- Email: [email protected]
CŒLIAC DISEASE AND SCHIZOPHRENIA
89
investigators. It is crucially important that the scientific community accepts s.l.D.s. as a real problem and begins to prove or disprove the theses and data presented at the conference. The essential point of the Second International Conference was to provide a substantial body of data upon which the academic world can begin to construct experimental approaches to the problem. It has been the lack of testable hypotheses that has hindered progress to date. ABRAHAM B. BERGMAN Children’s Orthopedic Hospital J. BRUCE BECKWITH and Medical Center, C. GEORGE RAY. Seattle, Washington 98105. courage potential
CŒLIAC DISEASE AND SCHIZOPHRENIA Sm,-In his letter last April,! Dr. F. C. Dohan drew an analogy between the psychiatric symptoms of the coeliac child and " those of the schizophrenic or autistic child ". While the association between disorders of affect and coeliac disease in children 2-10 and adults 21-29 is well known, the similarity to childhood autism is perhaps an overstatement. The affective changes, variously described as irritability, moroseness, apathy, and depression, are most 7 apparent in children aged between 1 and 3 years. Prugh has also described a non-specific type of emotional disorder that precedes the onset of clinical symptoms. It might be argued that these mood changes are a nonspecific manifestation of ill-health similar to that of any childhood illness. However, clinicians interested in this subject are aware that the changes of mood form an integral part of the diagnosis of coeliac disease. Also the improvement of mood following a gluten-free diet is often dramatic and occurs within the first week of treatment. These signs are reversible, as has been demonstrated by the reintroduction of gluten into the diet.8 Dr. Lancaster-Smith and Dr. Strickland (Nov. 21, p. 1090), correlate the immunological and biochemical associations between coeliac disease and schizophrenia. They demonstrate clearly the difficulty of relating changes in the blood or urine with comparable chemical events in The enzyme monoamine oxidase (M.A.O.) the brain. 1. Dohan, F. C. Lancet, 1970, i, 897. 2. Gibbons, R. A. Edinb. med. J. 1889, 35, 321. 3. Emmett Holt, L. The Diseases of Infancy and
Childhood; p. 416.
London, 1906. 4. Still, G. F. Lancet, 1918, ii, 163. 5. Parsons, L. G. Am. J. Dis. Child. 1932, 43, 1293. 6. Andersen, D. H. J. Pediat. 1947, 30, 564. 7. Prugh, D. G. Psychosomat. Med. 1951, 13, 220. 8. Anderson, C. M., Frazer, A. C., French, J. M., Gerrard, J. W., Sammons, H. G., Smellie, J. M. Lancet, 1952, i, 836. 9. Andersen, D. H., di Sant’Agnese, P. A. Pediatrics, Springfield, 1953, 11, 207. 10. Sheldon, W. Lancet, 1955, ii, 1097. 11. Daynes, G. Proc. R. Soc. Med. 1956, 49, 391. 12. Weijers, H. A., Dicke, W. K. Adv. Pediat. 1957, 9, 277. 13. Rohmer, P. Annls pœdiat. 1956, 187, 278. 14. Alvey, C., Anderson, C. M., Freeman, M. Archs Dis. Childh. 1957, 32, 434. 15. Sheldon, W. Pediatrics, Springfield, 1959, 23, 132. 16. Paulley, J. W. Am. J. dig. Dis. 1959, 4, 352. 17. Käser, H. Annls pœdiat. 1961, 197, 320. 18. Asperger, H. ibid. p. 346. 19. Weiss, A. A., Sterk, V. V. Annls pœdiat. 1962, 198, 35. 20. Anderson, C. M. Archs Dis. Childh. 1966, 41, 571. 21. Bennett, T. I., Hunter, D., Vaughan, J. M. Q. Jl Med. 1932, 25,
has a high level of activity in the human small intestine.30 A decrease of this activity in patients treated with M.A.O. inhibitors is probably an important factor in the circulatory reactions that occur when foods containing monoamines are ingested.31 Low levels of M.A.O. have been described in the duodenal mucosa of children with coeliac disease, 32 and although follow-up biopsies were not performed, histochemical evidence 33,34 suggests that this enzyme reappears rapidly in the epithelial cell following exclusion of gluten from the diet. While it is not possible to suggest a mechanism to explain the changes of affect in cceliac disease, it is interesting to speculate whether an enzymatic barrier in the small bowel, normally responsible for protecting the brain against toxic amines, is breached in coeliac disease, giving rise to alteration of cerebral function.
normally
Institute of Child Health, Birmingham 16.
