Therapygenetics: the 5HTTLPR and response to psychological therapy

Although pharmacogenetic research thrives,1 genetic determinants of response to purely psychotherapeutic treatments remain unexplored. In a sample of children undergoing cognitive behaviour therapy (CBT) for an anxiety disorder, we tested whether treatment response is associated with the serotonin transporter gene promoter region (5HTTLPR), previously shown to moderate environmental influences on depression.

Neurotrophic gene polymorphisms and response to psychological therapy

Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes represent plausible candidate genes: they are implicated in synaptic plasticity, response to stress, and are widely expressed in brain areas involved in mood and cognition. Allelic variation at both loci has shown associations with anxiety-related phenotypes. A sample of 374 anxiety-disordered children with white European ancestry was recruited from clinics in Reading, UK, and in Sydney, Australia. Participants received manualised CBT treatment and DNA was collected from buccal cells using cheek swabs. Treatment response was assessed at post-treatment and follow-up time points. We report first evidence that children with one or more copies of the T allele of NGF rs6330 were significantly more likely to be free of their primary anxiety diagnosis at follow-up (OR=0.60 (0.42–0.85), P=0.005). These effects remained even when other clinically relevant covariates were accounted for (OR=0.62 (0.41–0.92), P=0.019). No significant associations were observed between BDNF rs6265 and response to psychological therapy. These findings demonstrate that knowledge of genetic markers has the potential to inform clinical treatment decisions for psychotherapeutic interventions.

Exploring homeless people’s use of outreach services: applying a social psychological perspective

A number of critiques have been published drawing attention to the gaps in research methods applied to issues surrounding homelessness and service utilisation in Britain. This paper discusses the use of social identity, a theory drawn from the field of applied social psychology, and synthesises it with the pathways model, thereby providing a framework to further explore service utilisation. The synthesised framework was used to predict the uptake of outreach services in a prospective study of 121 homeless people in a major UK city. In general, homeless people's use of intervention services was affected by the extent to which they identified with the support services themselves. The study demonstrates the central role of social identity in understanding service utilisation patterns, and shows the importance of applying fresh techniques to fine-tune our understanding of uptake in the long term.

Neural and psychological maturation of decision-making in adolescence and young adulthood

We examined the maturation of decision-making from early adolescence to mid-adulthood using fMRI of a variant of the Iowa gambling task. We have previously shown that performance in this task relies on sensitivity to accumulating negative outcomes in ventromedial PFC and dorsolateral PFC. Here, we further formalize outcome evaluation (as driven by prediction errors [PE], using a reinforcement learning model) and examine its development. Task performance improved significantly during adolescence, stabilizing in adulthood. Performance relied on greater impact of negative compared with positive PEs, the relative impact of which matured from adolescence into adulthood. Adolescents also showed increased exploratory behavior, expressed as a propensity to shift responding between options independently of outcome quality, whereas adults showed no systematic shifting patterns. The correlation between PE representation and improved performance strengthened with age for activation in ventral and dorsal PFC, ventral striatum, and temporal and parietal cortices. There was a medial-lateral distinction in the prefrontal substrates of effective PE utilization between adults and adolescents: Increased utilization of negative PEs, a hallmark of successful performance in the task, was associated with increased activation in ventromedial PFC in adults, but decreased activation in ventrolateral PFC and striatum in adolescents. These results suggest that adults and adolescents engage qualitatively distinct neural and psychological processes during decision-making, the development of which is not exclusively dependent on reward-processing maturation.

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

A longitudinal study of child sleep in high and low risk families: relationship to early maternal settling strategies and child psychological functioning

Objectives To investigate whether sleep disturbances previously found to characterise high risk infants: (a) persist into childhood; (b) are influenced by early maternal settling strategies and (c) predict cognitive and emotional/behavioural functioning. Methods Mothers experiencing high and low levels of psychosocial adversity (risk) were recruited antenatally and longitudinally assessed with their children. Mothers completed measures of settling strategies and infant sleep postnatally, and at 12 and 18 months, infant age. At five years, child sleep characteristics were measured via an actigraphy and maternal report; IQ and child adjustment were also assessed. Results Sleep disturbances observed in high-risk infants persisted at five years. Maternal involvement in infant settling was greater in high risk mothers, and predicted less optimal sleep at five years. Poorer five year sleep was associated with concurrent child anxiety/depression and aggression, but there was limited evidence for an influence of early sleep problems. Associations between infant/child sleep characteristics and IQ were also limited. Conclusions Early maternal over-involvement in infant settling is associated with less optimal sleep in children, which in turn, is related to child adjustment. The findings highlight the importance of supporting parents in the early development of good settling practices, particularly in high-risk populations.

A grounded investigation of Chinese employees' psychological capital

Purpose – This paper explores the “Western” concept of psychological capital in the People's Republic of China (PRC) and highlights critical areas of divergence and notable dimensions of similarity. Design/methodology/approach – This is an empirical study conducted in a wide range of Chinese organisational forms, employing an inductive approach based on critical incident technique. Findings – This research showed that the concept of psychological capital appears to have a degree of applicability and salience in China. A series of dimensions common in Western organisations were found in our research, including Optimism, Creativity, Resiliency, Self-confidence, Forgiveness and Gratitude, Courage and Ambition (Hope). These were found to be common types of psychological capital both in China and in the West. However, the dimensions of Courtesy and Humility (Qian-gong-you-li in Chinese), Self-possession and Sincerity fell into the “different” category. Originality/value – This paper is a first attempt to examine psychological capital in a range of organisational forms and industrial sectors in China using a grounded theory approach. It not only reports various dimensions of Chinese psychological capital, some unique to this research, but also compares and contrasts these dimensions between China and the West, highlighting further research opportunities.

Non-replication of the association between 5HTTLPR and response to psychological therapy for child anxiety disorders

Background We previously reported an association between 5HTTLPR genotype and outcome following cognitive–behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome. Aims To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829). Method Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed. Results There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes. Conclusions The association between 5HTTLPR genotype and CBT outcome did not replicate. Short-allele homozygotes showed more positive treatment outcomes, but with small, non-significant effects. Future studies would benefit from utilising whole genome approaches and large, homogenous samples.

The regulation of cyber warfare under the jus ad bellum

This chapter evaluates the potential for legal regulation of the resort to cyber warfare between states under the ‘jus ad bellum’ (the law on the use of force). Debate in the literature has largely concerned whether cyber warfare falls within the scope of Article 2(4) UNC. The first part of this chapter sets out this debate. It then goes on to argue that the ‘Article 2(4) debate’ often misses the fact that an act of cyber warfare can be considered a breach of a different legal rule: the principle of non-intervention. The chapter further considers some of the issues in applying either the prohibition of the use of force or the principle of non-intervention to cyber warfare, and then concludes by arguing that the debate should be reoriented to focus on another existing international legal obligation: the duty to prevent cyber-attacks.

Cyber warfare: a multidisciplinary analysis

Cyber warfare is an increasingly important emerging phenomenon in international relations. The focus of this edited volume is on this notion of cyber warfare, meaning interstate cyber aggression, as distinct from cyber-terrorism or cyber-crime. Waging warfare in cyberspace has the capacity to be as devastating as any conventional means of conducting armed conflict. However, while there is a growing amount of literature on the subject within disciplines, there has been very little work done on cyber warfare across disciplines, which necessarily limits our understanding of it. This book is a major multidisciplinary analysis of cyber warfare, featuring contributions by world-leading experts from a mixture of academic and professional backgrounds.