Hormonal influence on language development in physically advanced children

BRAIN

AND

LANGUAGE

38, 410-423 (1990)

Hormonal Influence on Language Development in Physically Advanced Children PEGGY MCCARDLE Departments of Pediatrics,

Walter Reed Army Medical Center and Uniformed Services University of the Health Sciences AND BRUCE

E.

WILSON

Department of Pediatrics and Human Development, Michigan State University Sex differences in language performance have long been noted, with females more verbal and males superior in visual-spatial tasks. Two theories seek to explain the differences in language function. Waber (1976, Science, 193, 572574) suggests that these sex differenes are secondary to differences in bilateral language function related to the faster maturation rate in girls. Geschwind and Galaburda (1985, Archives of Neurology, 42,(I), 428-459; (II), 521-552; (III), 634-654) on the other hand posit an intimate interrelationship of sex hormones, the immune system, and laterality as influencing the ultimate asymmetry of the nervous system, which in turn could account for such differences. In the present study, language function was examined in patients with accelerated maturation caused by conditions with sex hormone elevation (idiopathic precocious puberty and congenital adrenal hyperplasia). The degree of maturational advancement was similar between the two groups. However, significant language performance differences were noted between androgen- vs. estrogen-exposed patients. regardless of genetic sex or diagnosis of the patient, indicating a hormonal effect on language development over time. These data support Geschwind and Galaburda’s multifactorial theory for the origin of sex differences in language performance, and argue against Waber’s maturational hypothesis. o IWO Academic Press. Inc.

INTRODUCTION Males and females have long been noted to possess differences in language abilities (Kelly, 1981; Maccoby & Jacklin, 1974; Staz & Zaide, Reprint requests should be addressed to Peggy McCardle. Military Pediatric HIV Program, Bldg. 1, Ward 11, Walter Reed Army Medical Center, Washingon, DC 20307-5001. The views expressed herein are those of the authors, and do not represent the views of the United States Army or the Department of Defense. 410 0093-934x/90 $3.00 Copyright All rights

0 1990 by Academic Press, Inc. of reproduction in any form reserved.

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1983; Waber, 1976, 1977), with females most often labeled as “more verbal” and facile in language-related skills, while the incidence of language difficulties is much higher in males (Kelly, 1981; Staz & Zaide, 1983). Some theories to account for this have been based on observations that language function is less completely lateralized in girls (Kelly, 1981; Staz & Zaide, 1983; Waber, 1977). Although current understanding of the neural handling of language related tasks is rapidly expanding, cerebral asymmetry has remained a prominent component. As this asymmetry and its relation to language has become well-documented, evidence that the left temporal planum (the area to which much linguistic function is attributed) is enlarged, as compared to the homologous area in the right hemisphere, has had a prominent role (Geschwind & Levitsky, 1968; Galaburda, Sanides, & Geschwind, 1978). In adult women, the temporal planum shows increased development on the right side compared to that of males (Kelly, 1981; Wada, Clarke, & Hamm, 1975; Witelson & Pallie, 1973). This difference was not found in infancy. The apparent change in structure with age is consistent with the proposals by Lenneberg (1966, 1967) and Zangwill (1960) that a critical period of neurologic development responsible for the observed differences in language development occurs between the ages of 2 and 12 years. The effects of differential rates of maturation might well affect neurolinguistic development during this critical period. Waber (1976, 1977) has shown less lateralization of several brain functions in individuals with relatively rapid maturation. Several other studies have shown specific language difficulties associated with conditions which include slowed physical maturation, often evidenced by bone age delays (Garvey & Mutton, 1973; Glorieux, Dussault, Letarte, Guyda, & Morisette, 1985; Netley, 1984; Netley & Rovet, 1982; Schlager, Newman, Dunn, Crichton, & Schulzer, 1979; Sparks, 1984). Unfortunately, this issue is clouded by the fact that many of these conditions affect multiple physiologic systems and the effect on cognitive development may be secondary to these other anomalies. One theory regarding sex differences in language (Staz & Zaide, 1983; Waber, 1976) is that the observed differences arise from the relatively faster rate of physical development seen in girls compared to boys. Within Waber’s theory, rapid maturation leads to increased bilateral language representation in the brain. The slower maturation rate in males is thought to allow for increased lateralization of language; available cortical areas of the nondominant hemisphere are then dedicated to visual-spatial function, an area in which males usually demonstrate superior performance. An alternate theory is presented in Geschwind and Galaburda’s (1985) three-article series on cerebal lateralization. This theory posits in considerable detail an extremely complex interrelationship of sex hormones, the immmune system, and laterality. This hypothesis is intended to ac-

