Ana Mendes-Silva - Academia.edu (original) (raw)

Papers by Ana Mendes-Silva

Research paper thumbnail of Exosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults

Journal of affective disorders, Jun 1, 2024

Research paper thumbnail of Major depression, physical health and molecular senescence markers abnormalities

Previous studies suggested the role of cellular senescence in late-life depression (LLD). However... more Previous studies suggested the role of cellular senescence in late-life depression (LLD). However, it is unclear how this finding relates to common features of LLD, such as medical and cognitive problems. We applied factor analyses to an extensive battery of clinical variables in 426 individuals with LLD. Here we tested the relationship between these factors, age and sex, with an index of cellular senescence based on 22 senescence-associated secretory phenotype proteins. We found four factors: 'depression and anxiety severity', 'cognitive functioning', 'cardiovascular and cardiometabolic health' and 'blood pressure'. A higher senescence-associated secretory phenotype index was associated with poorer 'cognitive functioning' and 'cardiovascular and cardiometabolic health' but not with 'depression and anxiety severity'. These findings highlight the role of cellular senescence in poorer physical and cognitive health in LLD. They are consonant with the viewpoint that co-occurring medical burdens and their associated disabilities are part of a phenotype of accelerated ageing in LLD. Late-life depression (LLD) is a major depressive disorder in older adults. LLD is common and poses a substantial burden for affected individuals, their families and society 1. These burdens include worse quality of life, impaired activities of daily living 2 and increased frailty 3. Previous studies demonstrated a strong link among LLD, poor physical health 4 , cognitive impairment, an increased risk for dementia and mortality 5. These clinico-epidemiological findings suggest that older adults with LLD may experience an accelerated ageing phenotype 6. Accelerated ageing processes in LLD may be driven by increased allostatic load, altered proteostasis control, pro-inflammatory mechanisms and systemic oxidative stress 7,8. Research also suggests that accelerated ageing in LLD may occur on the cellular and subcellular level 9 and be linked to enhanced senescence processes 10. Cellular senescence 11 has emerged as a pivotal hallmark of the biology of ageing. It is a complex stress response in which cells irreversibly lose their proliferative capacity, become resistant to apoptosis 12 and develop a multicomponent secretory phenotype 13 , referred to as the senescence-associated secretory phenotype (SASP) 12. The SASP includes proteins involved in cycle control, intercellular communication, the immune-inflammatory response and tissue remodelling 14. Under non-pathological conditions,

Research paper thumbnail of Liquid Brain Biopsy in Late-Life Depression and Alzheimer’s Disease Using Circulating Brain-Derived Exosomes

Biological Psychiatry, May 1, 2022

Research paper thumbnail of 98. Cellular Senescence in Late-Life Depression

Biological Psychiatry, May 1, 2023

Research paper thumbnail of Epidermal Growth Factor and Fibroblast Growth Factor-2 Circulating Levels in Elderly with Major Depressive Disorder

American Journal of Geriatric Psychiatry, Mar 1, 2018

Research paper thumbnail of A highly reusable genosensor for late-life depression diagnosis based on microRNA 184 attomolar detection in human plasma

Research paper thumbnail of Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

JAMA network open, Jun 30, 2022

IMPORTANCE Many older adults with depression do not experience remission with antidepressant trea... more IMPORTANCE Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population. OBJECTIVE To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

Research paper thumbnail of Differential gene expression by RNA-seq during Alzheimer’s disease-like progression in the Drosophila melanogaster model

