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Etiology of Schizophrenia
www.sciencedirect.com/topics/neuroscience/etiology-of-schizophrenia
Schizophrenia
Kathleen L. Benson, Vincent P. ZarconeJr., in Principles and Practice of Sleep Medicine (Fourth Edition), 2005
PATHOGENESIS
The etiology of schizophrenia is poorly understood, but accumulating evidence has revealed a wide range of brain abnormalities.611 Brain structural abnormalities have been found in postmortem studies as well as in in vivo imaging using computed tomography (CT) and magnetic resonance imaging technology. Regarding the latter, structural dysmorphologies have included enlarged lateral and third ventricles, loss of total gray matter, frontal, and temporal lobe volume, as well as a reduction in total brain size. These findings seem to be present at the onset of illness and cannot be attributed to progressive degeneration; however, most findings are nonspecific, having been observed in other psychiatric disorders. Functional imaging studies utilizing positron emission tomography or regional cerebral blood flow have observed decreased metabolism in the frontal cortex (hypofrontality), as well as left hemisphere dysfunction.
Abnormalities of neurotransmitter systems have also been extensively investigated. For many years, the prevailing theory of schizophrenia has centered on the dopamine (DA) system. The DA hypothesis of schizophrenia derived from two observations. First, the potency of standard AP medication correlates with the amount of DA (D2) receptor blockade. Second, drugs such as amphetamines, which enhance DA activity, can cause psychosis or exacerbate schizophrenic symptoms. The DA hypothesis holds that psychotic symptoms such as hallucinations and delusions are associated with hyperactivity of the DA mesolimbic system. In a similar vein, both serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine have been associated with the pathophysiology of schizophrenia because the potency of the newest generation of APs has been linked to 5-HT and alpha-adrenergic receptor blockade. Finally, the role of the neurotransmitter glutamate in the pathophysiology of schizophrenia is gaining greater credence in part because several of the recently identified schizophrenia susceptibility genes target glutamatergic transmission.713
The range of these findings may reflect both genetic and environmental effects as well as the clinical heterogeneity of schizophrenia. Because no discrete pathologic abnormality has emerged as an etiologic factor, schizophrenia could be an abnormality of neuronal connectivity14 or of integrative neuronal circuits.15 Neither of these theories is inconsistent with the broader and prevailing view that schizophrenia is a neurodevelopmental disorder.16 Although abnormal events may occur early in development (prenatal or perinatal), maturational abnormalities may present during the second decade of life17 or even into middle age.18
www.sciencedirect.com/topics/neuroscience/etiology-of-schizophrenia
Schizophrenia
Kathleen L. Benson, Vincent P. ZarconeJr., in Principles and Practice of Sleep Medicine (Fourth Edition), 2005
PATHOGENESIS
The etiology of schizophrenia is poorly understood, but accumulating evidence has revealed a wide range of brain abnormalities.611 Brain structural abnormalities have been found in postmortem studies as well as in in vivo imaging using computed tomography (CT) and magnetic resonance imaging technology. Regarding the latter, structural dysmorphologies have included enlarged lateral and third ventricles, loss of total gray matter, frontal, and temporal lobe volume, as well as a reduction in total brain size. These findings seem to be present at the onset of illness and cannot be attributed to progressive degeneration; however, most findings are nonspecific, having been observed in other psychiatric disorders. Functional imaging studies utilizing positron emission tomography or regional cerebral blood flow have observed decreased metabolism in the frontal cortex (hypofrontality), as well as left hemisphere dysfunction.
Abnormalities of neurotransmitter systems have also been extensively investigated. For many years, the prevailing theory of schizophrenia has centered on the dopamine (DA) system. The DA hypothesis of schizophrenia derived from two observations. First, the potency of standard AP medication correlates with the amount of DA (D2) receptor blockade. Second, drugs such as amphetamines, which enhance DA activity, can cause psychosis or exacerbate schizophrenic symptoms. The DA hypothesis holds that psychotic symptoms such as hallucinations and delusions are associated with hyperactivity of the DA mesolimbic system. In a similar vein, both serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine have been associated with the pathophysiology of schizophrenia because the potency of the newest generation of APs has been linked to 5-HT and alpha-adrenergic receptor blockade. Finally, the role of the neurotransmitter glutamate in the pathophysiology of schizophrenia is gaining greater credence in part because several of the recently identified schizophrenia susceptibility genes target glutamatergic transmission.713
The range of these findings may reflect both genetic and environmental effects as well as the clinical heterogeneity of schizophrenia. Because no discrete pathologic abnormality has emerged as an etiologic factor, schizophrenia could be an abnormality of neuronal connectivity14 or of integrative neuronal circuits.15 Neither of these theories is inconsistent with the broader and prevailing view that schizophrenia is a neurodevelopmental disorder.16 Although abnormal events may occur early in development (prenatal or perinatal), maturational abnormalities may present during the second decade of life17 or even into middle age.18