Exploration of the relevance of values to clinical interventions and working with Mentally Disordered Offenders

The relevance of individuals' values to clinical situations is increasingly recognised in political and clinical contexts. Enhancing an individual's capacity to live consistently with their values is assumed to facilitate mental well-being and quality of life (QoL). However, little research has empirically investigated whether this focus is appropriate. This collection of studies will examine the relationship between values, well-being and QoL. "Valued living" is a core aim of Acceptance and Commitment Therapy (ACT) but it has received little empirical attention. The values identified within ACT may not be equally applicable to all clinical populations. Encouraging value-consistent action is often assumed to be inappropriate to offender populations. Schwartz‟s universal model of human values is introduced to inform understanding of the relationship between values and well-being and whether mentally disordered offenders (MDOs) have similar values to a non-psychologically distressed comparison group. Method Study 1 investigated the relationship between values, quality of life (QoL), psychological distress and psychological inflexibility (cognitive fusion and experiential avoidance) amongst a sample from the non-clinical sample (N = 109) using an online survey. Study 2 compared a subsample from study 1 with MDOs detained in medium security (N = 15) on the same measures. Study 3 explored participants‟ beliefs about the origin and maintenance of meaningful values. Responses were coded according to ACT literature and analysed using content analysis. Results Amongst the non-clinical population, QoL was positively correlated with „valued living‟, and negatively correlated with psychological inflexibility and distress. Psychological distress and psychological inflexibility correlated positively with the Openness to Change value domain and conservatism correlated negatively with psychological distress. No other relationships were observed between psychological flexibility or distress and value domain in the non-clinical population. MDOs had higher rates of psychological distress and lower psychological flexibility and QoL than the non-distressed population; they also attributed less importance to the self-transcendence value domain and more to self-enhancement. Benevolence was ranked significantly lower by the MDO sample. Other large effect sizes were detected reflecting differences between the samples, but they were not statistically significant. Intrinsic reinforcement was considered an important factor that maintained values as meaningful to all participants. Self-report data suggests that there are similarities and differences to how each sample conceptualises values. Discussion A clinical focus on values appears to be justified. The addition of Schwartz‟s model provided insight into the values of MDOs. The clinical and theoretical implications of the results are discussed as are the strengths and limitations of the study

Guided self-help cognitive behavioural therapy for depression in primary care : a randomised controlled trial

Peer reviewedPublisher PD

Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

<p>Abstract</p> <p>Background</p> <p>Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (<it>AVPR1A</it>) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at <it>AVPR1A </it>has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5'-flanking region of <it>AVPR1A </it>in variable gene expression and social behaviour.</p> <p>Methods</p> <p>We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the <it>AVPR1A </it>gene for association in an autism cohort from Ireland. Two 5'-flanking region polymorphisms in the human <it>AVPR1A</it>, RS3 and RS1, were also tested for their effect on relative promoter activity.</p> <p>Results</p> <p>The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (<it>P </it>= 0.036 and <it>P </it>= 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y.</p> <p>Conclusions</p> <p>These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased <it>AVPR1A </it>transcription, which may proffer increased susceptibility to the autism phenotype.</p

Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference.

Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

The development and initial validation of The Cognitive Fusion Questionnaire

Acceptance and Commitment Therapy (ACT) emphasizes the relationship a person has with their thoughts and beliefs as potentially more relevant than belief content in predicting the emotional and behavioral consequences of cognition. In ACT, ‘defusion’ interventions aim to ‘unhook’ thoughts from actions and to create psychological distance between a person and their thoughts, beliefs, memories and self-stories. A number of similar concepts have been described in the psychology literature (e.g. decentering, metacognition, mentalization and mindfulness) suggesting converging evidence that how we relate to mental events may be of critical importance. Whilst there are some good measures of these related processes, none of them provides an adequate operationalization of cognitive fusion. Despite the centrality of cognitive fusion in the ACT model, there is as yet no agreed measure of cognitive fusion. This paper presents the construction and development of a brief, self-report measure of cognitive fusion: The Cognitive Fusion Questionnaire (CFQ). The results of a series of studies involving over 1800 people across diverse samples show good preliminary evidence of the CFQ’s factor structure, reliability, temporal stability, validity, discriminant validity, and sensitivity to treatment effects. The potential uses of the CFQ in research and clinical practice are outlined

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe