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Biomedical subjects

B H King

Publications and source records attributed to B H King.

At least 19 recordsLinked to original sources

Males mate guard in absentia through extended effects of postcopulatory courtship in the parasitoid wasp Spalangia endius (Hymenoptera: Pteromalidae).

The proximal mechanisms leading to monandry have been little studied in most insect orders, including Hymenoptera. In the parasitoid wasp Spalangia endius, mated females are less attractive (less often mounted) than virgins and are unreceptive (unlikely to allow copulation). Which aspects of mating are responsible was tested by observing male responses toward females whose mating had been interrupted at various stages. All females were allowed to receive precopulatory courtship and to open their genital aperture to copulate. Then some were interrupted before copulation, some after copulation but before postcopulatory courtship, and some were allowed to complete postcopulatory courtship. Females that had copulated were not less attractive than females that had not. In contrast, females that had received postcopulatory courtship were clearly both less attractive and less receptive. Thus, postcopulatory courtship functions as extended mate guarding, by making the female less attractive and less receptive to subsequent males even after the original male is no longer present. The effect of postcopulatory courtship on female attractiveness was persistent but imperfect: when males were presented sequentially to mated females, most but not all males retreated without mounting, and a female could repulse more than twenty males in succession.

Animals↗

Maladaptive behaviour in children and adolescents with Down's syndrome.

BACKGROUND: Although children with Down's syndrome (DS) are at lower risk for psychopathology than others with intellectual disability, they do show more problems than typically developing children. However, age-related trends in these problems remain unclear. METHODS: The present authors examined age-related changes in the maladaptive behaviours of 211 children and adolescents with DS aged between 4 and 19 years (mean = 9.74 years). Most participants (n = 180) were recruited from families residing in the greater Los Angeles area, California, USA, while a minority (n = 31) were patients from a clinic specializing in the psychiatric management of people with DS. The participants were divided into four age groups: (1) 4-6 years, (2) 7-9 years, (3) 10-13 years and (4) 14-19 years. RESULTS: Externalizing behaviours were lower across both the community and clinic samples, while internalizing behaviours were significantly higher in older adolescents aged between 14 and 19 years. Increases were found in withdrawal, seen in 63% of community-based adolescents, and 75% of clinic adolescents. CONCLUSIONS: Older adolescents with DS may show decreased externalizing symptoms and subtle increases in withdrawal. Possible relationships are discussed between these shifts and increased risks of later-onset depression and Alzheimer's disease in adults with DS.

Adolescent↗

Self-injurious behavior: gene-brain-behavior relationships.

This paper summarizes a conference held at the National Institute of Child Health and Human Development on December 6-7, 1999, on self-injurious behavior [SIB] in developmental disabilities. Twenty-six of the top researchers in the U.S. from this field representing 13 different disciplines discussed environmental mechanisms, epidemiology, behavioral and pharmacological intervention strategies, neurochemical substrates, genetic syndromes in which SIB is a prominent behavioral phenotype, neurobiological and neurodevelopmental factors affecting SIB in humans as well as a variety of animal models of SIB. Findings over the last decade, especially new discoveries since 1995, were emphasized. SIB is a rapidly growing area of scientific interest to both basic and applied researchers. In many respects it is a model for the study of gene-brain-behavior relationships in developmental disabilities.

Animals↗

Autism spectrum disorders: update of evaluation and treatment.

Autistic spectrum disorders are a group of neurodevelopmental conditions that are increasingly capturing the attention of clinicians and investigators. New insights from genetics and neuropathophysiology of autism will increasingly inform treatment. Presently, individualized treatment approaches typically include a mix of behavioral and, occasionally, pharmacotherapeutic strategies. Concerning the latter, exquisite sensitivity to medication is not uncommon in some children with autism.

Antipsychotic Agents↗

Case series: amantadine open-label treatment of impulsive and aggressive behavior in hospitalized children with developmental disabilities.

OBJECTIVE: A growing body of literature implicates interactions between glutamatergic and neostriatal dopaminergic neurotransmitter systems in the development and expression of impulsivity, hyperactivity, and stereotypy. Amantadine hydrochloride, a drug used in young children for influenza prophylaxis, acts both as an indirect dopamine agonist as well as an N-methyl-D-aspartate (NMDA) receptor antagonist. Thus an open clinical trial of this medication for the treatment of symptoms of impulse control disorders in children was performed. METHOD: A total of eight children (seven with neurodevelopmental disorders and all inpatients) with target behaviors refractory to other treatments were selected after parental informed consent. All patients were male and ranged in age from 4 to 12 years. Outcome was based on subjective consensus clinical ratings by the multidisciplinary treatment team. RESULTS: For four of the children, amantadine was associated with marked clinical improvement. In the remainder, improvement was also observed. Amantadine was well tolerated. CONCLUSIONS: On the basis of this experience, it appears that amantadine hydrochloride or related NMDA antagonists may warrant additional study in this and related populations.

