The 2000 Ogura Lecture: Olfactory neural cells: An untapped diagnostic and therapeutic resource

Objective. This is an over-view of the cellular biology of upper nasal mucosal cells that have special characteristics that enable them to be used to diagnose and study congenital neurological diseases and to aid neural repair. Study Design: After mapping the distribution of neural cells in the upper nose, the authors' investigations moved to the use of olfactory neurones to diagnose neurological diseases of development, especially schizophrenia. Olfactory-ensheating glial cells (OEGs) from the cranial cavity promote axonal penetration of the central nervous system and aid spinal cord repair in rodents. The authors sought to isolate these cells from the more accessible upper nasal cavity in rats and in humans and prove they could likewise promote neural regeneration, making these cells suitable for human spinal repair investigations. Methods: The schizophrenia-diagnosis aspect of the study entailed the biopsy of the olfactory areas of 10 schizophrenic patients and 10 control subjects. The tissue samples were sliced and grown in culture medium. The ease of cell attachment to fibronectin (artificial epithelial basement membrane), as well as the mitotic and apoptotic indices, was studied in the presence and absence of dopamine in those cell cultures. The neural repair part of the study entailed a harvesting and insertion of first rat olfactory lamina propria rich in OEGs between cut ends of the spinal cords and then later the microinjection of an OEG-rich suspension into rat spinal cords previously transected by open laminectomy. Further studies were done in which OEG insertion was performed up to 1 month after rat cord transection and also in monkeys. Results: Schizophrenic patients' olfactory tissues do not easily attach to basement membrane compared with control subjects, adding evidence to the theory that cell wall anomalies are part of the schizophrenic lesion of neurones. Schizophrenic patient cell cultures had higher mitotic and apoptotic indices compared with control subjects. The addition of dopamine altered these indices enough to allow accurate differentiation of schizophrenics from control patients, leading to, possibly for the first time, an early objective diagnosis of schizophrenia and possible assessment of preventive strategies. OEGs from the nose were shown to be as effective as those from the olfactory bulb in promoting axonal growth across transected spinal cords even when added I month after injury in the rat. These otherwise paraplegic rats grew motor and proprioceptive and fine touch fibers with corresponding behavioral improvement. Conclusions. The tissues of the olfactory mucosa are readily available to the otolaryngologist. Being surface cells, they must regenerate (called neurogenesis). Biopsy of this area and amplification of cells in culture gives the scientist a window to the developing brain, including early diagnosis of schizophrenia. The Holy Grail of neurological disease is the cure of traumatic paraplegia and OEGs from the nose promote that repair. The otolaryngologist may become the necessary partner of the neurophysiologist and spinal surgeon to take the laboratory potential of paraplegic cure into the day-to-day realm of clinical reality.

Myths and plain truths about schizophrenia epidemiology - the NAPE lecture 2004

Objective: Science needs to constantly match research models against the data. With respect to the epidemiology of schizophrenia, the widely held belief that the incidence of schizophrenia shows little variation may no longer be supported by the data. The aims of this paper are (i) to explore data-vs.-belief mismatch with respect to the incidence of schizophrenia, and (ii) to speculate on the causes and consequences of such discrepancies. Method: Based on a recently published systematic review of the incidence of schizophrenia, the distribution of incidence rates around the world was examined. In order to examine if the incidence of schizophrenia differed by sex, male vs. female risk ratios were generated. Results: The distribution of incidence rates for schizophrenia is asymmetrical with many high rates skewing the distribution. Based on the central 80% of rates, the incidence of schizophrenia varies in a five-fold range (between 7.7 and 43.0 per 100 000). Males have a significantly higher incidence of schizophrenia compared with females (median male to female risk ratio = 1.4), and this difference could not be accounted for by diagnostic criteria or age range. Conclusion: The beliefs that (i) the incidence of schizophrenia does not vary between sites and (ii) males and females are equally affected, may have persisted because of an unspoken deeper belief that schizophrenia is an egalitarian and exceptional disorder. Our ability to generate productive hypotheses about the aetiology of schizophrenia rests on an accurate appraisal of the data. Beliefs not supported by data should be identified and relabelled as myths.