412

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count for the facts that (1) left-handedness is found more frequently in males than in females; (2) developmental disorders of speech/language, cognition, and emotion are more frequent among males; (3) males have better visual-spatial abilities while females have better language skills; (4) left-handers and learning-disabled persons often have superior right hemisphere functions; (5) non-right-handedness is more frequent in children with developmental disabilities; (6) immune disorders and other diseases are more common in non-right-handers. Key among these mechanisms are sex hormones, particularly their intrauterine (prenatal) influence on the developing nervous system. The perinatal hormonal milieu with androgen exposure as the main variable has also been entertained as an explanation (Kelly, 1976; Staz & Zaide, 1983), although the critical period time frame as set by Lenneberg and Zangwill is not consistent with a predominant perinatal influence. Because of the inconsistencies with observed data, these theories have fallen from favor. Geschwind and Galaburda proposed that the same processes which modify structural brain asymmetries also modify other systems, some of which are directly observed through functions such as motor skills (handedness), language difficulties (especially dyslexia), and developmental disorders in general. Geschwind and Galaburda maintain that there is a multifactorial source for laterality, with the most powerful nongenetic factors being variations in the intrauterine chemical environment and to a lesser extent, neurochemical effects in infancy and early childhood. This study set out to investigate Waber’s (1976) maturation hypothesis in children with either of two conditions which increase their rate of maturation, those diagnosed as having idiopathic precocious puberty (IPP) and those with congenital adrenal hyperplasia (CAH). If Waber’s theory were correct, language function should be similar in these two groups of early-maturing children. However, since the differences in language function seem to appear in late childhood or early adolescence, it was hypothesized that, in contrast to Waber’s theory, sex hormones might play a role. That is, when maturation rate is controlled, children exposed to androgens should perform differently on tests of language function than children exposed to estrogen. Soon after this study was initiated, Geschwind and Galaburda’s (1985) review article was published, offering a theoretic framework highly compatible with this hypothesis. Precocious puberty is defined as the onset of pubertal signs before the age of 8 years in girls and before the age of 9 in boys. Terming it “idiopathic precocious puberty” implies two things: first, that there is activation of the same hypothalamic-pituitary-gonadal axis which governs normal puberty, and second, that there is no evidence of pathology causing the precocious puberty. Thus it might be described as being “the right thing at the wrong time.” Activation of the hypothalamic-pituitary-

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413

gonadal axis is demonstrated by elevated levels of gonadal hormones (either estrogen or testosterone) and by elevation of gonadotropins (hormones released by the pituitary to stimulate the gonads) to pubertal levels. The activation of this axis results in progressive pubertal development, generally paralleling normal puberty, but with a more variable rate of progression. Idiopathic precocious puberty is much more frequently seen in girls than in boys. Congenital adrenal hyprplasia refers to a group of enzyme defects involving the synthetic pathway of the adrenal gland, illustrated diagrammatically in Fig. 1. The majority of these conditions result in an inefficiency in the production of cortisol by the adrenal gland. Since cortisol is the major hormone which results in feedback to the pituitary, deficient cortisol production results in increased adrenocorticotropin (ACTH) stimulation to the adrenal gland. This causes a buildup of precursors prior to the blocks in synthesis created by the enzyme deficiency. In the two most common forms of CAH. 21 hydroxylase deficiency and 11 hydroxylase deficiency (which together represent 95% of the cases of CAH), these extra amounts of precursor flow down the remaining open pathways, resulting in increased amounts of adrenal androgens (male hormones). Exposure to these hormones results in virilization with the onset of penile or clitoral enlargement, the development of pubic and axillary hair, and increased bony growth and maturation. SUBJECTS Thirty-two children between 5 and 12 years of age who were diagnosed with CAH or IPP participated in the study. To be included in the IPP Normal Adrenal Gland *

Cholesterol

I

Negative

Feedback

CongenitalAdrenalHyperplasia

tr-iJ+1 Pituitary I ACTH i 1

I Androgens corljsol

NegativeFeedback FIG.

1.

Adrenal

biosynthetic

pathways.

