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PubMedDate not supplied

Pilot assessment of the subtelomeric regions of children with autism: detection of a 2q deletion.

PURPOSE: Autism is a chronic neurodevelopmental disorder characterized by deficits in reciprocal social interaction, language and communication, and by the presence of stereotypical behaviors. The disorder is a complex genetic trait with no known predisposing genes. We report the results of a pilot project to screen for aberrations in the gene-rich subtelomeric chromosomal regions of a cohort of children with autism. METHODS: For our pilot project, we used a multiprobe system that includes probes for the subtelomeric regions of all human chromosomes. We assessed the subtelomeric regions of chromosomes from 10 children with a diagnosis of autism. RESULTS: The screen identified one child with an apparent deletion of the subtelomeric region of chromosome 2q; nine children and pooled control samples yielded normal results. The deletion in our patient was confirmed with two other subtelomeric probes and a targeted cytogenetic study revealed a subtle difference in appearance for one chromosome 2 homologue. CONCLUSION: There have been several reports of children with dysmorphic features, autistic behaviors, and 2q deletions detectable with standard cytogenetic techniques. It may be that the distal region of chromosome 2q harbors a gene or genes that may predispose to autism.

Autistic Disorder↗
PubMed2006

Fmr1 KO mice as a possible model of autistic features.

Autism is a pervasive developmental disorder appearing before the age of 3, where communication and social interactions are impaired. It also entails stereotypic behavior or restricted interests. Although this disorder was first described in 1943, little is still known about its etiology and that of related developmental disorders. Work with human patients has provided many data on neuropathological and cognitive symptoms, but our understanding of the functional defects at the cellular level and how they come about remains sketchy. To improve this situation, autism research is in need of valid animal models. However, despite a strong hereditary component, attempts to identify genes have generally failed, suggesting that many different genes are involved. As a high proportion of patients suffering from the Fragile X Syndrome show many autistic symptoms, a mouse model of this disorder could potentially also serve as a model for autism. The Fmr1 KO mouse is a valid model of the Fragile X Syndrome and many data on behavioral and sensory-motor characteristics of this model have been gathered. We present here an assessment of autistic features in this candidate model. We conclude that Fmr1 KO mice display several autistic-like features, but more work is needed to validate this model.

Animals↗
PubMed2000

Characterization of nonfunctional V1R-like pheromone receptor sequences in human.

The vomeronasal organ (VNO) or Jacobson's organ is responsible in terrestrial vertebrates for the sensory perception of pheromones, chemicals that elicit stereotyped behaviors among individuals of the same species. Pheromone-induced behaviors and a functional VNO have been described in a number of mammals, but the existence of this sensory system in human is still debated. Recently, two nonhomologous gene families, V1R and V2R, encoding pheromone receptors have been identified in rat. These receptors belong to the seven-transmembrane domain G-protein-coupled receptor superfamily. We sought to characterize V1R-like genes in the human genome. We have identified seven different human sequences by PCR and library screening with rodent sequences. These human sequences exhibit characteristic features of V1R receptors and show 52%-59% of amino acid sequence identity with the rat sequences. Using PCR on a monochromosomal somatic cell hybrid panel and/or FISH, we demonstrate that these V1R-like sequences are distributed on chromosomes 7, 16, 20, 13, 14, 15, 21, and 22 and possibly on additional chromosomes. One sequence hybridizes to pericentromeric locations on all the acrocentric chromosomes (13, 14, 15, 21, and 22). All of the seven V1R-like sequences analyzed show interrupted reading frames, indicating that they represent nonfunctional pseudogenes. The preponderence of pseudogenes among human V1R sequences and the striking anatomical differences between rodent and human VNO raise the possibility that humans may have lost the V1R/VNO-mediated sensory functions of rodents.

Amino Acid Sequence↗
PubMed2006

Evaluation of the stability of intracortical microelectrode arrays.

In order to use recorded neural activities from the brain as control signals for neuroprosthesis devices, it is important to maintain a stable interface between chronically implanted microelectrodes and neural tissue. Our previous paper introduced a method to quantify the stability of the recording microelectrodes. In this paper, the method is refined 1) by incorporating stereotypical behavioral patterns into the spike sorting program and 2) by using a classifier based on Bayes theorem for assigning the recorded action potentials to the underlying neural generators. An improved method for calculating stability index is proposed. The results for the stability of microelectrode arrays that differ in structure are presented.

Action Potentials↗
PubMed1986

A critical appraisal of recent drug research in mental retardation: the Coldwater studies.

