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A J Pelosi

Publications and source records attributed to A J Pelosi.

At least 19 recordsLinked to original sources
PubMed2005

Mutational screening and association study of glutamate decarboxylase 1 as a candidate susceptibility gene for bipolar affective disorder and schizophrenia.

Recent evidence from postmortem studies suggests that GAD1 encoding the gamma-aminobutyric acid (GABA) synthetic enzyme GAD67 is a functional candidate susceptibility gene for both bipolar affective disorder (BPAD) and schizophrenia. Previous studies suggest linkage between D2S326 near GAD1 and BPAD. We systematically screened GAD1 exons, flanking intronic sequences, and the promoter sequence for polymorphisms in 16 BPAD patients and five controls from Denmark. We identified eight single nucleotide polymorphisms (SNPs) including two in the promoter sequence. An association study of SNPs covering GAD1 was performed in a Danish sample of 82 BPAD subjects and 120 controls and in a Scottish sample of 197 individuals with schizophrenia, 200 BPAD subjects and 199 controls. Linkage disequilibrium (LD) and haplotype frequencies were estimated from genotype data from eight SNPs. Strong pairwise LD was observed among all pairs of neighboring markers. In the Danish sample, we found weak association between BPAD and two promoter SNPs spaced 1 kb apart. Furthermore, one, two, and three loci haplotype analysis showed weak association with BPAD in the Danish sample. The results from the association studies indicate that promoter variants are of importance for the Danish BPAD cases and we cannot reject the hypothesis of GAD1 as a functional candidate gene for BPAD. No association was observed between BPAD or schizophrenia and any of the investigated SNPs in the Scottish sample set. Thus the results obtained from the Scottish sample suggest that the GAD1 gene variants do not play a major role in the predisposition to schizophrenia.

Bipolar Disorder↗
PubMed2005

Dimensions and classes of psychosis in a population cohort: a four-class, four-dimension model of schizophrenia and affective psychoses.

BACKGROUND: Classification of psychosis lacks a biological basis and current diagnostic categories may obscure underlying continuities. Data reduction methods of symptom profiles within a population-based cohort of people with a wide range of affective and non-affective psychoses may permit an empirical classification of psychosis. METHOD: OPCRIT (operational criteria) analysis was performed on 387 adults aged 18-65 years in an attempted ascertainment of all patients with psychosis from a geographical area with a stable population. The data were analysed firstly using principal components analysis with varimax rotation to identify factors, and secondly to establish latent classes. Information relating to key variables known to be of relevance in schizophrenia was coded blind to the establishment of the classes and dimensions. RESULTS: Striking correspondence was obtained between the two methods. The four dimensions emerging were labelled 'depression', 'reality distortion', 'mania' and 'disorganization'. Latent classes identified were 'depression', 'bipolar', 'reality distortion/depression' and 'disorganization'. The latent classes corresponded well with DSM-III-R diagnoses, but also revealed groupings usually obscured by diagnostic boundaries. The latent classes differed on gender ratio, fertility, age of onset and self-harming behaviour, but not on substance misuse or season of birth. CONCLUSIONS: Both dimensional and categorical approaches are useful in tapping the latent constructs underlying psychosis. Broad agreement with other similar studies suggests such findings could represent discrete pathological conditions. The four classes described appear meaningful, and suggest that the term non-affective psychosis should be reserved for the disorganization class, which represents only a subgroup of those with schizophrenia.

Adolescent↗
PubMed2004

Unexplained swelling symptoms in women (idiopathic oedema) comprise one component of a common polysymptomatic syndrome.

BACKGROUND: Non-menstrually-related swelling symptoms (idiopathic oedema) are common in women. The community prevalence of such symptoms, their association with other symptoms, and their underlying aetiology, are uncertain. AIM: To determine the community prevalence of swelling symptoms and the independent contributions of major risk factors. DESIGN: Comparison of major risk factors in women with and without swelling symptoms. METHODS: We assessed 196 women attending a menopause clinic, 201 women attending a fracture clinic and 201 women attending their general practitioner. Each documented family histories of swelling symptoms and diabetes mellitus, age, height and current weight. Women attending the menopause and fracture clinics also completed Visual Analogue Symptom (VAS) scales documenting the perceived severity of swelling symptoms, and of 20 affective, somatic and functional autonomic symptoms. The independent contributions of risk factors to swelling symptom risk were estimated by logistic regression analysis. RESULTS: Of those attending a fracture clinic or their general practitioner, 28% and 33%, respectively, experienced non-menstrually-related swelling symptoms in the month before interview. Severe (RR 43, 95%CI 16-112, p < 0.001) and moderate (RR 7.8, 95%CI 4-15, p < 0.001) affective symptoms, a family history of swelling symptoms (RR 4.5, 95%CI 2.3-8.8, p < 0.001) and a body mass index (BMI) >or=25 kg/m(2) (RR 4.8, 95%CI 2.5-8.9, p < 0.001) were significantly associated with the presence of mild to severe swelling symptoms (VAS 1-9). The prevalence of swelling symptoms increased from 8% in women with no risk factors to 100% in women with three risk factors, which included severe affective symptoms. DISCUSSION: Affective symptom severity provides the principal independent contribution to swelling symptom risk. BMI >or=25 and a family history of swelling symptoms provide smaller independent contributions. The nature of the mechanisms underlying these associations remains uncertain.

Adolescent↗
PubMed2001

The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia.

The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology of schizophrenia as they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensorimotor gating deficit characteristic of schizophrenia and in another, a key rôle for this gene in the modulation of hippocampal NMDA-dependent synaptic plasticity. In humans, GRM5 levels are increased in certain pyramidal cell neurons in schizophrenics vs controls.(6) Finally, GRM5 has been mapped to 11q14, neighbouring a translocation that segregates with schizophrenia and related psychoses in a large Scottish family, F23 (MLOD score 6.0). We determined the intron/exon structure of GRM5 and identified a novel intragenic microsatellite. A case-control association study identified a significant difference in allele frequency distribution between schizophrenics and controls (P = 0.04). This is suggestive of involvement of the GRM5 gene in schizophrenia in this population.

Case-Control Studies↗
PubMed2001

Identification of polymorphisms within Disrupted in Schizophrenia 1 and Disrupted in Schizophrenia 2, and an investigation of their association with schizophrenia and bipolar affective disorder.

We have undertaken a search for polymorphic sequence variation within Disrupted in Schizophrenia 1 and Disrupted in Schizophrenia 2 (DISC1 and DISC2), which are both novel genes that span a translocation breakpoint strongly associated with schizophrenia and related psychoses in a large Scottish family. A scan of the coding sequence, intron/exon boundaries, and part of the 5' and 3' untranslated regions of DISC1, plus 2.7 kb at the 3' end of DISC2, has revealed a novel microsatellite and 15 novel single nucleotide polymorphisms (SNPs). We have tracked the inheritance of four of the SNPs through multiply affected families, and carried out case-control association studies using the microsatellite and four common SNPs on populations of patients with schizophrenia or bipolar affective disorder versus normal control subjects. Neither co-segregation with disease status nor significant association was detected; however, we could not detect linkage disequilibrium between all these markers in the control population, arguing that an even greater density of informative markers is required to test rigorously for association in this genomic region.

Alleles↗
PubMed2001

Mental health and foster carer training.

AIMS: To evaluate the impact of training foster carers on children's emotional and behavioural functioning. METHODS: In a randomised controlled trial in 17 Scottish local council areas, with immediate and nine month follow up, 182 children and their foster families were randomly allocated to either standard services alone or standard services plus extra training for foster carers on communication and attachment. Main outcome measures were child psychopathology, attachment disorder, self esteem, and cost of foster care. RESULTS: Over 60% of children had measurable psychopathology at baseline. The training was perceived as beneficial by participants. Scores for parent reported psychopathology and attachment disorders decreased by around 5%, self esteem increased by 2%, and costs by 22% in the intervention group. Results were non-significant. CONCLUSIONS: Despite being well received by foster carers, the training was not sufficient to make a useful impact on the high level of psychopathology. This group may warrant more intensive interventions.

Caregivers↗
PubMed1997

A population-based incidence study of chronic fatigue.

BACKGROUND: Most research on syndromes of chronic fatigue has been conducted in clinical settings and is therefore subject to selection biases. We report a population-based incidence study of chronic fatigue (CF) and chronic fatigue syndrome (CFS). METHODS: Questionnaires assessing fatigue and emotional morbidity were sent to 695 adult men and women who had replied to a postal questionnaire survey 1 year earlier. Possible CFS cases, subjects with probable psychiatric disorder and normal controls were interviewed. RESULTS: Baseline fatigue score, the level of emotional morbidity and a physical attribution for fatigue were risk factors for developing CF. However, after adjusting for confounding, premorbid fatigue score was the only significant predictor. A minority of CF subjects, all female, had consulted their general practitioner; higher levels of both fatigue and emotional morbidity were associated with consultation. Possible CFS cases reported similar rates of current and past psychiatric disorder to psychiatric controls, but after controlling for fatigue or a diagnosis of neurasthenia the current rates were more similar to those of normal controls. Two new cases of CFS were confirmed. CONCLUSIONS: Both fatigue and emotional morbidity are integral components of chronic fatigue syndromes. The demographic and psychiatric associations of CFS in clinical studies are at least partly determined by selection biases. Given that triggering and perpetuating factors may differ in CFS, studies that examine the similarities and differences between chronic fatigue syndromes and psychiatric disorder should consider both the stage of the illness and the research setting.

Adult↗
PubMed1996

Needs for care from a demand led community psychiatric service: a study of patients with major mental illness.

