ABSTRACT
Mitochondrial dysfunction is an important cellular hallmark of aging and neurodegeneration. Platelets are a useful model to study the systemic manifestations of mitochondrial dysfunction. To evaluate the age dependence of mitochondrial parameters, citrate synthase activity, respiratory chain complex activity, and oxygen consumption kinetics were assessed. The effect of cognitive impairment was examined by comparing the age dependence of mitochondrial parameters in healthy individuals and those with neuropsychiatric disease. The study found a significant negative slope of age-dependence for both the activity of individual mitochondrial enzymes (citrate synthase and complex II) and parameters of mitochondrial respiration in intact platelets (routine respiration, maximum capacity of electron transport system, and respiratory rate after complex I inhibition). However, there was no significant difference in the age-related changes of mitochondrial parameters between individuals with and without cognitive impairment. These findings highlight the potential of measuring mitochondrial respiration in intact platelets as a means to assess age-related mitochondrial dysfunction. The results indicate that drugs and interventions targeting mitochondrial respiration may have the potential to slow down or eliminate certain aging and neurodegenerative processes. Mitochondrial respiration in platelets holds promise as a biomarker of aging, irrespective of the degree of cognitive impairment.
ABSTRACT
We analyzed activities of complex I, II, III, and IV, and citrate synthase (CS) in patients with major depressive disorder (MDD) or Alzheimer's disease (AD) presenting with or without depression. Associations of these parameters with disease or disease severity were observed in both AD and MDD; however, mean values of mitochondrial parameters were significantly altered in AD but not in MDD. Potential mitochondrial dysfunction in MDD seems not to be caused by disturbed activity of CS or respiratory complexes. In AD, a decrease in the activity of CS and complex IV may cause mitochondrial dysfunction, whereas an increase in activities of other mitochondrial complexes or their ratios to CS may be an adaptive response. The data indicate that comorbid depression in AD is associated with increased complex II activity. The mitochondrial parameters measured can be included in the panel of biomarkers of AD.
Subject(s)
Alzheimer Disease/metabolism , Blood Platelets/metabolism , Depressive Disorder, Major/metabolism , Electron Transport Chain Complex Proteins/metabolism , Electron Transport/physiology , Mitochondria/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/metabolism , Case-Control Studies , Female , Humans , Male , Middle Aged , Mitochondrial Membranes/metabolismABSTRACT
OBJECTIVES: Altered amyloid metabolism and mitochondrial dysfunction play key roles in the development of Alzheimer's disease (AD). We asked whether an association exists between disturbed platelet mitochondrial respiration and the plasma concentrations of Aß40 and Aß42 in patients with AD. DESIGN AND METHODS: Plasma Aß40 and Aß42 concentrations and mitochondrial respiration in intact and permeabilized platelets were measured in 50 patients with AD, 15 patients with vascular dementia and 25 control subjects. A pilot longitudinal study was performed to monitor the progression of AD in a subgroup 11 patients with AD. RESULTS: The mean Aß40, Aß42 and Aß42/Aß40 levels were not significantly altered in patients with AD compared with controls. The mitochondrial respiratory rate in intact platelets was significantly reduced in patients with AD compared to controls, particularly the basal respiratory rate, maximum respiratory capacity, and respiratory reserve; however, the flux control ratio for basal respiration was increased. A correlation between the plasma Aß42 concentration and mitochondrial respiration in both intact and permeabilized platelets differs in controls and patients with AD. CONCLUSIONS: Based on our data, (1) mitochondrial respiration in intact platelets, but not the Aß level itself, may be included in a panel of biomarkers for AD; (2) dysfunctional mitochondrial respiration in platelets is not explained by changes in plasma Aß concentrations; and (3) the association between mitochondrial respiration in platelets and plasma Aß levels differs in patients with AD and controls. The results supported the hypothesis that mitochondrial dysfunction is the primary factor contributing to the development of AD.
