Is There a Neuroanatomic Basis for Schizophrenia? An Old Question Revisited

Abstract

In the past century, the finding of ventricular enlargement in structural brain imaging studies of schizophrenia has stimulated interest in the question of whether this disorder may involve an underlying neurodegenerative process. Recent microscopic investigations have revealed a subtle loss of neurons but no gliosis in several corticolimbic regions of schizophrenic brain, a pattern that is not consistent with a typical adult pattern of neuronal degeneration. The fact that a variety of histopathological changes have been found in cortical layer II of schizophrenic subjects has suggested that an early disturbance of neuronal migration may play an etiological role in this disorder. Overall, many investigators now consider schizophrenia to be a neurodevelopmental disorder in which a latent defect present from birth requires normal maturational changes in the brain to trigger the characteristic onset of illness during adolescence and early adulthood. The Neuroscientist 1: [104][105][106][107][108][109][110][111][112][113][114][115] 1995

Identification of neural circuits underlying P300 abnormalities in schizophrenia

“…Some recent models of the pathophysiology of schizophrenia posit a disturbance of neuromodulation and synaptic connectivity, partially manifesting in brain development and partially later in time (Benes, 1995;McCarley et al, 1996;Olney & Farber, 1995). If schizophrenia entails a component with a disorder of neural circuits, then the measurement of electrical currents produced by activity in these circuits should provide an important method to investigate the disorder.…”

“…At the end of the 19th century, investigators speculated that damage or destruction of cells in the cerebral cortex must be associated with the devastating behavioral abnormalities and cognitive deficits of schizophrenia (Kraepelin, 1919(Kraepelin, /1971. Evidence of structural damage to the brain, however, proved to be elusive, with persuasive findings only emerging in the 1980s (Benes & Bird, 1987;Kovelman & Scheibel, 1984;McCarley, Hsiao, Freedman, Pfefferbaum, & Donchin, 1996; McCarley et al, in press;.Some recent models of the pathophysiology of schizophrenia posit a disturbance of neuromodulation and synaptic connectivity, partially manifesting in brain development and partially later in time (Benes, 1995;McCarley et al, 1996;Olney & Farber, 1995). If schizophrenia entails a component with a disorder of neural circuits, then the measurement of electrical currents produced by activity in these circuits should provide an important method to investigate the disorder.…”

D4 dopamine receptor-mediated phospholipid methylation and its implications for mental illnesses such as schizophrenia

“…1 Decades of research have yielded many theories on the origin of schizophrenia, although none provides a satisfying mechanistic explanation. Logically, dysfunctional neurotransmission is the most widely held theory, and specific abnormalities involving dopaminergic, 2 glutamatergic, 3 GABAergic 4 and nicotinic cholinergic 5 signaling have been proposed. Of these, the 'Dopamine Hypothesis' is dominant, based largely on the recognized therapeutic efficacy of drugs which block D2-like dopamine receptors (ie D2, D3 and D4 receptors), although their specific mechanism of benefit and the importance of individual receptor subtypes remains unclear.…”

A review of MRI findings in schizophrenia

“…This one study, coupled with new post-mortem findings of Kovelman (1979, 1981), led to renewed interest and to a proliferation of CT, and later magnetic resonance imaging (MRI) studies of schizophrenia (see reviews by Buckley, 1998;Gur and Pearlson, 1993;Henn and Braus, 1999;Lawrie and Abukmeil, 1998;McCarley et al, 1999b;Nelson et al, 1998;Pearlson and ; Pfefferbaum et al, 1990;Pfefferbaum and Zipursky, 1991;Rauch and Renshaw, 1995;Raz and Raz, 1990;Seidman, 1983;Shelton and Weinberger, 1986;Shenton, 1996;Shenton, 1996;Shenton et al, 1997Shenton et al, , 2001Weight and Bigler, 1998;Yurgelun-Todd and Renshaw, 1999), as well as to more methodologically rigorous post-mortem neurochemical and cellular studies (e.g. Benes, 1995;Bogerts et al, 1985Bogerts et al, , 1993aBrown et al, 1986;Stevens, 1973).…”

“…Although the underlying pathology remains unknown, both Kraepelin (1919Kraepelin ( /1971 and Bleuler (1911Bleuler ( /1950, who first described 'dementia praecox' and the 'schizophrenias', believed that brain abnormalities would ultimately be linked to the etiology of schizophrenia. This conviction was fueled by important inroads being made, during this same time period, into the neuropathology of Alzheimer's disease, Huntington's Chorea, Pick's disease, tertiary syphilis and some forms of epilepsy (see reviews in Benes, 1995;Bogerts et al, 1993aBogerts et al, , 1999Chua and McKenna, 1995;Harrison, 1999;Heckers, 1997).…”