Are Families of Children with Reading Difficulties at Risk for Immune Disorders and Nonrighthandedness?

ARE FAMILIES OF CHILDREN WITH READING DIFFICULTIES AT RISK FOR IMMUNE DISORDERS AND NONRIGHTHANDEDNESS? Susan G. Crawford1, \ Bonnie J. Kaplan 1,2,3 and Marcel Kinsbourne4 (Departments of IPsychology and 2Pediatrics, University of Calgary, 3Alberta Children's Hospital Research Centre; 4Centre for Cognitive Studies, Tufts University, Medford, Massachusetts)

Several investigators have reported assocIatIOns between developmental learning difficulties and immunologic dysfunction (Hartsough and Lambert, 1985; Hugdahl, Synnevag and Satz, 1990; Pennington, Smith, Kimberling et aI., 1987; Shaw and Brown, 1990), as well as between nonrighthandedness and immune/ autoimmune disorders (Geschwind and Behan, 1982, 1984; Searleman and Fugagli, 1987; Smith, 1987), There is also some evidence that nonrighthandedness is more common among subjects with learning difficulties (Bakan, 1988; Porac and Coren, 1981; Schacter, Ransil and Geschwind, 1987); however, this relationship has been disputed (Gilger, Pennington, Green et aI., 1992; Pennington et aI., 1987; Satz and Soper, 1986), Finally, immunologic dysfunction may be inferred from studies which found that children with attention deficits and/or hyperactivity have an elevated prevalence of allergic symptoms (Behan and Geschwind, 1985; Hartsough and Lambert, 1985; Kaplan, McNicol, Conte et aI., 1987; Shaw and Brown, 1990), Geschwind and Galaburda (l985a, 1985b, 1985c) elaborated on a theory of cerebral lateralization that would account for the above findings, plus the data which show that more males are nonrighthanded than females (Oldfield, 1971), and that developmental learning difficulties are more common among males (Taylor, 1974), Pleiotropism is a phenomenon where certain genetic predispositions manifest themselves in diverse ways in different members of the same family (Borecki, Rao, Lalouel et aI., 1985), Geschwind (1983) suggested that the relationships among nonrighthandedness, immune disorders, and developmental learning difficulties may represent a case of pleiotropism, Recently, we analyzed a set of questionnaire data (Crawford, Kaplan and Kinsbourne, 1992) to address questions of parental immunoreactivity stimulated by the theory of Gualtieri and Hicks (1985), In the present study we examine the same dataset from an entirely different perspective to evaluate some variables implicated in Geschwind and Galaburda's theory of cerebral lateralization, We examined, in a group of school children and their families, the relationships among (a) reading comprehension difficulties, (b) immune and autoimmune disorders, and (c) nonrighthandedness. In order to investigate these variables as an example of pleiotropism, the present study focused on the overall familial prevalences of all variables. It was hypothesized that the prevalences of immune Cortex, (1994) 30, 281-292

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disorders and nonrighthandedness would be higher for children with reading problems and their families. Immune disorders and nonrighthandedness were also expected to be more frequent among children with characteristics of attention deficit hyperactivity disorder (ADHD) and their families, who have not been studied much in this regard. MATERIALS AND METHOD

