Sayeed Haque

The impact of disease recurrence on graft survival following liver transplantation: a single centre experience

Many diseases that cause liver failure may recur after transplantation. A retrospective analysis of the rate and cause of graft loss of 1840 consecutive adults receiving a primary liver transplant between 1982 and 2004 was performed to evaluate the rate of graft loss from disease recurrence. The risk of graft loss from recurrent disease was greatest, when compared to primary biliary cirrhosis (PBC), in those transplanted for hepatitis C virus (HCV) [hazard ratio (HR) 11.6; 95% confidence interval (CI) 5.1–26.6], primary sclerosing cholangitis (PSC) (HR 6.0; 95% CI 2.5–14.2) and autoimmune hepatitis (AIH) (HR 4.1; 95% CI 1.3–12.6). The overall risk of graft loss was also significantly greater in HCV (HR 2.1 vs. PBC; 95% CI 1.5–3.0), PSC (HR 1.6 vs. PBC; 95% CI 1.2–2.3) and AIH (HR 1.6; 95% CI 1.0–2.4) than in PBC. There was no statistically significant difference in the risk of graft loss because of recurrent disease, when compared with PBC, for patients transplanted for alcohol related liver disease, nonalcoholic steatohepatitis and fulminant hepatic failure. Disease recurrence is a significant cause of graft loss particularly in HCV, PSC and AIH. Recurrent disease, in part, explains the increased overall risk of graft loss in these groups.

Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen: evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21, 10p14-p12 and 18q22

Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16–q21 (MLS=2.61) and 4q12–q21 (MLS=2.38). 6q16–q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male–male pairs. Our scan also provides support for linkage (MLS≥1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14–p12 and 18q22.

Role of 5HT2A and 5HT2C polymorphisms in behavioural and psychological symptoms of Alzheimer's disease

Abstract Objective Alzheimers disease (AD) patients suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. Polymorphisms within serotonin receptors 5HT2A and 5HT2C have been previously investigated in a few interesting studies reviewed here, however, their role remains unclear. Methods Our large cohort of 394 patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period and give each patient a severity score. These measures were related to the 5HT2A T102C and 5HT2C cys23ser genotype and allele frequencies. Results Our data supports previous reports of an increased frequency of the C allele and CC genotype of the T102C variant of 5HT2A with hallucinations, delusions, psychosis and aberrant motor behaviour, however, we dispute previous associations with depression and aggression. We describe for the first time an increase in the C allele and CC genotype frequencies of the cys23ser variant of 5HT2C with anxiety and support previous associations with appetite disturbances in females. Conclusion This review and extension of previous data presents support for the role of 5HT2A and 5HT2C in the development of certain symptoms, although the effect size may be small.

The effect of the apolipoprotein E gene polymorphisms and haplotypes on behavioural and psychological symptoms in probable Alzheimer’s disease

Background: Patients with Alzheimer’s disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer’s disease has been demonstrated. Several studies have investigated whether the exon 4 ε2/ε3/ε4 haplotype of the apolipoprotein E (APOE) gene is associated with BPSD, with variable results. Objective: We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene. Methods: Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD. Results: We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings. Conclusions: Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.

Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease.

Alzheimers disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort.

Clinical presentation of postnatal and non-postnatal depressive episodes.

BACKGROUND The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. METHOD In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. RESULTS The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. CONCLUSIONS The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.

Sexual Dysfunctions in Male Opiate Users: A Comparative Study of Heroin, Methadone, and Buprenorphine