414

MCCARDLE

AND WILSON

group, the child had to have documented activation of the hypothalamicpituitary-gonadal axis and could not have evidence of other neurologic dysfunction. The children with CAH each had documented deficiency of either 21 or 11 hydroxylase, with elevated adrenal androgens. None of the children with 21 hydroxylase deficiency were salt-losers. There was an even distribution of patients between the various diagnostic and hormone exposure groups (see Table 1). Girls with CAH provided a crossover between genetic sex and hormonal exposure. Boys with IPP provided a crossover between diagnosis and hormonal exposure. Two boys with CAH had developed sufficient advancement of their bone age so as to enter puberty markedly early; these two patients were considered to have both diagnoses, and their test results were used only in the comparisons of androgen- versus estrogen-exposed groups. METHODS Diagnostic information included documentation of estrogen or androgen elevation and bone age, as determined by the coordinated reading of radiographs by a pediatric radiologist and a pediatric endocrinologist. A maturation index (bone age to chronologic age ratio) was calculated for each patient. Socioeconomic status was based on sponsor’s military rank. For language data, the Clinical Evaluation of Language Functions (Semel-Mintz & Wiig, 1982) was administered to each child. This test battery is subdivided into language processing and production sections, and consists of I I subtests. The CELF is an instrument designed to investigate the nature of language disorders associated with learning disabilities and examines semantics, syntax, and memory through a variety of language tasks. The various subtests are briefly described below. There are six processing subtests. Subtest 1, “Processing Word and Sentence Structure,” examines “referential sentence interpretation with minimal grammatical contrasts in the foils” (Sabers & Wiig, 1983). The second subtest, “Processing Word Classes,” tests the strength of word associations among selected concepts. “Processing Linguistic Concepts” (subtest 3) and “Processing Oral Directions” (subtest 5) both involve following orally presented directions. “Linguistic Concepts” probes the child’s knowledge of concepts such as inclusion, exclusion, cause, condition, and time used in the creation of complex sentences. “Oral Directions” offers a controlled investigation of variables which can influence a child’s ability to recall and perform these directions; these are one-, two-, and three-level commands, number of modifiers, and serial vs. left-right orientation. Subtest TABLE BACKGROUND

N BA/CA ratio CA Sponsor rank

1 DATA

Estrogen

Androgen

16 1.28 f 0.06 93.6 f 4.0 7.3 ” 0.6

16 1.43 k 0.11 103.4 2 5.8 9.3 2 1.0

T

P

1.337 - 1so3 1.684

.1308 ,076s <.lO

Note. BA represents Bone Age in months; CA represents Chronologic Age in months. Sponsor Rank is a numeric representation of the sponsor’s military rank with enlisted ranks as 1 through 9 and officer ranks as 10 through 16.

HORMONAL

INFLUENCE

ON LANGUAGE

DEVELOPMENT

415

4, “Processing Relationships and Ambiguities,” assesses “the interpretation of sentences with semantic relationships and figurative expressions, which require logical processing and transformation from the literal to the abstract, figurative levels of interpretation” (Sabers & Wiig, 1983). The last of the processing subtests. “Spoken Paragraphs,” “provide(s) a format for testing the recall of semantic details, such as names, attributes, location, price, temperature, and dates” (Sabers & Wiig. 1983). The production subtests investigate automatic-sequential recall (“Producing Word Series,” subtest 7; naming days of the week or months of the year. depending on age). dysnomia (subtest 8, “Producing Names on Confrontation”), and verbal fluency (subtest 9, “Producing Word Associations”), which can be expected to be depressed by dysnomia. Subtest IO, “Producing Model Sentences,” examines productive control of sentence structure during verbatim repetition of sentences varying from semantically or syntactically appropriate to anomalous or ungrammatical. Subtest I I. “Producing Formulated Sentences,” is a measure of syntactic ability controlled by word selections which semantically and syntactically constrain the form of the sentence produced. The authors of the CELF categorize the subtests linguistically as pertaining to semantics (processing subtests 2-6, production subtests 7, 9, I I). syntax (processing I, 4, and production IO, I I), and memory recall and retrieval (processing 4-6 and all production subtests). From the CELF testing, percentile scores were obtained for each subtest. for total language processing, and for total language production. For the present study, a comparison or difference score for language processing vs. production was calculated. Group mean scores for the primary variable studied, the comparison score, were compared using the Student t test. One way analysis of variance was used to compare the group means on each of the subtests, and the total processing and production scores. Linear regression and multiple correlation analysis were performed to ascertain the relationship between the various subtests, and between hormonal factors (such as degree of hormonal elevation, duration of exposure, and degree of bone age advancement) and the observed scores. This study included no control group. The test instrument used for language testing had been standardized on a large group of normal children (1378 students, with complete test data on 998). This normative sample was balanced for race, geographic region, socioeconomic status, and sex (Sabers & Wiig, 1983). The multivariate nature of the current study allows isolation of the independent variables. Further, perinatal hormonal exposure and some variability in maturation rate are universal factors seen in the general population.