Subjects

Parents of all 220 children attending two private academies for learning disabled (LD) children were sent a questionnaire, and more than 1000 children attending regular classrooms in the public school system were given questionnaires to take home to their parents. The latter sample consisted of children in grades 4 through 12 in randomly selected public schools. The computer program, SPSS-X, was used to randomly select from a list of all schools in the city four schools from each of grades 4 through 12, with one school being chosen from each quadrant of the city (NW, NE, SW, SE). Of these 36 randomly selected schools, 13 principals agreed to have their schools participate in the project. In order to compensate for anticipated poor response rates, it was decided to give questionnaires to 100 students from each of grades 4 through 12 to take home to their parents. If there were more than 100 students in the respective grade, the principal was asked to randomly select a number of classrooms to yield approximately 100 students. Questionnaires were returned for 468 children and their families: 132 students (101 males and 31 females, aged 8 to 18 years) were from the two LD academies, and 336 students (145 males and 191 females, aged 8 to 19 years) were from the public schools. The ratio of males to females was approximately 3: 1 for the LD academy group and approximately 1: I for the public school group. None of the children from the two LD academies were mentally retarded. Sixty percent of the parents of children from the private academies returned questionnaires, while 33% of the parents of the children from the public schools returned questionnaires. The different methods used to distribute questionnaires to the parents no doubt was responsible for the discrepancy in response rates. It is likely that the questionnaires were often not taken home by children in the public schools; however, all questionnaires were mailed directly to the parents of children attending the academies. The response rate for the public schools is, however, comparable to response rates from mail surveys in epidemiological studies (e.g., Spry, Hovell, Sallis et aI., 1987). The relatively high response rate from the academies is probably because our laboratory has a closer relationship with them, as demonstrated by their staffs cooperation and a number of their families ' participation in our previous studies. Because the goal of this study was not to obtain overall popUlation prevalences, but rather, to obtain pools of subjects from which to select our matched samples, the response rates were of no concern. Some private academies for LD children may have only students of high socioeconomic status; however, this is not the case for these particular academies. Yearly tuition fees range widely from approximately $1,000 to $8,000, depending on the family's financial situation. Financial assistance is given to all parents who require it, so that no child is denied admission becau.se of financial problems. Thus, unlike many private schools in other settings, socioeconomic status (SES) is not a deciding factor in determining which children enter these particular academies. We were able to confirm this fact by statistically comparing SES (Blishen and McRoberts, 1976) between our two samples: overall there was no difference in SES (chi-square = 8.28; d.f. = 5) between the children in the academies and those in the public schools. Our goal was to derive from our pool of 468 questionnaires two samples of children carefully matched for age and sex, but clearly differing in reading comprehension abilities. Following parents' written consent, the child's most recent scores from the Canadian Test of Basic Skills (CTBS; King, Hieronymus and Lindquist, 1971) were obtained. The Reading

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TABLE I

Distribution of Scores on Reading Comprehension (CTBS) Percentile

Reading problem group

Control group

o

0-5 6-10 11-15 16-20 21-25 26-30 31-35 36-40 41-45 46-50 51-55 56-60 61-65 66-70 71-75 76-80 81-85 86-90 95-100

28 8 4 I 8

o o o o o o o o o o

9 4 4 4 4 5 6 10 9

Total

55

55

o 2

2

2

o o o o o o o o o

Comprehension subtest from the CTBS was the only reading measure that had been administered in both the academies and the public schools, so scores from this subtest were used to select the samples. The 50th percentile (based on national norms) was chosen as the cutoff point, so that to remain part of the reading problem group, subjects had to be attending one of the LD academies and had to have scored below the 50th percentile on reading comprehension. To remain part of the control group, subjects had to be from the public schools, and had to have scored above the 50th percentile. In addition, nine children were excluded because of the presence of a neurological disorder such as epilepsy. Nineteen other children were excluded because they were adopted, and no family history was available. This series of steps resulted in a selected sample of 70 subjects who were receiving remediation for reading problems at the two LD academies and 72 control subjects who attended a public school. Subject losses were due to either scoring below the 50th percentile on reading comprehension (control group) or having no CTBS scores available. The largest loss of subjects was the considerable number of randomly selected public school children (N = 127) whose CTBS scores were below the 50th percentile. As a final step, the subjects that remained in the reading problem group were matched to the remaining control subjects, on the basis of age and sex. Each of the resulting matched groups consisted of 40 males and 15 females. The maximum difference in ages of the matched subjects was 0.66 years. Fifteen male reading problem subjects could not be matched to male control subjects, because the maximum difference in ages of matched subjects would have been over one year had these subjects been included. The final matched sample consisted of 55 students in the reading problem group (40 males and 15 females, mean = 12.80 years, SD = 2.47), and 55 age- and sex-matched control subjects (40 males and 15 females, mean = 12.84 years, SD = 2.44). The distribution of scores for the final sample on the reading comprehension subtest is shown in Table I. There were no significant differences between the two final matched groups in terms of socioeconomic status (chi-square = 7.01; dJ. = 5), or in terms of the level of education attained by the child's mother (chi-square=4.94; dJ. =5), and the child's father (chi-square = 3.47; d.f. =5).

