ORCID Profile
0000-0002-4768-5452
Current Organisation
University of Adelaide
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Publisher: Elsevier
Date: 2020
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.NEUBIOREV.2016.08.018
Abstract: There is a growing body of research investigating the gene expression signature of depression at the genome-wide level, with potential for the discovery of novel pathophysiological mechanisms of depression. However, heterogeneity of depression, dynamic nature of gene expression patterns and various sources of noise have resulted in inconsistent findings. We systematically review the current state of transcriptome profiling of depression in the brain and peripheral tissues with a particular focus on replicated findings at the single gene level. By examining 16 brain regions and 5 cell types from the periphery, we identified 57 replicated differentially expressed genes in the brain and 21 in peripheral tissues. Functional overlap between brain and periphery strongly implicates shared pathways in a comorbid phenotype of depression and cardiovascular disease. The findings highlight dermal fibroblasts as a promising experimental model for depression biomarker research, provide partial support for all major theories of depression and suggest a novel candidate gene, PXMP2, which plays a critical role in lipid and reactive oxygen species metabolism.
Publisher: BMJ
Date: 06-02-2019
DOI: 10.1136/BMJ.L94
Abstract: To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Systematic analysis. Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Elsevier BV
Date: 05-2017
Publisher: Cold Spring Harbor Laboratory
Date: 07-05-2020
DOI: 10.1101/2020.05.05.075606
Abstract: The critical role of blood lipids in a broad range of health and disease states is well recognised, while an understanding of the complex genetic regulation of lipid homeostasis is emerging. Traditional blood lipids (LDL-C, HDL-C and triglycerides) are known to be substantially regulated by genetic variation. Less well explored is the interplay of genetics and environment within the broader blood lipidome. Here we use the twin model to examine heritability of the plasma lipidome among healthy older aged twins and explore gene expression and epigenetic (DNA methylation) associations of these lipids. Heritability of 209 plasma lipids quantified by liquid chromatography coupled mass spectrometry (LC-MS) was assessed in 75 monozygotic and 55 dizygotic twin pairs enrolled in the Older Australian Twins Study (OATS), aged 69-93 years. Only 27/209 lipids (13.3%) were significantly heritable under the classical ACE twin model ( h 2 = 0.28-0.59). Ceramides (Cer) and triglycerides (TG) were most heritable, while sphingomyelins (SM) and most phospholipids, especially lysophospholipids, were not significantly heritable. Lipid levels correlated with 3731 transcripts. Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, which were not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for a proportion of variability in some non-heritable lipids, especially lysophosphatidylcholine (LPC). We found a complex interplay of genetic and environmental influences on the ageing plasma lipidome, with most of the variation controlled by unique environmental influences.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 10-2020
Publisher: SAGE Publications
Date: 11-01-2018
Abstract: Timely and accurate assessments of disease burden are essential for developing effective national health policies. We used the Global Burden of Disease Study 2015 to examine burden due to mental and substance use disorders in Australia. For each of the 20 mental and substance use disorders included in Global Burden of Disease Study 2015, systematic reviews of epidemiological data were conducted, and data modelled using a Bayesian meta-regression tool to produce prevalence estimates by age, sex, geography and year. Prevalence for each disorder was then combined with a disorder-specific disability weight to give years lived with disability, as a measure of non-fatal burden. Fatal burden was measured as years of life lost due to premature mortality which were calculated by combining the number of deaths due to a disorder with the life expectancy remaining at the time of death. Disability-adjusted life years were calculated by summing years lived with disability and years of life lost to give a measure of total burden. Uncertainty was calculated around all burden estimates. Mental and substance use disorders were the leading cause of non-fatal burden in Australia in 2015, explaining 24.3% of total years lived with disability, and were the second leading cause of total burden, accounting for 14.6% of total disability-adjusted life years. There was no significant change in the age-standardised disability-adjusted life year rates for mental and substance use disorders from 1990 to 2015. Global Burden of Disease Study 2015 found that mental and substance use disorders were leading contributors to disease burden in Australia. Despite several decades of national reform, the burden of mental and substance use disorders remained largely unchanged between 1990 and 2015. To reduce this burden, effective population-level preventions strategies are required in addition to effective interventions of sufficient duration and coverage.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 2017
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2017
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.EURONEURO.2015.12.017
Abstract: Cognitive impairment, or decline, is not only a feature of Alzheimer׳s disease and other forms of dementia but also normal ageing. Abundant evidence from epidemiological studies points towards perturbed inflammatory mechanisms in aged in iduals, though the cause-effect nature of this apparent relationship is difficult to establish. Genetic association studies focusing on polymorphism in and around inflammatory genes represent a viable approach to establish whether inflammatory mechanisms might play a causal role in cognitive decline, whilst also enabling the identification of specific genes potentially influencing specific cognitive facets. Thus, here we provide a review of published genetic association studies investigating inflammatory genes in the context of cognitive decline in elderly, non-demented, s les. Numerous candidate gene association studies have been performed to date, focusing almost exclusively on genes encoding major cytokines. Some of these studies report significant cognitive domain-specific associations implicating Interleukin 1β (IL1β) (rs16944), Tumour Necrosis Factor α (TNFα) (rs1800629) and C-reactive protein (CRP) in various domains of cognitive function. However, the majority of these studies are lacking in statistical power and have other methodological limitations, suggesting some of them may have yielded false positive results. Genome-wide association studies have implicated less direct and less obvious regulators of inflammatory processes (i.e., PDE7A, HS3ST4, SPOCK3), indicating that a shift away from the major cytokine-encoding genes in future studies will be important. Furthermore, better cohesion across studies with regards to the cognitive test batteries administered to participants along with the continued application of longitudinal designs will be vital.
