Biomedical subjects

P Sham

Publications and source records attributed to P Sham.

At least 73 records · Page 4Linked to original sources

PubMed1997

A controlled family study of late-onset non-affective psychosis (late paraphrenia).

BACKGROUND: The relationship between those schizophrenia-like conditions that have their onset in late life and early-onset schizophrenia is unclear. Very few family history studies of patients with late-onset psychosis have been reported, and it is not known whether their relatives have an increased risk of psychosis. METHOD: Information was collected on the psychiatric morbidity of 269 first-degree relatives of patients with schizophrenia or delusional disorder with an onset after the age of 60 (late paraphrenia), and 272 first-degree relatives of healthy elderly control subjects, using a research diagnostic instrument. RESULTS: With a narrow age range (15-50 years) at risk, the estimated lifetime risk of schizophrenia was 1.3% in the relatives of both cases and controls. With a wider age range (15-90 years) at risk, estimated lifetime risk of schizophrenia was 2.3% for the relatives of cases and 2.2% for the relatives of controls. However, depression was significantly more common among the relatives of cases than controls. CONCLUSIONS: Those schizophrenia-like psychoses with onset in late life are not genetically associated with schizophrenia.

Adult↗

PubMed1997

Carers' knowledge of dementia and their expressed concerns.

OBJECTIVE: The authors wished to determine how much carers from different settings caring for patients with dementia knew about the disorder and elicit their main concerns about the disease. DESIGN: A survey questionnaire was administered to 136 carers. SETTING: Two old age psychiatric services and an Alzheimer's support group in urban areas of the UK. PARTICIPANTS: The carers came from one of three categories: (1) carers with no prior contact with elderly mental health services (preassessment group); (2) carers who had been in contact with mental health care professionals (postassessment group); (3) carers in contact with an Alzheimer's Disease Society support group. MEASURES: A questionnaire on the subject of dementia. Carers' worries about the disorder were also recorded. RESULTS: Carers in contact with an Alzheimer's support group were the most knowledgeable and carers in the preassessment group were the least knowledgeable on the subject of dementia. While carers in the postassessment group had a level of knowledge above that of the preassessment group, this difference failed to reach statistical significance. CONCLUSION: The study highlights the need for elderly mental health teams to evaluate their methods of dissemination of knowledge to carers, develop educational packages for carers and evaluate their effectiveness.

Aged↗

PubMed1997

Carers' knowledge of dementia, their coping strategies and morbidity.

OBJECTIVE: The main hypothesis was that carers of dementia sufferers who have a higher level of knowledge on the subject of dementia have lower rates of physical and psychological morbidity. We also wanted to examine whether a carer's level of knowledge bears any relation to their attributional style and coping mechanisms. DESIGN: Informal carers, caring for patients who fulfilled the CAMDEX criteria for mild or moderate dementia, were approached to participate in the study. SETTING: Old age psychiatry services in the West Midlands and Bristol. PARTICIPANTS: Informal carers, caring for relatives with dementia. MEASURES: Trained researchers administered the Geriatric Mental State Schedule, the Dementia Knowledge Questionnaire, the Pennebaker Inventory of Limbic-Languidness (an inventory of common physical symptoms) and the Carer Stress Scale. RESULTS: More knowledgeable carers experienced significantly lower levels of depression but also higher rates of anxiety. Carers' level of knowledge on the subject of dementia showed no association with their physical health. More knowledgeable carers were more likely to have 'reduced expectations' of their dependants' abilities and make 'positive comparisons'; they were also more likely to feel competent and confident as carergivers. CONCLUSION: The findings support the main hypothesis when considering carers' rates of depression but not when considering rates of anxiety or physical ill-health.

Adaptation, Psychological↗

PubMed1996

Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine.

Clozapine is an atypical antipsychotic with affinity for a broad range of receptors, including serotonin (5-HT) and dopamine receptors. It is successful in treating about 60% of patients refractory to other antipsychotic drugs. Since genetic variation in clozapine's neurotransmitter receptor targets may affect clinical response through altering drug binding or receptor expression, we have studied a His452Tyr polymorphism in the 5-HT2A receptor (HTR2A) in a sample of 153 schizophrenic patients undergoing clozapine treatment and 178 normal controls. An association was found between the allele Tyr452 and poor clinical response.

Alleles↗

PubMed1996

The serotonin transporter is a potential susceptibility factor for bipolar affective disorder.