This paper attempts to assess public and professional attitudes toward drug treatment in mental retardation and concludes that considerable sentiment has developed in recent years against the use of pharmacotherapy. A number of factors contributing to this prevailing attitude were identified and discussed. In particular, a series of investigations carried out by researchers at the Coldwater Regional Center for Developmental Disabilities (Michigan), which have had negative implications for drug treatment, were summarized. These studies have suggested that psychotropic drugs, especially the antipsychotics, may adversely affect clinical management of mentally retarded persons, depress learning performance, and interfere with the efficacy of reinforcement contingencies. However, certain features of these studies, such as the procedures for selecting subjects, the doses utilized and overall guiding philosophy, appear to limit their relevance. Balanced against these are a number of other investigations showing circumscribed positive clinical effects, a lack of interference with learning and little or no disruption of reinforcement contingencies. It was concluded that all-encompassing judgments about the value of pharmacotherapy in mentally retarded people are premature at this time. We suggested that a major objective of clinical drug research should be to look for enhancement of adaptive functioning by discovering appropriate subject-treatment combinations, while remaining vigilant for adverse effects.

Aggression↗
PubMed1993

Superpotent synthetic tripeptide mimics of the mud-crab pumping pheromone.

Soluble pheromones released by the mud crab, Rhithropanopeus harrisii (Gould) during egg hatching cause the female crab to contract her abdomen rapidly (the pumping response). This stereotypical behavior can be induced in the laboratory by exposing egg-bearing females to solutions containing certain amino acids or peptides. Twelve amino acids exhibited response thresholds of 10(-3)-10(-10) M, the most potent (norleucine, methionine and tryptophan) having a hydrophobic sidechain. Four synthetic tripeptides of the form Gly-X-Arg, where the hydrophobic residue X was isoleucine, norleucine, methionine or phenylalanine, were superpotent agonists over a limited concentration range. Gly-Ile-Arg was a significant agonist at 10(-17) and 10(-16) M, both Gly-Nle-Arg and Gly-Met-Arg at 10(-20) and 10(-19) M, and Gly-Phe-Arg at 10(-21), 10(-20) and 10(-19) M. At the subattomolar concentration of 10(-20) M the superpotent pheromone mimics Gly-Met-Arg and Gly-Phe-Arg produced not only a statistically significant increase in the relative number of pumping mud crabs but also a substantial increase in the pumping rate ratio. In contrast, at 10(-13) M the tripeptide Gly-Met(O)-Arg with an internal residue of methionine sulfoxide blocked the abdominal pumping response of egg-bearing mud crabs.

Amino Acid Sequence↗
PubMed1995

Follow-up of two-year-olds referred for possible autism.

Thirty, 2-year-old children referred for possible autism were evaluated using a parent interview, a rating scale and psychometric tests and reassessed one year later. Clinical diagnosis was relatively stable across time; diagnosis using the formal measures changed significantly, particularly for younger and more developmentally delayed children. Several patterns contributed to the increasing differentiation of children with autism from age 2 to 3, including the development of clearly recognizable, repetitive behaviors in the autistic children and significant improvements in basic social skills in the children judged not to be autistic.

Autistic Disorder↗
PubMed2004

The factor structure of autistic traits.

BACKGROUND: Although DSM-IV requires symptoms in three criterion domains for a diagnosis of autistic disorder, the extent to which those domains are phenotypically independent is an unanswered and important question. The identification of 'endophenotypes' of the autistic syndrome may be very useful for genetic and neurobiologic studies of autism, but only if they represent truly independent sub domains of the disorder. METHODS: In this study we examined the factor structure of autistic traits using data from 226 child psychiatric patients with and without pervasive developmental disorders, employing cluster analysis of data from the Autism Diagnostic Interview-Revised (ADI-r) and principal components factor analysis of data from the Social Responsiveness Scale (SRS, a quantitative genetic measure of autistic traits formerly known as the Social Reciprocity Scale). RESULTS: The results were consistent with the existence of a singular, continuously distributed underlying factor, resulting in disparate phenotypic manifestations across the three criterion domains for autistic disorder (social deficits, language deficits, and repetitive/stereotypic behaviors). CONCLUSION: The analyses generally failed to support the existence of independent sub domains of dysfunction in autism spectrum conditions. Future studies of the association between genetic/neurobiologic markers and autistic symptomatology may be enhanced by approaches which consider autistic symptoms as quantitative traits, and which are informed by ongoing research on the development and phenomenology of core deficiencies in reciprocal social behavior.

Adolescent↗
PubMed1986

Dose response for amphetamine-induced changes in dopamine levels in push-pull perfusates of rat striatum.