Aggression↗

Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder.

OBJECTIVE: To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. METHOD: Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. RESULTS: When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. CONCLUSIONS: Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.

Adolescent↗

Pharmacological treatment of mood disturbances, aggression, and self-injury in persons with pervasive developmental disorders.

Aggression, self-injury, and mood disturbances in persons with autistic disorders, while not uncommon, do not constitute core features of autism. Moreover, these problems can occur for a variety of reasons, which need to be assessed in order to plan appropriate and frequently combined (behavioral-pharmacological) treatments. Drugs acting primarily in the dopaminergic, serotonergic, adrenergic, opioidergic, and glutamatergic systems all have been explored in the treatment of aggression and self-injury. While no single drug or class of medication has yet emerged as consistently effective, a number of drugs appear promising. Advances in the assessment of aggressive behaviors, the identification of predictors of drug response, and additional controlled clinical drug trials specifically aimed at these target behaviors are essential in improving the approach to these problematic behaviors in the context of autistic disorder.

Aggression↗

Pharmacologic management of psychiatric and behavioral symptoms in mental retardation.

Compared with the general population, individuals with mental retardation demonstrate more susceptibility to psychiatric illness and may display disruptive behaviors. These symptoms significantly can affect an already compromised ability to function and the patient may benefit from pharmacologic intervention. Clinical characteristics of individuals with mental retardation warrant special consideration regarding diagnosis and treatment of their psychiatric and behavioral problems. This article describes the nature of symptoms that are typically the target of pharmacologic intervention, outlines special diagnostic considerations, and examines recent findings and experience with psychotropic medication in mental retardation.

Adolescent↗

Cortical damage enhances pemoline-induced self-injurious behavior in prepubertal rats.

Self-injurious behavior (SIB) is a devastating characteristic of several developmental disorders including a number of mental retardation syndromes. The functional neuroanatomy and neuropharmacology of SIB is not well understood. Self-biting behavior (SBB) can be induced in rats by a high dose, systemic injection of pemoline (250 mg/kg, SC). This animal model allows for the investigation of anatomical and pharmacological aspects of SIB. Cortical pathology is a common occurrence in human disorders with SIB, and may be a fundamental pathological factor in producing the behavior. The present experiment was designed to investigate the effects of cortical damage on pemoline-induced SBB in prepubertal rats. Bilateral cortical aspirations were performed in 3-5-week-old rats. One week postsurgery, a pemoline challenge was administered. Behavioral comparisons were completed between the lesion group and an anesthetized-only control group. Results indicated that cortical damage significantly enhanced pemoline-induced SBB, along with some of the other pemoline-induced stereotypical behaviors. These results support the hypothesis that cortical damage influences the expression of stimulant-induced self-injury, and potential mechanisms for this influence are suggested.

Animals↗

Practice parameters for the assessment and treatment of children, adolescents, and adults with mental retardation and comorbid mental disorders. American Academy of Child and Adolescent Psychiatry Working Group on Quality Issues.

Mental retardation (MR) is a heterogeneous condition defined by significantly subaverage intellectual and adaptive functioning and onset before age 18 years. With an approach underscored by principles of normalization and the availability of appropriate education and habilitation, persons with MR generally live, are educated, and work in the community. Mental disorders occur more commonly in persons with MR than in the general population. However, the disorders themselves are essentially the same. Clinical presentations can be modified by poor language skills and by life circumstances, so a diagnosis might hinge more heavily on observable behavioral symptoms. The diagnostic assessment considers and synthesizes the biological, psychological, and psychosocial context of mental disorders. Comprehensive treatment integrating various approaches, including family counseling, pharmacological, educational, habilitative, and milieu interventions is the rule.

Adolescent↗

Obsessive-compulsive symptoms in Prader-Willi and "Prader-Willi-Like" patients.

