-
Gastrointestinal
infections and Schizophrenia: Professor V M Buscaino examined the gut at
autopsy of 82 patients who had been diagnosed with schizophrenia. Gastritis
was found in 50%, enteritis in 85% and colitis in 92%.
Some signs of catarrhal and haemorrhagic inflammation of the intestinal
mucosa, patchy areas of sclerosis and also of atrophy were noted. Professor
Henri Baruk also understood schizophrenia as it is rarely understood today.
He said the cause must be found in every case and that very often that cause
would be found far from the brain. He understood the nature of
schizophrenia. Baruk found that one patient with long-standing schizophrenia
had an e-coli infection. Baruk cured him. The man lost his schizophrenia and
went on to become a well-known New York banker, after having spent years in
a psychiatric hospital. Then, in the 1970s, the late Dr F Curtis Dohan spoke
at our first conference. Curtis Dohan4
reported differences in the incidence of schizophrenia worldwide and noted
that the highest incidence was in the wheat and rye eating areas of the
world. Dohan told me he was 99% certain of a genetic association between
schizophrenia and coeliac disease. Furthermore, a
report by Eaton and colleagues5
concluded that a history of coeliac disease was a risk factor for
schizophrenia. This hypothesis is
now being investigated further by Dr Jun Wei in Inverness.Schizophrenia Association of Great Britain, Bryn Hyfryd, Bangor, Gwynedd
LL57 2AG, UK
-
In 1928, said
Malis, a special monograph by Reuter read ‘From his observations signs of
schizophrenia are a decrease or absence of the acidity of the gastric juices
and a state of inflammation of the walls of the intestine accompanying (in
75% of all patients) a rise of temperature’ Malis continued ‘Those
observations were also supported by the results of post-mortem examinations
according to which the evidence of inflammatory changes in the intestine in
schizophrenia patients varied between 10% and 44% or more. About 20% of
schizophrenic patients die with signs of gastroenteritis’. This was in
the 1950s.Thus the early research workers in schizophrenia examined the
bodies of their patients and found much damage at autopsy, as indeed did
Prof V M Buscaino. These researchers found changes also in the acidity of
the gastric juice and noted a change in the micro organisms in the gut. All
these investigations, which took place in the pre-neuroleptic period, are of
very great importance to us. Had the drugs not been invented (a blessing
though they have proved) schizophrenia might be a curable disease by now.
-
The Russian
Professor G. Yu Malis in his book ‘Research on the aetiology of
schizophrenia’ (published in 1959) said that there ‘was a disturbance of
intestinal activity in schizophrenia, and some researchers attached much
importance to this area of research. ‘These findings’ said Malis ‘encouraged
the search for the causes of psychosis in intestinal infection (in
conjunction with tuberculosis) which was pointed out in 1905 by Dide, Blin
et al who in the same year concluded that dementia praecox (the old name for
schizophrenia) was a toxico-infectious sub-acute or chronic psychosis of
intestinal origin’.
-
Abnormal
intestinal permeability. An aetiological factor in chronic psychiatric
disorders? Wood NC, Hamilton I, Axon AT,
-
Khan SA, Quirke P, Mindham RH,
McGuigan K, Prison HM. Gastroenterology Unit, General Infirmary, Leeds.
Abnormal intestinal absorption has been suggested as an aetiological factor
in schizophrenia. A procedure for investigating intestinal permeability was
carried out in a group of chronic psychiatric in-patients. A proportion
of the subjects studied showed abnormal intestinal permeability which could
not be attributed to established bowel disease. Patients who were
receiving neuroleptic but not anticholinergic drugs were those most often
showing abnormal intestinal permeability. This work is at an early stage of
development but preliminary findings suggest that further investigations
should be carried out to establish the circumstances in which changes in
intestinal permeability may be associated with mental illness.