Levels of dopamine were determined in push-pull perfusates of striatum in chloral hydrate-anesthetized rats as a function of increasing systemic doses of amphetamine over the range 0.5-5.0 mg/kg. In the absence of amphetamine administration, basal dopamine levels remained stable for at least 6 h. Perfusate levels of dopamine responded in a quantitatively predictable fashion to increasing doses of amphetamine: (1) the maximal increase in perfusate levels of dopamine after amphetamine, relative to predrug levels, was directly proportional to the dose of the drug up to 3 mg/kg (fivefold after 0.5 mg/kg to 30-fold after 3 mg/kg); (2) the duration over which perfusate levels of dopamine were significantly elevated, with respect to preamphetamine levels, was proportional to the dose of amphetamine up to 5 mg/kg; and (3) each successively higher dose of amphetamine significantly increased the perfusate level of dopamine over that observed at the next lower dose up to 3 mg/kg amphetamine. However, maximal levels of dopamine in striatal perfusates were achieved following 3 mg/kg amphetamine and were not increased further at higher doses of the drug. The data suggest that, at higher doses of amphetamine, extraneuronal metabolism of dopamine may be of sufficient capacity to limit increases in synaptic levels of dopamine. The absence of further increases in perfusate levels of dopamine as the dose of amphetamine is increased beyond 3 mg/kg is discussed in terms of potential relevance to mechanisms of amphetamine-induced stereotyped behaviors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Dopamine agonist-mediated inhibition of acetylcholine release in rat striatum is modified by thyroid hormone status.

K(+)-evoked acetyl[3H]choline ([3H]ACh) release was inhibited in a concentration-dependent manner by apomorphine and the D2 agonist quinpirole in striatal slices prepared from euthyroid and hypothyroid rats. However, there was a significant increase in the maximum inhibition observed with both agonists in the hypothyroid compared with the euthyroid group, which paralleled the increased D2 agonist sensitivity reported for stereotyped behavior. The D2 antagonist raclopride decreased, and the D1 antagonist SCH 23390 increased, the inhibition of [3H]ACh release by apomorphine, confirming an inhibitory role for D2 receptors and an opposing role for D1 receptors. Because there is no difference in D1 or D2 receptor concentration between the euthyroid and hypothyroid groups, it is suggested that thyroid hormone modulation of D2 receptor sensitivity affects a receptor-mediated event. Following intrastriatal injection of pertussis toxin (PTX), apomorphine no longer inhibited [3H]ACh release. In fact, increased [3H]-ACh release was observed, an effect reduced by SCH 23390, providing evidence that D1 receptors enhance [3H]-ACh release, and confirming that a PTX-sensitive G protein mediates the D2 response. As it has been reported that thyroid hormones modulate G protein expression, this mechanism may underlie their effect on dopamine agonist-mediated inhibition of ACh.

Acetylcholine↗
PubMed2001

Client experience of gender in therapeutic relationships: an interpretive ethnography.

The purpose of this study was to explore clients' experiences of gender in therapeutic relationships in order to inform therapists of critical issues from clients' perspectives. To capture clients' views, the researchers chose an interpretive ethnographic design that used unstructured, collaborative interviews with clients who had worked with both female and male therapists. The interviews were analyzed using procedures developed by Kvale (1996), who emphasizes the importance of including the client's voice in data gathering, analysis, and final presentation. The results were reviewed with the clients to insure accurate presentation of their views. The final results were organized into six themes: client-therapist connection, male therapists, female therapists, topics discussed, effectiveness, and confounding factors. Researchers discuss the implications of gender-stereotyped behavior in therapy, the relationship between therapist gender and therapeutic alliance, and recommendations for practicing gender-sensitive therapy.

Adolescent↗
PubMed1995

Self-injurious behaviour. Psychopathological and nosological characteristics in subtypes of self-injurers.

This study explored the symptoms of self-injurious behaviour (SIB) in a consecutive sample of 54 mostly female psychiatric inpatients. The phenomenological analysis presented SIB as quite a uniform syndrome that starts latest in early adulthood, is often committed impulsively, is used in the function of releasing tension and occurs in patients with eating and psychoactive substance use but also schizophrenic disorders. The quality of mood preceding SIB was best characterized as dysphoria and was qualitatively not different from patients' longstanding affective traits. Two subgroups were differentiated, those with borderline personality disorder and those without; there was some evidence that patients with borderline personality disorder present a quite homogeneous core group of SIB, whereas others show a higher variety of psychopathological features. The hypothesis is proposed that poor affect regulation is the underlying psychopathological dimension.

Adolescent↗
PubMed2006

A hitchhiker's guide to behavioral analysis in laboratory rodents.

Genes and environment are both essential and interdependent determinants of behavioral responses. Behavioral genetics focuses on the role of genes on behavior. In this article, we aim to provide a succinct, but comprehensive, overview of the different means through which behavioral analysis may be performed in rodents. We give general recommendations for planning and performing behavioral experiments in rats and mice, followed by brief descriptions of experimental paradigms most commonly used for the analysis of reflexes, sensory function, motor function and exploratory, social, emotional and cognitive behavior. We end with a discussion of some of the shortcomings of current concepts of genetic determinism and argue that the genetic basis of behavior should be analyzed in the context of environmental factors.

Animals↗