Search PubMed⌕ Search

Biomedical subjects

H Meltzer

Publications and source records attributed to H Meltzer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neurotic disorders and the receipt of psychiatric treatment.

BACKGROUND: Access to psychiatric treatment by people with neurotic disorders in the general population is likely to be affected both by the severity of disorder and by sociodemographic differences. METHOD: In the household component of the National Surveys of Psychiatric Morbidity > 10,000 subjects in Great Britain with psychiatric symptoms were interviewed using the CIS-R. They were also asked about difficulties experienced in performing seven types of everyday activity. All subjects classed as having an ICD-10 disorder were questioned about their experience of treatment with antidepressants, hypnotics, and counselling or psychotherapy. RESULTS: Less than 14% of people with current neurotic disorders were receiving treatment for them. Within the previous year, only a third had made contact with their primary care physician for their mental problem: of these < 30% were receiving treatment. Overall, 9% of people with disorders were given medication and 8% counselling or psychotherapy. A diagnosis of depressive episode was that most associated with antidepressant medication. Treatment access was affected by employment status, marital status, and age, but the major determinant was symptom severity. Neither sex nor social class influenced which people received treatment. CONCLUSIONS: People with psychiatric disorders seldom receive treatment, even when they have consulted their primary care physician about them. In many cases, this must represent unmet needs with a strong claim on health resources. There are also inequalities in the receipt of treatment, although the major influence is the severity of disorder.

Adolescent↗
PubMed2000

Alteration in p53 modulates glial proteins in human glial tumour cells.

In transformed human glial cells, abnormalities of the p53 gene and altered expression of glial-specific properties (GSPs) have been observed. We therefore investigated whether (i) expression of the altered p53 protein is involved in the reduced expression of GSPs; and (ii) expression of the wild-type p53 (wt-p53) gene leads to induction of GSPs. We first determined that the p53 gene is mutated in human glioblastoma U-373MG cells. In these cells, and in human T-98G glioblastoma cells reported to possess a mutated p53 (m-p53) gene, nuclear m-p53 expression was intense while GSP expression was low in the same cell as revealed by double labelling immunocytochemistry. Conversely, glial fibrillary acidic protein (GFAP) and glutamate synthase (GS) were expressed in cells devoid of nuclear m-p53 immnunoreactivity. Therefore, a mutually exclusive relationship exists between the cytoplasmic GSPs and nuclear m-p53. Upon treatment with retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP), overall GSP staining were increased concomitant with suppression of nuclear m-p53. Their mutually exclusive expression pattern was maintained suggesting a functional relationship. This is supported by the observation of a similar mutually exclusive expression pattern for p53 and GSPs in pathologic specimens of human glioblastoma tissues. We then explored the role of the wt-p53 gene in the induction of GSPs using a wt-p53 tetracycline-regulated conditional expression system in human LN-Z308 glioblastoma cells. These cells normally express no p53 and no appreciable levels of GS or GFAP. Induced expression of wt-p53 lead to induction of GSP. These observations are consistent with the hypotheses that (i) nuclear m-p53 expression and cytoplasmic expression of GFAP and GS are inversely correlated, and (ii) expression of the wt-p53 gene leads to the expression of GSPs.

Amino Acid Sequence↗
PubMed2000

Clarifying the relationship between unexplained chronic fatigue and psychiatric morbidity: results from a community survey in Great Britain.

OBJECTIVE: The study examined the associations between several sociodemographic and psychosocial variables and unexplained chronic fatigue in the community before and after adjustment for psychiatric morbidity and determined the prevalence of fatigue and rate of disability resulting from fatigue in the general population. METHOD: The study is a secondary analysis of 1993 data from a household survey of psychiatric morbidity conducted by the Office for Population Censuses and Surveys in Great Britain. The survey included 12,730 subjects age 16-64 years. Unexplained chronic fatigue was used as the dependent variable in a logistic regression analysis, with various sociodemographic and psychosocial variables and psychiatric morbidity as the independent variables. Psychiatric morbidity was assessed by using the Revised Clinical Interview Schedule. Fatigue was measured by using the fatigue section of the Revised Clinical Interview Schedule. RESULTS: A total of 10,108 subjects agreed to cooperate (79.4% participation rate). The prevalence of unexplained chronic fatigue was 9%. Subjects with psychiatric morbidity had higher rates of fatigue. Adjustment for psychiatric morbidity had a minor effect on the associations between sociodemographic factors and chronic fatigue. After adjustment, older subjects, women, and couples with children had higher rates of fatigue. Single subjects, widowed subjects, adults living with parents, and economically inactive subjects had lower rates of fatigue. Fatigue was associated with considerable disability, but most of this disability was explained by the association between fatigue and psychiatric morbidity. CONCLUSIONS: Unexplained chronic fatigue is a common condition, strongly associated with psychiatric morbidity. The close relationship between fatigue and psychiatric morbidity should not obscure the possibility of differences as well as similarities in their etiologies.

