Of sound mind and body: depression, disease, and accelerated aging

Major depressive disorder (MDD) is associated with a high rate of developing serious medical comorbidities such as cardiovascular disease, stroke, dementia, osteoporosis, diabetes, and the metabolic syndrome. These are conditions that typically occur late in life, and it has been suggested that MDD may be associated with “accelerated aging.” We review several moderators and mediators that may accompany MDD and that may give rise to these comorbid medical conditions. We first review the moderating effects of psychological styles of coping, genetic predisposition, and epigenetic modifications (eg, secondary to childhood adversity). We then focus on several interlinked mediators occurring in MDD (or at least in subtypes of MDD) that may contribute to the medical comorbidity burden and to accelerated aging: limbic-hypothalamic-pituitary-adrenal axis alterations, diminution in glucocorticoid receptor function, altered glucose tolerance and insulin sensitivity, excitotoxicity, increases in intracellular calcium, oxidative stress, a proinflammatory milieu, lowered levels of “counter-regulatory” neurosteroids (such as allopregnanolone and dehydroepiandrosterone), diminished neurotrophic activity, and accelerated cell aging, manifest as alterations in telomerase activity and as shortening of telomeres, which can lead to apoptosis and cell death. In this model, MDD is characterized by a surfeit of potentially destructive mediators and an insufficiency of protective or restorative ones. These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators

Pineal-adrenal interactions: The effect of acute pharmacological blockade of nocturnal melatonin secretion

The pineal gland is a complex neuroendocrine organ which is under photoneuroendocrine control. Previous studies in animals and humans have suggested reciprocal variations in pineal melatonin biosynthesis and adrenal glucocorticoid output; it remains unclear, however, whether a causal relationship exists between these two systems. To address this question, we examined the overnight secretory activity of the hypothalamic-pituitary-adrenal (HPA) axis in conjunction with acute pharmacological suppression of pineal melatonin biosynthesis in 11 healthy volunteers. Results of the current study are consistent with the hypothesis that melatonin does not function as a tonic inhibitor of the HPA axis on an acute basis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28590/1/0000398.pd

Smoking Cessation Outcomes Among Sexual and Gender Minority and Nonminority Smokers in Extended Smoking Treatments

IntroductionSexual and gender minority individuals (i.e., lesbian, gay, bisexual, and transgender [LGBT]) have a higher smoking prevalence than nonminority individuals. There is limited evidence of smoking abstinence success in nontailored smoking treatments among LGBT smokers.MethodsThis study is a secondary data analysis comparing the efficacy of extended, nontailored treatments among sexual and gender minority and nonminority smokers. Data from two clinical trials were combined to increase power and generalizability of the findings. Trials began with 12 weeks of counseling, nicotine replacement, and bupropion, after which participants were randomized to an extended treatment.ResultsFollow-up occurred at weeks 12, 24, 52, 64, and 104. Of the sample (n = 777), 17% identified as sexual and gender minority and 83% as nonminority. The sample was 75% non-Hispanic White, with 86% completing at least some college, and 68% were employed. Sexual and gender minorities were younger and indicated a greater desire to quit smoking than nonminority smokers. No other differences emerged on demographic, smoking, or mood variables. The average Fagerström Test for Nicotine Dependence score was 4.8, and mean daily cigarettes was 19.8. The generalized estimating equations model revealed no significant differences in abstinence between sexual and gender minority smokers and nonminority smokers at all follow-up assessments.ConclusionsSexual and gender minority smokers appear as likely to quit or abstain as nonminority smokers in extended, nontailored interventions. However, these findings may not generalize to other geographic areas, where access to treatment is limited or a higher stigma of sexual orientation exists

Prevalence and clinical correlates of explosive outbursts in Tourette Syndrome

The aim of this study was to examine the prevalence and clinical correlates of explosive outbursts in two large samples of individuals with Tourette syndrome (TS), including one collected primarily from non-clinical sources. Participants included 218 TS-affected individuals who were part of a genetic study (N=104 from Costa Rica (CR) and N=114 from the US). The relationships between explosive outbursts and comorbid attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), tic severity, and prenatal and perinatal complications were examined using regression analyses. Twenty percent of participants had explosive outbursts, with no significant differences in prevalence between the CR (non-clinical) and the US (primarily clinical) samples. In the overall sample, ADHD, greater tic severity, and lower age of tic onset were strongly associated with explosive outbursts. ADHD, prenatal exposure to tobacco, and male gender were significantly associated with explosive outbursts in the US sample. Lower age of onset and greater severity of tics were significantly associated with explosive outbursts in the CR sample. This study confirms previous studies that suggest that clinically significant explosive outbursts are common in TS and associated with ADHD and tic severity. An additional potential risk factor, prenatal exposure to tobacco, was also identified

Improving Project Logistics by using IoT

This Bachelor´s thesis is made on behalf of Wärtsilä Energy Solutions, Project Logistics & Transport Management department whose main task is to coordinate and ensure that materials and products are transported to the right place and on time in Project Logistics. This thesis examines how you could improve Wärtsilä´s Project Logistics by using Internet of Things. By developing IoT, there has been an increased chance to get more information about transports than before and Wärtsilä is currently looking for new solutions to use that could improve their current logistics system. The purpose of this thesis is to review new, and used, solutions on the market, and then see what could work in practice at Wärtsilä. Material to this thesis are gathered from books, web pages and articles that reviewed interesting IoT solutions and which also gave examples on different solutions that are used by other companies in the same business. The Result is two different methods that could improve Wärtsilä´s Project Logistics in different occasions. These results are intended to give tips on how IoT could improve the department´s ways of coordinating and check transports and logistics within a project.Detta examensarbete är gjort i uppdrag av Wärtsilä Energy Solutions, Project logistics & Transport Management avdelningen vars huvuduppgift är att koordinera och se till att material och produkter transporteras till rätt plats i rätt tid inom projekt logistiken. Examensarbetet behandlar hur man kunde förbättra Wärtsiläs projekt logistik genom att använda Internet of Things. Genom att IoT har utvecklats har det uppstått möjligheter att få fram mer information om transporter än tidigare och Wärtsilä söker för tillfället nya lösningar som kunde användas för att förbättra deras nuvarande logistiksystem. Syftet med arbetet är att gå igenom nya, men även redan befintliga, lösningar som används på dagens marknad - för att sedan se vad som kunde fungera i praktiken hos Wärtsilä. Material till arbetet är samlat från böcker, webbsidor och artiklar som gick igenom intressanta IoT lösningar och som också gav exempel på hur olika system fungerar och används av andra företag inom samma bransch. Slutresultatet blev två olika metoder som kunde förbättra Wärtsiläs projekt logistik vid olika tillfällen. Dessa resultat är tänkta för att ge tips på hur IoT kunde förbättra avdelningens sätt hur man koordinerar och granskar transporter och logistiken inom ett projekt

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants

Genome-wide association study of Tourette Syndrome

Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder

Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure