Search results

Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents

3 November 2018

© 2015, The Author(s). Occurrence of psychotic experiences is common amongst adolescents in the general population. Twin studies suggest that a third to a half of variance in adolescent psychotic experiences is explained by genetic influences. Here we test the extent to which common genetic variants account for some of the twin-based heritability. Psychotic experiences were assessed with the Specific Psychotic Experiences Questionnaire in a community sample of 2152 16-year-olds. Self-reported measures of Paranoia, Hallucinations, Cognitive Disorganization, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms were obtained. Estimates of SNP heritability were derived and compared to the twin heritability estimates from the same sample. Three approaches to genome-wide restricted maximum likelihood (GREML) analyses were compared: (1) standard GREML performed on full genome-wide data; (2) GREML stratified by minor allele frequency (MAF); and (3) GREML performed on pruned data. The standard GREML revealed a significant SNP heritability of 20 % for Anhedonia (SE = 0.12; p < 0.046) and an estimate of 19 % for Cognitive Disorganization, which was close to significant (SE = 0.13; p < 0.059). Grandiosity and Paranoia showed modest SNP heritability estimates (17 %; SE = 0.13 and 14 %; SE = 0.13, respectively, both n.s.), and zero estimates were found for Hallucinations and Negative Symptoms. The estimates for Anhedonia, Cognitive Disorganization and Grandiosity accounted for approximately half the previously reported twin heritability. SNP heritability estimates from the MAF-stratified approach were mostly consistent with the standard estimates and offered additional information about the distribution of heritability across the MAF range of the SNPs. In contrast, the estimates derived from the pruned data were for the most part not consistent with the other two approaches. It is likely that the difference seen in the pruned estimates was driven by the loss of tagged causal variants, an issue fundamental to this approach. The current results suggest that common genetic variants play a role in the etiology of some adolescent psychotic experiences, however further research on larger samples is desired and the use of MAF-stratified approach recommended.

The role of sleep dysfunction in the occurrence of delusions and hallucinations: A systematic review.

3 November 2018

BACKGROUND: Sleep dysfunction is extremely common in patients with schizophrenia. Recent research indicates that sleep dysfunction may contribute to psychotic experiences such as delusions and hallucinations. OBJECTIVES: The review aims to evaluate the evidence for a relationship between sleep dysfunction and individual psychotic experiences, make links between the theoretical understanding of each, and highlight areas for future research. METHOD: A systematic search was conducted to identify studies investigating sleep and psychotic experiences across clinical and non-clinical populations. RESULTS: 66 papers were identified. This literature robustly supports the co-occurrence of sleep dysfunction and psychotic experiences, particularly insomnia with paranoia. Sleep dysfunction predicting subsequent psychotic experiences receives support from epidemiological surveys, research on the transition to psychosis, and relapse studies. There is also evidence that reducing sleep elicits psychotic experiences in non-clinical individuals, and that improving sleep in individuals with psychosis may lessen psychotic experiences. Anxiety and depression consistently arise as (partial) mediators of the sleep and psychosis relationship. CONCLUSION: Studies are needed that: determine the types of sleep dysfunction linked to individual psychotic experiences; establish a causal connection between sleep and psychotic experiences; and assess treatments for sleep dysfunction in patients with non-affective psychotic disorders such as schizophrenia.

A randomised controlled trial of positive memory training for the treatment of depression within schizophrenia

3 November 2018

Multiple imputation to deal with missing EQ-5D-3L data: Should we impute individual domains or the actual index?

3 November 2018

PURPOSE: Missing data are a well-known and widely documented problem in cost-effectiveness analyses alongside clinical trials using individual patient-level data. Current methodological research recommends multiple imputation (MI) to deal with missing health outcome data, but there is little guidance on whether MI for multi-attribute questionnaires, such as the EQ-5D-3L, should be carried out at domain or at summary score level. In this paper, we evaluated the impact of imputing individual domains versus imputing index values to deal with missing EQ-5D-3L data using a simulation study and developed recommendations for future practice. METHODS: We simulated missing data in a patient-level dataset with complete EQ-5D-3L data at one point in time from a large multinational clinical trial (n = 1,814). Different proportions of missing data were generated using a missing at random (MAR) mechanism and three different scenarios were studied. The performance of using each method was evaluated using root mean squared error and mean absolute error of the actual versus predicted EQ-5D-3L indices. RESULTS: In large sample sizes (n > 500) and a missing data pattern that follows mainly unit non-response, imputing domains or the index produced similar results. However, domain imputation became more accurate than index imputation with pattern of missingness following an item non-response. For smaller sample sizes (n < 100), index imputation was more accurate. When MI models were misspecified, both domain and index imputations were inaccurate for any proportion of missing data. CONCLUSIONS: The decision between imputing the domains or the EQ-5D-3L index scores depends on the observed missing data pattern and the sample size available for analysis. Analysts conducting this type of exercises should also evaluate the sensitivity of the analysis to the MAR assumption and whether the imputation model is correctly specified.

Examining the Factor Structure of the 39-Item and 15-Item Versions of the Five-Facet Mindfulness Questionnaire Before and After Mindfulness-Based Cognitive Therapy for People with Recurrent Depression

3 November 2018

The role of different strain backgrounds in bacterial endotoxin-mediated sensitization to neonatal hypoxic-ischemic brain damage.