RESULTS

There were no significant differences between diagnostic groups or hormonal exposure groups for rate of physical maturation as measured by the maturation index. Similarly, socioeconomic status and chronologic age were not significantly different for any groups. When language scoring categories were compared for diagnostic groups, no significant differences were found (Table 2). However, when the data were analyzed by hormonal exposure, the androgen-exposed group had significantly lower comparison scores (with opposite direction of difference) than the estrogen-exposed group (see Fig. 2). Production scores, both for subtests and for total production, were more different between groups than were processing scores. Thus, the difference in language production ability appears to be the major contributing factor in the difference between the estrogen- and androgenexposed groups. The crossover groups, male patients with precocious

MCCARDLE

416

TABLE 2 TESTING DATA

Subtest

AND WILSON

Estrogen

-

Androgen

T

P

Processing Battery 1. Word and Sentence Structure 2. Word Classes 3. Longuistic Concepts 4. Relationships and Ambiguities 5. Oral Directions 6. Spoken Paragraphs Overall Processing 7. Word Series 8. Confrontation Naming a. Accuracy b. Time 9. Word Association 10. Model Sentences 11, Formulated Sentences Overall Production Comparison Score

52.2 2 5.4 57.5 2 6.2 48.4 k 6.4

53.5 2 6.8 55.6 2 7.4 40.8 k 6.8

0.159 0.198 0.889

NS NS NS

54.7 50.0 71.1 57.8

57.4 38.4 68.8 51.5

iT 7.4 _’ 7.0 ?z 6.0 ” 7.7

0.279 1.278 0.318 0.700

NS <.I5 NS NS

Production Battery 57.8 k 1.3

50.6 t 5.2

1.340

<.I0

55.7 48.5 53.8 53.4 66.5 52.8

49.1 57.3 65.0 54.3 66.1 59.9

2 2 t k 2 +

7.1 7.1 7.1 8.5 6.5 7.9

0.706 0.992 1.272 0.091 0.046 0.750

NS NS <.15 NS NS NS

-8.4

-c 4.0

2.080

<.03

f k + ”

‘k r t t 2

6.3 5.8 6.3 4.8

6.1 5.4 5.3 5.0 5.8 5.7

5.0 r 4.1

Note. Scores are listed as the mean percentile for each group plus or minus 1 standard error of the mean (SEM).

I

lt5.00

I

f-8.38 I

n m

Estrogen Exposed Androgen Exposed P< 0.025

FIG. 2. Comparison score results.

HORMONAL

INFLUENCE

ON LANGUAGE

DEVELOPMENT

417

puberty and females with CAH, tested similarly to the androgen-exposed group as a whole, indicating that diagnosis and genetic sex were not important factors in determining language function. Subtest scoring patterns (Figs. 3 and 4) differed between groups, although individual subtest differences were not statistically significant. In relatively rare conditions resulting in low numbers of subjects, this is not surprising. However, some patterns approaching significance were observed. The estrogen-exposed group performed notably better on “Processing Oral Directions.” They also performed better than the androgen-exposed group on “Processing Linguistic Concepts,” the other direction-following subtest, although the difference is smaller. On a timed subtest, “Producing Word Associations,” the androgen-exposed group performed better than the estrogen-exposed group, although this difference was not significant. Further study will be required to determine whether these differences are real or artifacts of the current small sample size. On the “Confrontation Naming” subtest (8a and 8b, Fig. 4), there are two subcomponents in scoring. Accuracy (8a) and Speed (8b). While the androgen-exposed group scored higher in speed on this task, the estrogen group’s responses were more accurate (Fig. 4). A linear regression analysis showed correlation between the difference in subcomponent score and the comparison score to covary with a p value of
.$ 61.5 z 57 u 52.5 z= 48 43.5 39 34.5 30 1

2

3

4

5

6

TOTAL

EXPOSURE m

Estrogen

&J Androgen

FIG. 3. Processing subtests are I, Word and Sentence Structure; 2, Word Classes; 3, Linguistic Concepts; 4, Relationships and Ambiguities; 5, Oral Directions; and 6, Spoken Paragraphs.

