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Synapses, sea slugs, and psychiatry
  1. A S DAVID
  1. Departments of Neuropsychiatry and Psychological Medicine
  2. GKT School of Medicine and the Institute of Psychiatry, Denmark Hill
  3. London SE5 8AF, UK
  4. a.david{at}iop.kcl.ac.uk

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    This year's Nobel Prize in physiology or medicine, announced on 9 October 2000, has gone to Arvid Carlsson, Paul Greengard, and Eric Kandel. The citation states that the prize is shared for pioneering discoveries in slow synaptic transmission, which are “crucial for an understanding of how the normal functioning of the brain and how disturbances in this signal can give rise to neurological and psychiatric diseases” (www.nobel.se/announcement/2000/medicine.html). Carlsson proved the importance of dopamine as a neurotransmitter and subsequently its role in Parkinson's disease and schizophrenia. The strongest pillar of the dopamine theory of schizophrenia is the linear relation between potency of antipsychotic drugs and their dopamine antagonist potential. The theory has taken some knocks recently. A minority of patients remain symptomatic despite the demonstration in vivo using positron and single photon emission tomography of effective dopamine receptor blockade; the efficacy of atypical antipsychotic drugs with low affinity for dopamine receptors; the growing acceptance of a premorbid fall off in the anticipated trajectories in behaviour and intellect which seems to point the finger at brain and social development rather than neurotransmitters. Nevertheless, the theory survives.1

    Greengard wrote recently that the relevance of Carlsson's work for schizophrenia was one of his inspirations for pursuing dopamine transmission.2 His contribution was to show how transmitters such as dopamine exert their effects by inducing in the cell a series of biochemical events involving phosphorylation and dephosphorylation, which amount to signal transduction.

    Kandel's work has also focused on neuronal signalling, but in particular, the mechanisms by which learning and memory are effected at the level of the single cell. His partner for much of this work has been Aplysia californica, the humble sea slug, whose simple nervous system and set of reflexes designed to protect its gills has been the perfect “preparation” for studying conditioning (it is fitting that the conditioned reflex earned Pavlov the same honour in 1904). Kandel, an émigré from prewar Vienna, studied psychiatry and psychoanalysis in Boston in the early 1960s. He does not mind being referred to as a psychiatrist, although would certainly not claim to be one currently competent to practice (ER Kandel, personal communication, 13 October 2000). He has published some memorable articles on the relation between his work and that of modern neuroscience in general, to psychiatric disorders, and to Freudian theory, including the brilliantly titledPsychotherapy and the single synapse, 3 updated recently.4

    Freud was not awarded a Nobel Prize—modern critics may question whether he was more eligible for the one in literature than medicine. However, his Austrian contemporary, Wagner von Jauregg, became the first psychiatrist laureate in 1927 for his observations on the beneficial effects of induced fever (for example, malaria) on the symptoms of neurosyphillis—not, it has to be said, a treatment that has stood the test of time. But European psychiatry at the fin de siecle was resolutely biological. Egaz Moniz, the Portuguese neurosurgeon who developed psychosurgery, shared the prize in 1949, although the invention of arterial angiography was perhaps a more enduring legacy. Neuroscientists have been so rewarded on many occasions—but as in this year, the contributions tended to be at the “basic” level5—for example, Golgi and Cajal (1903), Sherrington and Adrian (1932), Eccles, Hodgkin, and Huxley (1963), and Gadjusek (1976).

    Exceptions are Konrad Lorenz and Niko Tinbergen for their popular work on animal ethology, awarded in 1973. Similarly, American scientist Roger Sperry, who shared the prize in 1981, is best known for his work with “split brain” patients, in whom the distinct and at times independent abilities of the right and left cerebral hemispheres were unveiled. We should also mention Cormack and Hounsfield, who were honoured for developing computed axial x ray tomography in 1979; and the inventors of magnetic resonance imaging in medicine have been tipped for a similar fate. For once it is no exaggeration to say that these technological developments have revolutionised the way we see the brain. Finally, Nobel laureates in other fields—notably Francis Crick and Gerald Edelman—have turned their attention to the neurosciences and have had a significant impact.

    The importance of all this is that it shows the protracted maturation and continuing uncertain status of psychiatry as a scientific discipline. It is anticipated that the work of the winners of this year's prize and its consequences will lead to ever more effective treatments for major mental illness and degenerative disorders of the nervous system.6 However, equally inspiring is work in the cognitive and social sciences. Such work does not seem to be accorded the same status as that in biology. Only when cognitive, social, and biological sciences are integrated, or when their separate spheres of influence on mental life and behaviour are demarcated, will we have a truly scientific, and hopefully clinically relevant, cognitive neuropsychiatry.7 8

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