ObjectiveThe aim of this study was to compare sexual dysfunctions in male patients dependent on heroin and those on methadone or buprenorphine treatment for opiate dependence. MethodsNinety-one patients (30 in the heroin group, 33 in the methadone group, and 28 in the buprenorphine group) were recruited from outpatient attendees at a community drug team in Birmingham, UK. The “Loyola University Clinic-special history sheet for men” was administered to assess sexual functioning (self-reports), and the Brief Psychiatric Rating Scale was used to assess psychopathology. ResultsA wide range of sexual dysfunctions was reported by these patients (n=90): low sex drive (n=38; 41.8%), loss of sexual fantasy life (n=17; 18.7%), loss of morning erection (n=25; 27.5%), premature ejaculation (n=54; 59.3%), and ejaculation with soft penis (n=67; 73.6%). Fewer patients on buprenorphine (as compared with those on heroin and methadone) reported loss of sexual fantasy, loss of sexual desire, loss of erection with movement, premature ejaculation, and loss of angulation of penis (all P<0.05). ConclusionsThe results of this study indicate that sexual dysfunctions are common in male opiate misusers and that buprenorphine is significantly less likely than methadone or heroin to induce this side effect. Further research is needed to explore the pathophysiology and treatment implications of these findings. From a clinical perspective, it is imperative that patients misusing opiates and those treated with methadone or buprenorphine are routinely asked about their sexual functioning and appropriate investigations and treatment planned if indicated.

No Association Between Neuregulin 1 and Psychotic Symptoms in Alzheimer's Disease Patients

Alzheimers disease (AD) patients commonly suffer from behavioral and psychological symptoms of dementia (BPSD). Variants within the neuregulin-1 (NRG1) gene have been investigated both in early onset psychiatric disorders, such as schizophrenia and recently in AD patients with psychosis. In this study, we analyzed NRG1 variants in AD patients with and without psychosis. Our large cohort of 399 probable AD patients had longitudinal information on the BPSD, which was used to dichotomize patients into whether they had ever suffered from psychotic symptoms within the study period. The NRG1 single nucleotide polymorphisms rs3924999, rs35753505 (SNP8NRG221533) and the microsatellites 478B14-848 and 420M9-1395 were investigated for association with psychosis using genotype, allele, and haplotype analyses. No associations were found between any of these variants or haplotypic combinations with delusions, hallucinations, psychosis, or elation/mania in our cohort. Positive associations with polymorphisms and haplotype combinations of NRG1 have been reported in psychiatric disorders. One previous study found an association with psychosis in AD, with a SNP outside the haplotype block first reported for association with schizophrenia. We found no association with any of these variants in our cohort. Further investigations of this region on chromosome 8 are clearly required, with replication in different large longitudinal cohorts.

Possible Predictors of Outcome for Conditionally Discharged Patients – A Preliminary Study:

Conditional discharge for restricted hospital order patients is by and large a successful process. The present study aimed to identify variables among a cohort of conditionally discharged patients in the West Midlands that would predict whether an individual was more likely to be readmitted to hospital, involved in a serious incident, to be recalled to hospital or given an absolute discharge. A retrospective case note analysis was undertaken. Logistic regression analysis was used to identify variables that could predict outcome. Patients were six times more likely to be readmitted to hospital if they misused drugs and nine times more likely if they self-harmed. They were also six and four times more likely to be involved in a serious incident if they misused alcohol and drugs respectively. Patients were five times more likely to be recalled to hospital if they did not have close social support and were four and a half times more likely to get an absolute discharge if they lived in supported accommodation. Conditional discharge is an effective model of community care for restricted hospital order patients. Addressing the problems caused by drug and alcohol misuse, self-harming behaviour, recognising the importance of a close social support network and developing more appropriate housing for these individuals will help make the process more successful.

Measuring hypomania in the postpartum: a comparison of the Highs Scale and the Altman Mania Rating Scale

We examine the prevalence of hypomania on day 3 postpartum using two self-report mania scales: The Highs Scale and Altman Mania Rating Scale (AMRS). 279 women were recruited from postnatal wards and completed the questionnaires on day 3 postpartum. The scales show good correlation, however, 11% of women meet the suggested threshold for caseness on the Highs Scale and 44% on the AMRS. Hypomanic symptoms are commonly experienced in the early postpartum. Although there is some evidence that the Highs Scale might be conservative, the AMRS likely overestimates hypomania in the postpartum. The definition of what constitutes ‘a case’ of postnatal hypomania requires further validation against clinical interview and ability to predict variables of clinical importance. Mania scales developed in bipolar disorder populations must be specifically validated for postpartum use.