OBJECTIVE: To compare obsessive-compulsive (OC) symptoms in patients with Prader-Willi syndrome (PWS) and symptoms in a group of patients presenting with "Prader-Willi-like" features but without the genetic abnormalities associated with PWS. METHOD: 16 patients aged 4 through 20 years were evaluated in a clinic specializing in the assessment and management of behavioral and food-related problems in PWS. Eight patients were found to have key features of the syndrome but did not have a PWS genotype. These PWS-like subjects were matched to 8 clinic patients with a confirmed deletion of the PWS critical region of the paternally derived chromosome 15. All subjects were evaluated for obesity, IQ, food-related problems, maladaptive behaviors, and non-food-related OC symptoms. RESULTS: There were no differences between the 2 groups with respect to measures of obesity, IQ, food-related difficulties, or overall maladaptive behaviors. The PWS group showed significantly greater numbers of OC symptoms and greater symptom severity. CONCLUSIONS: Patients with PWS have elevated numbers of OC symptoms and significant symptom-related impairment which are not explained by developmental delay, food-related difficulties, or obesity. OC symptoms are part of a behavioral phenotype that accompanies deletions on the proximal long arm of chromosome 15 in PWS.

Adolescent↗

Summary of the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults with Mental Retardation and Comorbid Mental Disorders. American Academy of Child and Adolescent Psychiatry.

This summary provides an overview of the assessment and treatment recommendations contained in the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults With Mental Retardation and Comorbid Mental Disorders. The parameters were written to aid clinicians in the assessment and treatment of children, adolescents, and adults with symptoms of mental retardation (MR) and comorbid mental disorders. MR is a heterogeneous condition defined by significantly subaverage intellectual and adaptive functioning and onset before age 18 years. With an approach underscored by principles of normalization and the availability of appropriate education and habilitation, persons with MR generally live, are educated, and work in the community. Mental disorders occur more commonly in persons with MR than in the general population. However, the disorders themselves are essentially the same. Clinical presentations can be modified by poor language skills and by life circumstances, so a diagnosis might hinge more heavily on observable behavioral symptoms. The diagnostic assessment considers and synthesizes the biological, psychological, and psychosocial context of mental disorders. Comprehensive treatment integrating various approaches, including family counseling, pharmacological, educational, habilitative, and milieu interventions is the rule.

Adolescent↗

Maladaptive behavior differences in Prader-Willi syndrome due to paternal deletion versus maternal uniparental disomy.

Maladaptive behavior was compared across 23 people with Prader-Willi syndrome due to paternal deletion to 23 age- and gender-matched subjects with maternal uniparental disomy. Controlling for the higher IQs of the uniparental disomy group, deleted cases showed significantly higher maladaptive ratings on the Child Behavior Checklist's Internalizing, Externalizing, and Total domains as well as more symptom-related distress on the Yale-Brown Obsessive-Compulsive Scale. Across both measures, deleted cases were more apt to skin-pick, bite their nails, hoard, overeat, sulk, and withdraw. A dampening of symptom severity is suggested in Prader-Willi syndrome cases due to maternal uniparental disomy. Findings are compared to Angelman syndrome, and possible genetic mechanisms are discussed, as are implications for Prader-Willi syndrome and obsessive-compulsive behaviors.

Adolescent↗

Association of an X-chromosome dodecamer insertional variant allele with mental retardation.

Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X-chromosome and contains the sequence of a 7.3-kb mRNA. Initial polymorphism analysis across a region of repetitive DNA in this gene revealed a rare 12-bp exonic variation (<< 1% in non-iII males) having an increased prevalence in non-Fragile X males with mental retardation (4%, P < 0.04, n = 81). This variant was not present in the highly conserved mouse homologue that has 100% amino acid identity to the human sequence near the polymorphism. Subsequent screening of two additional independent cohorts of non-Fragile X mentally retarded patients and ethnically matched controls demonstrated an even higher prevalence of the 12-bp variant in males with mental retardation (8%, P < 0.0003, n = 125, and 14%, P < 0.10, n = 36) vs the controls. Multivariate analysis was conducted in an effort to identify other phenotypic components in affected individuals, and the findings suggested an increased incidence of histories of hypothyroidism (P < 0.001) and treatment with antidepressants (P < 0.001). We conclude that the presence of this 12-bp variant confers significant susceptibility for mental retardation.

Alleles↗

Open-label olanzapine treatment in five preadolescent children.

