Neuropathology In the postmortem brains of schizophrenic patients there is an absence of gliosis which is the necessary hallmark of neurodegeneration (Roberts et al. 1986). The prominent neuropathology in schizophrenia is not the classic form involving neuronal cell death, but instead a loss or reduction in dendritic spines and synapses which are the elements of neural connectivity (Garey et al. 1998; Glantz & Lewis 2000). As a result, the brain in schizophrenia is characterized by increased neuronal density,  decreased intraneuronal space and reduced overall brain volume. Furthermore, the decrease in dentritic spine density appears to be both region and disease specific. A reduction in dendritic spine density has been reported on pyramidal cells in layer III of the temporal cortex (Garey et al. 1998) and the dorsolateral prefrontal cortex (Glantz & Lewis 2000) but not on pyramidal cells in the visual cortex of schizophrenic patients (Glantz & Lewis 2000). These findings are compatible with the hypothesis of reduced cortical and/or thalamic excitatory glutaminergic inputs to the dorsolateral prefrontal cortex in schizophrenia. Structural brain abnormalities Neuroimaging and postmortem studies have shown that the brain as a whole and the frontal and temporal cortices in particular are smaller than in normal subjects (Andreasen et al. 1990; Nopoulos et al. 1995). Brain volume reductions in schizophrenia are specific to grey matter (Gur et al. 2000a) which supports neuropathological findings of increased neuronal density and reduced intraneuronal neurophil rather than neuronal loss (Selemon et al. 1995). Across a range of neuroimaging studies, the volume of the hippocampus and amygdala is reduced bilaterally by 4.5 - 10% (Nelson et al. 1998; Gur et al. 2000a). Prefrontal grey matter volume is reduced by about 10% (Gur et al. 2000b). Enlargement of the third and lateral ventricles is a consistent finding, with ventricular volume increased by about 40%  bilaterally (Lawrie &  Abukmeil 1998).  Ventricular enlargement is associated with neuropsychological impairment and negative symptoms (Vita et al. 1991). Studies of the basal ganglia have produced more inconsistent results, possibly as a function of the increase in basal ganglia volume associated with the use of traditional antipsychotics. Interestingly, when patients are switched to the atypical antipsychotic clozapine there is a reduction of basal ganglia volume (Chakos et al. 1995). The brain changes reported in child and adolescent onset schizophrenia appear to be very similar to those described in adult onset schizophrenia, supporting the idea of an underlying neurobiological continuity. In the NIMH study of childhood onset schizophrenia (onset less than 12 years of age), subjects had smaller brains than normal subjects,  with larger lateral ventricles and reduced prefrontal lobe volume (Jacobsen & Rapoport 1998). Similar to findings from adult studies, reduced total cerebral volume is associated with negative symptoms (Alaghband-Rad et al. 1997). The midsagittal thalamic area is decreased while the midsagittal area of the corpus callosum is increased (Giedd et al. 1996), suggesting that the reduction in total cerebral volume in childhood onset schizophrenia is brought about by a relative reduction in grey matter with sparing of white matter. Childhood onset patients have a higher rate of developmental brain abnormalities than controls, including an increased frequency of an enlarged cavum septum pelucidum (Nopoulos et al. 1998). Abnormalities of the cerebellum have also been found including reduced volume of the vermis, midsagittal area and inferior posterior lobe (Jacobsen et al. 1997a).