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Differential development of autistic symptoms in a pair of fraternal twins.

The following case study reports the differential development of autistic symptoms over a 9-year period in a pair of fraternal twins. Neither of the twins developed normally. Evaluations revealed that although the older (male) twin showed some early signs of pathology and suffered from frequent illnesses, he ultimately has developed more normally than his sister, who likely sustained brain damage as a result of perinatal anoxia. Significant improvements has occurred in both cases. Diagnostic, etiological, and treatment implications are discussed.

Autistic Disorder↗

Deficits in social behavior in autism and their modification by a synthetic adrenocorticotrophic hormone (4-9) analog.

When charting the structure of the social behavior of autistic children by means of an ethologically analyzed playroom session, deficits appeared in the reciprocity of eye-contact and in the location of verbal initiatives. These deficits in social behavior were beneficially influenced by treatment with the adrenocorticotrophic hormone (4-9) analog ORG 2766.

Adrenocorticotropic Hormone↗

Assessing the functions of aberrant behaviors: a review of psychometric instruments.

Reviewed the psychometric properties, treatment utility, and conceptual basis of psychometric instruments used to identify the functions of aberrant behaviors in people with developmental disabilities. The instruments reviewed are the Motivational Assessment Scale (Durand & Crimmins, 1992), the Motivation Analysis Rating Scale (Weisheler, Hanson, Chamberlain, & Thompson, 1985), the Functional Analysis Interview Form (O'Neill, Horner, Albin, Storey, & Sprague, 1990), and the Functional Analysis Checklist (Van Houten & Rolider, 1991). Recurrent problems in this area include the lack of replicability of the reliability of these instruments, difficulties in summarizing the information from these assessment devices, difficulties in translating the assessment into treatment packages, strong individual differences in the functions of behavior problems, and, finally, issues relating to the concurrent validity, both across these instruments and across other assessment methods.

Adolescent↗

The pre-linguistic autism diagnostic observation schedule.

The Pre-Linguistic Autism Diagnostic Observation Schedule (PL-ADOS) is a semistructured observation scale designed for use as a diagnostic tool for children less than 6 years old who are not yet using phrase speech and are suspected of having autism. The PL-ADOS takes approximately 30 minutes to administer and is appropriate for use with this population because of its emphasis on playful interactions and the use of toys designed for young children. Reliability studies indicated that both individual activity ratings and summary ratings could be reliably scored from videotaped assessments by naive raters. Additionally, PL-ADOS scores of nonverbal preschool-aged children referred for clinical diagnosis and classified on the basis of a diagnostic team's clinical judgment, clearly discriminated between autistic and nonautistic developmentally disabled children. The resulting diagnostic algorithm is theoretically linked to diagnostic constructs associated with ICD-10 and DSM-IV criteria for autism.

Autistic Disorder↗

An examination of the phenomenology and the reliability of ratings of compulsive behavior in autism.

To clarify the nature of compulsive behavior in autism, staff reports of behavioral patterns of 17 young autistic adults living in a farmstead residential facility were analyzed. Three staff members, who had worked most closely with each resident for at least 3 months completed three questionnaires, including Quantitative and Qualitative compulsive behavior scales, and the Childhood Autism Rating Scale (CARS). The questionnaires were completed on two occasions with a 2-week interval between administrations. Test-retest and interrater consistencies were examined for each of the scales. Both the Qualitative and Quantitative questionnaires show promise as instruments that could be used as objective baselines or descriptors for compulsive behavior in autism. Information gathered from these scales could be utilized to determine how to intervene in the behavior, and to assess progress in treatment programs.

Adult↗

Fragile X syndrome: genetic predisposition to psychopathology.

Fragile X syndrome is a newly recognized X-linked disorder which has been associated with a high prevalence of psychiatric disturbance, particularly attention deficit disorder and autism. The present study involved the neuropsychiatric evaluation of 14 males with the disorder who were between the ages of 3 to 27 years. Pervasive hyperactivity, impulsivity, and attentional deficits were found among all of the subjects, while a significant degree of anxiety was manifested by more than half. Although the majority of subjects exhibited poor eye contact, atypical speech and language functioning, and stereotyped behavior, only one met DSM-III diagnostic criteria for a persistent pervasive developmental disorder. Gaze aversion, noted among half of the subjects, was attributed to underlying anxiety rather than to autistic social dysfunction because of the otherwise socially engaged and affectionate behavior exhibited by the subjects. Failure to make this distinction in the context of cognitive and linguistic impairments associated with fragile X syndrome may account for the high rates of autism reported by other investigators.

Adolescent↗

Infantile autism and developmental receptive dysphasia: a comparative follow-up into middle childhood.

An interim follow-up study of a group of "higher functioning" boys with infantile autism and control group of boys with severe (receptive) developmental language disorder (or dysphasia) is reported. The boys were compared both initially and at follow-up for overall functioning in the areas of language, peer relationships, stereotyped behaviors, and disruptive public behaviors, as well as for the presence of a number of specific symptoms. In some respects, the behaviors that differentiated the groups initially did so also at follow-up, although there were important differences. Very few of the autistic boys had good language skills at follow-up, whereas nearly half of the dysphasic group were communicating well, a difference that is striking in view of the initial general similarity between the groups in terms of poor language functioning. However, some of the dysphasic children had developed greater difficulties in peer relationships. The implications for concepts of the nature of the deficit in severe receptive developmental language disorders are considered.

Autistic Disorder↗

Dopaminergic control of locomotion, mouthing, snout contact, and grooming: opposing roles of D1 and D2 receptors.

The study compares the behavioral profiles induced in rats (N = 118) by the D2-dopaminergic receptor agonist quinpirole (0.03 and 0.5 mg/kg), and the D1-agonist SKF38393 (1.25-40 mg/kg), and both agonists administered together. Locomotion and snout contact frequency were reduced by the low but increased by the high dose of quinpirole; SKF38393 also reduced these behaviors and attenuated the effect of the high quinpirole dose. Only the high dose of quinpirole increased the duration of snout contact bouts and the frequency of mouthing; SKF38393 had no effect but in combination with the high dose of quinpirole, it enhanced the performance of these behaviors greatly. The duration of mouthing bouts was not affected by either agonist but was greatly extended when SKF38393 was administered together with the high dose of quinpirole. Grooming was inhibited by both the low and the high dose of quinpirole, and stimulated by the injection of SKF38393 or its addition to the low dose of quinpirole. These findings suggest that snout contact is controlled by modulating the frequency of episodes whereas mouthing is controlled by modulating the duration of episodes. Moreover, although they do not disprove the prevailing notion of D1-D2 receptor synergism, the present data are consistent also with an oppositional model of D1-D2 receptor interaction in the regulation of locomotion, snout contact, mouthing, and grooming in intact animals.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Scopolamine prevents augmentation of stereotypy induced by chronic methamphetamine treatment.

Cholinergic neurotransmission has been implicated in various forms of neural plasticity such as kindling and learning. We have previously shown that blockade of muscarinic cholinergic receptors prevents the development of locomotor sensitization to methamphetamine. The present study was conducted to examine whether scopolamine, a muscarinic cholinergic antagonist, would also block augmentation of stereotypy induced by chronic methamphetamine (MA) treatment. Rats treated with MA (2.5 mg/kg, SC) for 10 days indicated significantly enhanced stereotyped behavior when tested with MA (2.5 mg/kg) after a 7- to 8- day withdrawal. Pretreatment with scopolamine (3 mg/kg) prior to MA administration prevented the augmentation of stereotypy. Rats treated with scopolamine alone showed no difference in MA-induced stereotypy compared to those treated with saline. Scopolamine methylbromide, a derivative of scopolamine that does not easily cross the blood-brain barrier, had no effect on the augmentation of stereotypy. These results suggest that stimulation of central muscarinic cholinergic receptors plays a role in the development of sensitization to the stereotypy stimulating effect of methamphetamine.

Animals↗

[Speech development and intelligence in autism. How uniform is Asperger syndrome?].

Since the introduction of a separate diagnosis for Asperger's syndrome in the ICD-10 and DSM-IV classification systems, a controversial debate has continued on whether Asperger's syndrome is a specific, clearly distinguishable disorder within the autistic spectrum or whether it represents a milder phenotypical variation of autism. The effect on the amount of autistic symptoms of the variables language delay and level of intelligence was analyzed within a sample of individuals exhibiting autism diagnosed by standardized methods. Both variables showed a significant effect on the degree of autistic symptoms in that impairments in social interaction were less noticeable. In addition, a subsample of individuals exhibited symptoms assumed to be characteristic for Asperger's syndrome. The findings support the assumption that autism and Asperger's syndrome represent "extreme points" on a scale of severity, which leads to the suggestion that the classification of different subtypes of autism could be abandoned in favor of a dimensional (multiaxial) approach.

Adolescent↗

Occurrence of bicuculline-, NMDA- and kainic acid-induced seizures in prenatally methamphetamine-exposed adult male rats.

Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory gamma-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play an important role in the effect of stimulants on epileptic seizures. No studies investigating the effect of prenatal methamphetamine (MA) exposure on seizures are available. In this study, bicuculline (GABAA receptor antagonist), NMDA (NMDA receptor agonist) and kainic acid (non-NMDA receptor agonist) were used to induce seizures in adult male rats. Three groups of animals were tested in each seizure test: prenatally MA- (5 mg/kg) exposed, prenatally saline-exposed, and absolute controls without any prenatal exposure. In bicuculline-induced seizures, the latency to onset of tonic-clonic seizures was shorter in MA-exposed rats than in controls, but it did not differ from saline-exposed rats. There were no differences in clonic seizure onset between groups. In NMDA-induced seizures, the latency to onset of clonic-tonic seizures was shorter in prenatally MA-exposed rats than in controls; however, the latency to onset of saline-exposed animals did not differ from either MA-exposed or from control rats. There were no differences in seizure susceptibility in kainic acid-induced clonic seizures. There were no differences in seizure incidences or stereotypical behavior in any seizure model. The question remains as to how much the present data demonstrate the effect of prenatal drug exposure on seizure susceptibility per se, and how much they may be explained by the effect of prenatal stress or by other mechanism(s).

Animals↗

Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial.

RATIONALE: Patients with frontal variant frontotemporal dementia (fvFTD) present with disinhibition, impulsiveness, apathy, altered appetite and stereotypic behaviors. A non-randomized clinical trial found improvement in these symptoms after treatment with a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES: We aimed to subject a SSRI, paroxetine, to a more rigorous test of its efficacy using a double-blind, placebo-controlled experimental design. METHODS: Ten subjects meeting the consensus criteria for FTD were entered into a double-blind, placebo-controlled crossover trial. Doses of paroxetine were progressively increased to 40 mg daily. The same regimen was used for placebo capsules. Subjects were assessed with a battery of cognitive tests in the sixth week of paroxetine and placebo treatment. At each assessment, caregivers were interviewed using the Neuropsychiatric Inventory and asked to complete the Cambridge Behavioral Inventory. RESULTS: There were no significant differences on the Neuropsychiatric Inventory or the Cambridge Behavioral Inventory. Paroxetine caused a decrease in accuracy on the paired associates learning task, reversal learning and a delayed pattern recognition task. There were no changes on the decision-making task, in spatial span, spatial recognition, spatial working memory, digit span and verbal fluency. CONCLUSIONS: This study finds no evidence for the efficacy of paroxetine in the treatment of fvFTD. The results suggest that a chronic course of paroxetine may selectively impair paired associates learning, reversal learning and delayed pattern recognition. This pattern of deficits closely resembles that seen after tryptophan depletion. Results are discussed with respect to current theories on serotonergic modulation of orbitofrontal/ventromedial prefrontal cortex.

