High Heritability for a Composite Index of Children’s Activity Level Measures

Despite the high heritability of children's activity level, which forms part of the core symptom domain of hyperactivity-impulsivity within attention deficit hyperactivity disorder (ADHD), there has only been a limited success with identifying candidate genes involved in its etiology. This may reflect a lack of understanding about the different measures used to define activity level across studies. We aimed to study the genetic and environmental etiology across three measures of activity level: parent and teacher ratings of hyperactivity-impulsivity and actigraph measurements, within a population-based sample of 463 7-9 year old twin pairs. We further examined ways in which the three measures could be combined for future molecular studies. Phenotypic correlations across measures were modest, but a common underlying phenotypic factor was highly heritable (92%); as was a simple aggregation of all three measurements (77%). This suggests that distilling what is common to all three measures may be a good method for generating a quantitative trait suitable for molecular studies of activity level in children. The high heritabilities found are encouraging in this respect

Cannabis and depression: A twin model approach to co-morbidity

Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935–953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high

Investigating the genetic and environmental aetiologies of non-suicidal and suicidal self-harm: a twin study

BACKGROUND: Self-harm is a major health concern, not only as a signal of distress but also as a strong predictor of later suicide. Self-harm can be further refined into suicidal self-harm (SSH, i.e. suicide attempt) and non-suicidal self-harm (NSSH). Understanding the aetiologies of NSSH and SSH can help inform suicide prevention strategies. Using a twin design, we investigated the phenotypic and aetiological relationships between NSSH and SSH, and their aetiological overlap with mental health problems. METHODS: We analysed data from the Twins Early Development Study using structural equation modelling. At age 21 years, 9063 twins (62.4% female) answered questions related to self-harm. At age 16 years, 19 self- or parent-reported mental health measures were administered, including measures of internalising and externalising problems, psychotic-like experiences and substance abuse. RESULTS: Prevalences for NSSH and SSH were 21.9% and 10.5%, respectively. Additive genetic factors explained half of the variance in NSSH (55%) and SSH (50%), with the rest explained by non-shared environmental factors. Phenotypically, NSSH and SSH were strongly correlated (r = 0.87) with their correlation explained by genetic (57%) and non-shared environmental (43%) factors. We found no evidence that NSSH and SSH differed in their phenotypic and aetiological relationships with mental health measures. CONCLUSION: Our findings suggest no aetiological difference between NSSH and SSH. NSSH and SSH should be regarded as two different ends of a continuum, rather than as two distinct categories

Rejection sensitivity relates to hypocortisolism and depressed mood state in young women

Rejection sensitivity and the associated fear of negative social evaluation (FNSE) trait are characteristics of hypocortisolemic syndromes such as atypical depression. However, a meta-analysis showed that acute FNSE evokes strong cortisol responses in humans. This is consistent with suggestions that hypocortisolism reflects a protective adaptation to a history of high cortisol responses. This leads us to hypothesize that measures of trait FNSE relate to hypocortisotism. Moreover, because FNSE relates positively to depressed mood state, but negatively to cortisol, we expect that the positive relationship between depressed mood state and cortisol will show up most clearly when controlling for the confounding effect of FNSE on this relationship. In the present study we measured salivary cortisol awakening response and psychological variables in 194 community women aged 18-30 years. The results confirmed our hypotheses. We propose that dispositional FNSE is associated with a history of frequent high cortisol responses, leading to long-term protective inhibition of further cortisol and energy mobilization. The present results have special relevance for mental health problems that have high prevalence among young women. (C) 2008 Elsevier Ltd. All rights reserved.</p

The Etiological and Predictive Association Between ADHD and Cognitive Performance From Childhood to Young Adulthood

Objective: Evidence about the etiology of the predictive associations between a diagnosis of ADHD and cognitive performance over time is scarce. Here, we examine these predictive and etiological patterns using a cross-lagged model design in a sample of 404 participants (74% males) from ADHD and control sibling pairs aged 6 to 17 years at baseline and 12 to 24 years at follow-up. Methods: Data included IQ, short-term and working memory measures, and response speed and variability from a four-choice reaction-time task. Results: ADHD and IQ predicted each other over time. ADHD at baseline predicted lower working memory performance at follow-up. Stable etiological influences emerged in the association between ADHD and cognitive variables across time. Conclusion: Whether early interventions can reduce negative interference with learning at school requires further study

Multidisciplinary strategies to treat painful mononeuropathies in the upper extremity: from lab to bedside

Neuropathic pain in the upper extremity is a serious problem, commonly involving relatively young patients. The pain causes loss of function and productivity, changes a patient’s lifestyle and can progress into a chronic pain syndrome with secondary psychosocial co-morbidities. Treating patients with a painful mononeuropathy remains challenging, with a monodisciplinary approach often having limited treatment efficacy. This narrative review discusses how to deal with this challenge in the treatment of patients with peripheral nerve injury pain, addressing the four important pillars: (1) diagnosing a painful mononeuropathy; (2) clinical pain phenotyping; (3) personalized pain treatment; and (4) using a multidisciplinary team approach