Autism is a syndrome that is characterized by the impairment of social interaction skills, verbal and nonverbal communication, and a decreased interest in participating in a variety of activities. In 1943, Kanner, the man who is attributed with the identification of this disease, hypothesized that autism might be a biological disorder as opposed to a psychological one. Numerous studies have been conducted supporting Kanner’s hypothesis. These studies have ranged from examining the effects of rubella to investigating certain purine metabolic disorders as possible etiological agents. Recently, the areas of neuroanatomy, neurochemistry, and genetics have played a crucial role in developing a clearer picture into the etiology of this disease. Upon exploring the biological aspects of autism, the fields of neuroanatomy, neurochemistry, and genetics have offered new insights concerning their association with the onset of this disease.

Neuroanatomy is one of the latest fields involved in uncovering the possible causes of autism. Many past studies conducted in this area found that autistic patients had enlarged lateral ventricles, however, this abnormality didn’t reveal any damage to a specific anatomical site. The most recent studies conducted on the cerebella of autistic patients showed much more dramatic results. In one specific experiment conducted by Dr. Courchesne, the cerebellar lobules of eighteen autistic patients were compared with the lobules of twelve subjects within a normal control group.

The eighteen autistic patients were chosen on the basis that their autistic state was "... not complicated by severe mental retardation, cerebral palsy, epilepsy, genetic abnormality, other neurologic disease, or the use of anti-psychotic medication" (Courchesne, 1349). Dr. Courchesne conducted this experiment by taking magnetic resonance images from all of the subjects and then specifically examining the vermal lobules of the cerebellum. Courchesne directed his focus on the vermal lobules of these subjects based on a previous study he conducted on a non-retarded, autistic individual who displayed severe underdevelopment of vermal lobules VI and VII. In order to compare the differences between the scans, Courchesne made tracings of the scans and superimposed these tracings according to whether the subject was in the normal control or the autistic group. Tracings were only made of vermal lobules I-V and VI-VII, respectively. Tracings of vermal lobules IX and X weren’t taken because the MRI scans didn’t display well-defined boundaries for them.

Upon comparison of the control tracings and the autistic tracings, Courchesne found that "…vermal lobules VI-VII of the patients with autism were found to be significantly smaller than those of the controls…lobules I to V (the anterior vermis) were similar in size in the autistic and normal groups" (1350). Due to the correlation of the underdeveloped vermal lobules VI and VII within the autistic group, Courchesne drew the conclusion hat this anatomical abnormality was related to the disease. Courchesne, through examining the width of the fissures and the overall proportions of the lobules, also concluded that the diminished size of these lobules could be attributed to developmental hypoplasia. This developmental hypoplasia of the neocerebellum could be used to explain the pathological element of autism, namely the significant decrease in cognitive functioning. "...Since it has been suggested that the neocerebellum is involved in the acquisition and execution of skilled cognitive and motor operations, early damage to this area might hinder the normal, smooth acquisition and execution of sensorimotor schema from which human intellectual growth normally proceeds" (1352). Another way in which this underdeveloped neocerebellum could cause cortical malfunctioning is by damaged outputs to various places within the brainstem and thalamus. One of the major outputs from the neocerebellum, via the deep cerebellar nuclei, is to the reticular activating system at all levels throughout the brainstem and midbrain. "Disturbances in the functioning of the reticular activating system were among the first neurobiologic explanations of the cognitive deficits of autism" (Courchesne, 1352). Both of these pathological explanations, associated with the neuroanatomical etiology, support the hypothesis that autism is a result of a defect in biological development as opposed to psychological disorder.

Another etiological aspect that is associated with a possible biological explanation for autism is the field of biochemistry. One particular biochemical model associated with the etiology of this disease is the opioid system. Recently, a number of researchers have proposed that a hyperactivity of the opioid system may be involved with specific behavioral aspects exhibited in autism. "This hypothesis was derived from animal research suggesting that there is an important relationship between brain opioid systems and social attachment in infant animals" (Chamberlain, 779). The study conducted on the infants involved monitoring of the level of distress vocalizations, or crying, that the infants exhibited when they were willfully separated from their mother. Herman and Panksepp found that administrations of low doses of morphine decreased the separation anxiety of infant dogs, guinea pigs, and chickens. Also, when naloxone, a specific opiate antagonist, was administered, the frequency of distress vocalizations increased. Therefore, this study suggests that the lack of socialization behaviors in autism is possibly related to an increased circulation of brain opioids.

