Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = ?0.164 to ?0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = ?0.173 to ?0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.     

Total-body 3D magnetic resonance angiography influences the management of patients with peripheral arterial occlusive disease

High-resolution total-body 3D MR angiography (MRA) has recently become available, revealing additional clinically relevant disease in patients with peripheral arterial occlusive disease (PAOD). However, the actual impact of total-body MRA on patient management in patients with PAOD has not been investigated so far. Two hundred forty-nine consecutive patients with angiographically proven PAOD were prospectively examined by means of contrast-enhanced total-body 3D MRA on a 1.5-T MR scanner. All correlative imaging studies performed within 60 days of total-body MRA were included in the efficacy analysis. Additional clinically relevant disease (luminal narrowing >50%, aneurysmal changes or dissections) was found in 73 segments (52 patients), including the renal arteries (36 segments), carotid arteries (28 segments), subclavian arteries (four segments) and abdominal aortic aneurysms (AAA) (five segments). Of the 73 segments, 36 were deemed necessary for further investigation by means of focused MRA examinations; the diagnosis was confirmed in all cases. Within the 60-day follow-up period, interventional or surgical therapy outside the peripheral arterial tree was performed in nine patients (11 segments), including carotid endatherectomy and renal artery angioplasty. The outlined total-body 3D MRA approach permits a comprehensive evaluation of the arterial system in patients with atherosclerosis and does indeed have an impact on patient management in patients with PAOD.     

Liver X receptors downregulate 11beta-hydroxysteroid dehydrogenase type 1 expression and activity

11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) converts inactive corticosteroids into biologically active corticosteroids, thereby regulating the local concentration of active glucocorticoids, such as cortisol. 11beta-HSD-1 is particularly expressed in adipocytes and liver and appears to be causally linked to the development of type 2 diabetes and the metabolic syndrome. Liver X receptor (LXR)-alpha and -beta are nuclear oxysterol receptors whose key role in lipid metabolic regulation has recently been established. In this study, we show that treatment of adipocytes derived from 3T3-L1 cells and mouse embryonic fibroblasts in vitro with synthetic or natural LXR agonists decreases mRNA expression of 11beta-HSD-1 by approximately 50%, paralleled by a significant decline in 11beta-HSD-1 enzyme activity. Downregulation of 11beta-HSD-1 mRNA by LXRs started after a lag period of 8 h and required ongoing protein synthesis. Moreover, long-term per os treatment with a synthetic LXR agonist downregulated 11beta-HSD-1 mRNA levels by approximately 50% in brown adipose tissue and liver of wild-type but not of LXRalpha(-/-)beta(-/-) mice and was paralleled by downregulation of hepatic PEPCK expression. In conclusion, LXR ligands could mediate beneficial metabolic effects in insulin resistance syndromes including type 2 diabetes by interfering with peripheral glucocorticoid activation.     

Statins and Angiotensin‐Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease

Liver fibrosis is a common response to many chronic liver diseases. The aim of our study was to explore whether pharmacotherapy for concurrent diseases affects overall mortality, liver‐related mortality and liver‐related morbidity in patients with chronic liver disease. We performed a register‐based cohort study of all patients with a first‐time diagnosis of chronic liver disease between 2005 and 2012 in Sweden (n = 70 546). Data from the Patient Register, the Prescribed Drug Register and the Death Certificate Register were linked . We studied whether the use of statins, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers and antibiotics affected the risk of total mortality, liver‐specific mortality and morbidity. We found a reduction in mortality risk for statin users (n = 11,245) with hazard ratios from 0.57 (95% CI: 0.32–0.99) for patients with autoimmune hepatitis to 0.84 (95% CI: 0.75–0.95) for patients with alcoholic liver disease. There was a significantly reduced liver‐related mortality for patients with alcoholic liver disease who used angiotensin‐converting enzyme inhibitors, 0.85 (95% CI: 0.65–0.96). There were increased overall mortality risks for antibiotic users (n = 44,572), with hazard ratios up to 1.67 (95% CI, 1.55–1.80) for viral hepatitis. Statin use was associated with decreased risks of liver‐specific mortality and morbidity, and reduced total mortality foremost among patients with alcoholic liver disease. Angiotensin ‐converting enzyme inhibitors was associated with reduced liver‐related mortality among patients with alcoholic liver disease.     