Neuroscience Research, 2022

Alzheimer's disease (AD) is characterized by progressive, irreversible loss of memory and cog... more Alzheimer's disease (AD) is characterized by progressive, irreversible loss of memory and cognitive function. Drosophila melanogaster and other animal models are used to study several diseases, in order to elucidate unknown mechanisms and develop potential therapies. Molecular studies require biological samples and, for neuropathologies such as AD biopsy of the human brain, are invasive and potentially damaging. The solution is to use animal models, such as D. melanogaster, which is a model organism that can replace mammalian organisms in such studies. In this study, we evaluated the climbing ability and differential gene expression during AD progression due to the amylodoigenic pathway using RNA-seq, and we performed an in silico analysis of a fruit fly AD-like GFP (Green Fluorescent Protein) model with GFP expression in the pan-neural elav driver. A total of 1388 genes were differentially expressed in all analyzed groups. The main pathways related to those Differentially Expressed Genes (DEGs) during aging and AD progression were evaluated using the fly genes and human orthologs, in order to link genomic information to higher-order functional information with gene pathway mapping. We identified pathways present in all analyzed groups, such as metabolic pathways, ribosomal pathways, proteasome pathways and immune system pathways. Some of the genes were validated by qPCR. Knockdown of CG17754 gene by RNAi promoted degeneration in the fly eye, validating these findings in vivo. The identification of similarities in molecular pathways between the transgenic fly AD-like GFP model and mammals related to AD provides new insights into the use of this fly in screening novel anti-AD drugs.

Research paper thumbnail of Plasma proteomic signature of major depressive episode in the elderly

Research paper thumbnail of Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine

The American Journal of Geriatric Psychiatry

Research paper thumbnail of Genetic overlap between mood disorders and Alzheimer’s disease: Could it explain the clinical and epidemiological overlap of these disorders?

Alzheimer's & Dementia, 2021

Mood disorders such as major depressive (MD) and bipolar (BD), are major risk factors for Alzheim... more Mood disorders such as major depressive (MD) and bipolar (BD), are major risk factors for Alzheimer’s disease (AD). History of MD and BD can double the risk of developing AD in older adults, and this risk is even higher when depressive symptoms co‐occur with mild cognitive impairment. These evidences suggest that mood disorders and AD may share common biological mechanisms, such as genetic risk factors. However, challenges on conducting multi‐phenotype long‐follow up studies limit the direct assessment of this hypothesis. Recently, bioinformatics methods using Genome‐wide association studies (GWAS) results have been developed and applied to assess the existence of genetic overlap among disorders. Herein, we carried out a multilevel approach to investigate the genetic overlap between mood disorders (MD and BD) and AD, by assessing their genetic correlation, polygenic overlap and shared biological pathways.

Research paper thumbnail of Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress

Frontiers in Cellular Neuroscience

BackgroundThe cell cycle is a critical mechanism for proper cellular growth, development and viab... more BackgroundThe cell cycle is a critical mechanism for proper cellular growth, development and viability. The p16INK4a and p21Waf1/Cip1 are important regulators of the cell cycle progression in response to internal and external stimuli (e.g., stress). Accumulating evidence indicates that the prefrontal cortex (PFC) is particularly vulnerable to stress, where stress induces, among others, molecular and morphological alterations, reflecting behavioral changes. Here, we investigated if the p16INK4a and p21Waf1/Cip1 expression are associated with behavioral outcomes.MethodsPrefrontal cortex mRNA and protein levels of p16INK4A and p21Waf1/Cip1 of mice (six independent groups of C57BL/6J, eight mice/group, 50% female) exposed from 0 to 35 days of chronic restraint stress (CRS) were quantified by qPCR and Western Blot, respectively. Correlation analyses were used to investigate the associations between cyclin-dependent kinase inhibitors (CKIs) expression and anxiety- and depression-like beha...

Research paper thumbnail of Plasma IL-17A levels in patients with late-life depression

Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), Jan 19, 2017

A consistent body of research has confirmed that patients with major depressive disorder (MDD) ha... more A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Plasma IL-17A levels were not statistically different between LLD patients and controls (p...

Research paper thumbnail of Plasma IL-17A levels in patients with late-life depression

Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), Jan 19, 2017

A consistent body of research has confirmed that patients with major depressive disorder (MDD) ha... more A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Plasma IL-17A levels were not statistically different between LLD patients and controls (p...