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Procedure One parent of each child completed a questionnaire on the child's personal history and any familial history of learning difficulties, immune disorders and autoimmune disorders (see Table II and Table III for list). The Medical History Questionnaire and scoring protocol from Burke, Yeo, Vranes et al. (1988) were adapted for this section of the questionnaire. For each item, 1 point was awarded if the child was afflicted, 0.50 points for each member of the child's immediate family (parents and/or siblings) who was afflicted, and 0.25 points for each second degree blood relative afflicted (aunts, uncles, cousins, and/or grandparents). Second degree relatives who had married into the family and were not biologically related to the child in the study were not included. An overall familial prevalence was obtained by adding the points awarded for each item. Overall familial prevalences were used for two reasons: 1) The children themselves were too young to have developed many of the immunologic disorders, and 2) The overall familial prevalences permitted us to evaluate the variables as a case of pleiotropism. Note that the categorization of some of the medical disorders is controversial. For instance, possibly some of the bowel diseases and certainly multiple sclerosis and myasthenia gravis would now be categorized as autoimmune diseases. We employed the same categorization as Burke et al. (1988), from which our scoring system was also adopted. The child's handedness was determined by an abbreviated version of Crovitz and Zener's (1962) scale, that featured five items: printing, throwing a ball, drawing a picture, holding scissors, and unscrewing the lid of a jar. For each item, zero points were awarded for a response of "always right", 1 point for "usually right", 2 points for "either hand", 3 points for "usually left", and 4 points for "always left". Thus, the child's overall handedness score could range from zero points indicating strong righthandedness to 20 points indicating strong nonrighthandedness. Questions dealing with the handedness of each family member were also included. Following Burke et al. (1988), 0.50 points were awarded for each parent and/or sibling who was nonrigththanded, 0.25 points for each relative of the child who was nonrighthanded. One point was awarded if the child was reported to exhibit nonrighthandedness, which was defined as a score of 9 or above on the handedness scale. A cutoff of 9 was selected because it resulted in defining 11 % of the children in the initial public school sample as being nonrighthanded, which is consistent with most published data (Porac and Coren, 1981). An overall index of familial nonrighthandedness was generated by adding together the points awarded for nonrighthandedness in the child, parents, siblings and relatives. Once again, only biological relatives were included. The lO-item Abbreviated Symptom Questionnaire (ASQ; Conners, 1973) was also included in the questionnaire, as an indicator of children who might have some of the characteristics of Attention Deficit Hyperactivity Disorder (ADHD). The ASQ has been established to be a valid and reliable measure for evaluating symptoms of ADHD (Conners, 1973; Rosenberg, Wilson and Legenhausen, 1989), although reliance on it for the diagnosis of ADHD has been criticized by many (e.g., Ullman, Sleator and Sprague, 1985), particularly with respect to the way researchers have used cutoff scores to define hyperactive samples. Thus, we made no attempt to use a cutoff score, but instead, we used the ASQ score to identify the degree of parental concerns associated with ADHD.

