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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
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

Mental retardation: a review of the past 10 years. Part I.

OBJECTIVE: To review the literature over the past decade on mental retardation, particularly as regards its definition, prevalence, major causes, and associated mental disorders. METHOD: A computerized search was performed for articles published in the past decade, and selected papers were highlighted. RESULTS: The study of mental retardation has benefited considerably by advances in medicine generally and by developments in molecular neurobiology in particular. Increasing awareness of psychiatric comorbidity in the context of intellectual disability highlights the need for studies of the phenomenology and treatment of mental disorders in this population. CONCLUSIONS: Although the study of developmental disorders has advanced significantly over the past decade, considerable work remains. Mental retardation is a model for the utility of the biopsychosocial approach in medicine.

Adolescent↗
PubMed1997

Mental retardation: a review of the past 10 years. Part II.

OBJECTIVE: To review the literature over the past decade on mental retardation, particularly with respect to genetics and behavioral phenotypes. METHOD: A computerized search was performed for articles published in the past decade, and selected papers were highlighted. RESULTS: The study of mental retardation has benefited considerably by advances in medicine generally, and by developments in molecular neurobiology in particular. These advances in genetics have led to new insights regarding the causes of mental retardation, as well as a growing appreciation of behavioral phenotypes associated with some mental retardation syndromes. CONCLUSIONS: Although the study of developmental disorders has advanced significantly over the past decade, considerable work remains. Mental retardation should remain the model for the utility of the biopsychosocial approach in medicine.

Adolescent↗
PubMed1997

Pemoline alters dopamine modulation of synaptic responses of neostriatal neurons in vitro.

Pemoline, a central stimulant, administered systemically at high doses (300 mg/kg) reliably produces self-biting behavior in rats. Pemoline-induced self-biting shares many similarities with self-injury seen in certain human disorders. Recent evidence has shown that alterations in neostriatal neurochemistry accompany the self-biting behavior seen in the rat. The present study used intracellular electrophysiological techniques to reveal changes in neostriatal cellular physiology in slices from rats which had displayed self-injury. Depolarizing postsynaptic potentials (DPSPs) were examined in neostriatal slices from rats that received pemoline and had been engaging in self-injurious behavior and from two control populations: rats that received the same concentration of pemoline and did not engage in self-biting, and rats that received vehicle alone (peanut oil). Data were acquired in standard artificial cerebral spinal fluid. DPSPs were evoked by cortical electrical stimulation in the slice. In neurons from rats that received the vehicle or that had received pemoline but had not engaged in self-injury, dopamine (DA, 20 microM) application produced a significant decrease in the size of the cortically evoked neostriatal DPSP. In contrast, DA application produced an increase in DPSP size in neurons from rats which had received pemoline and had engaged in self-injury. Bath application of a combination of D1 and D2 receptor agonists best replicated the enhancing effect of DA. Furthermore, the enhancement could be blocked by pretreatment with the competitive N-methyl-d-aspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid. The results indicate that alterations in neostriatal DA-glutamate interactions accompany pemoline injections which produce self-injurious behavior.

Animals↗
PubMed1996

Pemoline produces ipsilateral turning behavior in unilateral 6-OHDA-lesioned rats.

1. Male Sprague-Dawley rats received either a unilateral injection of 6-hydroxy-dopamine or vehicle injection into the medial forebrain bundle. 2. Two weeks post surgery, all rats received a pemoline challenge (250 mg/kg s.c.), and rotational and stereotyped behaviors were videotaped and analyzed. 3. All rats regardless of injection expressed stereotyped behaviors and hyper-locomotion after pemoline challenge. 4. High performance liquid chromatography (HPLC) with electrochemical detection was used to evaluate changes in the levels of dopamine, serotonin and their metabolites in neostriata. 5. Rats with dopamine depleting lesions exhibited ipsilateral rotational behavior, indicating that pemoline, a central stimulant, is an indirect dopamine agonist in the rat. 6. The extent of dopamine depletion and serotonin elevation in the neostriatum in lesioned animals was related to the expression and degree of rotational behavior.

Animals↗
PubMed1996

Open trial lamotrigine in the treatment of self-injurious behavior in an adolescent with profound mental retardation.

This single case reports an open trial of lamotrigine in the treatment of self-injurious behavior (SIB) and epilepsy in an 18-year-old female diagnosed with generalized seizure disorder, stereotypic movement disorder, and compulsive SIB in the context of profound mental retardation. Animal models of SIB suggest that the glutamate neurotransmitter systems, involved in the generation of epileptic seizures, may also have a role in the pathophysiology of SIB. Data suggesting that lamotrigine may decrease glutamate release encouraged an empirical trial of lamotrigine for treatment of SIB. After 4 weeks of treatment of lamotrigine 200 mg daily, decreases in agitation and fearfulness were clinically observed, along with a 50% reduction in the frequency of SIB as measured by standardized scales. Good seizure control was maintained throughout the trial. No significant adverse effects were observed. Positive effects persisted at 1-year follow-up. Symptoms of stereotypic movement disorder appeared unchanged. Because these findings are preliminary, no clinical recommendations for the treatment of SIB with lamotrigine can be made until controlled studies have been completed.

