Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression

<p>Abstract</p> <p>Background</p> <p>Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention.</p> <p>Methods</p> <p>The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.</p> <p>Trial registration</p> <p>Local Ethics Committee: H-KF 307413</p> <p>Danish Medicines Agency: 2612-3162.</p> <p>EudraCT: 2006-001750-28.</p> <p>Danish Data Agency: 2006-41-6737.</p> <p>ClinicalTrials.gov: NCT 00386841</p

Mode of Effective Connectivity within a Putative Neural Network Differentiates Moral Cognitions Related to Care and Justice Ethics

BACKGROUND: Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. METHODOLOGY/PRINCIPAL FINDINGS: Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. CONCLUSIONS/SIGNIFICANCE: These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses

Sex Differences and Autism: Brain Function during Verbal Fluency and Mental Rotation

Autism spectrum conditions (ASC) affect more males than females. This suggests that the neurobiology of autism: 1) may overlap with mechanisms underlying typical sex-differentiation or 2) alternately reflect sex-specificity in how autism is expressed in males and females. Here we used functional magnetic resonance imaging (fMRI) to test these alternate hypotheses. Fifteen men and fourteen women with Asperger syndrome (AS), and sixteen typically developing men and sixteen typically developing women underwent fMRI during performance of mental rotation and verbal fluency tasks. All groups performed the tasks equally well. On the verbal fluency task, despite equivalent task-performance, both males and females with AS showed enhanced activation of left occipitoparietal and inferior prefrontal activity compared to controls. During mental rotation, there was a significant diagnosis-by-sex interaction across occipital, temporal, parietal, middle frontal regions, with greater activation in AS males and typical females compared to AS females and typical males. These findings suggest a complex relationship between autism and sex that is differentially expressed in verbal and visuospatial domains

The parent?infant dyad and the construction of the subjective self

Developmental psychology and psychopathology has in the past been more concerned with the quality of self-representation than with the development of the subjective agency which underpins our experience of feeling, thought and action, a key function of mentalisation. This review begins by contrasting a Cartesian view of pre-wired introspective subjectivity with a constructionist model based on the assumption of an innate contingency detector which orients the infant towards aspects of the social world that react congruently and in a specifically cued informative manner that expresses and facilitates the assimilation of cultural knowledge. Research on the neural mechanisms associated with mentalisation and social influences on its development are reviewed. It is suggested that the infant focuses on the attachment figure as a source of reliable information about the world. The construction of the sense of a subjective self is then an aspect of acquiring knowledge about the world through the caregiver's pedagogical communicative displays which in this context focuses on the child's thoughts and feelings. We argue that a number of possible mechanisms, including complementary activation of attachment and mentalisation, the disruptive effect of maltreatment on parent-child communication, the biobehavioural overlap of cues for learning and cues for attachment, may have a role in ensuring that the quality of relationship with the caregiver influences the development of the child's experience of thoughts and feelings

AS03-01 - Reactions and consequences following judgements by the European Court of Human Rights in the UK

The Convention for the Protection of Human Rights and Fundamental Freedoms first came into force in 1953. The European Court of Human Rights was set up in 1959. In the UK, the Human Rights Act 1998 came into force in 2000 bringing the rights set out in the Convention into domestic law. Some commentators at that time feared that this would lead to an increase in cases brought by patients alleging violations of their fundamental rights, however, this did not occur. There have been a number of cases brought to the European Court of Human Rights, both prior to the Human Rights Act and subsequently after the UK courts had been exhausted. Recent relevant cases relate to voting rights for prisoners, indeterminate sentences and the sex offender register. In all these cases UK policy has been found to be incompatible with the Convention, however, subsequent change in national policy has been slow despite these rulings. In the UK, the concept of human rights has been met with increasing critcism and politicians have openly discussed the possiblity of abandoning the Human Rights Act or even leaving the Convention for the Protection of Human Rights. There is, worryingly, a view that the protection of human rights, particularly of offenders, interferes with UK policy development and that certain groups of individuals should not have the privilege of such protection.http://www.europsy-journal.com/article/S0924-9338(12)73958-5/abstrac

Long-stay in high and medium secure forensic psychiatric care – Prevalence, patient characteristics and pathways in England

IntroductionForensic psychiatric services are costly and highly restrictive for patients. Clinical experience and the limited research available indicate some patients stay for too long in these settings. A proportion of patients may, however, require long-term (potentially life-long) secure forensic psychiatric care but their needs may not be met by existing service provision designed for faster throughput.ObjectivesWe conducted a national, multi-centre, cross sectional study exploring the prevalence of long-stay and characteristics of long-stayers in high and medium secure forensic psychiatric care in England.Aims(1) Estimate the prevalence of long-stay in secure settings in England (length of stay over 5 years in medium secure care or 10 years in high secure care); (2) describe the characteristics, needs and care pathways of long-stay patients. Develop recommendations following the exploration of international models for this patient group.MethodsWe employed a mixed-methods approach including the analysis of administrative data, case file reviews, patient interviews, consultant questionnaires, interviews with clinicians and commissioners and a Delphi survey.ResultsTwenty-five percent (n = 401) of our sample were experiencing long-stay. This patient group has a heterogeneous set of characteristics and needs relating to their diagnosis, offending history, risk and therapeutic need and have experienced a variety of care pathways through secure care.ConclusionsWe found a greater number of long-stay patients than originally estimated with a set of characteristics and needs that are arguably different to that of the general forensic population, therefore calling for a specific care pathway and service provision for this patient group with a greater focus on autonomy and quality of life.Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec