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January2011 Vol.48 Issue:      1 Table of Contents
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Dermorphin Peptide Action in a Sample of Arab Children with Autistic Spectrum Disorder

Omnia R. Amin, Amany A. Abdou

 

Department of Child Psychiatry, Cairo University; Egypt

 



ABSTRACT

Background: The Dermorphin peptide hypothesis of autism suggests that autism is the consequence of the incomplete breakdown and excessive absorption of peptides with opioid activity, causing disruption to neuroregulatory processes. Dermorphin is thought to be one of the cause affecting brain neurons. This neuropeptide is 40 times more potent than morphine. It is hypothesized that there is blood brain barrier for this peptide causing autism. Biochemical evidence has demonstrated a connection between the exclusion of gluten and casein from the diet and improvements in the behavior of children with autism. Objective: To find the relation between autistic symptoms and Dermorphin peptide. To detect if gluten and casein elimination has a role in autism. Methods: 42 autistic spectrum disorder children according to DSM IV-R criteria between 3- 6 year old and the control group included 36, same age, normal children. The whole sample was subjected to full child psychiatric sheet, The Childhood Autism Rating Scale, Blood level of Dermorphin peptide and elimination of both casein and gluten products. Results: There was no significant difference in severity of autistic criteria in both Dermorphin positive and negative autistic children with Improvement of autistic criteria after casein and gluten. Conclusion: Diet elimination may have a role in improvement in all autistic children and not specific to the presence of Dermorphin like action (with and without Dermorphin action).This improvement may be related to the effect of the specific educational program received by each child. [Egypt J Neurol Psychiat Neurosurg.  2011; 48(1): 19-24]

 

Key Words: Dermorphin- Arab- Autistic- Children

 

Correspondence to Omnia R. Amin, Cairo, Department of Child Psychiatry, Cairo University Egypt.

Tel.: 002-0105107515    E-mail: omniaraffat@yahoo.com




INTRODUCTION

 

Autism is a severe lifelong developmental disorder, defined on the basis of behavioral characteristics which result from impairments in social communication and reciprocal social interaction, as well as repetitive and restrictive behaviors1. An underlying etiology for autism is identified only for a minority of children. There are no evidence-based biomedical investigations to guide intervention2. Both genetics and environments seem to play a role in 10 to 25% of cases3. Dermorphin is a toxic substance with opiate structure that is 30-40 times more potent than morphine4. The Dermorphin peptide hypothesis of autism suggests that some autistic symptoms may result from opioid peptides that formed from the incomplete breakdown of foods containing gluten and casein5. Increased intestinal permeability, also referred to as the "leaky gut syndrome," allows these peptides to cross the intestinal membrane, enter the bloodstream, and cross the blood–brain barrier, affecting the endogenous opiate system and neurotransmission within the central nervous system6.

 

Goday reported that Gluten Free Casein Free (GFCF) diet appears to have a rationale for its use and it is still offered as a form of therapy to children with autism7. Because there is no known cure, emphasis is on early identification and intervention, aimed at maximizing the quality of life for children with ASD8,9. 

The hypothesis of this study was that autistic symptoms may be related to the excess opioid that formed from incomplete breakdown of casein and gluten. So, elimination of casein and gluten may cause improvement of autistic criteria.

Aim: To find the relation between autistic symptoms and Dermorphin peptide action in serum of autistic children. To detect whether the elimination of gluten and casein on autistic children’s diet has a role in improving of symptoms in those who have serum Dermorphin.

 

SUBJECTS AND METHODS

 

This study is a case-control study that included 42 autistic spectrum disorder (ASD) children (29 boys and 13 girls) between the age of 3 and 6 years [Thirty four were diagnosed with autism, four with Asperger Syndrome, four with pervasive developmental disorder (NOS)]. All children attended the Jeddah Child and Adolescent Psychiatric Services (JCAPS). It is under the authority of Erfan Psychiatric Hospital in Jeddah, KSA. The sample was collected during the period from January 2004 to March 2005. Each child in the sample had been subjected to a specific educational program according to his deficits. 

The control group included 36 normal children (26 boys and 10 girls) who were siblings of nursing and personal staff in Erfan General Hospital. They have no past history of neuropsychiatric disorder or even language delay. Informed consent was obtained from the parents of the autistic and control children. Both samples were on an unrestricted diet. There was a special concern about the presence or absence of prominent past history of gastrointestinal tract (GIT) symptoms (vomiting, diarrhea, constipation, colic, abdominal cramps) as reported by parents or care takers.

Exclusion criteria included refusal to participate, physically handicapped children and children with progressive neurological disorders and unstable epilepsy. Children who were taking regular medications including stimulants, anticonvulsants, and atypical antipsychotic, in addition to children with clinically assessed mental delay.

 

Methods

1-      The whole autistic spectrum disorder children were subjected to full clinical child psychiatric sheet aiming at proper psychiatric diagnosis according to DSM-IV R criteria. This was followed by application of The Childhood Autism Rating Scale (CARS)10 for initial assessment of children with ASD, followed by assessment 3 and 6 months later. The CARS is a 15-item behavioral rating scale developed to identify children ages 2 years and older with autism. It provides quantifiable ratings based on direct behavior observation. This scale had been subjected to translation and then back translation followed by application to 5 children with autistic spectrum disorder as a form of pilot study.

2-      Both autistic and control groups provided blood sampling for testing the presence of Dermorphin Peptide action. Excessive activity of Dermorphin can be detected by evaluating its antibody level. This level of antibody can be measured by ELISA technique in which purified Dermorphin is attached to the walls of the ELISA microplates. The blood samples were taken and centrifuged in the main laboratory in Erfan Hospital. Samples were collected and sent by mail to the Alletess Medical Laboratory for allergic and immunological disorders, Rockland, USA. Results were sent from the laboratory in the USA by electronic mail back to the main laboratory in Erfan Hospital.

3-      For 6 months under the care of a dietitian, casein and gluten products were eliminated from the diet of ASD children with both positive and negative Dermorphin like action (GFCF). Also, the same diet elimination had been done for the control group who had positive Dermorphin like action.  

 

Statistical Analysis:

Descriptive statistics have been used to estimate the mean and standard deviation. T-test had been used. Multiple sets of values were subjected to Kruskal-Wallis Test. Differences with a p value <0.05 is significant.

 

RESULTS

 

  A total of 42 children met the eligibility criteria of Autistic Spectrum Disorder (ASD). The mean age was 50.60 months ± 11.38 versus 36 children as healthy control children with mean age 54.00 months ± 10.55. Autistic sample was classified as twenty-nine (69%) boys and thirteen (31%) girls. Control group included 26 (72%) boys and 10 (28%) girls. Table (1) showed 18 (42.85%) autistic children with positive reaction to Dermorphin in contrast with 14 (38.89%) in the control group. There was no significant difference between the mean levels of Dermorphin peptide in both groups. No significant differences in the mean of the total scores of CARS in those who have or have not Dermorphin like action and also GIT symptoms (Table 2). There were statistically significant decline in the mean of total CARS score (severity in autistic criteria) in autistic children with and without Dermorphin action after six months of diet elimination (Table 3). Improvement in GIT symptoms in autistic children with Dermorphin action (60%) after 6 months of diet elimination more than the control group with Dermorphin action (50%) (Table 4). Autistic children without Dermorphin action showed more statistically significant improvement in CARS subscales than those with Dermorphin action (Table 5). 


Table 1. Comparison between autistic and control group regarding serum Dermorphin like action.

 

 

Autistic group (42 )

Control group (36)

P

No.

%

Mean

SD

No.

%

Mean

SD

Total

18

42.85

1.89

0.76

14

38.89

1.71

0.76

0.60

+1

6

33.33

 

 

6

42.85

 

 

 

+2

8

44.44

 

 

6

42.85

 

 

 

+3

4

22.23

 

 

2

14.30

 

 

 

SD standard deviation

 

 

Table 2. Comparison between mean total scores of CARS in autistic children with and without Dermorphin action and GIT symptoms.

 

 

No.

SD

Mean CARS score

SD

P

Autistic children with Dermorphin action

18

42.85

45.17

7.20

0.613

Autistic children without Dermorphin action

24

57.15

46.29

6.95

Autistic children with GIT symptoms

27

64.29

44.93

8.2

0.071

Autistic children without GIT symptoms

15

35.71

40.15

7.61

CARS Childhood Autism Rating Scale, SD standard deviation

 

 

Table 3. Comparison between Dermorphin positive and negative autistic children regarding improvement in mean total scores of CARS after three and six months of casein and gluten elimination.

 

 

Dermorphin positive autistic children

Dermorphin negative autistic children

Mean

SD

Mean

SD

0 month

45.17

7.20

46.29

6.95

3 months

40.67

7.89

42.78

7.01

P

0.083

0.088

0 month

45.17

7.20

46.29

6.95

6 months

34.83

8.40

40.15

6.73

P

0.000*

0.003*

CARS Childhood Autism Rating Scale SD standard deviation                 

* significant at p<0.01

 

Table 4. Effect on GIT symptoms after diet elimination in both autistic and control children with Dermorphin action.

 

 

Before diet elimination

Improvement After diet elimination

No

%

No

%

GIT symptoms in Autistic children with Dermorphin action 18 (42.9%)

15

100

9

60%

GIT symptoms in Control with Dermorphin action 14 (38.9)

6

100

3

50%

GIT gastrointestinal

Table 5. Comparison between autistic children with and without Dermorphin action regarding improvement in mean scores of subscales of CARS after six months of casein and gluten elimination.

 

 

Dermorphin positive autistic children

P

Dermorphin negative autistic children

P

Mean

SD

Mean

SD

Relation to people

0 month

3.57

0.33

0.000*

2.99

0.33

0.000*

6th month

2.90

0.57

2.01

0.23

Imitation

0 month

2.99

0.87

0.141

3.09

0.34

0.000*

6th month

2.55

0.88

2.45

0.45

Emotional response

0 month

3.20

0.18

0.095

3.56

0.47

0.000*

6th month

2.88

0.77

1.90

0.28

Body use

0 month

3.10

0.79

0.000*

3.22

0.95

0.183

6th month

2.14

0.78

2.55

0.34

Object use

0 month

3.15

0.56

0.000*

3.57

0.86

0.000*

6th month

2.55

0.35

2.38

0.33

Auditory response

0 month

2.55

0.76

0.350

3.56

0.68

0.000*

6th month

2.79

0.76

1.85

0.13

Verbal communication

0 month

3.29

0.55

0.015*

3.44

0.55

0.000*

6th month

2.86

0.45

2.12

0.39

Non-verbal communication

0 month

3.28

0.76

0.017*

2.78

0.76

0.002*

6th month

2.60

0.86

2.21

0.34

Intellectual response

0 month

3.21

0.77

0.000*

3.43

0.45

0.010*

6th month

2.34

0.32

2.99

0.67

CARS Childhood Autism Rating Scale,, SD standard deviation               

* Significant at p<0.01

 

 

 


DISCUSSION

 

The etiology of autism is unknown with no evidence-based lines of management. This study confirms that Dermorphin peptide has been found in serum of autistic children as well as in control children. Also, we made an emphasis on the severity of autistic criteria in autistic children with and without Dermorphin action and found no significant difference. This result may refer to the non specific effect of Dermorphin peptide in autistic children. In contrast with Millward et al.11, it has been suggested that peptides from gluten and casein may have a specific role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides.

In our patients, there is an improvement in severity of autistic criteria after diet elimination for 6 months in both Dermorphin positive and negative autistic children. This result may point to the improvement effect of diet elimination in autistic children regardless of the etiology. Also, this improvement can be rationalized by the effect of the specific educational program that has been given for every child. Knivsber et al.12 stated that diet elimination led to reduction of autistic behavior and reappearance of autistic traits after the diet has been broken. With such diets, some studies show symptom regression but others report negative side effects, essentially protein malnutrition13.

In the present study, there is significant improvement in some autistic symptoms and CARS subscales in autistic children with Dermorphin positive action after CFGF diet. An extensive search through Cochrane,   the first study indicated that a combined gluten and casein free diet reduced autistic traits11. However the second study showed no significant difference in outcome measures between the diet group and the control group. Surprisingly, this study showed that CFGF diet improves more subscales of CARS in autistic children without Dermorphin action than those with the same action. The results can be explained by the non specific effect of Dermorphin peptide as an etiology of autistic criteria, but it may be a contributing factor. Also their elimination in diet is not a specific line of management. This result may encourage CFGF diet to all autistic children regardless of the etiology is. Wakefield et al.14 concluded that CFGF diet can improve the behavior of autistic children particularly in communication, attention, and concentration.

This study failed to make a relation between presence of GIT symptoms and severity of autistic criteria. Wakefield et al.14 stated that there is a possibility of extracranial abnormalities in autism, notably with the GIT and opioid receptors. There was an improvement in GIT symptoms in autistic children with Dermorphin action after diet elimination more than the control group with Dermorphin action.  This improvement may be accidental and not specific to effect of Dermorphin peptide on the improvement of GIT symptoms in autistic children. Latcham et al.15 agreed with this result and found that there is no evidence that autistic children were more likely than non-autistic in having GIT symptoms or show improvement in these symptoms after gluten and casein elimination.

The GFCF diet appears to have at least a weak rationale for its use. In this study, there was no difference between the control and autistic groups. However parents of most of the children elected to continue the diet despite being told that the results did not show any difference.

In conclusion, diet elimination may have a role in improvement in all autistic children and not specific to the presence of Dermorphin like action (with and without Dermorphin action). This improvement may be related to the effect of the specific educational program received by each child. Interestingly, all of these families chose to continue the diet at the completion of the study, even after being told about the non significant results. Consideration should be given to include larger number of participants and for longer period of time.