Research paper thumbnail of Expressão gênica associada à resistência da soja a Piezodorus guildinii

Research paper thumbnail of Increased levels of circulating cell-free mtDNA in plasma of late life depression subjects

Journal of psychiatric research, 2021

BACKGROUND Oxidative stress (OS) has been implicated in the pathophysiology of late-life depressi... more BACKGROUND Oxidative stress (OS) has been implicated in the pathophysiology of late-life depression (LLD). Mitochondria are the primary source of oxidative stress and can be significantly damaged with increased OS. Circulating cell-free mtDNA (ccf-mtDNA) is a marker of cellular stress and mitochondria damage triggered by oxidative stress. METHODS We evaluated the plasma levels of ccf-mtDNA in between 32 LLD and 21 never-depressed participants. We also investigated the association between ccf-mtDNA and the severity of depressive episodes and cognition performance. RESULTS We found a higher ccf-mtDNA level in LLD cases compared with controls (t = -2.91, p = 0.005). Also, ccf-mtDNA was significantly correlated with the severity of depression (r = 0.42, p = 0.001). There was no significant correlation between ccf-mtDNA and measures of cognitive decline. LIMITATIONS The small sample size and cross-sectional design were the main limitations of this study. CONCLUSION Our results suggest th...

Research paper thumbnail of Using Circulating Cell-free mtDNA to Examine the Synergetic Effects of Major Depressive Disorder and Frailty

American Journal of Geriatric Psychiatry, 2021

Research paper thumbnail of Author response for "Telomere shortening in late‐life depression: A potential marker of depression severity

Research paper thumbnail of Expressão do microRNA 184 em idosos com depressão maior: uma perspectiva translacional

A depressao e a desordem psiquiatrica mais comum e causa graves consequencias em idosos. Os mecan... more A depressao e a desordem psiquiatrica mais comum e causa graves consequencias em idosos. Os mecanismos biologicos envolvidos na depressao geriatrica (DG) sao complexos e envolvem muitos genes. Os MicroRNAs (miRNAs) sao pequenos RNAs nao codificadores que regulam pos transcricionalmente a expressao genica. O desequilibrio na expressao de miRNAs esta relacionado a muitas doencas, incluindo DG. Nosso objetivo foi avaliar os miRNAs plasmaticos associados a DG e possivelmente a gravidade dos sintomas depressivos e ao desempenho cognitivo nesses individuos. Um total de 116 amostras de plasma de idosos (63 com DG e 53 controles) foram divididas aleatoriamente para fazer o sequenciamento de nova geracao (SNG) e a validacao por RT-qPCR. Drosophila melanogaster foi utilizado como modelo translacional para avaliar fenomenos comportamentais associados a superexpressao e ao nocaute do ortologo de hsa-miR-184. A analise SNG encontrou o hsa-miR-184 (log2foldchange=-4,205 e p-valor=1,195e-03) e o h...

Research paper thumbnail of Genetic overlap between major depression, bipolar disorder and Alzheimer’s Disease

ABSTRACTBackgroundMood disorders, including major depression (MD) and bipolar disorder (BD), are ... more ABSTRACTBackgroundMood disorders, including major depression (MD) and bipolar disorder (BD), are risk factors for Alzheimer’s disease (AD) and possibly share an overlapping genetic architecture. However, few studies have investigated the shared loci and potential pleiotropy among these disorders.MethodsWe carried out a systematic analytical pipeline using GWAS data and three complementary (genome-wide, single variant, and gene-level) statistical approaches to investigate the genetic overlap among MD, BD, and AD.ResultsGWAS summary statistics data from 679,973 individuals were analyzed herein (59,851 MD cases and 113,154 controls; 20,352 BD cases and 31,358 controls; and 71,880 AD cases and 383,378 controls). We identified a significant positive genetic correlation between MD and AD (rG = 0.162; s.e. = 0.064; p = 0.012), and between BD and AD (rG = 0.162; s.e. = 0.068; p = 0.018). We also identified two pleiotropic candidate genes for MD and AD (TMEM106B and THSD7A) and three forBD a...

