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H Meltzer

Publications and source records attributed to H Meltzer.

At least 19 recordsLinked to original sources
PubMed2001

A general population comparison of the Composite International Diagnostic Interview (CIDI) and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN).

BACKGROUND: In psychiatric surveys of the general population, there has been considerable discrepancy between diagnoses obtained by fully structured interviews and those established by systematic semi-structured clinical evaluation. The Composite International Diagnostic Interview (CIDI) is an example of the first type of interview widely used in general population surveys. We compared its performance in diagnosing current depressive and anxiety disorders with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), a semi-structured diagnostic interview administered by clinically trained interviewers. METHODS: Household addresses in Leicestershire, UK, were randomly sampled and 860 adults were screened with the Revised Clinical Interview Schedule. Adults with too few symptoms to fulfil diagnostic criteria for study disorders were excluded to increase the proportion re-interviewed who met such criteria. Repeat diagnostic interviews with the CIDI and SCAN, ordered randomly, were sought from eligible screen positive respondents. Recalibrated CIDI prevalence estimates were derived from the SCAN classification using Bayesian statistics. RESULTS: Concordance ranged between 'poor' and 'fair' across almost all types of study disorders, and for co-morbidity. Concordance was somewhat better for severity of depression and when lower diagnostic thresholds were used for depression. Interview order effects were suggested with lower concordance when CIDI followed SCAN. Recalibration reduced the prevalence of depressive or anxiety disorder from 9.0 to 6.2%. CONCLUSIONS: Community psychiatric surveys using structured diagnostic interview data must be interpreted cautiously. They should include an element of clinical re-appraisal so findings can be adjusted for estimation differences between fully structured and clinical assessments.

Adolescent↗
PubMed2001

Treatment with interferon-alpha (IFN alpha) of hepatitis C patients induces lower serum dipeptidyl peptidase IV activity, which is related to IFN alpha-induced depressive and anxiety symptoms and immune activation.

We have shown that treatment with interleukin-2 (IL-2) or interferon-alpha (IFN alpha) may induce depressive symptoms and activation of the cytokine network and that IL-2 treatment may diminish serum dipeptidyl pepdidase IV (DPP IV) activity. DPP IV (EC 3.4.14.5) is a membrane bound serine protease which catalyzes the cleavage of some cytokines and neuroactive peptides which modulate T cell activity. The aims of the present study were to examine the effects of IFN alpha-based immunotherapy on serum DPP IV activity in relation to induction of the inflammatory response system. In 18 patients with chronic active hepatitis C, we determined the Montgomery and Asberg Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), serum DPP IV activity, the kynurenine/tryptophan (K/T) quotient, which is an indicator of cytokine (in particular IFN)-induced catabolism of tryptophan, and serum interleukin-8 (IL-8) before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFN alpha. IFN alpha-immunotherapy significantly suppressed serum DPP IV 2--4 weeks and 16--24 weeks after starting IFN alpha-based immunotherapy. The reduction in serum DPP IV activity was more pronounced 16--24 weeks after starting immunotherapy than after 2--4 weeks. The IFN alpha-induced suppression of serum DPP IV activity was significantly correlated to IFN alpha-induced increases in the MADRS and HAM-A and increases in the K/T quotient and serum IL-8. In conclusion, long-term immunotherapy with IFN alpha suppresses serum DPP IV activity and the immunotherapy-induced changes in DPP IV are related to increases in severity of depression, anxiety and activation of the inflammatory response system.

Adult↗
PubMed2001

Prevalence of pervasive developmental disorders in the British nationwide survey of child mental health.

OBJECTIVE: The prevalence of pervasive developmental disorders (PDD) is not well established and needs monitoring. The prevalence of PDD in the 1999 nationwide British survey of child and adolescent mental health was investigated. METHOD: A randomized, stratified sample of children (N= 12,529) aged 5 to 15 years was generated from the Child Benefit Register. Trained interviewers interviewed parents and youths aged 11 or older with a standardized diagnostic interview (Development and Well-Being Assessment), and questionnaire data (Strengths and Difficulties Questionnaire) were obtained from teachers and parents, who also completed self-report measures of psychological distress. Final diagnostic determination was achieved by a team of experienced clinicians using all data sources. RESULTS: A total of 10,438 (83%) interviews were conducted. There were 2 girls with Rett syndrome (weighted prevalence: 3.8/10,000 girls) and 27 children with other PDD (weighted prevalence: 26.1/10,000). Compared with children with a psychiatric disorder other than PDD, social but not behavioral problems were more frequent in the PDD group. Parents of children with PDD had higher rates of psychological distress than those from the two comparison groups. CONCLUSIONS: Consistent with other recent surveys, PDD rates are higher than those reported 30 years ago. The burden associated with PDD is very high.

Adolescent↗
PubMed2001

Stimulation of the epidermal growth factor receptor induces glial-specific protein expression in the human DAOY neuroectodermal cell line.

Central nervous system (CNS) stem cells require epidermal growth factor (EGF) to survive and express glial-specific proteins (GSPs) under its influence. EGF and its receptor (EGF-R) therefore are involved in gliogenesis. We hypothesize that EGF selectively modulates GSP expression in pluripotential CNS cells and this effect is dependent on the degree of EGF-R activation (i.e., the amount of both EGF and the EGF-R present). In order to explore this, we investigated the effects of EGF on the expression of glial- and neuronal-specific proteins in the pluripotential human neuroectodermal cell line, DAOY. DAOY clones expressing different EGF-R levels were treated with EGF. The expression of glial fibrillary acid protein (GFAP), glutamine synthetase (GS) and neuron-specific enolase (NSE) were measured by ELISA. In a clone with low EGF-R levels (clone DAOY-YS-15), EGF selectively stimulated GSPs. In cells which express twice the EGF-R level, EGF (10(-8) M) stimulated both glial and neuronal proteins nonspecifically. In cells with higher EGF-R numbers, EGF suppressed both glial and neuronal proteins. These effects were not due to the negligible growth influences of EGF on the cells. In clone DAOY-YS-15, selective GSP expression was observed as early as 2 days after exposure to EGF (10(-9) M). In these cells, GFAP induction was also shown at the transcriptional level using a quantitative reverse transcriptase-polymerase chain reaction. This suggests one mechanism for EGF action. Our findings are therefore consistent with the hypothesis that the selective induction of GSPs in pluripotent cells is dependent on the EGF-R level and the degree of EGF-R activation.

Cell Division↗
PubMed2001

Prevalence of obsessive-compulsive disorder in the British nationwide survey of child mental health.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disorder that appears to be underdiagnosed and undertreated, despite the evidence for effective treatments. There are variable estimates of OCD prevalence in the under-16s and published rates give little indication of age trends. AIMS: To establish the prevalence and associates of OCD in young people aged 5-15 years. METHOD: A nationwide (UK) epidemiological study of rates of psychiatric disorder in 5- to 15-year-olds (1999 British Child Mental Health Survey): 10 438 children were assessed. RESULTS: Twenty-five children with OCD were identified (weighted overall prevalence 0.25%; 95% CI 0.14-0.35), with prevalence rising exponentially with increasing age. Compared with normal controls, children with OCD were more likely to be from lower socio-economic class and of lower intelligence. Only three of these children had been seen by specialist children's services. CONCLUSIONS: Although OCD is rare in young children, the rate increases towards the adult rates at puberty. Children with OCD have additional psychosocial disadvantage. The majority of the childhood cases identified in this survey appear to have been undetected and untreated.

Adolescent↗
PubMed2001

Nicotine, alcohol and drug dependence and psychiatric comorbidity. Results of a national household survey.

BACKGROUND: There is a well-recognised relationship between substance use disorders and other psychiatric disorders. This relationship has been well documented in a range of population-based studies. AIMS: This study aims to report on consumption patterns of and dependence on nicotine, alcohol and non-prescribed drugs and to report on the levels of psychiatric morbidity in these groups. METHOD: A national household study of psychiatric morbidity was conducted in England and Wales. Psychiatric assessment was based on the Clinical Interview Schedule-Revised (CIS-R). Measures of nicotine, alcohol and drug use and dependence were obtained. This paper compares the levels of psychiatric morbidity in the non-dependent and the nicotine-, alcohol- and drug-dependent cases. RESULTS: Twelve per cent of the non-dependent population were assessed as having any psychiatric disorder compared with 22% of the nicotine-dependent, 30% of the alcohol-dependent and 45% of the drug-dependent population. CONCLUSIONS: There is a clear relationship between dependence on nicotine, alcohol and drugs and other psychiatric morbidity.