Activities of Daily Living↗
PubMed2000

Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample.

BACKGROUND: Child psychiatric disorders are common and treatable, but often go undetected and therefore remain untreated. AIMS: To assess the Strengths and Difficulties Questionnaire (SDQ) as a potential means for improving the detection of child psychiatric disorders in the community. METHOD: SDQ predictions and independent psychiatric diagnoses were compared in a community sample of 7984 5- to 15-year-olds from the 1999 British Child Mental Health Survey. RESULTS: Multi-informant (parents, teachers, older children) SDQs identified individuals with a psychiatric diagnosis with a specificity of 94.6% (95% Cl 94.1-95.1%) and a sensitivity of 63.3% (59.7-66.9%). The questionnaires identified over 70% of individuals with conduct, hyperactivity, depressive and some anxiety disorders, but under 50% of individuals with specific phobias, separation anxiety and eating disorders. Sensitivity was substantially poorer with single-informant rather than multi-informant SDQs. CONCLUSIONS: Community screening programmes based on multi-informant SDQs could potentially increase the detection of child psychiatric disorders, thereby improving access to effective treatments.

Adolescent↗
PubMed2000

The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology.

The Development and Well-Being Assessment (DAWBA) is a novel package of questionnaires, interviews, and rating techniques designed to generate ICD-10 and DSM-IV psychiatric diagnoses on 5-16-year-olds. Nonclinical interviewers administer a structured interview to parents about psychiatric symptoms and resultant impact. When definite symptoms are identified by the structured questions, interviewers use open-ended questions and supplementary prompts to get parents to describe the problems in their own words. These descriptions are transcribed verbatim by the interviewers but are not rated by them. A similar interview is administered to 11-16-year-olds. Teachers complete a brief questionnaire covering the main conduct, emotional, and hyperactivity symptoms and any resultant impairment. The different sorts of information are brought together by a computer program that also predicts likely diagnoses. These computer-generated summary sheets and diagnoses form a convenient starting point for experienced clinical raters, who decide whether to accept or overturn the computer diagnosis (or lack of diagnosis) in the light of their review of all the data, including transcripts. In the present study, the DAWBA was administered to community (N = 491) and clinic (N = 39) samples. There was excellent discrimination between community and clinic samples in rates of diagnosed disorder. Within the community sample, subjects with and without diagnosed disorders differed markedly in external characteristics and prognosis. In the clinic sample, there was substantial agreement between DAWBA and case note diagnoses, though the DAWBA diagnosed more comorbid disorders. The use of screening questions and skip rules greatly reduced interview length by allowing many sections to be omitted with very little loss of positive information. Overall, the DAWBA successfully combined the cheapness and simplicity of respondent-based measures with the clinical persuasiveness of investigator-based diagnoses. The DAWBA has considerable potential as an epidemiological measure, and may prove to be of clinical value too.

Adolescent↗
PubMed1999

Oxidation sensitivity may be a useful tool for the detection of the hematotoxic potential of newly developed molecules: application to antipsychotic drugs.

Some antipsychotic agents have been found to produce agranulocytosis and aplastic anemia. The oxidation phenomena and/or the formation of free radicals has been suggested to be causally related to various hematological disorders, e.g., agranulocytosis. Using five experimental conditions, we tested the oxidative potential of compounds with and without a history of hematological side effects, e.g., agranulocytosis and aplastic anemia. A statistical analysis was undertaken for each experimental condition and a multivariate analysis combining all results was performed. Two peroxidase-induced free radical models did not successfully discriminate between drugs with and without a history of causing hematologic problems (<70%). The lipid peroxidation system provided even less satisfactory discrimination, with only 56.25% correct classification. However, an 87.5% correct classification was obtained when using the oxidation potentials of these drugs determined at pH 4.7 and at pH 7.4. A multivariate analysis taking into account the five variables provided 87.5% success in classification. The two clusters were better discriminated in terms of a "distance coefficient." In a second analysis, the putative antipsychotic pyridobenzodiazepine analogues (JL5, JL8, JL18, and JL25) were classified in the cluster of toxic compounds, while the oxa- and thiazepine analogues (JL2, JL3, and JL13) were classified as nontoxic compounds. On the other hand, a few metabolites of clozapine and fluperlapine were classified in the toxic compound group. The procedure described herein is, to our knowledge, the first which classifies molecules of different structures as well as different pharmacological profiles according to their hematotoxic potential. Such a procedure could be used to predict drug-induced hematological side effects.

Agranulocytosis↗
PubMed1999

The survey form of SCAN: the feasibility of using experienced lay survey interviewers to administer a semi-structured systematic clinical assessment of psychotic and non-psychotic disorders.

BACKGROUND: The success of large scale surveys depends on well designed questionnaires and the skills of lay interviewers. Discrepancies in prevalence rates between epidemiological surveys and poor agreement between survey interviewer and clinician diagnostic interviews are giving rise to increasing concern among researchers, public health planners and policy developers. New approaches to information collection are called for. The feasibility of training experienced survey interviewers in semi-structured, clinical, diagnostic interviewing has never been investigated systematically across the range of neurotic and psychotic disorders. METHODS: Eight experienced survey interviewers from the Office for National Statistics (ONS) were selected and underwent extended training in a Survey Form of SCAN (SCAN-SF). Sixty-four adults, including a majority of psychiatric in-patients were assessed by ONS interviewers and reinterviewed within a week by SCAN-trained clinicians. Feedback was sought from interviewers and trainers. RESULTS: Trainers found lay interviewers coped at least as well with psychotic as with neurotic symptoms. Concordance for any disorder was 0.74 (95% CI: 0.57 to 0.91); for any specific psychotic disorder 0.63 (0.40 to 0.86); for any specific neurotic disorder 0.63 (0.43 to 0.83). Sensitivity ranged from 0.6 to 0.9 and specificity from 0.8 to 0.9. There was no evidence of rater bias. CONCLUSIONS: These preliminary findings are very promising. However, before the SCAN-SF, administered by carefully trained lay interviewers, can be recommended in large scale surveys, further evaluations of its feasibility and reliability in the general population are needed.

Adaptation, Psychological↗
PubMed1999

Cross validation of a general population survey diagnostic interview: a comparison of CIS-R with SCAN ICD-10 diagnostic categories.

BACKGROUND: Comparisons of structured diagnostic interviews with clinical assessments in general population samples show marked discrepancies. In order to validate the CIS-R, a fully structured diagnostic interview used for the National Survey of Psychiatric Morbidity in Great Britain, it was compared with SCAN, a standard, semi-structured, clinical assessment. METHODS: A random sample of 1882 Leicestershire addresses from the Postcode Address File yielded 1157 eligible adults: of these 860 completed the CIS-R; 387 adults scores > or = 8 on the CIS-R and 205 of these completed a SCAN reference examination. Neurotic symptoms, in the previous week and month only, were enquired about. Concordance was estimated for ICD-10 neurotic and depressive disorders, F32 to F42 and for depression symptom score. RESULTS: Sociodemographic characteristics closely resembled National Survey and 1991 census profiles. Concordance was poor for any ICD-10 neurotic disorder (kappa = 0.25 (95% CI, 0.1-0.4)) and for depressive disorder (kappa = 0.23 (95% CI, 0-0.46)). Sensitivity to the SCAN reference classification was also poor. Specificity ranged from 0.8 to 0.9. Rank order correlation for total depression symptoms was 0.43 (Kendall's tau b; P < 0.001; N = 205). DISCUSSION: High specificity indicates that the CIS-R and SCAN agree that prevalence rates for specific disorders are low compared with estimates in some community surveys. We have revealed substantial discrepancies in case finding. Therefore, published data on service utilization designed to estimate unmet need in populations requires re-interpretation. The value of large-scale CIS-R survey data can be enhanced considerably by the incorporation of concurrent semi-structured clinical assessments.

Adult↗
PubMed1998

Socioeconomic status, standard of living, and neurotic disorder.

BACKGROUND: Evidence on the association between socioeconomic status and the prevalence of neurotic disorder is contradictory. We studied the association between three elements of socioeconomic status and the prevalence of neurotic psychiatric disorder in a representative sample of adults aged 16-64 living in private households in the UK. METHODS: A cross-sectional survey of 10,108 adults aged 16-65 resident in private households in the UK was selected by a multi-stage, clustered, random-sampling design. Neurotic disorders were defined using a standardised interview, the revised clinical interview schedule (CIS-R). Data for 9570 people were available for this study. FINDINGS: We used housing tenure and access to cars as measures of standard of living; both were associated with the prevalence of neurotic disorder even after adjustment for other socioeconomic and demographic variables, including Registrar General's Social Class and educational attainment. Those people with no access to a car had an odds ratio for neurotic disorder of 1.4 (95% CI 1.1-1.7), compared with those who had access to two or more cars. People who rented their homes were also at increased risk (1.3 [1.1-1.5]). We estimated that about 10% of the neurotic disorder in the UK could be attributed to the increased prevalence of those without cars who rented their homes. There was a complex interaction between Registrar General's Social Class and sex, and there was no independent association with educational attainment. INTERPRETATION: There is an independent association between low standard of living and the prevalence of neurotic psychiatric disorder. The UK has experienced one of the largest increases in income inequality within western market economies over the past 20 years, and this inequality may have had adverse consequences for the mental health of the population.