Research paper thumbnail of Exosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults

Journal of affective disorders, Jun 1, 2024

Research paper thumbnail of Major depression, physical health and molecular senescence markers abnormalities

Previous studies suggested the role of cellular senescence in late-life depression (LLD). However... more Previous studies suggested the role of cellular senescence in late-life depression (LLD). However, it is unclear how this finding relates to common features of LLD, such as medical and cognitive problems. We applied factor analyses to an extensive battery of clinical variables in 426 individuals with LLD. Here we tested the relationship between these factors, age and sex, with an index of cellular senescence based on 22 senescence-associated secretory phenotype proteins. We found four factors: 'depression and anxiety severity', 'cognitive functioning', 'cardiovascular and cardiometabolic health' and 'blood pressure'. A higher senescence-associated secretory phenotype index was associated with poorer 'cognitive functioning' and 'cardiovascular and cardiometabolic health' but not with 'depression and anxiety severity'. These findings highlight the role of cellular senescence in poorer physical and cognitive health in LLD. They are consonant with the viewpoint that co-occurring medical burdens and their associated disabilities are part of a phenotype of accelerated ageing in LLD. Late-life depression (LLD) is a major depressive disorder in older adults. LLD is common and poses a substantial burden for affected individuals, their families and society 1. These burdens include worse quality of life, impaired activities of daily living 2 and increased frailty 3. Previous studies demonstrated a strong link among LLD, poor physical health 4 , cognitive impairment, an increased risk for dementia and mortality 5. These clinico-epidemiological findings suggest that older adults with LLD may experience an accelerated ageing phenotype 6. Accelerated ageing processes in LLD may be driven by increased allostatic load, altered proteostasis control, pro-inflammatory mechanisms and systemic oxidative stress 7,8. Research also suggests that accelerated ageing in LLD may occur on the cellular and subcellular level 9 and be linked to enhanced senescence processes 10. Cellular senescence 11 has emerged as a pivotal hallmark of the biology of ageing. It is a complex stress response in which cells irreversibly lose their proliferative capacity, become resistant to apoptosis 12 and develop a multicomponent secretory phenotype 13 , referred to as the senescence-associated secretory phenotype (SASP) 12. The SASP includes proteins involved in cycle control, intercellular communication, the immune-inflammatory response and tissue remodelling 14. Under non-pathological conditions,

Research paper thumbnail of Liquid Brain Biopsy in Late-Life Depression and Alzheimer’s Disease Using Circulating Brain-Derived Exosomes

Biological Psychiatry, May 1, 2022

Research paper thumbnail of 98. Cellular Senescence in Late-Life Depression

Biological Psychiatry, May 1, 2023

Research paper thumbnail of Epidermal Growth Factor and Fibroblast Growth Factor-2 Circulating Levels in Elderly with Major Depressive Disorder

American Journal of Geriatric Psychiatry, Mar 1, 2018

Research paper thumbnail of A highly reusable genosensor for late-life depression diagnosis based on microRNA 184 attomolar detection in human plasma

Research paper thumbnail of Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

JAMA network open, Jun 30, 2022

IMPORTANCE Many older adults with depression do not experience remission with antidepressant trea... more IMPORTANCE Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population. OBJECTIVE To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

Research paper thumbnail of Differential gene expression by RNA-seq during Alzheimer’s disease-like progression in the Drosophila melanogaster model