EFFECT OF COLD ON BLEEDING
SIR,—Iam sure Dr. Kattlove and Professor Alexander right.35 There is little or no aggregation in cooled platelet-rich plasma when A.D.P. is added.36,37 Furthermore, the release reaction is highly temperature-dependent 38; for example, no serotonin or platelet factor 4 is released even at 20°C.39 The platelets also show a considerable change in shape at low temperatures.4o Thus platelet physiology is greatly altered by temperature, and it is impossible at present to decide which change is responsible for a given physiological event. are
Portsmouth and Isle of Wight Area
Pathology Service,
Hanes, F. M., McBryde, A. Archs intern. Med. 1936, 58, 1. Cooke, W. T., Peeney, A. L. P., Hawkins, C. F. Q. Jl Med. 1953,
24.
Bossak,
22. 59.
SONNET ON SMOKING
SIR,—Surely
25. 26.
27. 28. 29
are
capable of
a more
convincingly
put-on than " Shakespeare’s Sonnet on " Smoking ".41 Nicotina " indeed ! The Bard was not so benighted as to confuse the recognition afforded a tobacco-chewing contemporary with some pseudo-mythical A second point: Shakespeare’s grasp of medical muse. knowledge was admirable, but not sesquicentennially prescient of Heberden. The verse is not worthy of its assignment. Wallace Pharmaceuticals, Cranbury, WILLIAM KITTO. New Jersey 08512.
* ** Dr. Kitto’s letter was shown to our correspondent, replies that the Sonnet on Smoking came from the fly-leaf of the family bible of an old Warwickshire family, who have a strong tradition that the verse had been given to an ancestor by the Bard. Certainly, as Dr. Kitto notes, it has not the merit of the better-known sonnets published in 1609; but as a sonneteer, Shakespeare was somewho
30.
Levine, R. J., Sjoerdsma,
A. Proc. Soc. exp. Biol. Med.
1962, 109,
225.
35. 36.
Mustala, O., Solatunturi, E., Tarpila, S. Acta med. scand. 1969, 185, 145. Challacombe, D. N., Sandler, M., Southgate, J. Archs Dis. Childh. (in the press). Spiro, H. M., Filipe, M. I., Stewart, J. S., Booth, C. C., Pearse, A. G. E. Gut, 1964, 5, 145. Riecken, E. O., Stewart, J. S., Booth, C. C., Pearse, A. G. E. ibid. 1966, 7, 317. Kattlove, H., Alexander, B. Lancet, 1970, ii, 1359. Cuthbertson, W. F. J., Mills, D. C. B. J. Physiol., Lond. 1963, 169,
37. 38. 39. 40. 41.
O’Brien, J. R. J. clin. Path. 1962, 15, 446. Grette, K. Acta physiol. scand. 1962, 56, suppl. p. 195. Harada, K., Zucker, M. B. Unpublished. O’Brien, J. R., Heywood, J. B. J. clin. Path. 1966, 19, 148. Lancet, 1970, ii, 1183.
31. 32. 33.
T., Wang Chun, I., Adlersberg, D. J. Mt Sinai Hosp.
1957, 24, 286. Kelley, M. L., Terry, R. Am. J. Med. 1958, 25, 460. Rubin, C. E., Brandborg, L. L., Flick, A. L., Phelps, P., Parmentier, C. van Niel, S. Gastroenterology, 1962, 43, 621. Benson, G. D., Kowlessar, O. D., Sleisenger, M. H. Medicine, Baltimore, 1964, 43, 1. Goldberg, D. Gut, 1970, 11, 459. Morris, J. S., Ajdukiewicz, A. B., Read, A. E. ibid. p. 549.
you
constructed
34. E.
J. R. O’BRIEN.
Portsmouth.
603. 22. 23.