Adolescent↗
PubMed1998

The Strengths and Difficulties Questionnaire: a pilot study on the validity of the self-report version.

The self-report version of the Strengths and Difficulties Questionnaire (SDQ) was administered to two samples of 11-16 year olds: 83 young people in the community and 116 young people attending a mental health clinic. The questionnaire discriminated satisfactorily between the two samples. For example, the clinic mean for the total difficulties score was 1.4 standard deviations above the community mean, with clinic cases being over six times more likely to have a score in the abnormal range. The correlations between self-report SDQ scores and teacher- or parent-rated SDQ scores compared favourably with the average cross-informant correlations in previous studies of a range of measures. The self-report SDQ appears promising and warrants further evaluation.

Adolescent↗
PubMed1998

The influence of age and sex on the prevalence of depressive conditions: report from the National Survey of Psychiatric Morbidity .

BACKGROUND: Women are consistently reported to have a greater prevalence of depressive disorders than men. The reason for this is unclear, and is as likely to be social as biological. There is some evidence that the excess of depression is greater during women's reproductive lives. Data from the National Survey of Psychiatric Morbidity were used to test the hypothesis that the excess disappeared in the post-menopausal years and that obvious social explanations for this were inadequate. METHOD: Subjects (N = 9792) from a random sample of the British population provided data for the analysis. Psychiatric assessment was carried out by lay interviewers using the CIS-R. Subjects with ICD-10 depressive episode or mixed anxiety/depression were compared with the remainder. Social variables that were likely to contribute to a post-menopausal decline in depressive disorders were controlled in logistic regression analyses. RESULTS: There was a clear reversal of the sex difference in prevalence of depression in those over age 55. This could not be explained in terms of differential effects of marital status, child care, or employment status. CONCLUSIONS: This large and representative survey adds considerably to the increasingly held view that the sex difference in prevalence of depression is less apparent in later middle age. This may be linked to the menopause, and our attempts to explain it in terms of obvious conditions among social variables were not successful. More specific studies are required to clarify the finding.

Adolescent↗
PubMed1998

Cell type-specific development of rodent central nervous system progenitor cells in culture.

OBJECT: The aim of the study was to assess the pluripotential central nervous system (CNS) progenitor cells that give rise to the many differentiated neuronal and glial cell types of the adult mammalian brain and the role of peptide growth factors such as the epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). The action of these factors is crucial to the survival and ultimate differentiation of these CNS progenitor cells. However, the precise role of EGF and bFGF in the time course of cellular development, the acquisition of cell type specificity, and possible differential mitogenic behavior has not been clearly defined. METHODS: The authors defined the time course of CNS progenitor cell development in cultured embryonic rodent cells by using immunocytochemical analysis to identify the expression of pluripotential (nestin)-, neuron (microtubule-associated protein-2 [MAP-2])-, and glia (glial fibrillary acidic protein [GFAP])-specific proteins in response to treatment with EGF and bFGF alone or in combination. The bromodeoxyuridine (BUdR) labeling index for each treatment group was used to define the mitogenic effects of each growth factor. In this investigation, the authors observed that progenitor cells develop in a stereotypical fashion when exposed to bFGF or EGF. Marked staining for nestin was evident soon after plating. This declined over time as staining for MAP-2 and GFAP increased. When treated with EGF alone, cells maintained their nestin immunoreactivity longer than those treated with bFGF alone or in combination with EGF. Treatment with bFGF alone promoted a significant increase in MAP-2 and, to a much lesser extent, GFAP reactivity. This was observed concomitant with the decline in nestin staining. The BUdR labeling index was similar among the different treatment groups and declined similarly over time in all treatment groups. CONCLUSIONS: The effects of EGF and/or bFGF on the expression of development- and lineage-specific markers likely reflect the specific effects of these factors on developmental processes. These data indicate that bFGF exerts a preferential effect on neuronal development and, to a lesser extent, glial development, which is not explained by selective mitogenicity. The persistence of nestin staining seen in the cells treated with EGF alone indicates that EGF may function as a stem cell survival factor. This study provides evidence that CNS cell type-specific development can be altered by the manipulation of peptide growth factors that act as differentiation agents.

