Project description:This West Coast Metabolomics Center pilot and feasibility project was granted to Roel Ophoff (UC Los Angeles ) and Steve Horwath (UC Los Angeles ) . Major depressive disorder (MDD) is one of the most debilitating disorders in the United States with a 12-month prevalence of 6.7% in the adult population. The disorder affects millions of Americans daily and is a major health concern with enormous economic cost the society at large. Criteria for MDD diagnosis and treatment are based on various signs and symptoms not always fitting into strict diagnostic categories such as DSM-IV. Despite various known risk factors (such as family history, age, and gender), biological markers supporting diagnosis or prediction of MDD are unavailable. We have collected cerebrospinal fluid (CSF) and peripheral blood of more than 600 subjects from the general population. For each of the participants we also obtained biometric information as well as behavioral trait measures. One of the measures is the Beck Depression Inventory (BDI), a well-established questionnaire for measuring severity of depression. Based on the BDI, roughly 5% of participants suffer from severe depressive symptoms while most of these subjects are not under treatment or receiving any medication for depression
In the current investigation, untargeted analysis of primary metabolites was conducted on age and gender matched human cerebrospinal fluid (CSF) and plasma from subjects suffering with MDD ( n=50) and control subjects (n=50). Subjects were diagnosed as having MDD based on the Beck Depression Inventory.
The primary objectives of this study were to 1) identify metabolites which discriminate between subjects with and without depression symptoms in the CSF and plasma and 2) how changes correlate between CSF and plasma.
Project description:Exposure to traffic-related air pollution (TRAP) generates oxidative stress, with downstream effects at the metabolic level. Human studies of traffic density and metabolomic markers, however, are rare. The main objective of this study was to evaluate the cross-sectional association between traffic density in the street of residence with oxidative stress and metabolomic profiles measured in a population-based sample from Spain. We also explored in silico the potential biological implications of the findings. Secondarily, we assessed the contribution of oxidative stress to the association between exposure to traffic density and variation in plasma metabolite levels. Traffic density was defined as the average daily traffic volume over an entire year within a buffer of 50 m around the participants' residence. Plasma metabolomic profiles and urine oxidative stress biomarkers were measured in samples from 1181 Hortega Study participants by nuclear magnetic resonance spectroscopy and high-performance liquid chromatography, respectively. Traffic density was associated with 7 (out of 49) plasma metabolites, including amino acids, fatty acids, products of bacterial and energy metabolism and fluid balance metabolites. Regarding urine oxidative stress biomarkers, traffic associations were positive for GSSG/GSH% and negative for MDA. A total of 12 KEGG pathways were linked to traffic-related metabolites. In a protein network from genes included in over-represented pathways and 63 redox-related candidate genes, we observed relevant proteins from the glutathione cycle. GSSG/GSH% and MDA accounted for 14.6% and 12.2% of changes in isobutyrate and the CH2CH2CO fatty acid moiety, respectively, which is attributable to traffic exposure. At the population level, exposure to traffic density was associated with specific urine oxidative stress and plasma metabolites. Although our results support a role of oxidative stress as a biological intermediary of traffic-related metabolic alterations, with potential implications for the co-bacterial and lipid metabolism, additional mechanistic and prospective studies are needed to confirm our findings.
Project description:IntroductionWe examined the influence of common preanalytical factors on the measurement of Alzheimer's disease-specific biomarkers in human plasma.MethodsAmyloid β peptides (Aβ[1-40], Aβ[1-42]) and total Tau plasma concentrations were quantified using fully automated Roche Elecsys assays.ResultsAβ(1-40), Aβ(1-42), and total Tau plasma concentrations were not affected by up to three freeze/thaw cycles, up to five tube transfers, the collection tube material, or the size; circadian rhythm had a minor effect. All three biomarkers were influenced by the anticoagulant used, particularly total Tau. Aβ concentrations began decreasing 1 hour after blood draw/before centrifugation and decreased by up to 5% and 10% at 2 and 6 hours, respectively. For separated plasma, time to measurement influenced Aβ levels by up to 7% after 6 hours and 10% after 24 hours.DiscussionOur findings provide guidance for standardizing blood sample collection, handling, and storage to ensure reliable analysis of Alzheimer's disease plasma biomarkers in routine practice and clinical trials.
Project description:The human plasma proteome is clinically highly significant and has been studied extensively because it is thought that its molecular makeup provides a window into the health state of an individual. However, neither the quantitative variability of the plasma proteome nor the origins of the variation are known. To determine the relative contributions of heritability, environmental and longitudinal factors to plasma proteome variability we systematically decomposed the biological variance of 1904 peptides defining 342 unique plasma protein profiles from 232 plasma samples that were collected with 2-7 year intervals from monozygotic (MZ) and dizygotic (DZ) twins. The data were collected via SWATH mass spectrometry (SWATH-MS), an emerging technology characterized by high degree of reproducibility and quantitative accuracy. The data indicate abundance variability is an important feature for different proteins among population, that the abundances of about 20% of plasma protein are considerably heritable, and that the degrees of genetic control and aging effects vary across specific biological processes. Moreover, we identified 13 cis- SNPs significantly influencing the abundance level of specific plasma proteins. These results substantially extend the understanding of the impact of heritability on the human proteomic dynamics and therefore have implications for the effective design of plasma-based biomarker studies.
Project description:To examine associations between sexual behaviour, sexual function and sexual health service use of individuals with depression in the British general population, to inform primary care and specialist services.British general population.15,162 men and women aged 16-74 years were interviewed for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), undertaken in 2010-2012. Using age-adjusted ORs (aAOR), relative to a comparator group reporting no treatment or symptoms, we compared the sexual health of those reporting treatment for depression in the past year.Sexual risk behaviour, sexual function, sexual satisfaction and sexual health service use.1331 participants reported treatment for depression (5.2% men; 11.8% women). Relative to the comparator group, treatment for depression was associated with reporting 2 or more sexual partners without condoms (men aAOR 2.07 (95% CI 1.38 to 3.10); women 2.22 (1.68 to 2.92)), and concurrent partnerships (men 1.80 (1.18 to 2.76); women 2.06 (1.48 to 2.88)), in the past year. Those reporting depression treatment were more likely to be dissatisfied with their sex lives (men 2.32 (1.74 to 3.11); women 2.30 (1.89 to 2.79)), and to score in the lowest quintile on the Natsal-sexual function measure. They were also more likely to report a recent chlamydia test (men 1.92 (1.15 to 3.20)); women (1.27 (1.01 to 1.60)), and to have sought help regarding their sex life from a healthcare professional (men 2.92 (1.98 to 4.30); women (2.36 (1.83 to 3.04)), most commonly from a family doctor. Women only were more likely to report attending a sexual health clinic (1.91 (1.42 to 2.58)) and use of emergency contraception (1.98 (1.23 to 3.19)). Associations were broadly similar for individuals with depressive symptoms but not reporting treatment.Depression, measured by reported treatment, was strongly associated with sexual risk behaviours, reduced sexual function and increased use of sexual health services, with many people reporting help doing so from a family doctor. The sexual health of depressed people needs consideration in primary care, and mental health assessment might benefit people attending sexual health services.
Project description:In order to determine whether dis-regulation of a genetic pathway could explain the increased apoptosis of parp-2-/- double positive thymocytes, the gene expression profiles in double positive thymocytes derived from wild-type and parp-2-/- mice were analysed using Affymetrix oligonucleotide chips (mouse genome 430 2.0).