418

MCCARDLE

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70 67 64 <

61

>

58

% 56 B 52 z 49 46 43 40

aa

7

Bb

9

10

11

TOTAL

EXPOSURE I

Estrogen

q

Androgen

FIG. 4. Production subtests are 7, Word Series; 8a, Confrontation Naming-Accuracy; 8b, Confrontation Naming-Time; 9, Word Associations; 10, Model Sentences; and 11, Formulated Sentences.

lationships and Ambiguities,” “Producing Model Sentences,” and “Producing Formulated Sentences,” three of the four subtests probing syntax, as well as five of the seven probing recall and retrieval (“Processing Relationships and Ambiguities,” “Processing Spoken ParaNames on Confrontation: Speed,” “Producing graphs, ” “Producing Word Associations,” and “Producing Model Sentences”). Estrogen-exposed children performed better on semantic-dependent processing tasks. The estrogen group’s mean scores were higher for three of the five processing subtests probing semantics (“Word Classes,” “Linguistic Concepts,” and “Oral Directions”). Of the other processing subtests on which the estrogen-exposed group outperformed the androgenexposed group, it could also be argued that semantic skills were involved, although the test authors do not list these tasks as such. For example, subtest 1, “Processing Word and Sentence Structure,” requires interpreting the meaning of various syntactic distinctions, including pronouns, verb tenses, prepositional phrases, noun phrases and modifier sequences, negation, passives, relative clauses, and embeddings. While the test authors list this as a syntactic subtest, it involves a less automatic syntactic function than producing or repeating a sentence, two of the other syntax subtests. The estrogen group mean was higher for three of the seven subtests indicated by the test authors to probe memory functions. Two of these, “Processing Oral Directions” and “Producing Word Series,” are also listed as semantic, indicating that the estrogen-exposed group’s dominance in semantic tasks may have overshadowed the other tasks examined by these subtests. The third of the memory function subtests, “Confrontation Naming,” is not a semantic subtest according to the test authors; the estrogen-exposed group performed better than the androgenexposed group on accuracy while the androgen-exposed group was better

HORMONALINFLUENCEONLANGUAGEDEVELOPMENT

419

on the speed component. While the androgen-exposed group was generally better on automatic tasks, they did not outperform the estrogenexposed group on the “Word Series” subtest (naming days of the week and months of the year); as with the accuracy aspect of the “Confrontation Naming” task, this task involves retrieval of automatic-sequential, overlearned information which is lexically specific, as opposed to spontaneously generated using an internal syntax. In summary, the estrogen-exposed group appears to have greater strength in semantic-dependent tasks, while the androgen-exposed group performed better on timed tasks, more automatic syntactic functions, and memory-dependent tasks. Both study groups’ mean percentile scores were above the 65th percentile for spoken paragraphs and formulated sentences. While these tests do not appear to involve common lnguistic processes, they may indicate one or more maturation rate-dependent functions unaffected by the other study variables. All other subtest scores cluster around the 50th percentile. Thus we were unable to identify any specific maturation rate-dependent linguistic functions, although they may exist. DISCUSSION

Androgen-exposed children exhibited significant language differences from estrogen-exposed children. Specifically, the androgen-exposed children had significantly lower comparison scores, with opposite direction of difference from the estrogen-exposed group. The comparison score contrasts language processing vs. production ability within the same individual. Thus, patients exposed to estrogens processed language better than they produced it, while androgen-exposed patients produced better than they processed. The unusual pattern of production exceeding processing may represent an educational liability since it may give a falsely high impression of the actual level of comprehension and overall language function. Such an impression is also encouraged by the fact that these children physically appear much older than their chronologic age. Examining subtest performance further supports the finding that androgen-exposed children present themselves verbally in a way that belies their comprehension skills, while estrogen-exposed children are better at comprehending and attend more to the accuracy of the task. Androgenexposed children scored significantly higher for speed in confrontation naming than did the estrogen-exposed group, and significantly lower in accuracy. They also performed better on verbal fluency (the word association subtest which was also the only other timed task). In general, the estrogen-exposed group appears to have greater strength in semanticdependent tasks, while the androgen-exposed group performed better on timed tasks, more automatic syntactic functions, and memory-dependent tasks.