In light of this animal study and related research, a recent proposal suggesting the mechanism that may occur within humans was outlined by Dr. Chamberlain. First, he proposed that a hypersecretion of B-endorphin from the hypothalamus resulted in a decreases release of ACTH from the pituitary which, in turn, caused a drop in the plasma concentrations of ACTH and cortisol. This pathway was proposed after consideration of an experiment by Taylor in 1983 where "... systemic administration of B-endorphin [in humans] had been found to produce decreases in ACTH and cortisol plasma concentrations" (Chamberlain, 777). To this date, the role that these hormones play in relation to behavioral control is still unclear, although the release of B-endorphin and ACTH from the pituitary has been seen with acute stress.

In addition, Chamberlain proposed that a second regulatory feedback loop may exist. This second loop involves the pineal gland, where secretion of melatonin and other opioids occur. "This axis includes an inhibitory effect of melatonin on CRH release from the hypothalamus which, in turn, inhibits the secretion of B-endorphin from the pituitary" (Chamberlain, 777). Furthermore, a study conducted by Dr. Lowenstein in 1984 showed that a feedback pathway exists where increased B-endorphin stimulates melatonin secretion. Dr. Chamberlain suggests that a breakdown in the functioning of either of these pathways may account for the psychiatric problems associated with autism. These various hormonal pathways offer possible biochemical etiology of autism.

One of the largest areas of research being conducted in discovering the etiology of autism is in the field of genetics. Current research has uncovered many different genetic abnormalities associated with the development of autism. One particular genetic condition that appears to be linked to the development of autism is the fragile X syndrome. The fragile X syndrome is the result of a constriction or a possible break on the distal, or q, arm of the X chromosome at band Xq28. Since this disease involves the X chromosome, it is more prevalent in males due to the fact that they only possess one X chromosome. "The frequency of the fragile X syndrome in the general population has been reported to be as high as O.9 per 1000 live male births, making it at least the second leading cause of mental retardation due to chromosomal abnormality after Down’s syndrome" (Reiss, 725). This genetic and phenotypic expression of fragile X varies both within and across families and many times, there is no sign of the chromosome in the parents, which leads to the conclusion that it is a new mutation.

The autistic syndrome has been reported to be associated with the fragile X syndrome in a fashion that could not be explained by chance alone. Several studies have been done on this subject to try and determine what genetic factors might be common to both fragile X and autism. There are two prominent autistic behaviors that have been frequently manifested in individuals with fragile X. These two behaviors of gaze avoidance and hand flapping have a higher occurrence among fragile X individuals than other mentally retarded individuals, suggesting a relationship between fragile X and autism. This relationship does not imply that fragile X is the cause of autism, rather this association could be helpful in genetic studies of autism. Autism may have a gene locus near the fragile site on the X chromosome, or the fragile condition might make the child susceptible to autism in the presence of other contributing factors.

The fields of neuroanatomy, neurochemistry, and genetics have each offered different avenues in uncovering some of the mysteries linked to the etiology of autism. In taking a neuroanatomical approach to the disease, consistent evidence was found linking autism to the atrophy of vermal lobules VI and VII. When examining autism from a neurochemical point of view, it was found that a hypersecretion of B-endorphin and a malfunction of the negative feedback system on B-endorphin could possibly lead to the lack of socialization behavior that is characteristic of autistic patients. Finally, the field of genetics offers the view that the fragile X syndrome has a possible involvement in the etiology of autism. With further research in these fields of neuroanatomy, neurochemistry, and genetics, hopefully an answer to the puzzle of autism will soon be discovered.

WORKS CITED:

Bregman, J. D., Leckman, J. K., Ort, S. I. Fragile X Syndrome: Genetic Predisposition to Psychopathology. J. Aut. Dev. Dis. ,18(3): 343-354, 1988.

Chamberlain, R. S. and B. H. Herman. A Novel Biochemical Model Linking Dysfunctions in Brain Melatonin, Proopiomelanocortin Peptides, and Serotonin in Autism. Biological Psychiatry, 28:773-793, 1991.

Courchesne, E. et. al. Hypoplasia of Cerebellar Vermal Lobules VI and VII in Autism. New England Journal of Medicine, 318:1349-1354, May 26, 1988.

Gillberg, C. et. al. Monozygotic Female Twins With Autism and the Fragile X Syndrome (AFRAX). J. Child Psychol. Psychiat., 29(4); 447-451, 1988.

Herman, B. H. and Panksepp, J. Effects of Morphine and Naloxone on Social Attachment in Infant Guinea Pigs. Pharmacol. Biochem. Behaviour, 9;213-220, 1978.

Lowenstein, P. R. et. al. Effects of Naloxone on the Nocturnal Rise of Rat Pineal Melatonin Content. Eur. J. Pharmacol., 98;26

Reiss, A. L. et. al. Autism and Genetic Disorders. Schizophrenic Bulletin.12(4); 724-38, 1986.