Genetic studies in autistic disorders

Since autism was first described by Leo Kanner the view on its etiology and pathogenesis has been changing. Recently there are more data on genetic and neurobiological background of autism. At the beginning it was noticed that autism appeared more frequently among boys, in population studies it was found that autism appeared more frequently among siblings, mostly among monozygotic twins. Many disorders like Tourett syndrome and tuberous sclerosis were reported in connection with autism. Recently research is focused mostly on chromosome abnormalities: chromosome 15 (locus 15q11-13), chromosome 7 (locus 7q), chromosome 16 (locus 16p) and gens of particular receptors (GABRB3, UBE3A/E6-AP, 5-HTT). These abnormalities may also be one of the causes of autism.     

Deterioration of word meaning: Implications for reading

We investigated six patients with progressive focal dementia or progressive aphasia, who showed impairments in knowledge of word meaning ranging from moderate to very severe. In all cases, a test of oral word reading demonstrated preserved reading of words with regular spelling-to-sound correspondences (e.g. MINT), but impaired reading of words with atypical correspondences (e.g. PINT). The level of success on these “exception” words was significantly related to word frequency, and the most common error was the assignment of a more typical spelling-sound correspondence. Various explanations are considered for this common association between loss of word meaning and a surface alexic pattern of reading performance.     

Psychopharmacology of autistic disorders

There is a growing number of studies on the efficacy of pharmacological interventions in autistic disorders. Although the core symptoms of autism can hardly be influenced by medication, drug treatment can be used as a valuable adjunct therapy, targeting above all externalizing disorders associated with autism. The primary goal of drug treatment in autism is to decrease maladaptive behaviors in order to allow the child to better benefit from other therapeutic interventions. Unfortunately, the combination of different psychopharmacological agents has not been studied so far, despite their pivotal role in practical clinical work. It remains to be seen whether future studies will explore the efficacy of a combination of drug treatment with other treatment modalities, respectively the seemingly useful combination of different medications. Newer medications effective in the treatment of autistic children cause fewer unwanted side effects. The number of pharmacological studies with good methodological standards is also increasing.     

Neuropsychology of autistic disorders

Autistic disorders are pervasive developmental disorders, which are characterised by social, communicative and stereotyped, repetitive behaviour patterns. The onset of these disorders is in early childhood and they are most likely of biological origin. A review of neuropsychological questions and results is presented. Special features are found with regard to intelligence, attention, memory, speech, executive functions, theory of mind and central coherence. The different neuropsychological features are explained in terms of an integrated model which takes into account the elementary functions, systems of functioning and the underlying theoretical concepts. Autistic disorders can be understood as an integration deficit of these different functions.     

Cognitive rehabilitation of word meaning deafness

Theoretical accounts of pure word meaning deafness are rare; accounts of its rehabilitation are virtually non-existent. We contrast the effects of two therapies in a patient with pure word meaning deafness. One therapy required only implicit auditory access from the patient (silent reading comprehension exercises). The second required explicit auditory access (auditory comprehension exercises), and thus appeared to be more suited to the exact locus of the patient's impairment. Improvement was observed after both types of therapy. However, improvement on implicit access therapy was influenced by the use of a compensatory strategy developed by the patient. In contrast, improvement on explicit access therapy was more durable, and appeared to be due to a direct effect on the audition–semantics link, rather than to compensation. We conclude that pure word meaning deafness is amenable to treatment, and that cognitive models can be useful in designing such therapy studies.     

The genetics of autistic disorders

Autistic disorders are heterogeneous. Affected individuals show impairments in communication and social interaction, as well as stereotypic, repetitive behaviour and special interests. The majority of autistic disorders are genetic in origin. The current article presents an overview of cytogenetic findings, as well as of results of molecular genetic linkage and association studies. Important differential diagnoses will be described. The results of genetic studies are especially relevant with regard to genetic counselling for affected families.     

Intervention for autistic spectrum disorders

A comprehensive approach to the assessment of any child with autism must be matched specifically to each individual child and family. This premise holds for medical therapies and special education services as well as psychopharmacologic interventions. Behavioral, as opposed to pharmacologic, treatment is the hallmark of effective intervention for autism. Physicians involved in the care of children with autism need to become familiar with educational law and intervention recommendations. Goals should include improved functional verbal and nonverbal communication and social skills, increased engagement in developmentally appropriate activities, improved fine and gross motor skills, and the development of independent academic and organizations skills, as well as replacement of problem behaviors with developmentally appropriate behaviors. Medicating children with autism is difficult, but is often necessary for chronic behavioral difficulties. In the absence of clear and present guidelines, we have attempted to use evidence and clinical experience to suggest an algorithm based on symptom clusters. Although children with autism may be responsive to medications at lower doses and more susceptible to side effects than other children, medical intervention can produce a significant improvement in the quality of life for the child and family. Careful thought leading to correct identification of target behaviors can appropriately direct better alternatives for medication. Although these approaches are costly and time-consuming endeavors, the expenditure of such efforts is the only available pathway to improve the potential outcomes for individuals with autism as well as decrease the lifetime societal costs for each individual.     

Motor functioning in autistic spectrum disorders: a preliminary analysis

The study sought to identify differences in motor functioning between autism and Asperger syndrome while also assessing the diagnostic contribution of such assessment. A sample of 16 individuals with autism and 10 with Asperger syndrome completed the Dean-Woodcock Sensory-Motor Battery, and outcomes were compared. Significant differences were found in measures of cerebellar functioning, favoring Asperger subjects. Deficits in coordination, ambulation, and the Romberg test were associated with both disorders. On the basis of motor outcomes alone, 100% were accurately differentiated. Findings support the idea that motor dysfunction is a core feature of these presentations and demonstrated the utility of motor assessment in diagnostic practice.     