Controlling for Biases In retrospe<;tive self-report data for children with an identified problem (e.g., a learning disability), reporting or recall bias can influence the data. To control for recall bias, a second control group was used, consisting of children suffering from disordel~' thought to be unrelated to the dependent variables under investigation: chronic eye problems such as strabismus, or a lazy eye. The 35 children in the public school group whose parents reported they suffered from a chronic eye problem were compared to 35 age- and sex-matched children from the initial public school group using a multivariate analysis of variance (MANOVA). This analysis was conducted prior to selecting the samples and matching the remaining subjects on the basis of age and sex. The dependent variables for the MANOV A were the child's handedness, the overall familial nonrighthandedness index, as well as ov-

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TABLE II

Prevalence Rates of Learning Difficulties in the Child and the Rest of the Child's Family Proportion of group affected (%) Reading problem group

Control group

Variable

Child

Rest of family

Child

Rest of family

Stuttering Other speech disorders "Hyperactivity "Attention problems Reading problems Other learning difficulties

9.4 26.4 18.9 37.7 50.9 49.0

14.2 20.4 24.5 22.4 51.0 14.9

4.0 7.9 4.0 6.0 0.0 4.0

14.0 16.0 6.0 10.0 12.0 8.0

a

Significant predictor of presence/absence of reading problems in the child from the logistic regression results.

TABLE III

Prevalence Rates of Immunologic Dysfunction, Handedness and Control Variables Proportion of group affected (%) Variable "Overall familial prevalence of immune disorders Allergies Hay fever Asthma Eczema Hives Psoriasis Celiac disease aCrohn's disease Inflamm. bowel disease 'Under/overactive thyroid Migraine headache Multiple sclerosis Myasthenia gravis "Overall familial prevalence of autoimmune disorders Vitiligo 'Ulcerative colitis Hashimoto's thyroiditis Pernicious anaemia IDDM Rheumatoid arthritis Lupus Handedness Child's handedness cNonrighthanded mother Nonrighthanded father Nonrighthanded brothers Nonrighthanded sisters Familial handedness index Overall familial prevalence of control variables High blood pressure Heart disease Other chronic disorders

Reading problem group

Control group

72.7 47.3 49.0 45.4 29.1 9.1 1.8 9.1 5.4 27.3 49.1 9.1 0

67.2 56.4 41.8 40.0 23.6 20.0 1.8 0 3.6 14.6 30.9 5.5 0

3.6 10.9 0 3.6 21.8 14.6 1.8

1.8 0 3.6 7.3 14.5 20.0 1.8

18.2b 20.0 10.9 12.7 5.5 78.7 b

11.3b 7.3 7.3 5.4 12.7 66.7 b

41.8 32.7 9.1

49.0 50.9 16.3

Significant multivariate/univariate group differences on MANOVA results. Includes any handedness score ~9, indicating nonrighthandedness. , Significant univariate group difference. a

b

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erall indices for immune disorders and autoimmune disorders. None of the effects was significant. Because no differences were found between the children with a chronic eye problem and the other control children, it was concluded that recall bias was not a threat to the study, and the strabismus controls were combined with the rest of the nornlal controls, so that a single control group remained as a source for the matched sample. All subsequent analyses reported herein employed the selected matched samples of 55 children per group. The overall familial prevalences of heart disease, high blood pressure and miscellaneous other chronic disorders were used as dependent variables for another MANOV A. None of the effects was significant for this analysis, which used the selected matched sample of 55 children per group. These results were expected, since these variables are not related to immune or autoimmune diseases. The absence of differences between the reading problem and the control groups on these control variables strengthens our confidence that recall bias was not a threat to this study. It should also be noted that even though family size was not taken into account in our scoring protocol from Burke et a1. (1988), family size did not appear to be a threat to the internal validity of this study. Our indicator of family size was the number of brothers and sisters the child had, and no significant difference emerged between the reading problem and control groups on these variables. This finding is consistent with Burke et a1. (1988), who reported that partialling out family size did not affect the magnitude of the correlation between immune disorders and learning difficulties.