Adolescent↗
PubMed1995

Pretreatment with MK-801 inhibits pemoline-induced self-biting behavior in prepubertal rats.

The indirect dopamine agonist, pemoline (120-300 mg/kg s.c.), can induce self-biting behavior in the rat. The present study demonstrates that the non-competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801, 0.2 mg/kg s.c.), significantly attenuates pemoline-induced self-biting behavior, while simultaneously increasing locomotor activity. When animals received a fixed dose of MK-801 with increasing doses of pemoline, a competitive relationship emerged such that high-dose pemoline surmounted the antagonistic effect of MK-801. In contrast to spiperone, delayed administration of MK-801 was ineffective in blocking the subsequent expression of self-biting behavior, suggesting that dizocilpine exerts its protective effect early in the cascade of events which eventually leads to self-biting behavior in this paradigm.

Animals↗
PubMed1994

Psychiatric consultation in severe and profound mental retardation.

OBJECTIVE: This study was designed to examine the relationship between reason for referral and subsequent DSM-III-R diagnosis in institutionalized individuals with severe to profound mental retardation. A heavy emphasis was placed on articulating how diagnostic criteria are applied in this population. METHOD: The study population consisted of 251 patients consecutively referred for initial psychiatric consultation from a large series of institutionalized patients with predominately severe to profound mental retardation. On the basis of the chief complaint, subjects could be grouped into six overlapping categories: self-injury, aggression, hyperactivity, agitation, medical questions, and miscellaneous behaviors. Psychiatric diagnoses were made according to DSM-III-R criteria on the basis of simultaneous clinical examination, staff interview, and medical review. Relevant medical conditions were noted. RESULTS: The authors demonstrate, as have others, that it is possible to make psychiatric diagnoses in this population and that psychiatric disorder is common. The most frequent diagnoses were impulse control disorders, anxiety disorders, and mood disorders. Comorbid medical conditions, particularly seizure disorders, are also common. CONCLUSIONS: These results are consistent with the reported experience of others and underscore the importance of psychiatric involvement in the multidisciplinary assessment and treatment of individuals with retardation.

Adolescent↗
PubMed1993

Self-injury by people with mental retardation: a compulsive behavior hypothesis.

Self-injury is a significant problem for many individuals with developmental disabilities, particularly those with severe or profound mental retardation. Many hypotheses have been suggested to account for self-injury, but none has been comprehensive. In this paper hypotheses suggesting psychological, behavioral, physiological, or neurochemical factors as causes of self-injury were critically reviewed. A compulsive behavior hypothesis was then introduced, which allows for alternative interpretations of some existing data and suggests several readily testable predictions.

Brain↗
PubMed1992

Hyperserotoninemia and antiserotonin antibodies in autism and other disorders.

This study examined the linkage between elevated blood serotonin in autism and the presence of circulating autoantibodies against the serotonin 5HT1A receptor. Information was also obtained on the diagnostic and receptor specificity of these autoantibodies. Blood serotonin was measured as was inhibition of serotonin binding to human cortical membranes by antibody-rich fractions of blood from controls and from patients with childhood autism, schizophrenia, obsessive-compulsive disorder, Tourette's, and multiple sclerosis. The results showed elevated blood serotonin was not closely related to inhibition of serotonin binding by antibody-rich blood fractions. Inhibition of binding was highest for patients with multiple sclerosis and was not specific to the 5HT1A receptor as currently defined. Although inhibition was not specific to autism, the data were insufficient to establish if people with autism differed from normal controls on this measure.

Adolescent↗
PubMed1990

Proposals for the mechanism of action of convulsive therapy: a synthesis.

The convulsive therapies have been powerful additions to somatic treatment in psychiatry and have enjoyed widespread application for the benefit of many. A number of theories have been advanced in efforts to account for therapeutic efficacy but none has been comprehensive. These theories can be distinguished by whether they posit a central therapeutic role for stimulation, inhibition, psychological effects, or mixed processes induced by treatment. After critically reviewing extant theories, we propose a model for the effects of the convulsive therapies: Convulsive therapy is essentially nonspecific; "nonphysiological" depolarizations are distinctly important for the restoration of aberrant intravesicular transmitter ratios with resultant therapeusis. We present this model as a working hypothesis that may contribute to the guidance of research in the mechanism of action of convulsive treatment and offer several testable hypotheses in this regard.

Brain↗
PubMed1990

Hypothesis: involvement of the serotonergic system in the clinical expression of monosymptomatic hypochondriasis.

Monosymptomatic hypochondriasis, including delusional parasitosis and non-neurotic dysmorphophobia, are disorders which have been observed and recorded over the past century. These disorders occur commonly, and can be associated with significant morbidity. Once ominous of an extremely poor prognosis, there now exists a significant literature to suggest efficacy for pimozide. Taking LSD as a model for 5-HT2 agonist mediated hallucinogenesis, it is possible to draw comparisons to the clinical picture associated with MHP and to identify potent 5-HT2 antagonism as a shared and perhaps requisite criterion for the successful pharmacologic treatment of this disorder. Additional studies are suggested which would add to the understanding of the pathophysiology of MHP.

Humans↗