-
Gastric Ulcer disease in schizophrenia: variants of combination and
particular features of the course
Eksp
Klin Gastroenterol. 2006;(2):50-5, 127
It was
determined that the disease is characterized by the specific ulcer
localization of the concomitant Helicobacter pylori-associated gastritis
-
Gastric ulcer accompanying schizophrenia:
variants of combination and
particulars of development particular features of gastric ulcer accompanying
schizophrenia have been studied. It was determined that the disease is
characterized by the specific ulcer localization of the concomitant
Helicobacter pylori-associated gastritis and motor disorders of upper
gastro-intestinal tract in combination with psychiatric pathology unlike the
somatic group.
Eksp
Klin Gastroenterol.
2006;(2):50-5, 127.
-
The relationship of psychiatric illness with
gastrointestinal disease.
Department of Medicine, University of North Carolina, Chapel
Hill 27599-7080, USA.Fullwood
A,
Drossman DA. Higher rates of
psychiatric comorbidity as well as more impaired psychosocial adjustment
occur with the functional bowel disorders (irritable bowel syndrome) and are
particularly high in self-selected referral
patients compared with community populations. Reciprocally, some
studies show higher rates of functional bowel disturbances in patients
with psychiatric diagnoses.
-
5.6% of people with long term mental or behavioural problems also had
stomach, duodenal or gastrointestinal ulcers in Australia (ABS, 2004,
Australia’s Health 2004, AIHW)
-
Psychodynamics of Peptic Ulcer Pathogenesis
in Hospitalised ...
association between peptic ulcer and the manic. type of
manic-depressive psychosis
-
Prevalence of
Helicobacter pylori infection is significantly
higher in people with schizophrenia (odds ratio, 3.0).De Hert M,
Hautekeete M, De Wilde D, Peuskens J. High prevalence of
Helicobacter pylori in institutionalized
schizophrenic patients. Schizophr Res 1997; 26:
243-244.
<PubMed>
-
Peptic Ulcers in
Long-Term Institutionalized Schizophrenic Patient
-
Higher Incidence of Parasites
in schizophrenic patients
http://www.priory.com/pharmol/toxoplasmosis.htm
-
High Incidence of irritable bowel syndrome in
people with schizophrenia is 19% (versus 2.5% in the general
population).Gupta S, Masand PS, Kaplan D, et al. The relationship between
schizophrenia and irritable bowel syndrome (IBS). Schizophr Res 1997; 23: 265-268.
Comorbidity of irritable bowel syndrome in psychiatric patients: a review.
2003 Jan-Feb;10(1):61-7
-
Infection, treatment and immune response in patients with
bipolar disorder
versus patients with major depression, schizophrenia or healthy controls
Bipolar Disorders
Volume 4 Page 81 - September 2002
-
IgA antibodies against gliadin and gluten in multiple sclerosis
Acta Neurologica Scandinavica
Volume 110 Page 239 - October 2004
-
Excess mortality of
schizophrenia. High death rates from natural causes
The British Journal of Psychiatry 171: 502-508 (1997)http://bjp.rcpsych.org/cgi/content/abstract/171/6/502
-
Anxiety and the irritable bowel syndrome: psychiatric, medical, or both?
Institute of Psychiatry, Medical University of South Carolina, Charleston
29425, USA.
-
Depressive symptoms and inflammatory bowel
disease in children and adolescents: a cross-sectional study.
Pediatr Gastroenterol Nutr.
2004 Oct;39(4):395-403
-
Increased prevalence of functional gastrointestinal disorders in panic
disorder: clinical and theoretical implications.
CNS Spectr. 2005 Nov;10(11):857.
-
Gene, gut and schizophrenia: the meeting point for the gene-environment
interaction in developing schizophrenia.
Med Hypotheses. 2005;64(3):547-52.
-
Upper gastrointestinal and mental symptoms in the irritable bowel
Scand J Gastroenterol.
1985 Jun;20(5):595-601....
-
The relationship between
schizophrenia and irritable bowel ...
Br J Psychiatry. 1987 Jun;150:853-6.
-
Relationship between Helicobacter pylori infection and Alzheimer disease
-
The new epidemiology of schizophrenia.