Subject(s)
Alzheimer Disease/diagnosis , Amyloid beta-Peptides/blood , Mitochondria/metabolism , Mitochondrial Diseases/diagnosis , Peptide Fragments/blood , Aged , Alzheimer Disease/blood , Alzheimer Disease/complications , Biomarkers/blood , Cell Respiration , Female , Humans , Male , Middle Aged , Mitochondrial Diseases/blood , Mitochondrial Diseases/complications , Oxygen ConsumptionABSTRACT
OBJECTIVES: With over 35 million cases worldwide, Alzheimer's disease (AD) represents the main cause of dementia. The differentiation of AD from other types of dementia is challenging and its early diagnosis is complicated. The established biomarkers are not only based on the invasive collection of cerebrospinal fluid, but also lack sufficient sensitivity and specificity. Therefore, much current effort is aimed at the identification of new biomarkers of AD in peripheral blood. DESIGN AND METHODS: We focused on blood-based analyses using chiroptical spectroscopy (Raman optical activity, electronic circular dichroism) supplemented with conventional vibrational spectroscopy (infrared, Raman) and metabolomics (high-performance liquid chromatography with a high-resolution mass detection). RESULTS: This unique approach enabled us to identify the spectral pattern of AD and variations in metabolite levels. Subsequent linear discriminant analysis of the spectral data resulted in differentiation between the AD patients and control subjects. CONCLUSIONS: It may be stated that this less invasive approach has strong potential for the identification of disease-related changes within essential plasmatic biomolecules and metabolites.
Subject(s)
Alzheimer Disease/diagnosis , Blood Proteins/analysis , Aged , Aged, 80 and over , Alzheimer Disease/blood , Biomarkers/blood , Circular Dichroism , Discriminant Analysis , Humans , Metabolomics , Middle Aged , Spectrum Analysis, RamanABSTRACT
Due to the trend of prolonged lifespan leading to higher incidence of age-related diseases, the demand for reliable biomarkers of dementia rises. In this review, we present novel biomarkers of high potential, especially those found in blood, urine or saliva, which could lead to a more comfortable patient experience and better time- and cost-effectivity, compared to the currently used diagnostic methods. We focus on biomarkers that might allow for the detection of Alzheimer's disease before its clinical manifestations. Such biomarkers might be helpful for better understanding the etiology of the disease and identifying its risk factors. Moreover, it could be a base for developing new treatment or at least help to prolong the presymptomatic stage in patients suffering from Alzheimer's disease. As potential candidates, we present, for instance, neurofilament light in both cerebrospinal fluid and blood plasma or amyloid ß in plasma. Above all, we provide an overview of different approaches to the diagnostics, analyzing patient's biofluids as a whole using molecular spectroscopy. Infrared and Raman spectroscopy and especially chiroptical methods provide information not only on the chemical composition, but also on molecular structure. Therefore, these techniques are promising for the diagnostics of Alzheimer's disease, as the accumulation of amyloid ß in abnormal conformation is one of the hallmarks of this disease.
Subject(s)
Alzheimer Disease/diagnosis , Amyloid beta-Peptides/analysis , Nerve Tissue Proteins/analysis , Biomarkers/analysis , Humans , Saliva/chemistryABSTRACT
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. OBJECTIVE: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. METHOD: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. RESULTS: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. CONCLUSION: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.
Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/genetics , Apolipoproteins E/genetics , Biomarkers/blood , Aged , Aged, 80 and over , Female , Genotype , Homocysteine/blood , Humans , Hydrocortisone/blood , Male , Melatonin/blood , Middle Aged , Prolactin/bloodABSTRACT
BACKGROUND Several genetic susceptibility loci for major depressive disorder (MDD) or Alzheimer's disease (AD) have been described. Interactions among polymorphisms are thought to explain the differences between low- and high-risk groups. We tested for the contribution of interactions between multiple functional polymorphisms in the risk of MDD or AD. MATERIAL AND METHODS A genetic association case-control study was performed in 68 MDD cases, 84 AD cases (35 of them with comorbid depression), and 90 controls. The contribution of 7 polymorphisms from 5 genes (APOE, HSPA1A, SLC6A4, HTR2A, and BDNF) related to risk of MDD or AD development was analyzed. RESULTS Significant associations were found between MDD and interactions among polymorphisms in HSPA1A, SLC6A4, and BDNF or HSPA1A, BDNF, and APOE genes. For polymorphisms in the APOE gene in AD, significant differences were confirmed on the distributions of alleles and genotype rates compared to the control or MDD. Increased probability of comorbid depression was found in patients with AD who do not carry the ε4 allele of APOE. CONCLUSIONS Assessment of the interactions among polymorphisms of susceptibility loci in both MDD and AD confirmed a synergistic effect of genetic factors influencing inflammatory, serotonergic, and neurotrophic pathways at these heterogenous complex diseases. The effect of interactions was greater in MDD than in AD. A presence of the ε4 allele was confirmed as a genetic susceptibility factor in AD. Our findings indicate a role of APOE genotype in onset of comorbid depression in a subgroup of patients with AD who are not carriers of the APOE ε4 allele.