Neuroscience Research, 2022

Alzheimer's disease (AD) is characterized by progressive, irreversible loss of memory and cog... more Alzheimer's disease (AD) is characterized by progressive, irreversible loss of memory and cognitive function. Drosophila melanogaster and other animal models are used to study several diseases, in order to elucidate unknown mechanisms and develop potential therapies. Molecular studies require biological samples and, for neuropathologies such as AD biopsy of the human brain, are invasive and potentially damaging. The solution is to use animal models, such as D. melanogaster, which is a model organism that can replace mammalian organisms in such studies. In this study, we evaluated the climbing ability and differential gene expression during AD progression due to the amylodoigenic pathway using RNA-seq, and we performed an in silico analysis of a fruit fly AD-like GFP (Green Fluorescent Protein) model with GFP expression in the pan-neural elav driver. A total of 1388 genes were differentially expressed in all analyzed groups. The main pathways related to those Differentially Expressed Genes (DEGs) during aging and AD progression were evaluated using the fly genes and human orthologs, in order to link genomic information to higher-order functional information with gene pathway mapping. We identified pathways present in all analyzed groups, such as metabolic pathways, ribosomal pathways, proteasome pathways and immune system pathways. Some of the genes were validated by qPCR. Knockdown of CG17754 gene by RNAi promoted degeneration in the fly eye, validating these findings in vivo. The identification of similarities in molecular pathways between the transgenic fly AD-like GFP model and mammals related to AD provides new insights into the use of this fly in screening novel anti-AD drugs.

Research paper thumbnail of Plasma proteomic signature of major depressive episode in the elderly

Research paper thumbnail of Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine

The American Journal of Geriatric Psychiatry

Research paper thumbnail of Genetic overlap between mood disorders and Alzheimer’s disease: Could it explain the clinical and epidemiological overlap of these disorders?

Alzheimer's & Dementia, 2021

Mood disorders such as major depressive (MD) and bipolar (BD), are major risk factors for Alzheim... more Mood disorders such as major depressive (MD) and bipolar (BD), are major risk factors for Alzheimer’s disease (AD). History of MD and BD can double the risk of developing AD in older adults, and this risk is even higher when depressive symptoms co‐occur with mild cognitive impairment. These evidences suggest that mood disorders and AD may share common biological mechanisms, such as genetic risk factors. However, challenges on conducting multi‐phenotype long‐follow up studies limit the direct assessment of this hypothesis. Recently, bioinformatics methods using Genome‐wide association studies (GWAS) results have been developed and applied to assess the existence of genetic overlap among disorders. Herein, we carried out a multilevel approach to investigate the genetic overlap between mood disorders (MD and BD) and AD, by assessing their genetic correlation, polygenic overlap and shared biological pathways.

Research paper thumbnail of Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress

Frontiers in Cellular Neuroscience

BackgroundThe cell cycle is a critical mechanism for proper cellular growth, development and viab... more BackgroundThe cell cycle is a critical mechanism for proper cellular growth, development and viability. The p16INK4a and p21Waf1/Cip1 are important regulators of the cell cycle progression in response to internal and external stimuli (e.g., stress). Accumulating evidence indicates that the prefrontal cortex (PFC) is particularly vulnerable to stress, where stress induces, among others, molecular and morphological alterations, reflecting behavioral changes. Here, we investigated if the p16INK4a and p21Waf1/Cip1 expression are associated with behavioral outcomes.MethodsPrefrontal cortex mRNA and protein levels of p16INK4A and p21Waf1/Cip1 of mice (six independent groups of C57BL/6J, eight mice/group, 50% female) exposed from 0 to 35 days of chronic restraint stress (CRS) were quantified by qPCR and Western Blot, respectively. Correlation analyses were used to investigate the associations between cyclin-dependent kinase inhibitors (CKIs) expression and anxiety- and depression-like beha...

Research paper thumbnail of Plasma IL-17A levels in patients with late-life depression

Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), Jan 19, 2017

A consistent body of research has confirmed that patients with major depressive disorder (MDD) ha... more A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Plasma IL-17A levels were not statistically different between LLD patients and controls (p...

Research paper thumbnail of Plasma IL-17A levels in patients with late-life depression

Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), Jan 19, 2017

A consistent body of research has confirmed that patients with major depressive disorder (MDD) ha... more A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Plasma IL-17A levels were not statistically different between LLD patients and controls (p...