RESULTS

All the data were first analyzed by MANOV As. Because the weighting system of Burke et al. (1988) is not a standardized system and may not be intuitively logical to all readers, the learning-related variables (which had been stored in a way accessible for the determination of affected individuals per family) were reanalyzed with a logistic regression. There was no meaningful difference between the MANOV A results and the results of the logistic regression. In the following discussion, the learning-related variables are reported with the logistic regression, and the others with MANOV As to provide the reader with a broader perspective. For each MANOVA conducted, the main effects for group and for sex, and the sex by group interaction were examined. Only those results that reach significance beyond the .05 level are reported. Overall Familial Prevaz'ences of Learning Difficulties

A logistic regression was conducted using the overall familial prevalences of the six learning-related problems listed in Table II as the independent variables. The dependent variable was the presence or absence of reading problems in the child"which was the variable that defined our two groups of children (reading problem group and control group). The overall familial prevalences of hyperacti vity (R = .12) and attention problems (R = .14) were significant predictors of the presence/absence of reading problems in the child (X 2 = 14.94, d.f. = 2, p<.OOl). Higher overall familial prevalences of hyperactivity and attention problems were related to the presence of reading problems in the child. In total, 72.6% of children could be correctly classified as having reading problems (belonging to the reading problem group), or as not having any reading

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problems (belonging to the control group). The reading problem and control groups were also compared on their ASQ scores, and differed significantly (t=4.1O; d.f.= 108; p<.OOI). As expected, the reading problem group mean (mean=9.15, SD = 6 2. 3) was higher than the control mean (mean=5.07, SD=3.94). Overall Familial Prevalences of Immune Disorders and Autoimmune Disorders

The overall familial prevalences of 12 immune disorders were used as the dependent variables for another MANOV A. The thirteenth, myasthenia gravis, was excluded because it was zero for both groups. The overall effect for group was significant (Wilks' lambda F=2.13; d.f.=12, 84; p< .05). The univariate F tests revealed that the reading problem group and their families had significantly more Crohn's disease (F=9.21; d.f.= 1,95; p< .004) and underactive/ overactive thyroid gland (F = 4.36; d.f. = 1, 95; p<.05). The overall familial prevalences of the seven autoimmune disorders were used as the dependent variables for another MANOV A. The main effect for group was significant (Wilks' lambda F = 2.38; d.f. = 7, 89; p<.05). Results indicated that there was a significant group effect for ulcerative colitis (F = 10.61; d.f. = 1 , 95; p<.OO7), which was elevated for the reading problem group (Table III).

As mentioned above, the categorization of some of the diseases is contentious, and certainly multiple sclerosis (MS) and myasthenia gravis are now considered to be autoimmune disorders. The MANOV As were repeated with MS in the autoimmune category (and myasthenia gravis still excluded because of its zero prevalence) to ensure that following the Burke et al. (1988) system had not led to a Type 1 error: the results of the analysis were the same. Handedness

Another MANOV A was conducted using the handedness of the child, mother, father, brothers and sisters, as well as the overall index of familial nonrighthandedness as dependent variables. None of the multivariate effects was significant for this analysis. Familiallefthandedness has been defined as the presence of at least one lefthanded family member, in addition to the subject (Searleman, Porac and Coren, 1989), whereas pathological lefthandedness refers to a situation where the subject is the only lefthander in the family. Because the possibility remained that pathological lefthandedness was a potential confound for the present investigation, all of the above-mentioned analyses were conducted again on two entirely different comparison groups. It was not possible to evaluate pathological lefthandedness in the sample of 110 children because the expected prevalence would be so low. Therefore, we went back to the original sample of 468 children, employing our broad definition of nonrighthandedness (any non-zero score). One group contained 71 children (43 males and 28 females) who were pathological lefthanders, and the other group contained 148 children (86 males and