Publisher: Elsevier
Date: 2018
Publisher: Elsevier BV
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 03-08-2018
Publisher: Springer Science and Business Media LLC
Date: 03-08-2018
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JPSYCHIRES.2018.09.017
Abstract: The molecular factors involved in the pathophysiology of major depressive disorder (MDD) remain poorly understood. One approach to examine the molecular basis of MDD is co-expression network analysis, which facilitates the examination of complex interactions between expression levels of in idual genes and how they influence biological pathways affected in MDD. Here, we applied an unsupervised gene-network based approach to a prospective experimental design using microarray genome-wide gene expression from the peripheral whole blood of older adults. We utilised the Sydney Memory and Ageing Study (sMAS, N = 521) and the Older Australian Twins Study (OATS, N = 186) as discovery and replication cohorts, respectively. We constructed networks using Weighted Gene Co-expression Network Analysis (WGCNA), and correlated identified modules with four subtypes of depression: single episode, current, recurrent, and lifetime MDD. Four modules of highly co-expressed genes were associated with recurrent MDD (N = 27) in our discovery cohort (FDR<0.2), with no significant findings for a single episode, current or lifetime MDD. Functional characterisation of these modules revealed a complex interplay between dysregulated protein processing in the endoplasmic reticulum (ER), and innate and adaptive immune response signalling, with possible involvement of pathogen-related pathways. We were underpowered to replicate findings at the network level in an independent cohort (OATS), however we found a significant overlap for 9 in idual genes with similar co-expression and dysregulation patterns associated with recurrent MDD in both cohorts. Overall, our findings support other reports on dysregulated immune response and protein processing in the ER in MDD and provide novel insights into the pathophysiology of depression.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
Publisher: Elsevier BV
Date: 10-2020
Publisher: Massachusetts Medical Society
Date: 06-07-2017
Publisher: Public Library of Science (PLoS)
Date: 17-10-2022
DOI: 10.1371/JOURNAL.PONE.0272368
Abstract: Understanding the genomic architecture and molecular mechanisms of cognitive functioning in healthy in iduals is critical for developing tailored interventions to enhance cognitive functioning, as well as for identifying targets for treating impaired cognition. There has been substantial progress in uncovering the genetic composition of the general cognitive ability ( g ). However, there is an ongoing debate whether executive functioning (EF)–another key predictor of cognitive health and performance, is separable from general g . To provide an analytical review on existing findings on genetic influences on the relationship between g and EF, we re-analysed a subset of genome-wide association studies (GWAS) from the GWAS catalogue that used measures of g and EF as outcomes in non-clinical populations. We identified two sets of single nucleotide polymorphisms (SNPs) associated with g (1,372 SNPs across 12 studies), and EF (300 SNPs across 5 studies) at p x10 -6 . A comparative analysis of GWAS-identified g and EF SNPs in high linkage disequilibrium (LD), followed by pathway enrichment analyses suggest that g and EF are overlapping but separable at genetic variant and molecular pathway levels, however more evidence is required to characterize the genetic overlap/distinction between the two constructs. While not without limitations, these findings may have implications for navigating further research towards translatable genetic findings for cognitive remediation, enhancement, and augmentation.
Publisher: eLife Sciences Publications, Ltd
Date: 22-07-2020
DOI: 10.7554/ELIFE.58954
Abstract: The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h 2 = 0.28–0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.
Publisher: Elsevier BV
Date: 07-2022
No related grants have been discovered for Liliana Ciobanu.