and its possible application on prodromal phase of the ill- ness. Early detection of schizophrenia, especially in young subjects, could permit timely assessment and intervention in what is considered a crucial period of the illness, that could potentially influence its course, and during which neural plasticity is thought to play a major pathoplastic role [7] [8] [9]. This could justify the theoretical usefulness of interventions targeting cognitive improvement [10]. "
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    • "The growing amount of data on cognitive impairment and cognitive remediation refers mostly to adult and chronic patients with schizophrenia, but less is known about the effectiveness of cognitive remediation in the early course of the disease, and its possible application on prodromal phase of the ill- ness. Early detection of schizophrenia, especially in young subjects, could permit timely assessment and intervention in what is considered a crucial period of the illness, that could potentially influence its course, and during which neural plasticity is thought to play a major pathoplastic role [7] [8] [9]. This could justify the theoretical usefulness of interventions targeting cognitive improvement [10]. "
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    ABSTRACT: Background: The aim of cognitive remediation is to target the cognitive impairments of patients with psychosis, including attentional deficits, memory problems, and limitations in planning and problem solving. It is hoped that by addressing these deficits, patients will be more able to take advantage of other interventions and will be more able to function in social and other domains. Many results in controlled trials of cognitive remediation in adult patients affected by schizophrenia have demonstrated its effectiveness on different cognitive domains and on patient's functioning. Some researchers speculate that deficits in cognition are more amenable to remediation during earlier phases of illness than when chronicity has developed. For these reasons cognitive rehabilitation should be a key component of early intervention programs, seeking to produce durable functional changes in the early course of schizophrenia. Although there is strong evidence that cognitive remediation is effective in adult schizophrenia, there is little evidence about its efficacy and long-term generalized effectiveness in the early course of the disease, and its possible application in the prodromal phase of the disease. Purpose Of Review: The aim of this paper is to review the available literature on cognitive remediation in the prodromal phase and in the early course of schizophrenia. This review summarizes especially findings of cognitive changes induced in the early course or in the prodromal phases of schizophrenia by different remediation methods. Controlled studies of cognitive training are discussed in more detail. Conclusion: Few studies on the effects of cognitive training programs have been conducted in first episode or in early schizophrenia and only one study has been conducted in the prodromal phase of the disease. Although preliminary positive results have been achieved, more empirical research is needed to confirm the efficacy of cognitive remediation in the early course of schizophrenia, and future studies should address the issue of the usefulness of cognitive remediation in the prodromes of psychosis.
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