Pathology of schizophrenia

Another line of research is focused on the neurobiological development of the human brain in relation to schizophrenia. It has been hypothesised that schizophrenia is due to abnormal neurodevelopment, which results in a static encephalopathy that usually becomes manifest in adolescence. This abnormal development leads to morphological deviations such as enlarged or reduced brain structures, a disrupted communication between different brain structures, alterations in neuron density or decreased neuron size, and abnormal neuronal 

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Glantz L, Gilmore J, Lieberman J et al (2006) Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res 81 47-63... 

Crow TJ (1980). Molecular pathology of schizophrenia More than one disease process British Medical Journal, 280, 66-68. 

Abi-Dargham A, Moore H. Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia. Neuroscientist. 2003 9 404-416. 

The Synaptic Pathology of Schizophrenia Is Aberrant Neurodevelopment and Plasticity to... 

Eastwood SL. 2004. The synaptic pathology of schizophrenia Is aberrant neurodevelopment and plasticity to blame Int Rev Neurobiol 59 47-72. 

Despite a broad knowledge base about the pathology of schizophrenia, albeit fragmented and often inconsistent, no... 

Among these, neurotransmitter abnormalities are the best studied and best understood. However, it is accepted by most researchers that the neurotransmitter abnormalities are only a part, maybe even only a small one, of the biological pathology of schizophrenia. All in all, to date, no specific abnormality, or combination, has proved satisfactory in explaining the complex phenomena observed in schizophrenia. 

The prefrontal cortex (PFQ and in particular the dorsal lateral part (DLPFQ appear to be particularly important in schizophrenia (Kerwin 1992). Lesions there are known to produce functional defects in humans reminiscent of many of the negative symptoms of schizophrenia, such as attention and cognitive defects and withdrawal. Despite this, no specific pathology is seen in the DLPFC in schizophrenics although there is some atrophy and neuronal loss which are normally old and could be congenital. That being so, it is necessary to explain why the symptoms become apparent only in adolescence. 

Apomorphine is an agonist at both the and D2 receptors. From the pathological viewpoint, a malfunction of the receptors has been implicated in the negative s)nnptoms of schizophrenia but as there is a close interaction between these receptor types it is difficult to conclude whether the changes seen in schizophrenia are attributable to a primary decrease in receptor function or an increase in D2 receptor function. The function of the D5 receptors is unclear these receptors, though widely distributed in the brain, are only present in a relatively low density in comparison to the other dopamine receptor types. 

One of the few studies directly identifying an abnormality in dopamine neurotransmitter in schizophrenia demonstrated a lateralised, left hemisphere, elevation in the amygdala (Reynolds, 1983), which added to the evidence for the view of schizophrenia as a left temporal lobe disorder. This elevation is not, however, interpreted as a primary pathology it seems likely that it reflects a dysfunction or dehcit in the neuronal systems controlling dopaminergic activity, and a correlation with diminished levels of a marker for GABA support this interpretation (Reynolds et ah, 1990). 

Thus there is evidence, albeit circumstantial, of a disturbance of glutamate systems in the disease. In addition there is evidence of GABAergic deficits. Adding to the relevance of these hypotheses of amino acid transmitter dysfunction is the opportunity to relate neurochemical changes directly to a neuronal pathology and, with some further extrapolation, to the aetiology of schizophrenia. 

The story is really about the Pink Spot of Schizophrenia. Many years ago, an observation was made in a biochemical laboratory on the East Coast that stirred up a rolling controversy. It had been found that if the urines of schizophrenic patients (sloppily called schizophrenic urines ) were extracted in such and such a way, and the extracts chromatographed, a pink spot would develop at a particular place on the chromatogram. Well, if this proved to be true with urines of a sick population, and were this proved to be different from the urines of a healthy population, it would constitute an objective diagnosis of schizophrenia. A simple chemical test to confirm a pathology that had defied all efforts to achieve consensus amongst the psychiatrists of the world. 

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