D. N. CHALLACOMBE.
9P.
investigators. It is crucially important that the scientific community accepts s.l.D.s. as a real problem and begins to prove or disprove the theses and data presented at the conference. The essential point of the Second International Conference was to provide a substantial body of data upon which the academic world can begin to construct experimental approaches to the problem. It has been the lack of testable hypotheses that has hindered progress to date. ABRAHAM B. BERGMAN Children’s Orthopedic Hospital J. BRUCE BECKWITH and Medical Center, C. GEORGE RAY. Seattle, Washington 98105. courage potential
CŒLIAC DISEASE AND SCHIZOPHRENIA Sm,-In his letter last April,! Dr. F. C. Dohan drew an analogy between the psychiatric symptoms of the coeliac child and " those of the schizophrenic or autistic child ". While the association between disorders of affect and coeliac disease in children 2-10 and adults 21-29 is well known, the similarity to childhood autism is perhaps an overstatement. The affective changes, variously described as irritability, moroseness, apathy, and depression, are most 7 apparent in children aged between 1 and 3 years. Prugh has also described a non-specific type of emotional disorder that precedes the onset of clinical symptoms. It might be argued that these mood changes are a nonspecific manifestation of ill-health similar to that of any childhood illness. However, clinicians interested in this subject are aware that the changes of mood form an integral part of the diagnosis of coeliac disease. Also the improvement of mood following a gluten-free diet is often dramatic and occurs within the first week of treatment. These signs are reversible, as has been demonstrated by the reintroduction of gluten into the diet.8 Dr. Lancaster-Smith and Dr. Strickland (Nov. 21, p. 1090), correlate the immunological and biochemical associations between coeliac disease and schizophrenia. They demonstrate clearly the difficulty of relating changes in the blood or urine with comparable chemical events in The enzyme monoamine oxidase (M.A.O.) the brain. 1. Dohan, F. C. Lancet, 1970, i, 897. 2. Gibbons, R. A. Edinb. med. J. 1889, 35, 321. 3. Emmett Holt, L. The Diseases of Infancy and
Childhood; p. 416.
London, 1906. 4. Still, G. F. Lancet, 1918, ii, 163. 5. Parsons, L. G. Am. J. Dis. Child. 1932, 43, 1293. 6. Andersen, D. H. J. Pediat. 1947, 30, 564. 7. Prugh, D. G. Psychosomat. Med. 1951, 13, 220. 8. Anderson, C. M., Frazer, A. C., French, J. M., Gerrard, J. W., Sammons, H. G., Smellie, J. M. Lancet, 1952, i, 836. 9. Andersen, D. H., di Sant’Agnese, P. A. Pediatrics, Springfield, 1953, 11, 207. 10. Sheldon, W. Lancet, 1955, ii, 1097. 11. Daynes, G. Proc. R. Soc. Med. 1956, 49, 391. 12. Weijers, H. A., Dicke, W. K. Adv. Pediat. 1957, 9, 277. 13. Rohmer, P. Annls pœdiat. 1956, 187, 278. 14. Alvey, C., Anderson, C. M., Freeman, M. Archs Dis. Childh. 1957, 32, 434. 15. Sheldon, W. Pediatrics, Springfield, 1959, 23, 132. 16. Paulley, J. W. Am. J. dig. Dis. 1959, 4, 352. 17. Käser, H. Annls pœdiat. 1961, 197, 320. 18. Asperger, H. ibid. p. 346. 19. Weiss, A. A., Sterk, V. V. Annls pœdiat. 1962, 198, 35. 20. Anderson, C. M. Archs Dis. Childh. 1966, 41, 571. 21. Bennett, T. I., Hunter, D., Vaughan, J. M. Q. Jl Med. 1932, 25,
has a high level of activity in the human small intestine.30 A decrease of this activity in patients treated with M.A.O. inhibitors is probably an important factor in the circulatory reactions that occur when foods containing monoamines are ingested.31 Low levels of M.A.O. have been described in the duodenal mucosa of children with coeliac disease, 32 and although follow-up biopsies were not performed, histochemical evidence 33,34 suggests that this enzyme reappears rapidly in the epithelial cell following exclusion of gluten from the diet. While it is not possible to suggest a mechanism to explain the changes of affect in cceliac disease, it is interesting to speculate whether an enzymatic barrier in the small bowel, normally responsible for protecting the brain against toxic amines, is breached in coeliac disease, giving rise to alteration of cerebral function.
normally
Institute of Child Health, Birmingham 16.