-
Circulating immune complexes in blood of patients with positive family
history of schizophrenia.
-
Abnormal intestinal permeability. An aetiological factor in chronic
psychiatric disorders?
Br J Psychiatry. 1987 Jun;150:853-6.
-
The gut, genes, and brain of the schizophrenic.
-
A high prevalence of organ-specific autoimmunity in patients with bipolar
disorder. 200532(8):735-8.
Br Med J. 1977 Oct
15;2(6093):976- Med Hypotheses. 1991 Nov;36(3):225-7.
Review
-
Infectious and immune factors in neurodevelopmental damage.
Mol. Psychiatry 2002;
7: S34–5.Hornig M, Mervis R, Hoffman K, Lipkin WI.
-
Viruses, schizophrenia, and bipolar disorder.Yolken RH, Torrey EF.
Clin. Microbiol. Rev. 1995; 8: 131–45.\
-
Dr.Wank found that
a Chlamydia organism which can be a sexually transmitted disease has another
variant which can cause a serious respiratory tract infection similar to
SARS. Dr. Wank said schizophrenia patients may be infected by a variant of
this micro-organism. He found that targeting it with specially treated
immune cells improved the patients’ symptoms dramatically. Dr.Wank’s team
found that the risk of developing schizophrenia rose greatly for patients
with a certain group of immune system genes’. ‘Chlamydia pneumona’,
Dr. Wank thought, ‘could possibly contribute to Alzheimer’s disease.’ In the
same article Jerome Burne reported ‘that Dr. Rath Itzhabi, in the University
of Manchester, had been investigating a connection between herpes virus, the
one usually associated with cold sores on the lips, and Alzheimer’s disease.
She found signs of the virus in the brains of Alzheimer’s patients. Those
with the gene APOE4 were most likely to develop the disease’. Jerome Burne
ends his report by saying ‘It does suggest that already established
anti-viral or anti-bacterial treatments may have a part to play in the
treatment of mental illness’.
-
Dr Segundo Mesa
Castillo Rev. Neuro.2001:33:619-23 found at autopsy particles with viral
morphology in the brain which reacts to herpes simplex hominis type 1
antibody. He said ‘These findings were considered the first direct
evidence of a virus in the central nervous system in schizophrenia’ (Volben
RH, Torray EF, Viruses, Schizophrenia and Bipolar Disorder Clin Microb
Review 1995 1:13145. Dr Castillo wants ‘to clarify the possible relationship
among herpes simplex hominis type 1 virus, platelets and schizophrenia.’ He
says ‘The importance of a diagnostic biological test resides in that an
early diagnosis would modify the prognosis of the illness in a favourable
sense diminishing the direct, indirect and intangible costs of this
disabling disease’.
-
Celiac Disease and mental illness:
-
Celiac Disease and Schizophrenia: A 33-year-old patient, with pre-existing diagnosis of 'schizophrenic'
disorder, came to our observation for severe diarrhoea and weight loss. Use
of single photon emission computed tomography, (99mTc)HMPAO SPECT,
demonstrated hypoperfusion of the left frontal brain area, without evidence
of structural cerebral abnormalities. Jejunal biopsy showed villous atrophy.
Antiendomysial antibodies were present. A gluten-free diet was started,
resulting in a disappearance of psychiatric symptoms, and normalization of
histological duodenal findings and of (99mTc)HMPAO SPECT pattern. This is
the first case in which, in an undiagnosed and untreated coeliac patient
with psychiatric manifestations, the (99mTc) HMPAO SPECT demonstrated a
dysfunction of frontal cortex disappearing after a gluten-free
diet.Schizophrenic symptoms and SPECT abnormalities in a coeliac patient:
regression after a gluten-free dietDe Santis J Intern Med. 1997
Nov;242(5):421-3
-
Untreated Celiac Disease and Development of Mental Disorders in Children and
Adolescents (click here) - Since unrecognized Celiac disease may
predispose the sufferer to serious mental disorders and
behavioral problems, it should be taken into account in
differential diagnosis in all age groups. 2 examples from this
report:
Anne: 2 months after Anne started a gluten-free diet, her
depressive symptoms diminished, without psychiatric treatment or
known psychosocial factors to explain her remission.
