The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies

BACKGROUND: Co-morbidity within anxiety disorders, and between anxiety disorders and depression, is common. According to the theory of Gray and McNaughton, this co-morbidity is caused by recursive interconnections linking the brain regions involved in fear, anxiety and panic and by heritable personality traits such as neuroticism. In other words, co-morbidity can be explained by one disorder being an epiphenomenon of the other and by a partly shared genetic etiology. The aim of this paper is to evaluate the theory of Gray and McNaughton using the results of genetic epidemiological studies. METHOD: Twenty-three twin studies and 12 family studies on co-morbidity are reviewed. To compare the outcomes systematically, genetic and environmental correlations between disorders are calculated for the twin studies and the results from the family studies are summarized according to the method of Klein and Riso. RESULTS: Twin studies show that co-morbidity within anxiety disorders and between anxiety disorders and depression is explained by a shared genetic vulnerability for both disorders. Some family studies support this conclusion, but others suggest that co-morbidity is due to one disorder being an epiphenomenon of the other. CONCLUSIONS: Discrepancies between the twin and family studies seem partly due to differences in used methodology. The theory of Gray and McNaughton that neuroticism is a shared risk factor for anxiety and depression is supported. Further research should reveal the role of recursive interconnections linking brain regions. A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.     

Familial clustering in burnout: a twin-family study

BACKGROUND: Research on risk factors for burnout has mainly focused on circumstances at work and on personal characteristics. The aim of this study was to investigate whether burnout clusters within families and, if so, whether this is due to genetic influences or to environmental factors shared by family members. Finally, we tried to identify specific risk factors for burnout. METHOD: In 2707 twins, 736 of their siblings and 575 of their spouses from a population-based twin-family sample, burnout was measured using a self-report questionnaire. Correlations in burnout scores were obtained for monozygotic and dizygotic twin pairs and sibling pairs conditional on the pairs' sex. Correlations for twins and their spouses were derived conditional on the length of the relationship. RESULTS: In the final model, correlations of the monozygotic and dizygotic twin pairs and sibling pairs were significantly different from zero, but not significantly different from each other. The correlation was estimated at 0.22. The correlation between spouses was also significant. This was mainly due to the group with a relationship longer than 5 years in which the correlation was 0.24. Burnout scores were higher in subjects whose parents had a high level of education. CONCLUSIONS: There is familial clustering for burnout due to environmental factors shared by family members, explaining 22 % of the variance. Genetic factors do not seem to be of importance. The significant correlation between spouses supports the conclusion that common environment plays a role in burnout. A high parental education is one of the familial risk factors.     

The effect of m-CPP on tics and obsessive-compulsive phenomena in Gilles de la Tourette syndrome

  Rationale: Family genetic and phenomenological studies support an interrelationship between Gilles de la Tourette syndrome (GTS) and obsessive-compulsive disorder (OCD). Some authors consider GTS as part of a serotonergically mediated cluster of OCD spectrum disorders. Objective: To study serotonergic mechanisms in GTS, the effect of the relatively selective 5-HT_2c agonist meta-chlorophenylpiperazine (m-CPP) was assessed. Methods: We studied the behavioural effects of m-CPP on tics, obsessions, compulsions and impulsions of GTS. Twelve medication-free GTS patients (ten men, two women) were included in a single dose 0.5 mg/kg oral m-CPP challenge study with a double-blinded placebo-controlled cross-over design. Global symptom scores, target symptom scores as well as biochemical measures were followed up to 24 h after baseline. Results: While m-CPP caused a significant rise in plasma cortisol and prolactin levels, no significant effects were found on the tics, obsessions and compulsions. Impulsions showed a trend to ameliorate. Conclusions: This study does not support a predominant role for 5-HT on the tics in GTS. The trend of impulsions to ameliorate after m-CPP can be interpreted as circumstantial support for impulsivity-related 5-HT hypofunctionality in GTS. However, the large variability of m-CPP plasma concentrations found in this study casts doubts upon the reliability of m-CPP as a probe for challenge studies. Received: 31 July 1998 / Final version: 6 November 1998     

From individual behaviour strategies to sustainable food systems: Countering the obesity and non communicable diseases epidemic in New Zealand

New Zealand is currently facing an obesity and non communicable diseases (NCDs) epidemic. Recent studies have largely attributed these health issues to insufficient food and low-quality diets that cause micronutrient deficiencies. Improving healthy diets requires broader thinking and collaboration, particularly around maintaining sustainable food systems, which signifies a shift from individualistic/behavioural approaches in health promotion. This paper aims to extend solutions addressing increasing rates of obesity and diet-related NCDs in New Zealand while considering diet and human health in concurrence with sustainability. In particular, the three pillars of sustainability—economic, environmental, and social—will be considered, alongside application of a food systems approach to analysing the epidemic and policy developments in New Zealand. Given its proximity to smaller Pacific islands in the region, New Zealand is in a unique position to work multisectorally and be a leader in considering food system approaches to tackling obesity and NCDs in the Pacific.     

Bile acids increase the activity of the epithelial Na+ channel

The epithelial Na⁺ channel (ENaC) is a key regulator of Na⁺ absorption in various epithelia including the distal nephron and the distal colon. ENaC is a constitutively active channel, but its activity is modulated by a number of mechanisms. These include proteolytic activation, ubiquitination and cell surface expression, phosphorylation, intracellular Na⁺ concentration, and shear stress. ENaC is related to the bile acid-sensitive ion channel (BASIC), a channel that is expressed in the epithelial cells of bile ducts. BASIC is activated by millimolar concentrations of extracellular bile acids. Bile acids are synthesized by the liver and secreted into the duodenum to aid lipolysis. A large fraction of the secreted bile acids is absorbed by the ileum and recirculated into the liver, but a small fraction passes the colon and is excreted. Bile acids can influence the ion transport processes in the intestinal tract including the colon. In this study, we show that various bile acids present in rat bile potently and reversibly increase the activity of rat ENaC expressed in Xenopus oocytes, suggesting that bile acids are natural modulators of ENaC activity.     

Writer's cramp: Increased dorsal premotor activity during intended writing

Simple writer's cramp (WC) is a task‐specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task‐specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task‐specificity. We used fMRI to isolate cerebral alterations associated with the task‐specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task‐specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task‐specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

In vivo monitoring of implant osseointegration in a rabbit model using acoustic sound analysis

Implant osseointegration can currently only be assessed reliably post mortem. A novel method that relies on the principle of acoustic sound analysis was developed to enable examination of the longitudinal progress of osseointegration. The method is based on a magnetic sphere inside a hollow cylinder of the implant. By excitation using an external magnetic field, collision of the sphere inside the implant produces a sound signal. Custom‐made titanium implants equipped thusly were inserted in each lateral femoral epicondyle of 20 New Zealand White Rabbits. Two groups were investigated: Uncoated, machined surface versus antiadhesive surface; and calcium phosphate‐coated surface versus antiadhesive surface. The sound analysis was performed postoperatively and weekly. After 4 weeks, the animals were euthanized, and the axial pull‐out strengths of the implants were determined. A significant increase in the central frequency was observed for the loose implants (mean pull‐out strength 21.1 ± 16.9 N), up to 6.4 kHz over 4 weeks. In comparison, the central frequency of the osseointegrated implants (105.2 ± 25.3 N) dropped to its initial value. The presented method shows potential for monitoring the osseointegration of different implant surfaces and could considerably reduce the number of animals needed for experiments. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:606–612, 2014.