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62 females) who were familial lefthanders. No significant group differences emerged on any of these analyses. ASQ Scores To explore the possibility that the subgroup of children exhibiting some of the characteristics of ADHD and their families would be distinct, separate stepwise multiple regression analyses were conducted pooling the reading problem group and the control group. Instead of using cutoffs, the raw scores on the ASQ acted as the dependent variable for each multiple regression, and the child's age and sex were used as two of the various predictor variables for each regression. The first multiple regression conducted incorporated the overall familial prevalences of stuttering, other speech disorders, hyperactivity, attention problems, reading problems and other learning difficulties as predictor variables. Elevated overall familial prevalences of hyperactivity and of reading problems were predictive of elevations in the child's score on the ASQ (R 2 = .26; F= 17.51; dJ. = 2, 99; p<.OOOl). When the overall familial prevalences of the 12 immune disorders acted as predictor variables in another multiple regression, the prevalence rates of Crohn's disease and of migraine headache were found to account for a significant proportion of the variance in ASQ scores (R2 = .20, F = 12.36; dJ. = 2, 96; p<.OOl). Elevated overall familial prevalences of Crohn's disease and of migraine headache were both associated with the child having higher scores on the ASQ. In contrast, for the multiple regression using the overall familial prevalences of the seven autoimmune disorders, none of the variables reached the entry criterion (p to enter = .05). Thus, none of these variables appeared to be associated with scores on the ASQ. Another multiple regression was conducted using the child's handedness, and nonrighthandedness in the child's mother, father, brothers, sisters and relatives as predictor variables. Only nonrighthandedness in the child's mother was predictive of elevated scores on the ASQ Hyperactivity Index (R2 =.15, F=9.99; d.f. = 1, 94; p<.OOl). DISCUSSION

The results link learning difficulties with some immune/autoimmune disorders. They do not, however, provide support for an association between learning problems and nonrighthandedness. It had been predicted that children undergoing remediation for reading problems and their families would have significantly higher rates of (a) learning problems, (b) immune and autoimmune disorders, and (c) nonrighthandedness. The elevated prevalence of learning difficulties in the children with reading problems and their families probably reflects the heritability of some forms of reading difficulties and hyperactivity (Biederman, Faraone, Keenan et aI., 1990; Goodman, 1989; Pennington and Smith, 1988; Regehr and Kaplan, 1988). With respect to the second category of variables, there was also evidence

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for an elevation in the prevalences of immune and autoimmune disorders among the reading problem group and their families, namely ulcerative colitis, Crohn' s disease, and underactive or overactive thyroid gland. Taken together, these findings support a link between reading problems and immune/autoimmune disorders, in particular ones that involve the gastrointestinal tract and the thyroid gland. This finding is consistent with our previous work (Crawford et aI., 1992), where we found that both mothers and fathers with immunologic diseases tended to be more likely to have children with learning problems. It is important to note that there was no relationship between the prevalences of the various diseases and whether or not significant group differences emerged. This implies that our sample size of 110 was adequate to avoid a Type 2 error. In terms of the third category of variables, nonrighthandedness, no multivariate group differences were evident in the analysis of the matched samples. When we reanalysed the data using a broad definition of nonrighthandedness in the child, the results also showed no significant group differences. These findings led us to conclude that our data provide no support for the importance of nonrighthandedness as a correlate of learning problems. The present findings are consistent with other reports of developmental learning difficulties being associated with immune/autoimmune disorders specifically involving the two organ systems for which our data were strongest: the gastrointestinal tract and the thyroid gland. For example, Pennington et ai. (1987) found that dyslexics and their families had significantly more autoimmune diseases, such as Hashimoto's thyroiditis, ulcerative colitis, and rheumatoid arthritis, as compared to non-dyslexics and their families. Coleman (1976) reported that autistic children more commonly had celiac disease, whereas their parents more commonly had autoimmune thyroid disease. Humphreys, Kaufmann and Galaburda (1990) reported on a dyslexic patient whose brain at autopsy revealed neuronal dysgenesis; the authors commented on the patient's ulcerative colitis. Behan and Geschwind (1985) found that, in addition to dyslexic children having an elevated frequency of immune disorders, the children's mothers also showed some immunologic dysfunction, with the levels of antithyroglobulin antibodies being nearly three times as high as the levels of agematched control mothers. Urion (1988) reported that a subgroup of families with language-disabled boys had significantly more autoimmune disorders such as Hashimoto's thyroiditis, Crohn's disease, systemic lupus erythematosus, and rheumatoid arthritis, than did the families of control children (though this study has been criticized for its defective methodology; cf. Bishop, 1990). The gastrointestinal tract and thyroid gland begin to develop in the fourth and fifth weeks of gestation, as does the thymus gland (Pansky, 1987). Geschwind and Galaburda's (1985a, 1985b, 1985c) theory of cerebral lateralization posited a central role for testosterone, which was thought to inihibit the thymus gland. Conceivably then, hormonal interference with the developing thymus gland could concurrently affect the developing thyroid gland and gastrointestinal tract, potentially resulting in an increased susceptibility to immune disorders involving these two systems, as found in the present study. In contrast, relationships between immune disorders and nonrighthandedness were quite weak. Indeed, the evidence on this relationship is quite contradictory,