Characterisation of a monoclonal antibody detecting Atlantic salmon endothelial and red blood cells,and its association with the infectious salmon anaemia virus cell receptor

Endothelial cells (ECs) line the luminal surfaces of the cardiovascular system and play an important role in cardiovascular functions such as regulation of haemostasis and vasomotor tone. A number of fish and mammalian viruses target these cells in the course of their infection. Infectious salmon anaemia virus (ISAV) attacks ECs and red blood cells (RBCs) of farmed Atlantic salmon (Salmo salar L.), producing the severe disease of infectious salmon anaemia (ISA). The investigation of ISA has up to now been hampered by the lack of a functional marker for ECs in Atlantic salmon in situ. In this study, we report the characterisation and use of a novel monoclonal antibody (MAb) detecting Atlantic salmon ECs (e.g. vessel endothelium, endocardial cells and scavenger ECs) and RBCs. The antibody can be used with immunohistochemistry, IFAT and on Western blots. It appears that the epitope recognised by the antibody is associated with the ISAV cellular receptor. Besides being a tool to identify ECs in situ, it could be useful in further studies of the pathogenicity of ISA. Finally, the detection of an epitope shared by ECs and RBCs agrees with recent findings that these cells share a common origin, thus the MAb can potentially be used to study the ontogeny of these cells in Atlantic salmon.     

Effects of exposure to an estrous female on forebrain monoaminergic neurotransmission in the non-copulating male rat

Regional changes in the rate of brain monoamine synthesis were monitored in male rats exposed to, but prevented from physical contact with, an estrous or an ovariectomized female. The in vivo rate of tyrosine and tryptophan hydroxylase activities were estimated by measuring the accumulation of DOPA and 5-HTP following inhibition of cerebral aromatic l-amino acid decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015) treatment (100 mg/kg i.p.) 5 min upon NSD-1015 treatment, the males were exposed to an intact estrous female or an ovariectomized female for 20 min before decapitation and brain dissections. Exposure to an estrous female produced an increased rate of tyrosine and tryptophan hydroxylase activity in the medial prefrontal cortex, the dorso-lateral neostriatum and in the ventral neostriatum, in comparison with home-cage controls. By the same comparison, exposure to an ovariectomized female resulted in an increased rate of tyrosine hydroxylase activity in the medial prefrontal cortex, byt not in the neostriatal areas, whereas tryptophan hydroxylase activity was unaffected. Finally, exposure to the empty test cage, with no stimulus females present, did not produce any statistically significant changes in the rate of tyrosine or tryptophan hydroxylase activity in any of the brain areas sampled. Taken together with recent findings from this laboratory, the present results demonstrate that the level of sexual motivation brought about by the olfactory, auditory and/or visual stimulation of a receptive female is associated with an increased demand on catecholamine and 5-hydroxytryptamine synthesis in the limbic forebrain of the male rat. The finding that the presence of an unestrous female produced an enhanced demand on tyrosine hydroxylase activity in the medial prefrontal neocortex demonstrates that the sexual incentive provided by the estrous female may not be the only factor responsible for all the effects observed in the present study. In fact, there is a distinct possibility that the intense challenge produced by sexually significant stimuli is but an endpoint, and that the changes found in forebrain monoamine synthesis is a reflection of an environmental challenge not necessarily specifically linked to the sexual behavior.     

Predicting disability pension – depression as hazard: a 10 year population‐based cohort study in norway

Disability pension (DP) is an escalating challenge to individuals and the welfare state, with mental health problems as imminent hazard. The objective of the present paper was to determine if a diagnosis of depression increased the risk of subsequent DP, and whether the risk differed by gender. A population cohort of 1230 persons were diagnostically interviewed (Composite International Diagnostic Interview, CIDI) in a population study examining mental health, linked to the DP registry and followed for 10 years. The risk for DP following depression was estimated using Cox regression. Life‐time depression, as well as current depression, increased the risk of subsequent DP for both genders. The fully adjusted [baseline health, health behavior and socio‐economic status (SES)] hazard ratios (HRs) for life‐time depressed men and women were 2.9 [95% confidence interval (CI) 1.5–5.8] and 1.6 (95% CI 1.0–2.5) respectively. Men were significantly older at time of DP. There are reasons to believe that depression went under‐recognized and under‐treated. To augment knowledge in the field, without underestimating depression as risk for DP, a deeper understanding of the nature and effects of other distress is needed. Copyright © 2015 John Wiley & Sons, Ltd.