Adolescent↗
PubMed2000

Psychiatric disorder and dysfunction in the UK National Survey of Psychiatric Morbidity.

BACKGROUND: Psychiatric symptoms are wide-spread in the general population, but have little effect on performance. Deficits in performance and psychiatric symptoms may be the end point of processes common to both, or they may be caused by quite different factors. In this paper we examine the epidemiological distribution of psychiatric symptoms and performance deficits, as indicated by difficulties in activities of daily living (ADL). We hypothesised that ADL difficulties are partly independent of psychiatric symptoms, and that this is reflected in a different demographic distribution. METHOD: The household component of the National Surveys of Psychiatric Morbidity was based on a sample of around ten thousand subjects selected at random from the population of Great Britain. Psychiatric symptoms were elicited by lay interviewers using the revised Clinical Interview Schedule. Performance was assessed by asking about difficulties experienced in performing seven types of everyday activity. In this paper, our chosen variables were overall symptom and ADL deficit scores, and these were related to standard demographic variables. RESULTS: There were significant differences in the epidemiological distribution of psychiatric symptoms and ADL difficulties. In particular, men experienced more ADL difficulties at a given symptom level than women. There were also differences in relation to social class, employment status, marital status, ethnic group and age. CONCLUSIONS: ADL deficits and psychiatric symptoms are related in the general population, and this probably represents common factors in their origin. However, discrepancies in the social distribution of these phenomena suggest there are also aetiological differences. These do not appear to be the result of the impact of physical illness on activities of daily living. Our results emphasise that ADL difficulties should be studied separately, particularly in investigations of treatment seeking.

Activities of Daily Living↗
PubMed2000

Urban-rural mental health differences in great Britain: findings from the national morbidity survey.

BACKGROUND: Studies of urban-rural differences in prevalence of non-psychotic mental disorder have not given consistent findings. Such differences have received relatively little study in Great Britain. METHODS: Data from 9777 subjects in the Household Survey of the National Morbidity Survey of Great Britain were analysed for differences between urban, semi-rural and rural areas. Psychiatric morbidity was assessed by scores on the Revised Clinical Interview Schedule (CIS-R), together with alcohol dependence, drug dependence, receipt of treatment from general practitioners. Associations with other characteristics were examined by logistic regression. RESULTS: Urban subjects had higher rates than rural of CIS-R morbidity, alcohol dependence and drug dependence, with semi-rural subjects intermediate. Urban subjects also tended to be members of more deprived social groups, with more adverse living circumstances and greater life stress, factors themselves associated with disorder. Urban-rural differences in alcohol and drug dependence were no longer significant after adjustment for these factors by logistic regression, and differences on CIS-R morbidity were considerably reduced. There were no differences in treatment. CONCLUSIONS: There are considerable British urban rural differences in mental health, which may largely be attributable to more adverse urban social environments.

Adolescent↗
PubMed2000

Unequal access and unmet need: neurotic disorders and the use of primary care services.

BACKGROUND: In this paper we use data from the National Survey of Psychiatric Morbidity to examine how many people with neurotic disorders receive professional evaluation, and how this is affected by clinical and sociodemographic differences. We hypothesized that psychiatric symptoms and attendant dysfunctions would both have an effect on contacting, and that key demographic variables would not. METHOD: The household component of the British National Surveys of Psychiatric Morbidity was based on a random sample of > 10,000 subjects. Psychiatric symptoms and ICD-10 diagnosis were established by lay interviewers using the CIS-R. Social dysfunction was tapped by asking about difficulties in performing seven types of everyday activity. We examined symptom score, ADL deficit score and demographic variables in relation to contact with primary care physicians for psychiatric symptoms. RESULTS: The major determinant of contacting a primary care physician was severity, mainly due to the level of psychiatric symptoms, but with an independent contribution from social dysfunction. There were also significant contributions from sex, marital status, age, employment status and whether the subject had a physical condition as well. CONCLUSIONS: The major influence on whether people seek the help of their family doctors for mental health problems is the severity of disorder. Although there are some social inequalities in access to family doctors, these are less important. The most salient finding from our study is that even people suffering from high levels of psychiatric symptoms very often do not have contact with professionals who might help them.

Activities of Daily Living↗
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↗