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with positive (Kinsboume, 1986; Searleman and Fugagli, 1987; Smith, 1987) as well as negative outcomes (Bishop, 1990; Bryden, McManus and Steenhuis, 1991; Hugdahl et aI., 1990; Pennington et aI., 1987; Van Strien, Bouma and Bakker, 1987). An additional question addressed was whether there would be an elevation of learning problems, immune disorders and nonrighthandedness in subjects potentially suffering from ADHD (as indicated by the child's score on the ASQ) and in their families. As expected, high ASQ scores were associated with elevated overall familial prevalences of hyperactivity and reading difficulties. Interestingly, elevated ASQ scores were also associated with elevated overall familial prevalences of some immune disorders (migraine headache and Crohn's disease), and with nonrighthandedness in the child's mother. The association between ASQ scores and immune disorders complements other research suggesting elevated allergic problems in children with ADHD (Behan and Geschwind, 1985; Hartsough and Lambert, 1985; Kaplan et aI., 1987), although we found no specific relationships with allergies or hayfever. This study relied on self-report questionnaires. They have the advantage of reaching a large sample size in a short time. Self-report questionnaires have been criticized as being unreliable (Satz and Soper, 1986); however, Rugel (1978) claimed that parental report of family histories of reading disorders was reliable and of diagnostic value. Recall bias did not compromise the study, as demonstrated in two ways: the absence of differences between children with chronic eye disorders and normal control children, and the lack of group differences on the control diseases (e.g., high blood pressure). There has been very little media coverage on Geschwind and Galaburda's theory in this locale, and our cover letter for the questionnaires did not mention the theory, so as not to bias the participants. It is possible that parents who completed questionnaires had a particular interest in handedness and immunologic diseases, and this could have inflated the prevalence rates we obtained. This possibility does not compromise our results, for this inflation would apply equally to both groups, and since obtaining population prevalences was not our intention. Parents may not be aware of some immune and autoimmune disorders. For instance, some parents admitted not knowing if anyone in the family suffered from vitiligo, because they did not know what this disorder was. Rheumatoid arthritis could have been confused with non-autoimmune osteoarthritis, masking any underlying group differences. But including an explanation of the various disorders would have lengthened the questionnaire considerably, which could in tum have lowered the overall response rate. In any case, parents' lack of knowledge would tend to mitigate significant findings, not generate them. It should also be mentioned that many of the adult-onset disorders may not yet have developed in the parents of the children in this study, and certainly not in the children themselves. Thus, there may be a conservative bias in the data, in that many of the prevalence rates may be underestimates of eventual disease rates in these individuals. In conclusion, this study has found some evidence in support of an association between the overall familial prevalence of learning difficulties and the overall familial prevalence of certain immune/autoimmune disorders, particularly those involving the thyroid gland and the gastrointestinal tract.