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Linear regression analysis revealed a significant correlation between maturation index and comparison score for the androgen-exposed group (p < 0.011) but not for the estrogen-exposed group. This suggests that androgens are the active compounds, and that exposure to androgens accounts, at least in part, for the differences in language development. Androgens affect the maturation index both by the degree of hormonal elevation (the more hormone present, the faster the bone age advances) and duration of exposure. The maturation index represents the degree of bone age advancement relative to chronologic age, varying inversely with chronologic age in this group. Therefore the younger children in our androgen-exposed group tended to be exposed to higher hormone levels for a shorter period of time, while the older children had lower levels for a longer period of time. The latter group, who had lower maturation index scores, had the more negative comparison scores. Thus duration of exposure appears to be more important than the degree of hormonal elevation in determining the difference between language processing and language production in these patients. There are several possibilities for the mechanism of interaction between hormones and language. Evidence for morphologic sexual dimorphism of the central nervous system was reviewed by Kelly (1981). He cited several studies which evidenced sex steroid effect on the rate of axonal differentiation in multiple different neuronal regional populations, often in dose-dependent fashion. More recently, in reporting the presence of a sexually dimorphic area in the human brain, Swaab and Fliers (1985) reviewed literature documenting the effects of sex steroid manipulation on the sexually dimorphic nuclei in lower animal models. Sex steroids have been shown to influence a number of such nuclei during development, although not in adulthood. Most often, they act to preserve or increase size, although they have been associated with loss of cells in some nuclei (Nordeen, Nordeen, Sengelaub, & Arnold, 1985). These studies document the presence of sexually dimorphic nuclei, and the fact that sex steroids influence their development. Kelly went on to discuss studies which documented regional hormone responsive sexually dimorphic development of spatial discrimination in primates, These studies are of particular interest since visual-spatial function appears to interact with language function in humans. Taken in total, these studies raise the possibility that morphologically sex steroid responsive areas exist in the cerebral cortex. The second possible level of effect is that of the corpus callosum. This large nerve tract represents the most significant source of intrahemispheric neuronal exchange. It has been thought to have both ipsilateral and contralateral effects, with both stimulatory and inhibitory fibers represented to the language areas bilaterally (De Lacoste-Utamsing & Holloway, 1982; Rakic & Yakovlev, 1968; Witelson, 1985). Acallosal indi-

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viduals have been reported to have increased bilateral representation of language suggesting that a loss of inibitory input may be responsible for the bilaterality (Chiarello, 1980; Dennis, 1981, 1977). Also, the corpus callosum may be a sexually dimorphic area, although the studies performed thus far disagree about this point (De Lacoste-Utamsing & Holloway, 1982; Kertesz, Polk, Howell, & Black, 1986; Swaab & Fliers, 1985). In the studies which found a sex difference, there was a narrowing anterior to the splenum which gave a characteristic altered silhouette in females. This could be consistent with a loss of the inhibitory ipsilateral fibers permitting bilateral representation in females. In his recent review of structure-function correlates in the human brain, Gazzaniga (1989) cites evidence for epigenetic influence in the determination of callosal morphology and discusses alteration in language function in individuals with partial disruption of the corpus callosum. These support the concept that the effect of androgen exposure might be at the level of the corpus callosum. Finally, androgens may have no effect on anatomy, either gross or microscopic, but may instead affect the way the neuron in the language area communicates biochemically or electrically across synapses or other junctions (DeVoogd, 1987). Fischette, Biegon, and McEwen (1983) showed differences in neurotransmitter receptor binding in the rat but could not offer causal explanations. Matsumoto, Arnold, Zampighi, and Micevych (1988) demonstrated androgenic regulation of gap junctions in the central nervous system although primarily in motoneurons. In particular, dehydroepiandosterone (DHEA) and its sulfated form (DHEAS) have been shown to modulate the neuronal cell membrane response to neurotransmitters (Regelson, Loria, & Kalimi, 1988). Both DHEA and DHEA-S are elevated in any condition resulting in increased androgen output, but are characteristically more elevated in disorders of adrenal origin such as CAH. Our data indicate that androgens do affect language development, but we do not yet have data regarding the level of their effect. In summary, this study demonstrates evidence of hormonal effect on language function, represented by significant differences between patients with advanced physical maturation caused by androgen exposure compared to a group with a similar degree of maturational advancement caused by estrogens. This difference appears to result from the androgen exposure, and appears more affected by duration of exposure than degree of hormonal elevation. These findings suggest that Waber’s theory regarding the etiology of sex differences in language performance is overly simplistic, and, in turn, support the theoretical framework proposed by Geschwind and Galaburda. We suspect the differences noted between males and females are most likely multifactorial in origin, with hormone exposure playing an important role.

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