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Synapses, Sea Slugs, and Psychiatry

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Synapses, Sea Slugs, and Psychiatry J Neurol Neurosurg Psychiatry 2001;70:1–3 1 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.70.1.1 on 1 January 2001. Downloaded from EDITORIAL Synapses, sea slugs, and psychiatry This year’s Nobel Prize in physiology or medicine, announced literature than medicine. However, his Austrian contempo- on 9 October 2000, has gone to Arvid Carlsson, Paul Green- rary, Wagner von Jauregg, became the first psychiatrist lau- gard, and Eric Kandel. The citation states that the prize is reate in 1927 for his observations on the beneficial eVects shared for pioneering discoveries in slow synaptic transmis- of induced fever (for example, malaria) on the symptoms of sion, which are “crucial for an understanding of how the nor- neurosyphillis—not, it has to be said, a treatment that has mal functioning of the brain and how disturbances in this sig- stood the test of time. But European psychiatry at the fin de nal can give rise to neurological and psychiatric diseases” siecle was resolutely biological. Egaz Moniz, the Portu- (www.nobel.se/announcement/2000/medicine.html). Carls- guese neurosurgeon who developed psychosurgery, shared son proved the importance of dopamine as a neurotransmitter the prize in 1949, although the invention of arterial angio- and subsequently its role in Parkinson’s disease and graphy was perhaps a more enduring legacy. Neuroscien- schizophrenia. The strongest pillar of the dopamine theory of tists have been so rewarded on many occasions—but as in schizophrenia is the linear relation between potency of anti- this year, the contributions tended to be at the “basic” psychotic drugs and their dopamine antagonist potential. The level5—for example, Golgi and Cajal (1903), Sherrington theory has taken some knocks recently. A minority of patients and Adrian (1932), Eccles, Hodgkin, and Huxley (1963), remain symptomatic despite the demonstration in vivo using and Gadjusek (1976). positron and single photon emission tomography of eVective Exceptions are Konrad Lorenz and Niko Tinbergen for dopamine receptor blockade; the eYcacy of atypical anti- their popular work on animal ethology, awarded in 1973. psychotic drugs with low aYnity for dopamine receptors; the Similarly, American scientist Roger Sperry, who shared the growing acceptance of a premorbid fall oV in the anticipated prize in 1981, is best known for his work with “split brain” trajectories in behaviour and intellect which seems to point patients, in whom the distinct and at times independent the finger at brain and social development rather than neu- abilities of the right and left cerebral hemispheres were http://jnnp.bmj.com/ rotransmitters. Nevertheless, the theory survives.1 unveiled. We should also mention Cormack and Houns- Greengard wrote recently that the relevance of Carls- field, who were honoured for developing computed axial x son’s work for schizophrenia was one of his inspirations for ray tomography in 1979; and the inventors of magnetic pursuing dopamine transmission.2 His contribution was to resonance imaging in medicine have been tipped for a show how transmitters such as dopamine exert their eVects similar fate. For once it is no exaggeration to say that these by inducing in the cell a series of biochemical events technological developments have revolutionised the way involving phosphorylation and dephosphorylation, which we see the brain. Finally, Nobel laureates in other fields— amount to signal transduction. notably Francis Crick and Gerald Edelman—have turned on September 29, 2021 by guest. Protected copyright. Kandel’s work has also focused on neuronal signalling, their attention to the neurosciences and have had a signifi- but in particular, the mechanisms by which learning and cant impact. memory are eVected at the level of the single cell. His part- The importance of all this is that it shows the protracted ner for much of this work has been Aplysia californica, the maturation and continuing uncertain status of psychiatry humble sea slug, whose simple nervous system and set of as a scientific discipline. It is anticipated that the work of reflexes designed to protect its gills has been the perfect the winners of this year’s prize and its consequences will “preparation” for studying conditioning (it is fitting that lead to ever more eVective treatments for major mental ill- the conditioned reflex earned Pavlov the same honour in ness and degenerative disorders of the nervous system.6 1904). Kandel, an émigré from prewar Vienna, studied However, equally inspiring is work in the cognitive and psychiatry and psychoanalysis in Boston in the early 1960s. social sciences. Such work does not seem to be accorded He does not mind being referred to as a psychiatrist, the same status as that in biology. Only when cognitive, although would certainly not claim to be one currently social, and biological sciences are integrated, or when their competent to practice (ER Kandel, personal communica- separate spheres of influence on mental life and behaviour tion, 13 October 2000). He has published some memora- are demarcated, will we have a truly scientific, and ble articles on the relation between his work and that of hopefully clinically relevant, cognitive neuropsychiatry.78 modern neuroscience in general, to psychiatric disorders, ASDAVID and to Freudian theory, including the brilliantly titled Psy- 3 4 Departments of Neuropsychiatry and Psychological Medicine, chotherapy and the single synapse, updated recently. GKT School of Medicine and the Institute of Psychiatry, Denmark Hill, Freud was not awarded a Nobel Prize—modern critics London SE5 8AF,UK may question whether he was more eligible for the one in [email protected] www.jnnp.com 2 Wardlaw J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.70.1.1 on 1 January 2001. Downloaded from 1 Harrison PJ. Dopamine and schizophrenia-proof at last? Lancet 5 Jasper HH, Sourkes TL. Nobel laureates in neuroscience: 1904–1981. Ann 2000;356:958–9. Rev Neurosci 1983;6:1–42. 2 Nature (news). Medicine Nobel goes to raiders of the brain’s chemical 6 Cowan WM, Harter DH, Kandel ER. The emergence of modern secrets. Nature 2000;407:661. neuroscience: some implications for neurology and psychiatry. Ann Rev 3 Kandel ER. Psychotherapy and the single synapse. The impact of Neurosci 2000;23:343–91. psychiatric thought on neurobiologic research. N Engl J Med 1979;301: 7 David A, Halligan P. Cognitive neuropsychiatry. Cognitive Neuropsychiatry 1028–37. 1996;1:1–3 4 Kandel ER. Biology and the future of psychoanalysis: a new intellectual 8 David AS, Halligan PW.Cognitive neuropsychiatry: potential for progress. J framework for psychiatry revisited. Am J Psychiatry 1999;156:505–24. Neuropsychiatry Clin Neurosci 2000;12: EDITORIAL COMMENTARIES Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study: the Rotterdam Scan Study In the paper from the Rotterdam Scan Study (this issue pp diabetes, and carotid atheroma was equal between the 9-14),1 de Leeuw et al take another step towards sexes, it is unlikely that this finding is the result of some understanding the conundrum of white matter disease other association. (leukoarosis) and its associations with aging and gender. The major problem in this study was the declining This will hopefully lead towards better understanding of response rate with age, from 73% of all those invited to cognitive decline with age, Alzheimer’s disease, and vascu- come for a scan in the 60–70 year age group to only 48% lar dementia. in the 80–90 year age group. Therefore, as the authors The assessment of the role of white matter disease in rightly point out, their study may have underestimated the these processes poses several problems. White matter dis- true prevalence of white matter disease in the general ease is diYcult to quantify. The existence of upwards of population. The authors report elsewhere on the associ- some 12 diVerent scales for assessing white matter lesion ation with diabetes,5 carotid atheroma,6 atrial load, few of which have been validated for interobserver or fibrillation,7and cognitive ability.8 intraobserver variability, or tested in populations other The authors speculate on two points in need of future than the one in which they were generated, testifies to the study. Firstly, that the increased white matter lesions in diYculty of trying to make some sense out of diVerent women may be the cause of the observed increase in degrees of “spotty brains”.2 This diYculty in quantifica- dementia in women compared with men of the same age. http://jnnp.bmj.com/ tion combined with small sample sizes in some previous Secondly, they suggest that this might be due to loss of a studies, may have confounded the diYculty of trying to protective eVect of oestrogen in postmenopausal women. tease out any association between vascular risk factors However, they did not collect data in the present study to (hypertension, diabetes, carotid atheroma), so called vas- test this hypothesis, rather it was a suggestion based on cular dementia, Alzheimer’s disease, and “normal” age work elsewhere.9 Possible protective mechanisms for oes- related cognitive decline. Further diYculty is the clinical trogen suggested by the authors (reduced susceptibility to distinction of Alzheimer’s from vascular dementia. ischaemia, increased cerebral blood flow, protection on September 29, 2021 by guest. Protected copyright. Increasing recognition of the overlap in risk factors against oxidative stress, enhanced synaptogenesis, and between Alzheimer’s disease and vascular dementia,34 prevention of neuronal atrophy) simply serve to highlight suggests that in fact attempts to make too rigid a distinc- the fact that although we are better informed about asso- tion between the two may have been counterproductive ciations of white matter disease, cognitive decline, aging, rather than helpful in studies of possible disease vascular risk factors, and actual dementia, we still know mechanisms.
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