Olanzapine is a recently introduced atypical neuroleptic agent for which little information is available on its use in children. Open clinical trials of olanzapine treatment were conducted on five hospitalized children (ages 6 to 11 years) with varying diagnoses including bipolar disorder, psychosis not otherwise specified, schizophrenia, and attention-deficit/ hyperactivity disorder. Each patient had failed previous psychotropic medication trials, with a mean of four prior trials. The mean length of olanzapine treatment was 32 days (range, 2 to 7 weeks), and mean daily dose was 7.5 mg/day (range, 2.5 to 1.0 mg/day) or 0.22 mg/kg/day (range, 0.12 to 0.29 mg/kg/day). All children experienced adverse effects, including sedation (N = 3), weight gain of up to 16 pounds (N = 3), and akathisia (N = 2). Three patients showed some clinical improvement, but olanzapine treatment was discontinued in all five children within the first 6 weeks of treatment because of adverse effects or lack of clinically significant therapeutic response, although higher (or lower) doses, slower titration of dosage, or a longer duration of treatment might have produced more favorable results. Psychotic symptoms did not respond in the two patients with evidence of overt hallucinations and paranoid ideation. Improvement was observed in sleep in all five patients and in control of aggression in three. Before controlled trials of olanzapine in children are undertaken, further exploration of dose range and increased duration of treatment on an open basis are warranted. Until more encouraging data are available, clinicians should be cautious and conservative in their predictions about the potential value of olanzapine in treating preadolescent psychiatric disorders.

Akathisia, Drug-Induced↗

Molecular screening for proximal 15q abnormalities in a mentally retarded population.

Paternal or maternal deletions in the 15q11.2-q13 region are known to result in Prader-Willi syndrome (PWS) or Angelman syndrome (AS), respectively. Maternal duplications in 15q11.2-q13 have been found in patients with autism. A population of adults with moderate to profound mental retardation was studied to examine the usefulness of PCR based molecular methods in screening for proximal chromosome 15 abnormalities. Two hundred and eighty-five subjects were initially screened at five microsatellite markers with average heterozygosity values of 0.74 (range 0.54-0.82). Of these subjects, four had a single allele at all five loci, suggestive of a deletion or uniparental isodisomy. The four samples were further screened with additional markers located within 15q11.2-q13 as well as markers telomeric to this region. One subject had uniparental disomy (UPD) and three subjects had a deletion. To determine the parental origin of the 15q11-q13 region containing the single haplotype, samples were analysed with a newly developed methylation specific PCR technique at the SNRPN locus. Each of the four subjects showed presence of the paternal allele and absence of the maternal allele. All cases had a phenotype consistent with Angelman syndrome as expected for the level of mental retardation, but the subject with UPD was distinct from the other subjects with an absence of a history of seizures and presence of bilateral undescended testes and Parkinsonism. Although Angelman syndrome has an estimated population prevalence of 0.008%, at least 1.4% of the moderately to profoundly mentally retarded subjects screened were found to have Angelman syndrome.

Adult↗

Dopaminergic and glutamatergic interactions in the expression of self-injurious behavior.

Self-injurious behavior occurring in persons with severe mental retardation is a clinically significant and poorly understood problem. Multiple neurotransmitter systems have been implicated in the pathogenesis of this behavior, particularly dopaminergic, opioidergic, and serotonergic systems. Pemoline, a central stimulant, administered systemically at high doses reliably produces self-biting behavior in the rat. The systemic bolus of pemoline produces sustained neostriatal levels of pemoline for over 24 h in a continuous infusion paradigm. Studies of the effect of cortical lesions on pemoline-mediated behaviors reveal that cortical damage, as is common in profound mental retardation, lowers the threshold for pemoline-induced self-biting behavior. Data from the corticostriatal slice suggests that sustained exposure to pemoline produces a shift in N-methyl-D-aspartate receptor-mediated responses rendering them more susceptible to dopaminergic enhancement. Thus, dopaminergic and glutamatergic interactions appear to play an important role in the development and expression of self-biting in the pemoline model.

Animals↗

Paroxetine treatment of aggression and self-injury in persons with mental retardation.

An open, prospective assessment of the treatment of severe aggression and self-injurious behavior (SIB) with paroxetine, a serotonin re-uptake inhibitor, in 15 institutionalized persons with mental retardation was undertaken. Frequency and severity of aggression and SIB were charted by trained staff members. Only aggression severity was reduced over the entire 4-month follow-up period. Within the limits of an open trial, this effect was significant at one month but did not remain significant subsequently. The apparent diminution of effectiveness after 4 weeks of treatment may suggest adaptive changes warranting further study.

Adult↗