The serotonin transporter is a strong candidate for aetiological involvement in affective disorders and psychosis. We analysed a VNTR in intron 2 of the human serotonin transporter gene (hSERT) for allelic association with bipolar affective disorder, unipolar depression and schizophrenia. An increased frequency of allele 12 of the VNTR was observed in subjects with bipolar affective disorder (n = 191; chi 2 p = 0.00048 by allele) but not unipolar depression (n = 86; chi 2 p = 0.18, ns) or schizophrenia (n = 129; chi 2 p = 0.08, ns), although a trend towards an excess of allele 12 was observed for the latter. There was also a significant difference in the frequency of allele 12 between bipolar affective disorder and unipolar depression (p = 0.0087). The relative risk for bipolar affective disorder with respect to allele 12 was 1.84 (95% CI 0.97-3.56) for heterozygotes, and 3.10 (95% CI 1.60-6.07) for homozygotes, with evidence for a gene-dosage effect. Because allele 12 is common in the population, the attributable risk is 50.8% (95% CI 14.5%-73.3%). We hypothesize that either the VNTR affects regulation of expression of hSERT at the transcriptional level or it is in linkage disequilibrium with another functional polymorphism in the gene, and this results in an increased risk for the development of bipolar affective disorder.

Alleles↗

PubMed1996

A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets (Vallada et al., Am J Med Genet 60:139-146, 1995; Polymeropoulos et al., Neuropsychiatr Genet 54:93-99, 1994; Lasseter et al., Am J Med Genet, 60:172-173, 1995. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not share (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that may be a susceptibility locus for schizophrenia at 22q12.

Alleles↗

PubMed1996

Statistical methods of estimation and inference for functional MR image analysis.

Two questions arising in the analysis of functional magnetic resonance imaging (fMRI) data acquired during periodic sensory stimulation are: i) how to measure the experimentally determined effect in fMRI time series; and ii) how to decide whether an apparent effect is significant. Our approach is first to fit a time series regression model, including sine and cosine terms at the (fundamental) frequency of experimental stimulation, by pseudogeneralized least squares (PGLS) at each pixel of an image. Sinusoidal modeling takes account of locally variable hemodynamic delay and dispersion, and PGLS fitting corrects for residual or endogenous autocorrelation in fMRI time series, to yield best unbiased estimates of the amplitudes of the sine and cosine terms at fundamental frequency; from these parameters the authors derive estimates of experimentally determined power and its standard error. Randomization testing is then used to create inferential brain activation maps (BAMs) of pixels significantly activated by the experimental stimulus. The methods are illustrated by application to data acquired from normal human subjects during periodic visual and auditory stimulation.

Acoustic Stimulation↗

PubMed1996

Life events before psychotic episodes: do clinical and social variables affect the relationship?

We have previously used data from the Camberwell Collaborative Psychosis Study to demonstrate a strong relationship between life events and subsequent episodes of schizophrenic, manic and depressive psychoses. In the current paper, we confirmed the robustness of this relationship, which was not vitiated by controlling for clinical and social variables. Thus, the event-onset association was not affected by the type of onset or the number of previous episodes. The influences of social variables, such as social class, ethnicity and marital status, did not seriously diminish the importance of events, although there may be a role for other forms of social disadvantage as reflected in these variables.

Adolescent↗

PubMed1996

Assessing the statistical power to detect linkage in a sample of 51 bipolar affective disorder pedigrees.

We used computer simulation method to address the question of power in an initial collaborative sample of 51 bipolar affective disorder pedigrees. Simulations were performed for all possible combinations using (1) two levels of diagnostic stringency, (2) three transmission models, (3) locus heterogeneity, and (4) different assumed phenocopy rates. Some of the factors affect the power to detect linkage are (1) the specification of the correct genetic model, (2) the degree of locus heterogeneity, and (3) the frequency of phenocopies. The first two assertions were supported by our simulation results, but varying the rates of phenocopy did not substantially alter the power of the sample until a critical point. However, it is important to point out that these results are dependent on the genetic models under study and on the use of the "correct" model (i.e., the one used to simulate the data). If we assume a dominant mode of inheritance and locus homogeneity, the power to detect linkage is 97.5% at a theta of .01. However, the power declines dramatically, to 60.5% and 14.7%, if only 75 and 50% of the families are linked, respectively. Locus heterogeneity has a similar effect on the power of the sample to exclude linkage. The relative lack of power in our data, in the presence of significant locus heterogeneity, and for an intermediate mode of inheritance, underscores the need for multicenter collaboration.