She scored 0 on the BDI. Her abdominal pains and tiredness
subsided, and her weight began to increase slowly (her relative
weight was then 10% less than expected) without causing excessive
anxiety. Fifteen months later she was worried about her mood
swings and loneliness, but she did not meet the criteria for any
current mental disorder. Her scores on the CBCL indicated that
only the social problems remained at the borderline level. She
was 170.3 cm tall and weighed 54 kg (4% less than expected). She
had begun menstruating, and her adolescent development forged
ahead. She remained in remission throughout the follow-up period
of 2 years.
Tom: In the 5 months after starting a gluten-free diet, Tom
gradually remitted from the major depressive episode without
psychiatric treatment or known psychosocial factors to explain
the remission. Within 2 months his severe sleeping problems
subsided, and he was able to attend school normally. His school
performance improved. He learned how to control his obsessive
thoughts and fears, approaching them "on a philosophical level,"
and he felt able to believe in himself after 9 years of
depression. At age 17 Tom did not meet the diagnostic criteria
for any current mental disorder, although he had serious
difficulties in establishing contact with others. He scored 6 on
the BDI, and on the CBCL completed by the parent only his T-score
for withdrawal was clinically abnormal. Tom felt that his
self-esteem was beginning to improve and that he was coping
better with his chronic loneliness.
-
Mayo
Clinic Discovers Potential Link Between Celiac Disease And Cognitive Decline
-
The gluten connection:
the association between schizophrenia and
celiac disease Acta Psychiatrica
Scandinavica 2005 A drastic reduction, if not full
remission, of schizophrenic symptoms after initiation of gluten withdrawal
has been noted in a variety of studies
-
Relapsed schizophrenics: more rapid improvement on a milk- and
cereal-free diet.Br J Psychiatry. 1969 May;115(522):595-6.
Dohan FC, Grasberger JC, Lowell FM, Johnston HT Jr, Arbegast AW.
-
Psychiatric illness, gluten, and celiac
disease.1: Biol Psychiatry. 1982 Sep;17(9):959-61.Links
-
Individuals with Celiac Disease may be at
increased risk of non-affective psychosis. 1: Scand J
Gastroenterol. 2007 Feb;42(2):179-85.Coeliac disease and risk of
schizophrenia and other psychosis: a general population cohort
study.Ludvigsson JF, Osby U, Ekbom A, Montgomery SM.
-
Is celiac disease a clue to the pathogenesis of schizophrenia?
Dohan
FC.Ment Hyg. 1969 Oct;53(4):525-9.
-
Celiac syndrome in the case histories of five schizophreics.
GRAFF H, HANDFORD A. Psychiatr Q. 1961 Apr;35:306-13.Links
-
The gluten connection: the association between schizophrenia and
celiac
disease
Acta Psychiatrica Scandinavica
Volume 113 Page 82 - February 2006
-
Occipital Lobe Seizures Related to Clinically Asymptomatic
Celiac
Disease in Adulthood
Epilepsia Volume 33 Page 476 - May 19
-
Coeliac disease and schizophrenia: population based case control study with
linkage of Danish national registers.
BMJ. 2004 Feb 21;328(7437):438-9.
1803397,00.html
-
Schizophrenic symptoms and SPECT abnormalities in a coeliac patient:
regression after a gluten-free diet J Intern Med. 1997 Nov;242(5):421-3.
-
Depression in adult untreated celiac subjects:
diagnosis by the
pediatrician American Journal of
Gastroenterology 1999
-
Celiac disease
and schizophrenia: family occurrence.1: J Pediatr Gastroenterol Nutr.
1990 Aug;11(2):279.
Perisic VN, Lopicic Z, Kokai G.
