The dopamine hypothesis of schizophrenia was examined by measuring the density of dopamine receptors in the postmortem brains of 81 control subjects and 59 schizophrenics from four different countries. The densities of dopamine receptors in the tissues from the schizophrenic patients had a bimodal distribution in the caudate nucleus, putamen, and nucleus accumbens. One mode occurred 25 percent above the control density, and a second mode occurred at a density 2.3 times that of the control density for all three regions. Although almost all the patients had been medicated with neuroleptics, the two modes had the same dissociation constant for the labeled ligand used, suggesting that the neuroleptic doses were similar for the two populations of schizophrenics. The results thus provide direct evidence for two distinct categories of schizophrenia.

Notwithstanding that (excluding the dementias) they form the core of serious psychiatric illness the 'functional psychoses' lack a satisfactory label. The adjective 'functional' implies that, by contrast with the 'organic' dementias, there are no identifable changes in the brain. Seventeen years of neuroradiological research, backed up by post-mortem studies, have established beyond reasonable doubt that in schizophrenia at least such changes (a modest mean increase in ventricular size, a possible reduction in brain size and loss of asymmetry) are present but their meaning and the relationship to symptomatology is obscure.This modest gain in understanding has done little to illuminate nosology. The failure of the research community to establish whether schizophrenic, affective, schizo-affective and delusional psychoses (the subject matter of this volume) are distinct or overlapping disease entities (and if, in part, the latter -what overlaps with what?) represents the major unresolved crisis in psychiatric research. As this book makes abundantly clear there are an embarrassingly large number of ways of defining schizophrenia (or affective or schizo-affective psychoses) and, although this book does not document the evidence, they define quite different populations of patients. The Diagnostic Q Statistical Manual (DSM 111-R) criteria for example are considerably more restrictive than the criteria of Bleuler. There has been a welcome trend, well illustrated in this volume, towards the application of operational criteria. This helps us to agree on what (for a given purpose) we are going to call schizophrenia. but it docs not tell us whether what we are calling schizophrenia has any meaning in terms of predicting outcome or response to treatment. There is also the problem of labelling whatever illnesses have been excluded from the definition.The authors have provided a useful compendium of the different diagnostic systems that are now in use together with a brief commentary on the origins and application of each. What they have not done is to provide a critique of the validity (or otherwise) of the different systems, or to address the problem of whether there really are separable disease entities. Their own solution (the 'polydiagnostic approach') is to use an array of different criteria. This sounds cumbersome and evades the categorical question. A quite different approach (which I favour) is to accept that the categories are arbitrary, and to deal with continua which are defined by the frequency of occurrence of different psychopathological features (e.g. Schneiderian first rank symptoms, affective flattening, elation). One can then ask questions such as how age of onset and sex relate to form of psychosis, and what are the predictors of early relapse and response to neuroleptic medication without being too concerned about whether this is a case of true schizophrenia (according to x's criteria) or schizo-affective disorder. But for an account of which criteria are actually being used to reach diagnoses and what they...

In post-mortem putamen samples from 27 schizophrenics and 27 controls D2 receptors were measured by Scatchard analysis using 3H-spiperone as a ligand. Maximum number of binding sites (Bmax) and apparent dissociation constant (KD) were significantly increased only in patients in whom neuroleptic medication had been given within a three-month period before death. When the neuroleptic medication had been withdrawn at least 3 month before death, there was a slight, but not significant, reduction in Bmax values and unchanged KD values. Withdrawal of neuroleptic drugs was followed by a normalization of the KD values within 2 weeks and a slower reduction of Bmax values. There were 6 schizophrenic patients with mainly positive schizophrenic symptoms and 17 patients with mainly negative symptoms; positive schizophrenic symptoms were not related to higher Bmax values. There was no difference in 3H-spiperone binding between patients with and without movement disorders (tardive dyskinesia or extrapyramidal symptoms).

High concentrations of fulvic acid and selenium deficiency are the main causative factors of Kashin-Beck disease, an endemic, chronic and degenerative osteoarticular disorder found in China. In the search for an animal model of this disease, mice were exposed to these pathogenetic conditions for two generations and the collagen types from skin, bone and cartilage were analysed. The growth of the treated mice was slightly retarded, and the rate of reproduction was lower in animals maintained on a fulvic acid-supplemented and/or selenium-deficient diet. Irregular bone formation was seen by radiography and morphometry. Biochemical analysis indicated that lysine residues in collagen I from bone and in collagen II from cartilage were overmodified. The values of Hyl/(Hyl+Lys) in bone collagen alpha 1(I) chains from treated mice were about 0.434-0.484, i.e. substantially higher than that of the control (0.277). The values of this parameter for collagen II were 0.482 for control and 0.546-0.566 for treated mice. The melting temperature of collagen I from bones of treated mice was 1 degrees C lower than that of control collagen, indicating decreased thermal stability. The breakage point of the tibiae of treated mice occurred at a lower preload force than for controls, suggesting that the overmodified and thermally less stable collagen molecules are causally related to a lower mechanical strength of bones.

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