 

[Disclosure: Authors report no conflicts of interest]

 

REFERENCES

 

1.      Hofvander B, Delorme R, Chaste P, Nydén A, Wentz E, Ståhlberg O, et al.  Psychiatric and psychosocial problems in adults with normal-intelligence autism spectrum disorders.  BioMed Central psychiatry  2009; 9: 35-9.     

2.      Hunter LC, O'Hare A, Herron WJ, Fisher LA, Jones GE. Opioid peptides and dipeptidyl peptidase in autism. Dev Med Child Neurol. 2003 ; 45(2):121-8.      

3.      Desjardins S, Doyen C, Contejean Y, Kaye K, Paubel P. Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form. Encephale.  2009; 35(2):168-72. 

4.      Cass H, Gringras P,  March J, McKendrick I, O’Hare AE, Owen L, et al. Absence of urinary opioid peptides in children with autism. Arc Disease Child. 2008; 93:745-50     

5.      Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B.  Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatrics. 2005; 146(5): 605-10     

6.      Whiteley P,Shattock P. Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention P. Expert Opin Ther Targets. 2002; 6(2):175-83.    

7.      Black C, Kaye JA, Jick H. Relation of childhood gastrointestinal disorders to autism: nested case-control study using data from the UK General Practice Research Database. BMJ. 2002; 325(1): 419-421 

8.      Goday P. Whey Watchers and Wheat Watchers: The Case Against Gluten and Casein in Autism. Nutrition in Clinical Practice 2008; 23 (6): 581-582.

9.      Elder J. The Gluten-Free, Casein-Free Diet in Autism: An Overview With Clinical Implications. Nutr Clinl Pract. 2008; 23 (6), 583-8.

10.    Schopler E, Reichler RJ, DeVellis RF, Daly K. "Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS)". J Autism Dev Disord. 1980; 10 (1): 91–103.   

11.    MillwardC, Ferriter M, Calver S, Connell-Jones G.  Gluten- and Casein-free Diets for Autistic spectrum disorder. Cochrane Database of Systematic Reviews, Issue 4, 2009. The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.       

12.    Knivsber AM, Reichelt KL, Nødland M. Reports on dietary intervention in autistic disorders. Nutr Neurosci. 2001;  4(1):25-37.          

13.    Levy SE, Souders MC, Ittenbach RF, Giarelli E, Mulberg AE, Pinto-Martin JA. Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders. Biol Psychiatr. 2007.; 61(4): 492-7.       

14.    Wakefield AJ, Puleston JM, Montgomery SM, Anthony A, O'Leary JJ, Murch SH.   Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Aliment Pharmacol Ther. 2002; 16(4): 663-74.

15.    Latcham, F, Merino F, Winter C., Lang A, Garvey J. & Thomson MA. A Consistent Pattern of Minor Immunodeficiency and Subtle Enteropathy in Children with Multiple Food Allergy. J Pediatric. 2003; 143: 39-47.


 

 

الملخص العربي

 

دور الديرمورفين في عينه من الأطفال العرب الذين يقعون في مجال الذاتويه

 

الغرض : استكشاف ما إذا كان هناك علاقة بين مرض الذاتويه ومادة الديرمورفين في الدم. أيضا محاولة إيجاد ما اذا كان منتجات الكاريين والجلوتين لهما دورا في مرض الذاتويه.

اشتملت العينة غلى 42 طفلا (3-6 سنوات) يقعون في مجال الذاتويه مقابل 36 طفلا أصحاء كعينه ضابطه. وقد خضع أفراد العينة المصابة إلى تقييم نفسي عملي شامل مع تطبيق المقياس النفسي الخاص بالذاتويه للتقييم الكمي. كما خضع أطفال الدراسة إلى عمل تحليل بالدم للكشف عن وجود مادة الديرمورفين لديهم والمقارنة بينهم. كما تم تطبيق حميه غذائية تشتمل على استبعاد منتجات الكازيين والجلوتين من طعام هؤلاء الأطفال. وقد أظهرت النتائج وجود مادة الديرمورفين بالدم بنسبه متقاربة في كلا من العينة المصابة والضابطة. عدم وجود فروق ذات دلاله احصائيه بين شدة أعراض مرض الذاتويه في الأطفال الذين لديهم ديرمورفين بالدم مقابل الأطفال الذين أظهروا تفاعل سلبي للديرمورفين. كما أنه أظهرت العينة المصابة تحسنا ملحوظا في شدة الأعراض بعد تطبيق الحمية الغذائية للكازيين والجلوتين.



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