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ABSTRACT

This study used questionnaire data to examine immune disorders and nonrighthandedness in the families of children enrolled in a learning disabilities school and children attending regular classrooms in public schools. Groups were organized according to their performance on a standardized test of reading comprehension to avoid overlap. In total, 468 questionnaires were returned, from which we were able to derive a final sample of carefully matched subjects: 55 subjects undergoing remediation for reading problems and 55 age- and sexmatched control subjects. The results indicated that children with reading problems and their families more frequently suffered from some immune and autoimmune disorders, particularly those involving the gastrointestinal tract and the thyroid gland. In addition, symptoms of attention deficit hyperactivity disorder were associated with Crohn's disease and migraine headache in the families. There was no evidence of an elevated prevalence of nonrighthandedness in the children with reading problems and their families. Acknowledgements. We thank the Alberta Children's Hospital Foundation for funding support, and Dr. Tak Fung for his helpful comments. REFERENCES BAKAN, P. On the relationship between handedness and hyperkinesis. Canadian Psychology, 29: 32, 1988. BEHAN, P.O., and GESCHWIND, N. Dyslexia, congenital anomalies, and immune disorders: The role of the fetal environment. Annals of the New York Academy of Sciences, 457: 13-18, 1985. BIEDERMAN, 1., FARAONE, S.V., KEENAN, K., KNEE, D., and TSUANG, M.T. Family-genetic and psychosocial risk factors in DSM-III Attention Deficit Disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 29: 526-533, 1990. BISHOP, D.V.M. On the futility of using familial sinistrality to subclassify handedness group. Cortex, 26: 153-155, 1990. BLISHEN, B.R., and McRoBERTS, H.A. A revised socioeconomic index for occupations in Canada. Canadian Review of Sociology and Anthropology, 13: 71-79, 1976. BORECKI, LB., RAO, D.C., LALOUEL, 1.M., MCGUE, M., and GERRARD, l.W. Demonstration of a common major gene with pleiotropic effects on immunoglobulin E levels and allergy. Genetic Epidemiology, 2: 327-338, 1985. BRYDEN, M.P., McMANUS, I.C., and STEENHUIS, R.E. Handedness is not related to self-reported disease incidence. Cortex, 27: 605-611, 1991. BURKE, H.L., YEO, R.A., VRANES, L., GARRY, P.J., and GOODWIN, 1.S. Handedness, developmental disorders, and in vivo and in vitro measurements of immune responses. Developmental Neuropsychology, 4: 103-115, 1988. COLEMAN, M. (Ed.) The Autistic Syndromes. New York: Elsevier North Holland, 1976. CONNERS, C.K. Rating scale for use in drug studies with children. Psychopharmacology Bulletin, 9: 24-29, 1973. CRAWFORD, S.G., KAPLAN, B.K., and KINSBOURNE, M. The effects of parental immunoreactivity of pregnancy, birth, and cognitive development: Maternal immune attack on the fetus? Cortex, 28: 483-491, 1992. CROVITZ, H.F., and ZENER, K. A group-test for assessing hand- and eye-dominance. American Journal of Psychology, 75: 271-276, 1962. GESCHWIND, N. Biological associations of lefthandedness. Annals of Dyslexia, 33: 29-40, 1983. GESCHWIND, N., and BEHAN, P. Left-handedness: Association with immune disease, migraine, and developmental learning disorder. Proceedings of the National Academy of Sciences of the United States of America, 79: 5097-5100, 1982. GESCHWIND, N., and BEHAN, P. Laterality, hormones and immunity. In N. Geschwind and A.M. Galaburda (Eds.), Cerebral Dominance: The Biological Foundations. Cambridge, MA; Harvard University Press, 1984. GESCHWIND, N., and GALABURDA, A.M. Cerebral lateralization: Biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. Archives of Neurology, 42: 428-459, 1985a. GESCHWIND, N., and GALABURDA, A.M. Cerebral lateralization: Bliological mechanisms, associations, and pathology: II. A hypothesis and a program for research. Archives of Neurology, 42: 521-552, 1985b. GESCHWIND, N., and GALABURDA, A.M. Cerebrallateralization: Biological mechanisms, associations,

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