The Appeal
SANE set about raising funds and a £6million appeal was launched by SANE's patron, HRH The Prince of Wales, who then said 'leading scientists and doctors are confident the stage is now set for the great leap in imagination which could reveal the origin of this cruel affliction'.

HM King Fahd, Custodian of the Two Holy Mosques of Saudi Arabia through his nephew Prince Turki al-Faisal donated the first £1.75 million, which was matched by Nicholas and Matti Egon (Principal of the Greek shipping business founded by her father, Michael M Xylas). There were further donations, including an appeal in 'The Times' and a generous contribution to SANE by His Majesty the Sultan of Brunei.

Professor Timothy Crow, funded by grants from, amongst others, The Medical Research Council and The Stanley Foundation, became SANE's Honorary Scientific Director and Oxford University was selected in competition with 10 other leading universities as the home of the Centre. Research began in 1994 in temporary accommodation and laboratories donated by Oxford University. A 15 strong research team was established collaborating with 20 laboratories worldwide and publishing over 37 scientific papers. Professor Colin Blakemore is now Chair of the Scientific Committee and in 2002 the first major International Conference was held in London.

The Research
Professor Crow is an internationally renowned scientist, testing a specific hypothesis about the origins of psychosis. His approach is to relate the symptoms experienced by people with psychosis to changes within the brain. He believes that psychosis is associated with the specifically human capacity for language, such as the ability to use words and attach meanings to them, abilities that have developed greatly in our species relative to our nearest neighbours the Great Apes. Following this, symptoms, including hallucinations, delusions and thought disorders, can be understood as a disintegration of the neural components of language. The human brain differs from that of other primates by anatomical differences between the two hemispheres - this asymmetry being the basis for language.

To test this hypothesis and reinforce the quest for an organic basis for mental illness, three levels of explanation are being pursued: genetics, neuroimaging, and neuropathology.

Genetics
The major objective is to investigate genetic differences between humans and the Great Apes to explain the course of brain evolution in hominids, and to identify relevant genes. The focus is on the structure and mechanisms of control of a region of homology between the X and Y chromosomes, and specifically protocadherinXY. Samples from families with multiple cases of psychosis and from monozygotic twins (one ill and one well) are being used.

Assessing the effects of protocadherinXY interactions on growth and development of the brain is of potential relevance to the deviations in cortical development that are related to psychosis and in the longer term to devising interventions of therapeutic value.

Neuroimaging
This involves investigating the relationship between brain structure on MRI scans and behaviour, in particular between brain asymmetry and language function. Subtle asymmetries of development of the cerebral cortex are being assessed and applied to groups of patients with particular syndromes (negative symptoms, thought disorder, auditory hallucinations) in relation to assessments of their use of language.

Of particular interest is the development of methods (diffusion tensor imaging) for assessing the fibre connections between different areas of the cortex and the two hemispheres through functional imaging, to chart changes in blood flow. Included in these studies are individuals with an onset of psychosis in adolescence as well as those with psychoses associated with learning disability and the syndromes of autism, which recent studies reveal have significant features in common.

Neuropathology
This work examines the physical differences between the brains of those with schizophrenia and those without, assessing the convolutions of the cerebral cortex and relating them to its cellular composition layer by layer in the two hemispheres. Of particular interest is the relationship that changes in these variables may have to the long fibre tracts that connect different areas of cortex including particularly those that interconnect the left and right sides of the brain.

Researchers are studying the expression of protocadherinXY and its molecular variants in the developing brain, with particular reference to the cerebral cortex and to the development of asymmetries in associated areas.

The Future
The programme will include epidemiological studies aimed at investigating supposed environmental influences and clinical studies addressing new methods of diagnosis. It is hoped that this research will teach us more about the origins of psychosis, enabling better treatments to be developed.

SANE still seeks funds to sustain and develop the research programme, use the Centre to its full potential, build up information and education resources, and work alongside Oxford and other universities to house research in related specialities such as autism. The Centre will also establish a social research programme, using data gathered from calls to SANELINE, to identify better ways in which health and social services can meet the needs of people with mental health problems. SANE is also seeking to fund a Professorial Chair to be associated with one of the major projects within the Centre.