Aged↗

Invariant association of ecdysis with increases in cyclic 3',5'-guanosine monophosphate immunoreactivity in a small network of peptidergic neurons in the hornworm, Manduca sexta.

At the end of each molt insects shed their old cuticle by performing the stereotyped behavior of ecdysis. In the moth, Manduca sexta, this behavior is triggered by the neuropeptide eclosion hormone (EH). Insights into the mechanism of action of EH have come from the identification of a small network of peptidergic neurons that shows increased cyclic 3',5'-guanosine monophosphate (cGMP) immunoreactivity at ecdysis in insects from many different orders. Here we present further evidence that strengthens the association between ecdysis and the occurrence of this cGMP response in Manduca. We found that the cGMP increases occurred at every ecdysis, although some of the neurons that showed a response at larval ecdysis did not participate at pupal and adult ecdysis. Both ecdysis and the cGMP increases only required an intact connection with the brain for the first 30 min after EH injection. Interestingly, ecdysis in debrained animals only occurred if the cGMP response had been initiated, suggesting that the onset of this response marks the time at which the central nervous system is first able to drive ecdysis. Finally, we found that the appearance of sensitivity to EH for triggering the cGMP response coincided with the time at which EH first triggers ecdysis.

Animals↗

[Active ageing, decreasing capability, social disadvantage and age stereotypes: a contribution to resilience and vulnerability in older adulthood].

The starting-point of this contribution is the concept of active ageing as it has been propagated by the World Health Organization since the 1990s. Relationships between subjective experience of the potentials and barriers involved in leading a productive and responsible life, decreases in capability, small financial resources, and social isolation are analysed in a total sample of 1,275 participants. Based on this analysis, two subsamples are selected: a first characterised by a high level of risk, i.e. low opportunities for active ageing, and a second characterised by a low level of risk, i.e. high opportunities for active ageing. Four age stereotypes are analysed as predictors of experienced potentials and barriers in the total sample and the two subsamples. Results suggest varying significance of age stereotypes for constellations of resilience and vulnerability. From an age-stratification perspective, it is argued that results reflect a reservation against old age in our culture. The specific contribution of age stereotypes accentuating gains and chances versus losses and risks to understanding resilience and vulnerability are discussed from a social constructionist perspective.

Aged↗

Frontotemporal lobar degeneration with ubiquitin pathology: an autopsy case presenting with semantic dementia and upper motor neuron signs with a clinical course of 19 years.

We report a case of a right-handed 74-year-old man who showed semantic dementia with a disease duration of 19 years. He initially presented with excessive use of pronouns and semantic paraphasia at the age of 55 years. Impairment of object recognition developed 5 years after the onset. Face recognition impairment and stereotypic behaviors developed 11 years after onset, and pyramidal signs 2 years before death. Pathological examination disclosed circumscribed severe atrophy in not only the bilateral temporal tips but also in the left precentral gyrus and pars opercularis in a motor speech field. Pyramidal tract involvement and loss of Betz cells were also evident. On the other hand, neurons in the anterior horns and hypoglossal nuclei were spared in number, although astrocytes were mildly proliferated. Ubiquitin-positive lesions were observed in the hippocampus, and frontal and temporal cortices. Neither Bunina bodies nor Pick bodies were present. These features clinically fit the international diagnostic criteria of semantic dementia and, histopathologically, frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). This case suggests that (1) the distribution of cortical lesions associated with language disturbance is not uniform in FTLD-MND. It may be that only some cases of FTLD with ubiquitin pathology develop semantic dementia despite the high incidence of language disturbance, and (2) the precentral gyrus can be severely affected in FTLD-MND. After reviewing previous cases of FTLD-MND with a clinical course of more than 10 years, we also noticed that (3) FTLD-MND cases with a long disease duration often show upper motor neuron-predominant involvement.

Age of Onset↗