Adolescent↗

PubMed1996

Do obstetric complications cause the earlier age at onset in male than female schizophrenics?

We compared the age at onset of 184 patients with functional psychoses with and without a history of obstetric complications (OCs) as defined by the scale of Lewis et al. (1989). OCs had no significant influence on the age at onset in those patients who had affective psychoses or were non-white. There were 73 white patients with a DSM-III-R diagnosis of schizophrenia. The mean age at onset of those 25 who had a history of at least one definite OC was 2.6 years earlier than that of the 48 patients with no history of OCs. This effect was entirely due to the male patients with histories of OCs who had, on average, a 3.5 years earlier age at onset. There were no gender differences in age at onset among schizophrenics without a history of OCs. We suggest that a subgroup of male patients with a history of OCs is responsible for the earlier age at onset in male compared to female schizophrenics.

Black or African American↗

PubMed1996

Psychopathological syndromes in the functional psychoses: associations with course and outcome.

The aim of this study was to identify underlying dimensions of psychopathology in a cohort of patients with functional psychosis of recent onset, and to examine their prognostic value. Factor analysis of the psychopathological features of 166 consecutively admitted patients with functional psychosis of recent onset revealed seven psychopathological dimensions, which explained 63% of the variance. Five of these seven syndromes bore differential associations with subsequent treatment and illness course, independent of: (i) associations with DSM-III-R diagnosis; (ii) associations with other prognostic factors; and (iii) associations with the baseline values of outcome variables. The most striking associations were shown for an early and insidious onset syndrome with affective flattening, which predicted a more disabled course of illness on three of four outcome dimensions, and which was more common in males and unmarried individuals. A second syndrome, characterized by bizarre behaviour, inappropriate affect, catatonia, and poor rapport showed similar, slightly less striking, associations with illness course, as well as with poor pre-morbid social functioning. A third syndrome, characterized by positive psychotic symptoms was to a lesser degree associated with poorer outcome, whereas a fourth syndrome distinguished by manic symptomatology predicted a more benign illness course. A fifth syndrome identified by lack of insight predicted more time in hospital and admission under a section of the Mental Health Act during the follow-up period. A further finding was that dimensional representations of psychopathological features were considerably more useful than categorical representations (DSM-III-R and ICD-10) as predictors of illness course and treatment decisions.

Adolescent↗

PubMed1996

Genetic epidemiology.

Studies of families, twins, and adoptees have helped to quantify the genetic contributions to and overlaps between depression, anxiety, phobias and alcoholism, and to refine the boundaries of the schizophrenia spectrum. Analyses of covariance structures in twin data have confirmed genetic susceptibility and recent life stresses as the major determinants of depression. Genetic modelling of family data on schizophrenia and bipolar disorder indicates three or more common genes each having a small multiplicative effect on risk, although rare major genes may be present in some families. Linkage studies have localised genes for familial Alzheimer's disease on chromosomes 14 and 21; disease mutations on these chromosomes have since been isolated. Association studies have identified susceptibility (or protective) genes for Alzheimer's disease and alcoholism. Several tentative linkage and association findings in schizophrenia and bipolar disorder require further study.

Alcoholism↗

PubMed1996

A factor analytic study of symptoms in acute schizophrenia.

The three-syndrome model of schizophrenic phenomenology has been well established in chronic illness. We report an attempt to replicate this concept in a sample of acutely unwell schizophrenic patients. Factor analysis was performed using PSE data collected within a week of admission from 114 patients who met DSMIII(R) diagnostic criteria for schizophrenia. Four main factors accounted for 58% of the variance. The first two factors closely resembled Liddle's disorganisation and psychomotor poverty syndromes. Hallucinations and delusions loaded separately under the third and fourth factors. To examine the validity of these four syndromes, the relationships between factor scores and other clinical data were examined. The disorganisation syndrome was associated with a history of multiple past admissions and a longer lifetime duration of in-patient treatment.

Acute Disease↗

PubMed1996

Familial psychiatric presentation of Huntington's disease.