Research paper thumbnail of Expressão gênica associada à resistência da soja a Piezodorus guildinii

Research paper thumbnail of Increased levels of circulating cell-free mtDNA in plasma of late life depression subjects

Journal of psychiatric research, 2021

BACKGROUND Oxidative stress (OS) has been implicated in the pathophysiology of late-life depressi... more BACKGROUND Oxidative stress (OS) has been implicated in the pathophysiology of late-life depression (LLD). Mitochondria are the primary source of oxidative stress and can be significantly damaged with increased OS. Circulating cell-free mtDNA (ccf-mtDNA) is a marker of cellular stress and mitochondria damage triggered by oxidative stress. METHODS We evaluated the plasma levels of ccf-mtDNA in between 32 LLD and 21 never-depressed participants. We also investigated the association between ccf-mtDNA and the severity of depressive episodes and cognition performance. RESULTS We found a higher ccf-mtDNA level in LLD cases compared with controls (t = -2.91, p = 0.005). Also, ccf-mtDNA was significantly correlated with the severity of depression (r = 0.42, p = 0.001). There was no significant correlation between ccf-mtDNA and measures of cognitive decline. LIMITATIONS The small sample size and cross-sectional design were the main limitations of this study. CONCLUSION Our results suggest th...

Research paper thumbnail of Using Circulating Cell-free mtDNA to Examine the Synergetic Effects of Major Depressive Disorder and Frailty

American Journal of Geriatric Psychiatry, 2021

Research paper thumbnail of Author response for "Telomere shortening in late‐life depression: A potential marker of depression severity

Research paper thumbnail of Expressão do microRNA 184 em idosos com depressão maior: uma perspectiva translacional

A depressao e a desordem psiquiatrica mais comum e causa graves consequencias em idosos. Os mecan... more A depressao e a desordem psiquiatrica mais comum e causa graves consequencias em idosos. Os mecanismos biologicos envolvidos na depressao geriatrica (DG) sao complexos e envolvem muitos genes. Os MicroRNAs (miRNAs) sao pequenos RNAs nao codificadores que regulam pos transcricionalmente a expressao genica. O desequilibrio na expressao de miRNAs esta relacionado a muitas doencas, incluindo DG. Nosso objetivo foi avaliar os miRNAs plasmaticos associados a DG e possivelmente a gravidade dos sintomas depressivos e ao desempenho cognitivo nesses individuos. Um total de 116 amostras de plasma de idosos (63 com DG e 53 controles) foram divididas aleatoriamente para fazer o sequenciamento de nova geracao (SNG) e a validacao por RT-qPCR. Drosophila melanogaster foi utilizado como modelo translacional para avaliar fenomenos comportamentais associados a superexpressao e ao nocaute do ortologo de hsa-miR-184. A analise SNG encontrou o hsa-miR-184 (log2foldchange=-4,205 e p-valor=1,195e-03) e o h...

Research paper thumbnail of Genetic overlap between major depression, bipolar disorder and Alzheimer’s Disease

ABSTRACTBackgroundMood disorders, including major depression (MD) and bipolar disorder (BD), are ... more ABSTRACTBackgroundMood disorders, including major depression (MD) and bipolar disorder (BD), are risk factors for Alzheimer’s disease (AD) and possibly share an overlapping genetic architecture. However, few studies have investigated the shared loci and potential pleiotropy among these disorders.MethodsWe carried out a systematic analytical pipeline using GWAS data and three complementary (genome-wide, single variant, and gene-level) statistical approaches to investigate the genetic overlap among MD, BD, and AD.ResultsGWAS summary statistics data from 679,973 individuals were analyzed herein (59,851 MD cases and 113,154 controls; 20,352 BD cases and 31,358 controls; and 71,880 AD cases and 383,378 controls). We identified a significant positive genetic correlation between MD and AD (rG = 0.162; s.e. = 0.064; p = 0.012), and between BD and AD (rG = 0.162; s.e. = 0.068; p = 0.018). We also identified two pleiotropic candidate genes for MD and AD (TMEM106B and THSD7A) and three forBD a...