-
Gut
problem link to baby weaning: Delaying the introduction of cereal-based foods
into a child's diet could help avoid later gut problems, say University of
Colorado scientists."
-
Auto-Immunity
and Mental Illness:
-
Autoantibodies
associated with psychiatric disorders.
Growing evidence suggests that autoantibodies to neuronal
or endothelial targets in psychiatric disorders exist and may be pathogenic. This review describes and discusses the possible
role of autoantibodies related to the psychiatric manifestations in
autoimmune diseases, autoantibodies related to the psychiatric disorders
present in post-streptococcal diseases, celiac disease, chronic fatigue
syndrome and substance abuse, and autoantibodies related to schizophrenia
and autism, disorders now considered of autoimmune origin.Curr Neurovasc
Res. 2006 May;3(2):149-57
Margutti P, Delunardo F, Ortona E. Dipartimento di Malattie Infettive,
Parassitarie e Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
ortona@iss.it
-
Schizophrenia
is associated with a larger range of autoimmune diseases than heretofore
suspected. Future research on comorbidity has the potential to
advance understanding of pathogenesis of both psychiatric and autoimmune
disorders. 1: Am J Psychiatry. 2006 Mar;163(3):521-8.Click here to read
Links
Association of schizophrenia and autoimmune diseases: linkage of Danish
national registers.
Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E, Mortensen PB.
-
Antinuclear and gastric parietal cell autoantibodies in schizophrenic
patients.
Biol
Psychiatry. 1992 Oct 15
-
Schizophrenia and autoimmunity – a possible etiological mechanism?
Noy S, Achiron A, Laor N. Neuropsychobiology 1994; 30: 157–9.
-
An immunological basis of schizophrenia and affective disorders? Fontana A, Storck U, Angst J, Dubs R, Abegg A, Grob PJ.
Neuropsychobiology
1980; 6: 284–9.
-
Immune dysregulation and self-reactivity in schizophrenia: do some cases of
schizophrenia have an autoimmune basis?
Immunol
Cell Biol. 2005 Feb;83(1):9-17.
-
Can autoimmune mechanisms account for the genetic predisposition to
schizophrenia? Knight J, Knight A, Ungvari G. Br. J. Psychiatry 1992;
160: 533–40.
-
Autoimmunity and schizophrenia: an epiphenomenon or an etiology?
Amital H, Shoenfeld
Y. Isr. J. Med. Sci. 1993; 29: 593–7.
-
Autoimmunity in schizophrenia: a review of recent findings. Ganguli R, Brar JS, Chengappa KN, Yang ZW, Nimgaonkar VL,
Rabin BS. Ann. Med.
1993; 25: 489–96.
-
Immune abnormalities in schizophrenia: evidence for the autoimmune
hypothesis. Ganguli R, Brar JS, Rabin BS. Harv. Rev. Psychiatry 1994;
2: 70–83.
-
Schizophrenia. Prenatal influenza and autoimmunity. Wright
P, Murray RM.Ann. Med. 1993; 25: 497–502.
-
Is schizophrenia an autoimmune disease?
Sirota P. Isr. J. Med. Sci.
1990; 26: 694–7.
-
Schizophrenia, an immunologic disorder? Logan DG, Deodnar SD.
JAMA
1970; 212: 1703–4.
-
Infection and autoimmunity as etiologic factors in schizophrenia: a
review and reappraisal. Schizophr. Bull. 1993; 19:
355–70 .Kirch DG.
-
Is schizophrenia a viral or immunologic disorder?
Psychiatr. Clin. North Am. 1986;
9: 115–32.DeLisi LE, Crow TJ
-
Autoimmune response to dopamine-receptor as a possible mechanism
in the pathogenesis of Parkinson's disease and schizophrenia. Perspect.
Biol. Med. 1978; 22: 104–14.
-
Review of immunological and immunopathological findings in schizophrenia.Rothermundt M, Arolt V, Bayer TA.
Brain Behav. Immun.
2001; 15: 319–39.
-
Evolution of neuropathologic abnormalities associated with
blood–brain barrier breakdown in transgenic mice expressing interleukin-6 in astrocytesBrett FM, Mizisin AP, Powell HC, Campbell IL. .
J. Neuropathol.
Exp. Neurol. 1995; 54: 766–75.
-
Autoimmune diseases in the
pedigrees of schizophrenic and control subjects. Wright P, Sham PC, Gilvarry CM
et al.Schizophr. Res.
1996; 20: 261–7.
-
Family history of
autoimmune diseases in psychosis.Gilvarry CM, Sham PC, Jones PB et al.
Schizophr. Res. 1996; 19:
33–40.
-
Schizophrenia as an immunologic disorder. I. Demonstration of antibrain globulins by fluorescent antibody techniques. Heath RG, Krupp
IM.Arch. Gen. Psychiatry 1967; 16: 1–9.
-
Schizophrenia as an immunologic disorder:
2. Effects of
serum protein fractions on brain function.Heath R, Krupp I, Byers L, Liljekvist
J. Arch.
Gen. Psychiatry 1967; 16: 10–23.
-
Autoimmunity and mental illness
Fessel WJ.. Arch. Gen. Psychiatry
1962; 6: 320–3
-
Anticerebral antibodies in
functional psychoses. Biol. Psychiatry 1991; 29: 322–8.Shima S, Yano K, Sugiura M, Tokunaga Y.
-
Antiseptal brain antibody in IgG of
schizophrenic patients. Biol. Psychiatry 1989; 25: 725–33. Heath RG, McCarron KL, O'Neil CE.
-
The possible association between MMR vaccine,
regressive autism and intestinal symptoms was first recounted by parents to
Dr. Andrew Wakefield, a UK gastroenterologist at the Royal Free Hospital,
London, in 1995. The first group of children presenting in this way to
Wakefield and colleagues at the Royal Free were reported in The Lancet as a
clinical case series in February 1998 (1). Although the interpretation put
on this paper at the time was the subject of intense controversy -
particularly in the absence of corroborative clinical research by other
researchers at that time - the strong evidence of a hitherto-unreported link
between autism and a novel intestinal disease, ileal-lymphoid nodular
hyperplasia, has not been disputed, and still stands as an important initial
clue as to the causes of regressive autism.
• A group of researchers led by Horvath (2) subsequently independently
reported in 1999 upon patients with autism who had gastrointestinal
symptoms, including a study of 36 children with autism that found grade I
or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15 (42%) and
chronic duodenitis in 24 (67%).
-
Further research
published in September 2000 (3) by Wakefield, Anthony et al confirmed that
ileal-lymphoid nodular hyperplasia (ILNH) was found in 54 out of 58 (93%)
children with autism or other disorders (50 with autism, 5 Aspergers, 2
disintegrative disorder, one ADHD, one schizophrenia, one dyslexia), but
only 5 out of 35 (14.3%) normal controls, pointing to a very strong ILNH-autism
link.
• Research published in 2001 by Furlano, Anthony et al (4) reported on
ileocolonoscopy performed on 21 consecutively-evaluated children with
autistic spectrum disorders and bowel symptoms, and made “blinded”
comparisons with 8 children who had a histologically normal ileum and colon,
plus 10 developmentally-normal children with ILNH, 15 with Crohn’s Disease,
and 14 with ulcerative colitis. The study confirmed a distinct
lymphocytic colitis in the children with ASD, in which the epithelium
appeared particularly affected, offering further corroboration for gut
epithelial dysfunction in autism.
• Research reported in 2001 by Buie (5) reported that, as a result of over
400 gastrointestinal endoscopies with biopsies and evaluation of digestive
enzyme function, on children with autism, he had found the presence of
chronic inflammation of the intestinal tract, although the incidence was
less frequent than in the Royal Free Hospital group of patients reported by
Wakefield et al, and that biopsy results indicated the presence of chronic
inflammation of the digestive tracts, including esophagitis, gastritis and
enterocolitis. Ileal lymphoid nodular hyperplasia, as first found by the
Royal Free study, had been found in 15 of 89 children examined for it.
