Age of Onset of Schizophrenia: Perspectives From Structural Neuroimaging Studies (original) (raw)
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Imaging as a tool in exploring the neurodevelopment and genetics of schizophrenia
British Medical Bulletin, 1996
Neuroimaging has enabled us to address questions about the timing and origin of brain abnormalities in schizophrenia. First episode and longitudinal computed tomography (CT) and magnetic resonance imaging (MRI) studies of schizophrenic patients have shown that the brain abnormalities are present at onset of psychosis and are non-progressive. Such findings support the idea that schizophrenia is a developmental rather than a degenerative condition. Furthermore, the presence of ventriculomegaly and diminished hemispheric asymmetry in familial schizophrenics and in those of their relatives who appear to be transmitting the disorder, implies involvement of the genes controlling neurodevelopment. However, genetic factors do not fully account for the development of schizophrenia; early environmental insults such as obstetric complications are also important and may interact with genetic predisposition. Brain development continues postnatally and profound maturational events also occur in adolescence and early adulthood. Magnetic resonance spectroscopy (MRS) studies allow the investigation of the developmental biochemistry of the living brain and are being used to explore the role of maturational brain events in determining the onset of psychosis.
Schizophrenia Bulletin, 2005
The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an ''early neurodevelopmental'' lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre-or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of individuals, (i) an early (pre-and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions; and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness.
Brain changes during the onset of schizophrenia: implications for neurodevelopmental theories
The Medical journal of Australia, 2009
Neuroimaging studies of individuals at risk of psychosis have the potential to identify markers predictive of illness onset and features that progress with transition. To date, reduced brain volumes have shown weak predictive value for onset of psychotic illness. All published longitudinal studies of the transition to psychosis show progressive brain changes that are not seen in at-risk individuals who do not develop the disorder. Although the cause of these changes is unclear, they challenge the conventional neurodevelopmental model of schizophrenia.
Early Intervention in Psychiatry, 2009
Objective: Children and adolescents with schizophrenia share a similar pattern of phenomenological, genetic and cognitive abnormalities to adults with schizophrenia. However, an early-onset of schizophrenia (EOS) (prior to 18 years of age) is associated with a higher frequency of risk indicators associated with schizophrenia (e.g. developmental delays and familial spectrum disorders) and a worse long-term outcome. This overview examines recent research on the neurobiological alterations, possible causes, developmental trajectory and treatment of EOS and attempts to identify gaps in the field.
No evidence for structural brain changes in young adolescents at ultra high risk for psychosis
Schizophrenia Research, 2009
Objective: The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing of these changes has not been established. We investigated structural brain changes in a sample of young adolescents (12-18 years) at ultra high-risk for psychosis (UHR). Methods: Structural MRI data from young UHR subjects (n = 54) and typically developing, matched controls (n = 54) were acquired with a 1.5 Tesla scanner and compared. Results: None of the measures differed between UHR subjects and controls. Conclusions: Our results do not support the presence of gross neuroanatomical changes in young UHR subjects. This suggests that early changes are too subtle to detect with conventional imaging techniques. Therefore, changes observed in older cohorts may only onset later developmentally or occur secondary to prodromal symptoms.
Schizophrenia Bulletin, 2007
Although the underlying neurobiology of emerging psychotic disorders is not well understood, there is a growing conviction that the study of patients at clinical high risk for the illness will provide important insights. Further, a better understanding of the transition period may help the development of novel therapies. In this review, we summarize the extant neuroimaging and neuropsychological studies of people at clinical high risk for psychosis. By and large, there are few definitive markers that distinguish those who go on to develop the illness from those who do not. The 2 most consistently abnormal brain regions in schizophrenia research, the hippocampi and the lateral ventricles, are not significantly different from healthy controls prior to psychosis onset. However, frontal lobe measures (eg, cortical thickness in the anterior cingulate) do show promise, as do cognitive measures sensitive to prefrontal cortex dysfunction. Further, longitudinal magnetic resonance imaging findings in individuals at ultrahigh risk for developing a psychotic illness show that there are excessive neuroanatomical changes in those who convert to psychosis. These aberrant changes are observed most prominently in medial temporal and prefrontal cortical regions. While the pathological processes underlying such changes remain unclear, speculatively they may reflect anomalies in genetic and/or other endogenous mechanisms responsible for brain maturation, the adverse effects of intense or prolonged stress, or other environmental factors. Active changes during transition to illness may present the potential to intervene and ameliorate these changes with potential benefit clinically.