EFFECT OF COLD ON BLEEDING
SIR,—Iam sure Dr. Kattlove and Professor Alexander right.35 There is little or no aggregation in cooled platelet-rich plasma when A.D.P. is added.36,37 Furthermore, the release reaction is highly temperature-dependent 38; for example, no serotonin or platelet factor 4 is released even at 20°C.39 The platelets also show a considerable change in shape at low temperatures.4o Thus platelet physiology is greatly altered by temperature, and it is impossible at present to decide which change is responsible for a given physiological event. are
Portsmouth and Isle of Wight Area
Pathology Service,
Hanes, F. M., McBryde, A. Archs intern. Med. 1936, 58, 1. Cooke, W. T., Peeney, A. L. P., Hawkins, C. F. Q. Jl Med. 1953,
24.
Bossak,
22. 59.
SONNET ON SMOKING
SIR,—Surely
25. 26.
27. 28. 29
are
capable of
a more
convincingly
put-on than " Shakespeare’s Sonnet on " Smoking ".41 Nicotina " indeed ! The Bard was not so benighted as to confuse the recognition afforded a tobacco-chewing contemporary with some pseudo-mythical A second point: Shakespeare’s grasp of medical muse. knowledge was admirable, but not sesquicentennially prescient of Heberden. The verse is not worthy of its assignment. Wallace Pharmaceuticals, Cranbury, WILLIAM KITTO. New Jersey 08512.
* ** Dr. Kitto’s letter was shown to our correspondent, replies that the Sonnet on Smoking came from the fly-leaf of the family bible of an old Warwickshire family, who have a strong tradition that the verse had been given to an ancestor by the Bard. Certainly, as Dr. Kitto notes, it has not the merit of the better-known sonnets published in 1609; but as a sonneteer, Shakespeare was somewho
30.
Levine, R. J., Sjoerdsma,
A. Proc. Soc. exp. Biol. Med.
1962, 109,
225.
35. 36.
Mustala, O., Solatunturi, E., Tarpila, S. Acta med. scand. 1969, 185, 145. Challacombe, D. N., Sandler, M., Southgate, J. Archs Dis. Childh. (in the press). Spiro, H. M., Filipe, M. I., Stewart, J. S., Booth, C. C., Pearse, A. G. E. Gut, 1964, 5, 145. Riecken, E. O., Stewart, J. S., Booth, C. C., Pearse, A. G. E. ibid. 1966, 7, 317. Kattlove, H., Alexander, B. Lancet, 1970, ii, 1359. Cuthbertson, W. F. J., Mills, D. C. B. J. Physiol., Lond. 1963, 169,
37. 38. 39. 40. 41.
O’Brien, J. R. J. clin. Path. 1962, 15, 446. Grette, K. Acta physiol. scand. 1962, 56, suppl. p. 195. Harada, K., Zucker, M. B. Unpublished. O’Brien, J. R., Heywood, J. B. J. clin. Path. 1966, 19, 148. Lancet, 1970, ii, 1183.
31. 32. 33.
T., Wang Chun, I., Adlersberg, D. J. Mt Sinai Hosp.
1957, 24, 286. Kelley, M. L., Terry, R. Am. J. Med. 1958, 25, 460. Rubin, C. E., Brandborg, L. L., Flick, A. L., Phelps, P., Parmentier, C. van Niel, S. Gastroenterology, 1962, 43, 621. Benson, G. D., Kowlessar, O. D., Sleisenger, M. H. Medicine, Baltimore, 1964, 43, 1. Goldberg, D. Gut, 1970, 11, 459. Morris, J. S., Ajdukiewicz, A. B., Read, A. E. ibid. p. 549.
you
constructed
34. E.
J. R. O’BRIEN.
Portsmouth.
603. 22. 23.
D. N. CHALLACOMBE.
9P.