Communication training in mute autistic adolescents using the written word

The expressive and receptive use of three written words was taught to three mute autistic adolescents using a procedure based on Terrace's errorless discrimination model and Premack's language training with chimps. Expressive language was measured by the subject's selection of the appropriate word card from among the available alternatives when the corresponding object was presented. Receptive language was measured by the subject's selection of the appropriate object from among the available alternatives when the corresponding word card was presented. The sequence of the presentations and the order of placement of the available alternatives were randomized. The three subjects required 979, 1,791, and 1,644 trials, respectively, to master both the expressive and receptive use of the three words. The correct response rates for the three subjects over the entire training program were 92, 92, and 90%, respectively. It was concluded that, as concrete visual symbols, written words may provide a viable communication system for the mute autistic. The implications for treatment are discussed and suggestions for future research are made.     

Genetics of autistic disorders: review and clinical implications

Twin and family studies in autistic disorders (AD) have elucidated a high heritability of AD. In this literature review, we will present an overview on molecular genetic studies in AD and highlight the most recent findings of an increased rate of copy number variations in AD. An extensive literature search in the PubMed database was performed to obtain English published articles on genetic findings in autism. Results of linkage, (genome wide) association and cytogenetic studies are presented, and putative aetiopathological pathways are discussed. Implications of the different genetic findings for genetic counselling and genetic testing at present will be described. The article ends with a prospectus on future directions.     

Brief report: Comorbid psychiatric disorders of autistic disorder

Conclusion The behavioral and/or psychiatric symptoms in autistic people as described above have been viewed by many professionals dealing with autistic populations as associated features of autism that may result from these individuals' inability to cope with the environmental demands and physical discomfort. Traditionally, in treating individuals with autism, special education intervention including behavioral modifications has been the main emphasis. Such an approach has made some progress in milder and uncomplicated cases of autism. However, if many of these behavioral and/or psychiatric symptoms in those with more severe associated features can be viewed as symptoms of various comorbid psychiatric disorders, there are data suggesting that with an appropriate evaluation, predrug workups, a specific diagnosis, and multiple measures of outcome, pharmacotherapy can be a safe and efficacious adjunct treatment for some symptoms in autistic persons. Nevertheless, the data presented here were obtained mainly from autistic children. A great deal of work remains to be done Future research should put more emphasis on developing agreeable, reliable, and valid diagnostic instruments for identifying comorbid psychiatric disorders in autistic people. Future research should also emphasize employing a randomized double-blind placebo-controlled crossover design, as well as involving multicenters and using uniformed diagnostic criteria to study autistic adolescents and adults.     

Rett syndrome and the autistic disorders

Rett syndrome is a disorder noted to date only in females and characterized by a pervasive developmental disability following apparently normal early infancy. In addition to gait difficulties, stereotypic hand movements, and loss of communication and purposeful hand skills, autistic-like behavior is an early sign that often results in misdiagnosis. Despite these significant clinical abnormalities, neuropathologic features are modest, and no consistent laboratory abnormality or diagnostic marker has been identified. The current status of research in RS is considered within the context of autism and other disorders in which autistic features may occur, such as the fragile X syndrome. The concept of autism as neurobiologically based behavior is developed. As such, autism is regarded as an umbrella category containing an ever-expanding list of specific disorders.     

Brain signatures of meaning access in action word recognition

The brain basis of action words may be neuron ensembles binding language- and action-related information that are dispersed over both language- and action-related cortical areas. This predicts fast spreading of neuronal activity from language areas to specific sensorimotor areas when action words semantically related to different parts of the body are being perceived. To test this, fast neurophysiological imaging was applied to reveal spatiotemporal activity patterns elicited by words with different action-related meaning. Spoken words referring to actions involving the face or leg were presented while subjects engaged in a distraction task and their brain activity was recorded using high-density magnetoencephalography. Shortly after the words could be recognized as unique lexical items, objective source localization using minimum norm current estimates revealed activation in superior temporal (130 msec) and inferior frontocentral areas (142-146 msec). Face-word stimuli activated inferior frontocentral areas more strongly than leg words, whereas the reverse was found at superior central sites (170 msec), thus reflecting the cortical somatotopy of motor actions signified by the words. Significant correlations were found between local source strengths in the frontocentral cortex calculated for all participants and their semantic ratings of the stimulus words, thus further establishing a close relationship between word meaning access and neurophysiology. These results show that meaning access in action word recognition is an early automatic process ref lected by spatiotemporal signatures of word-evoked activity. Word-related distributed neuronal assemblies with specific cortical topographies can explain the observed spatiotemporal dynamics reflecting word meaning access.     

Medication treatment in subjects with autistic spectrum disorders

Autism is a pervasive developmental disorder that is aetiologically and clinically heterogeneous. Twin and family genetic studies provide evidence for strong genetic components. An international consortium using an affected sib pair strategy has found a promising linkage to a region on chromosome 7. In 10–15% of the cases autism is due to associated medical conditions that affect normal brain functioning. Post-mortem studies on small case series report cellular abnormalities in the limbic system and cerebellum. Between 10 and 20% of subjects with autism have macrocephalia, which is in accordance with MRI findings of an increased total brain tissue volume and enlargement most prominent in the occipital and parietal lobes. The most robust and well-replicated neurobiological abnormality in autism is an elevation of whole blood serotonin found in over 30% of the patients. Pharmacological interventions with serotonin reuptake blockers or with atypical neuroleptics that block both dopamine (D₂) and serotonin (5-HT₂) receptors seem to offer clinical benefit and merit further study.