• A review (6) published in September 2002 by Wakefield, Anthony, Montgomery
et al noted that as early as 1986, a researcher named Soddy had noted that
recurrent gastrointestinal upsets were a constant feature of autistic
children, and that in a systematic analysis of an unselected population of
385 children on the autistic spectrum, clinically-significant
gastrointestinal symptoms occurred in 46%, compared with 10% of 97
developmentally-normal controls, strongly suggesting a
gastrointestinal-autism link. Mucosal lesions in the small and large
intestine were consistent with an autoimmune pathology, and suggested the
possibility of an autoimmune response leading to cerebral damage.
• A June 2002 presentation (7) by Krigsman to the US Congressional
Committee on Government Reform reported that a large percentage of his
autistic patients suffered from chronic unexplained gastrointestinal symptoms.
Of 43 patients, the majority had a clear history of developmental
regression, after previous normal development, suffering gradual or
precipitous decline between age 12 months and 18 months. Most regressive
children also exhibited poor growth. Patients had undergone colonoscopy.
Findings were that the lymphoid nodules of the terminal ileum were markedly
enlarged, thus confirming the early work of the Royal Free team. Evaluation
of biopsy specimens confirmed that 65% had colitis, 51% had active colitis,
40% had chronic colitis, 7% had eosinophilic colitis, 90% had lymphoid
nodular hyperplasia of the terminal ileum, and 35% had neither active nor
chronic nor eosinophilic colitis. Patterns of inflammation were patchy and
unpredictable, but findings were similar and consistent from patient to
patient within affected sub-groups.
• A November 2003 paper (8) published by Ashwood, Murch et al reported on
the examination of 52 affected autistic children, compared with 25
histologically-normal developmentally-normal controls and a further 54
histologically-inflamed but developmentally-normal controls. Analysis of
intestinal biopsies in regressive-autistic children indicated a novel
lymphocytic enterocolitis with autoimmune features, though the precise
linkage between the finding and cognitive functions still remained unclear.
The study concluded that it provided further evidence of a pan-enteric
mucosal immunopathology in children with regressive autism, that is distinct
from other previously-known inflammatory bowel diseases.
• An April 2004 paper (9) by Torrente, Anthony et al identified, following
earlier reports of lymphocytic colitis and small bowel enteropathy in
children with regressive autism, that the gastritis in regressive autism
was clearly distinct from that in Crohn’s and other conditions, pointing to
a distinctive form of gastritis being linked with regressive autism.
• A November 2004 paper (10) by Ashwood, Anthony et al found that
molecules (cytokines) produced by immune cells in the intestine, that cause
or control inflammation, showed an abnormal pattern in autistic children
compared with non-autistic children. The pattern was different to other
forms of intestinal inflammation, and the disease resembled a longstanding
viral disease of the intestine, not unlike the intestinal inflammation seen
on patients with other viral infections such as HIV-associated enteropathy
(intestinal disease) that often accompanies infection with HIV.
• A February 2005 paper (11) by Jyonouchi, Geng et al further confirmed
the original ileal-lymphoid nodular hyperplasia/regressive autism link first
reported by the Wakefield team in 1998. The study again found evidence
of marked inflammatory and immune abnormalities in children with autism
associated with gastrointestinal symptoms.
• An April 2005 published letter (12) by Balzola, Barbon et al,
Pan-Enteric IBD-Like Disease in a Patient with Regressive Autism Shown for
the First Time by the Wireless Capsule Enteroscopy - Another Piece in the
Jigsaw of this Gut/Brain Syndrome?, reported that a 28-year-old male with
regressive autism, severe constipation, bloating, abdomen distension and
symptoms of gastroesophageal reflux was examined. Gastroscopy under general
anaesthesia revealed hemorrhagic gastritis with inflammatory
pseudopolypsthat had reached the pylorum, with a pearl-necklace
appearance, and a panenteric IBD-like disease consistent with
previously-published descriptions of autistic enterocolitis was finally
diagnosed. The wireless capsule images were the first to be obtained beyond
the limits of the duodenum and terminal ileum, and demonstrated the
potential for the entire bowel to be implicated in this inflammatory
disease.