Symptoms of schizophrenia may be encountered in Huntington's disease (HD) but usually when the full clinical syndrome is apparent; prechoreic psychosis is relatively uncommon. We describe a family where all four members affected with HD presented first with a severe psychiatric syndrome, which in three cases was schizophreniform in nature. Two other living members with no current signs of motor disorder have received psychiatric treatment, one for schizophrenia. Concurrence of psychosis and Huntington's disease in this family is unlikely to have occurred by chance, suggesting that there is some feature in this family which gives rise to the psychotic presentation. Families such as this may contribute to the investigation of genetic factors associated with psychiatric illnesses.

Adult↗

PubMed1996

Does familiality predispose to both emergence and persistence of psychosis? A follow-up study.

BACKGROUND: It as been suggested that in schizophrenia an association exists between family history of schizophrenia and poor outcome on the one hand, and family history of affective disorders and good outcome on the other. METHOD: We tested for associations between four-year outcome and familial loading for psychotic disorders in a mixed sample of 150 consecutively admitted patients with functional psychosis (schizophrenia, psychotic affective disorders, other psychotic disorders) of recent onset. For each proband, a familial loading score for (i) broadly defined psychotic disorder, (ii) schizophrenia, and (iii) affective disorder was calculated using information on relatives obtained through the Family History Research Diagnostic Criteria method and direct interviews of relatives with the Schedule for Affective Disorders and Schizophrenia. RESULTS: In our sample of psychotic patients, familial loading for psychotic disorder predicted persistent negative symptoms over the follow-up period (OR 1.5; 95% CI 1-2.2), especially in schizophrenia, and was also associated with more time hospitalised (P < 0.05) [corrected], and more social disability at follow-up (P < 0.05). Greater familial loading for schizophrenia predicted a greater likelihood of non-recovery (OR 2.2; 95% CI 1.1-4.4) and a greater likelihood to have had persistent negative symptoms over the follow-up period (OR 1.7; 95% CI 0.9-3.1). No association was found between outcome and familial loading for affective disorder. CONCLUSIONS: We conclude that familial loading may be a continuous risk factor for some dimensions of clinical outcome in the functional psychoses. This suggests that there is a continuum of genetic liability not only to the emergence of psychotic illness, but also the subsequent chronicity of the disorder.

Adolescent↗

PubMed1996

Morbid risk of schizophrenia in first-degree relatives of white and African-Caribbean patients with psychosis.

BACKGROUND: The high rate of schizophrenia among the second-generation African-Caribbean population in Britain has prompted much concern and speculation. Sugarman and Craufurd have reported that the morbid risk in the siblings of second-generation African-Caribbean schizophrenic patients was unusually high compared with that of the siblings of White patients. METHOD: We sought to replicate these findings by comparing the morbid risk for schizophrenia in the first-degree relatives of 111 White and 73 African-Caribbean psychotic probands. The latter comprised 35 first-generation (born in the Caribbean) and 38 second-generation (born in Britain) probands. RESULTS: The morbid risk for schizophrenia was similar for the parents and siblings of White and first-generation African-Caribbean patients, and for the parents of the second-generation African-Caribbean probands. However, the siblings of second-generation African-Caribbean psychotic probands had a morbid risk for schizophrenia that was seven times that of their White counterparts (P = 0.007); similarly, the siblings of second-generation African-Caribbean schizophrenic probands had a morbid risk for schizophrenia that was four times that of their White counterparts (P = 0.05). CONCLUSIONS: These findings replicate those of the earlier report of Sugarman and Craufurd, and suggest either that the second-generation African-Caribbean population in Britain is particularly vulnerable to some environmental risk factors for schizophrenia, or that some environmental factors act selectively on this population in Britain.

Adult↗

PubMed1996

A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders.

The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessively of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.

Alleles↗

PubMed1995

Association between clozapine response and allelic variation in the 5-HT2C receptor gene.

A cysteine to serine substitution at amino acid 23 in the 5-HT2C receptor gene alters the pharmacological properties of the protein. We investigated this polymorphism in subjects with schizophrenia resistant to conventional neuroleptic drugs, and analysed our data for allelic association between the disease state or clinical response to the atypical antipsychotic drug, clozapine. Ninety percent of subjects who had one or more 5-HT2Cser alleles (19/21) were classified as clozapine responders compared with 59% (84/141) without this allele (chi 2 = 7.7, p = 0.005), suggesting that this mutation is a predictor of good response to clozapine. There was no association between schizophrenia and the 5-HT2Cser allele, but our results indicate that the 5-HT2C receptor may contain the major site of action through which clozapine mediates its antipsychotic effects.

Alleles↗