Animals↗
PubMed1997

JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity: a review of its behavioural properties.

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5] benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50 = 3.9 mg kg-1 s.c.). It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse (ID50 = 4.4 mg kg-1 i.p.). JL13, like clozapine, was able to antagonize (+/-)-DOI-induced head-twitches in the mouse (ID50 = 2.0 mg kg-1 i.p.). In the open-field test in the rat and forced swimming test in the mouse a high similarity was noted between the two drugs in the same range of doses. In a complex temporal regulation schedule in the dog, JL13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats trained to discriminate clozapine, JL13 (10 mg kg-1 i.p.) induced a high level of generalization (70%) to clozapine. In a drug discrimination procedure in the squirrel monkey, JL13 (3-10 mg kg-1 i.m.) produced a full substitution of clozapine. On the basis of these preclinical data, it is thus predicted that JL13 would be a promising atypical antipsychotic drug.

Animals↗
PubMed1997

Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder.

It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity. The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan (200 mg, L-5-HTP; PO)-induced increases in plasma cortisol and prolactin (PRL) concentrations were studied in patients with major depression or obsessive compulsive disorder (OCD). Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD. The L-5-HTP-induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients. The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP. The L-5-HTP-induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different. The results suggest that fluoxetine, but not tricyclic antidepressants, potentiates 5-HT receptor-mediated stimulation of cortisol and PRL secretion in humans, consistent with available evidence that fluoxetine treatment, but not tricyclic antidepressants, increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism.

5-Hydroxytryptophan↗
PubMed1997

Diagnostic boundaries, reasoning and depressive disorder, II. Application of a probabilistic model to the OPCS general population survey of psychiatric morbidity in Great Britain.

BACKGROUND: Reliable prevalence and risk estimation of psychiatric disorder is a cornerstone to achieving objectives in public health psychiatry. Research strategies have increasingly depended, therefore, upon the progressive evolution and refinement of diagnostic approaches designed to reflect better current knowledge concerning prognosis, course and outcome but essentially the need to improve agreement between users of the various schemes. METHODS: This paper contrasts a conventional with a probabilistic approach to the diagnosis of depression based upon the OPCS United Kingdom National survey of psychiatric morbidity. The probabilistic approach, while designed to mimic current diagnostic practice in relation to the depressive disorders, naturally includes provision for the allocation of respondents on a scale of diagnostic uncertainty according to the severity of their presenting condition. RESULTS: Findings are reported arising from the application of the probabilistic method to three areas of research interest in public health psychiatry, namely; an evaluation of additivity of event exposure and depressive morbidity, secondly use of the approach for investigating psychosocial models of depressive disorder and thirdly for assessing the agreement between depressive disorder when classified according to competing diagnostic schemes. CONCLUSIONS: The results show application of the probabilistic approach to provide a firm basis for achieving gains in both the stability and precision of risk profile estimation for depressive conditions.

Adolescent↗
PubMed1997

The National Psychiatric Morbidity surveys of Great Britain--initial findings from the household survey.

BACKGROUND: This paper describes the Household Survey from the National Survey of Psychiatric Morbidity. This covered a sample drawn at random from the population of Britain, with the exception of the Highlands and Islands of Scotland. METHODS: The Postcode Address file was used as the sampling frame. Nearly 13000 adults aged 16-65 were selected for interview, of whom 10108 (79.4%) were successfully interviewed. Eight per cent could not be contacted and 13% refused interview. Psychiatric assessment was carried out by lay interviewers using the CIS-R. Subjects were also screened for psychosis, and screen-positive individuals were examined by psychiatrists using SCAN. RESULTS: Sixteen per cent of subjects scored above the standard cut-off of 12 on the CIS-R. The overall 1-week prevalence of neurotic disorder was 12.3% in males and 19.5% in females. Unmarried and post-marital groups had high rates of disorder, as did single parents and people living on their own. Respondents in Social Class I had notably lower rates of neurotic disorder than the remainder of the sample. Unemployment was strongly associated with disorder. Subjects living in urban areas had a higher overall prevalence, but there was no significant variation by region. Black respondents had higher rates of disorders that were entirely explained by their age, family type and social class. Individual neurotic disorders were all significantly commoner in women, with the exception of panic disorder. The 1-year prevalence of functional psychoses was 4 per 1000, with no sex difference. Alcohol and drug dependence was considerably more prevalent in men. CONCLUSIONS: For the first time, the survey provides data on the prevalence and correlates of psychiatric disorder on a nationwide sample that can be used to inform equitable and effective national psychiatric services.

Adolescent↗