• A May 2005 study (13) by Balzola, Daniela et al reported on 9 consecutive
patients (range 7-30 years) with autism and chronic intestinal symptoms
(abdominal pain, bloating, constipation and/or diahorrea). Routine blood and
stool tests and gastroscopy and colonoscopy with multiple biopsies were
performed under sedation, and wireless enteroscopy capsules were used in
three of the adult patients. Gastroscopy revealed mucosal gastritis in 4
patients, esophagitis in 1 patient and duodenitis in 1 patient, and
histological findings showed chronic inflammation of the stomach and
duodenum in 6 patients, inconsistent with celiac disease. The authors
reported that preliminary findings were strongly consistent with previous
descriptions of autistic enterocolitis, and supported a not-coincidental
occurrence. They showed for the first time a small-intestinal involvement,
suggesting a pan-enteric localization of this new inflammatory bowel
disease.
• Also in 2005, a further paper (14) by Wakefield, Ashwood et al was
published, assessing ileocolonic lymphoid nodular hyperplasia in ASD and
normal control children. Some 148 consecutive children with ASD, with
gastrointestinal symptoms, were investigated by ileocolonoscopy, with 74 ASD
children and 23 normal controls undergoing upper gastrointestinal endoscopy.
The presence of lymphoid nodular hyperplasia was significantly greater in
ASD children compared with controls, in the ileum (129 out of 144, compared
with 8 out of 27 controls), and in the colon (88 out of 148, compared with 7
out of 30 controls). Comparative percentages were 90% vs 30% and 59% vs 23%.
This was whether or not controls had co-existent colonic inflammation. The
severity of ILNH was significantly greater in ASD children compared with
controls, with moderate-to-severe ILNH present in 98 out of 144 ASD children
compared with 4 out of 27 controls; percentages were 68% and 15%. On
histopathological examination, hyperplasic lymphoid follicles were
significantly more prevalent in the ileum of ASD children (84 out of 138, or
61%) compared with normal controls (2 out of 23, or 9%). The data thus
further corroborated the finding that ileal lymphoid nodular hyperplasia is
a significant pathological finding in autistic children.
• Additionally in 2005, a study (15) was published by Gonzalez, Lopez et al,
seeking evidence of immunological alterations in 68 autistic children ages
22 months to 11 years and presenting with digestive systems, and examining
biopsies from their digestive tracts. Endoscopies and colosopies were
undertaken, with biopsies of the esophagus, stomach, duodenum and colon,
with verification of presence of inflammation, eosiophil infiltration,
lymphoid nodular hyperplasia and CD-4 and CD-8 cells. The results were that
lymphoid nodular hyperplasia was discovered in 2/68 esophagus, 6/68
stomachs, 8/68 duodenums and 36/68 (53%) of colons. Eosiophil infiltration
with more than 20 eosiphils per field were found in 3/68 eosphagus, 1/68
stomach, 8/68 duodenum and 24/68 (35%) colons. Inflammatory reactions were
found in 56/68 (82%) esophogitis, 64/68 (94%) gastritis, and all (100%)
presented with duodenitis and colitis. CD-4/CD-8 relationship existed of >3
in 42/68 (62%) and <1 in 16/68. The authors concluded that the children
presented immunological and immunohistochemical alterations of the biopsies
of their digestive tracts, and that there was a significant finding of
lymphoid nodular hyperplasia, eosiophilinfiltration, and that prevalence of
greater CD-4 than CD-8 cells in the inflammation of the intestinal wall
demonstrated in favour of a Th2 type allergic reaction.
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Biological Psychiatry, Volume 54, Issue 9, Pages 929-933