UNLABELLED: OBJECTIVE--To measure needs for care of patients aged 18-65 years with major mental illness. DESIGN: Identification of everyone in one area seen by a health professional within the previous five years because of a psychotic disorder. Interview of a one in three sample of patients and their main carers with the cardinal needs schedule. SETTING--Hamilton, a socially deprived district of Scotland. SUBJECTS--71 subjects were interviewed from the original sample of 263 patients. MAIN OUTCOME MEASURES--"Cardinal problems" in seven clinical and eight social areas of functioning; these are defined as problems requiring action. "Needs"-cardinal problems for which suitable interventions exist but have not been tried recently. RESULTS--High levels of morbidity were found. 30 interviewed patients (42%; 95% confidence interval 31% to 54%) had one or more clinical needs. 35 (49%; 38% to 61%) had one or more social needs. Skills to deal with all but seven needs in the sample were available at the time of investigation. Patients not being seen by the community mental health team were similar in severity and levels of need to those who were on the community team's caseload. Care was unequivocally and severely inadequate for four patients. Shortcomings in service delivery usually arose from failure to monitor some patients at home. Problems were not due to shortage of acute psychiatric beds nor the absence of an elaborate assertive community care team. CONCLUSIONS--Systematic assessment of needs with research instruments can give valuable insights into the successes and failures of community care of people with major mental illness. Most needs could be dealt with in these patients but in our area (and probably most other parts of the United Kingdom) this would entail diversion of resources from people with less severe disorders.

Adult↗
PubMed1996

Thyroid function in idiopathic oedema.

BACKGROUND: The role of abnormal thyroid function in the aetiology of idiopathic oedema is unclear. Previous studies of small samples of patients have suggested a high prevalence of latent hypothyroidism and a possible deiodination defect in the conversion of T4 to T3 in this condition. There is a need to clarify the possible significance of abnormal thyroid function in a larger sample of idiopathic oedema patients. OBJECTIVE: The study was undertaken to compare basal thyroid function in idiopathic oedema patients and in an age and sex-matched control group. PATIENTS AND DESIGN: After excluding one idiopathic oedema patient and three control subjects with abnormal thyroid function, basal thyroid function was compared in 44 idiopathic oedema patients and in 44 age and sex-matched controls. MEASUREMENTS: Basal thyroid function was assessed in patient and control groups by measuring serum T4, fT4, T3, fT3 and TSH by standard methods. RESULTS: There were no significant differences in basal thyroid function between patient and control groups except for an elevated mean fT4 concentration in the idiopathic oedema group (P = 0.03). Exclusion of patients and controls taking oestrogen abolished this difference. T4:T3 ratios were similar in patient and control groups. CONCLUSION: Abnormalities of basal thyroid function are uncommon in patients with idiopathic oedema and appear unrelated to the pathogenesis of this disorder. Similar T4:T3 ratios between patient and control groups exclude a deiodination defect in idiopathic oedema.

Adult↗
PubMed1996

Computerized assessment of common mental disorders in primary care: effect on clinical outcome.

OBJECTIVE: A randomized controlled trial was conducted to examine the clinical effectiveness of providing general practitioners (GPs) with the results of a self-administered computerized assessment of common mental disorders. METHOD: Attenders at a general practice in a deprived inner city area of South London were identified using case finding questionnaires. Six hundred and eighty-one subjects were randomly allocated to three groups which differed in the information provided to the GP: 1) no additional information was given to the GP; 2) the results of the 12 item General Health Questionnaire (GHQ) were given to the GP (the GHQ is a paper and pencil questionnaire that assesses common mental disorders); 3) the results of a self-administered computerized assessment (PROQSY) of common mental disorders were provided for the GP. RESULTS: Clinical outcome was assessed using the 12-item GHQ. Consultations with the GP, prescriptions and referrals within and outside the practice were also recorded. The group in whom the GP received the results of the computerized assessment showed a modest clinical improvement, relative to the other two groups after 6 weeks. There was no difference in clinical outcome between the groups at 6 months. There appeared to be no increase in consultations or prescriptions in the computerized assessment group. CONCLUSIONS: Self-administered computerized assessments for psychiatric disorder have potential as a means of improving the clinical outcome of patients in primary care. It is likely that the effectiveness of the approach would be greatly increased by linking the results of computerized assessments to clinical practice guidelines, tailored to the individual patient by means of computerized technology.

Adolescent↗
PubMed1995

Chronic fatigue syndrome in the community. Prevalence and associations.

BACKGROUND: Chronic fatigue syndrome (CFS) is a poorly understood condition, apparently related to both psychiatric disturbance and infectious illness. Little progress has been made in identifying aetiology, owing to a lack of epidemiological studies using case-definition criteria. METHOD: A community postal survey of a random sample of over 1000 patients registered at a local health centre comprised a fatigue questionnaire and the 12-item General Health Questionnaire (GHQ). RESULTS: Total fatigue scores were modestly higher in women than men. Fatigue was most frequently attributed to psychosocial factors. Fatigue and GHQ scores were strongly correlated. Two men and two women satisfied British criteria for CFS, a prevalence of 0.56% (95% Cl 0.16-1.47%); three were probable psychiatric cases. CONCLUSIONS: Previously reported sociodemographic associations of CFS may reflect medical referral patterns. A strong association exists with psychological morbidity, but relabelling CFS as a psychiatric disorder is not justified.

Adolescent↗