3 November 2018

Genetic background is known to influence the outcome in mouse models of human disease, and previous experimental studies have shown strain variability in the neonatal mouse model of hypoxia-ischemia. To further map out this variability, we compared five commonly used mouse strains: C57BL/6, 129SVJ, BALB/c, CD1 and FVB in a pure hypoxic-ischemic setup and following pre-sensitization with lipopolysaccharide (LPS). Postnatal day 7 pups were subjected to unilateral carotid artery occlusion followed by continuous 30 min 8% oxygen exposure at 36 °C. Twelve hours prior, a third of the pups received a single intraperitoneal LPS (0.6 μg/g) or a saline (vehicle) administration, respectively; a further third underwent hypoxia-ischemia alone without preceding injection. Both C57BL/6 and 129SVJ strains showed minimal response to 30min hypoxia-ischemia alone, BALB/c demonstrated a moderate response, and both CD1 and FVB revealed the highest brain damage. LPS pre-sensitization led to substantial increase in overall brain infarction, microglial and astrocyte response and cell death in four of the five strains, with exception of BALB/c that only showed a significant effect with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Saline administration prior to hypoxia-ischemia resulted in an increase in inflammatory-associated markers, particularly in the astroglial activation of C57BL/6 mice, and in combined microglial activation and neuronal cell loss in FVB mice. Finally, two of the four strongly affected strains--C57BL/6 and CD1--revealed pronounced contralateral astrogliosis with a neuroanatomical localization similar to that observed on the occluded hemisphere. Overall, the current findings demonstrate strain differences in response to hypoxia-ischemia alone, to stress associated with vehicle injection, and to LPS-mediated pre-sensitization, which partially explains the high variability seen in the neonatal mouse models of hypoxia-ischemia. These results can be useful in future studies of fetal/neonatal response to inflammation and reduced oxygen-blood supply.

The Impact of Self-harm by Young People on Parents and Families - A Qualitative Study

3 November 2018

Variation by ethnic group in premature mortality risk following self-harm: a multicentre cohort study in England.

3 November 2018

BACKGROUND: Incidence and risk factors for self-harm vary according to ethnicity. People who self-harm have been shown to have increased risk of premature death, but little is known about mortality following self-harm in ethnic minority groups. METHODS: A prospective cohort study of self-harm presentations to three English cities (Derby, Manchester, Oxford) between 2000 and 2010. We linked to a national mortality dataset to investigate premature death in South Asian and Black people in comparison with White people to the end of 2012. RESULTS: Ethnicity was known for 72% of the 28,512 study cohort members: 88% were White, 5% were South Asian, and 3% were Black. After adjusting for age, gender and area-level socioeconomic deprivation, the risk of all-cause mortality was lower in South Asian (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.42 - 0.62) and Black people (HR 0.46, 95% CI 0.39 - 0.55) versus White people. Suicide risk was significantly lower in Black people (HR 0.43, 95% CI 0.19 - 0.97) than in White people. Prevalence of risk factors for premature death, such as previous self-harm, psychiatric treatment or concurrent alcohol misuse, was lower in South Asian and Black people than in White people. CONCLUSIONS: The risk of death following self-harm is lower in South Asian and Black people than White people in the UK, and they also have lower prevalence of risk factors for premature death. Awareness of both protective and risk factors might help to inform clinical decisions following assessment.

Distinguishing bipolar disorder from borderline personality disorder: A study of current clinical practice.

3 November 2018

BACKGROUND: Diagnosing mental illness is a central role for psychiatrists. Correct diagnosis informs both treatment and prognosis, and facilitates accurate communication. We sought to explore how psychiatrists distinguished two common psychiatric diagnoses: bipolar disorder (BD) and borderline personality disorder (BPD). METHODS: We conducted a qualitative study of psychiatrists to explore their practical experience. We then sought to validate these results by conducting a questionnaire study testing the theoretical knowledge and practical experience of a large number of UK psychiatrists. Finally we studied the assessment process in NHS psychiatric teams by analysing GP letters, assessments by psychiatrists, and assessment letters. RESULTS: There was broad agreement in both the qualitative and questionnaire studies that the two diagnoses can be difficult to distinguish. The majority of psychiatrists demonstrated in survey responses a comprehensive understanding DSM-IV-TR criteria although many felt that these criteria did not necessarily assist diagnostic differentiation. This scepticism about diagnostic criteria appeared to strongly influence clinical practice in the sample of clinicians we observed. In only a minority of assessments were symptoms of mania or BPD sufficiently assessed to establish the presence or absence of each diagnosis. CONCLUSION: Clinical diagnostic practice was not adequate to differentiate reliably BD and BPD. The absence of reliable diagnostic practice has widespread implications for patient care, service provision and the reliability of clinical case registries.

Mood instability: significance, definition and measurement.

3 November 2018

Mood instability is common, and an important feature of several psychiatric disorders. We discuss the definition and measurement of mood instability, and review its prevalence, characteristics, neurobiological correlates and clinical implications. We suggest that mood instability has underappreciated transdiagnostic potential as an investigational and therapeutic target.