Subject(s)
Alzheimer Disease/genetics , Depressive Disorder, Major/genetics , Epistasis, Genetic , Genetic Loci , Genetic Predisposition to Disease , Polymorphism, Genetic , Aged , Alleles , Case-Control Studies , Demography , Female , Gene Frequency , Genetic Association Studies , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide/geneticsABSTRACT
Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer's disease (AD). Here, we studied the relationship between AD and changes in the mitochondrial rates of respiration in blood platelets, respiratory chain complexes activity, and coenzyme Q10 plasma concentrations. In intact platelets obtained from AD patients, we observed a decrease in endogenous basal respiration rates, a decrease in the maximal capacity of the electron transport system (ETS), and higher respiratory rates after inhibiting complex I of the ETS. When normalized for citrate synthase activity, rotenone inhibited respiratory rates and complex I activity was significantly altered. In permeabilized platelets, mitochondrial respiration was completely rescued by the addition of complex I substrates. The changes in mitochondrial respiratory parameters were not associated with the progression of AD except for the capacity of the ETS in permeabilized platelets. In AD, complex I activity was increased, complex IV activity was decreased, and coenzyme Q10 plasma concentrations were decreased. Our data indicate that both insufficiency in substrates entering into the oxidative phosphorylation system and functional disturbances in the ETS complex are responsible for the decrease in respiration observed in intact platelets in AD patients. Analyses of complex IV activity, the respiratory rates of intact platelets, and the capacity of the ETS in permeabilized platelets may enable the characterization of mitochondrial dysfunctions in the initial stage of AD.
Subject(s)
Alzheimer Disease/metabolism , Blood Platelets/metabolism , Mitochondria/metabolism , Aged , Alzheimer Disease/genetics , Apolipoproteins E/genetics , Biomarkers/metabolism , Citrate (si)-Synthase/metabolism , Electron Transport Complex I/metabolism , Electron Transport Complex IV/metabolism , Female , Gene Frequency , Humans , Male , Mental Status Schedule , Middle Aged , Polymorphism, Genetic , ROC Curve , Ubiquinone/analogs & derivatives , Ubiquinone/bloodABSTRACT
OBJECTIVE: Elevated homocysteine is associated with a variety of diseases, including Alzheimer's disease (AD) and depressive disorder. This study was designed to detect an association between plasma homocysteine and AD with or without co-morbid depressive symptoms. METHODS: Plasma homocysteine concentrations were measured in 85 AD patients (36 of them with depressive symptoms), 33 non-AD patients with a depression diagnosis and 44 healthy controls, all aged above 50 years. RESULTS: Positive correlation between age and homocysteine was confirmed. Significantly higher mean plasma homocysteine was found in AD patients, but not in depressive patients, when compared with controls. We confirmed significant correlation between homocysteine concentration and the degree of cognitive impairment in AD patients. There was no incremental effect of concurrent depressive symptoms on homocysteine concentration in AD patients. CONCLUSION: The association of high homocysteine with degree of cognitive impairment or stage of dementia in AD indicate potential role of high plasma homocysteine as a biomarker of the disease and/or indicator of brain damage during the progression of AD dementia.
Subject(s)
Alzheimer Disease/blood , Depressive Disorder/blood , Homocysteine/blood , Severity of Illness Index , Age Factors , Aged , Aged, 80 and over , Alzheimer Disease/epidemiology , Alzheimer Disease/physiopathology , Biomarkers/blood , Comorbidity , Depressive Disorder/epidemiology , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Unfavorable post-partum changes to mental well-being affect more than half of all women, and are a risk to the health of both mother and baby. Their effects place strains on health and social systems. Currently, no generally accepted theory exists of the causes and mechanisms of post-partum mental disorders. METHODS: Literature search up to 2012, using PubMed and search words: neuroactive steroids, post-partum mental disorders, depression, corticotropin-releasing hormone and estrogens. RESULTS: There are several theories for post-partum depression. One is that autoimmune diseases are involved. Others revolve around genes responsible or that lead to increased disposition to the disorder. It is likely however that the process is associated with the separation of the placenta and the fetal zone of fetal adrenal gland, the main sources of corticotropin-releasing hormone and sexual and neuroactive steroids during pregnancy, and the ability of the receptor system to adapt to these changes. The central nervous system is able to produce neurosteroids, but the drop in levels of peripheral steroids likely leads to a sudden deficit in neuroinhibitory steroids modulating ionotropic receptors in the brain. CONCLUSIONS: Post-partum depression is a multifactorial disease with unknown etiology. It is probably associated with sudden changes in the production of hormones influencing the nervous system, and on the other hand the ability of the receptor system to adapt to these changes. When the relative changes in concentrations of hormones, rather than their absolute levels, is likely more important.
Subject(s)
Depression, Postpartum/blood , Gonadal Steroid Hormones/blood , Adult , Female , Humans , Metabolomics/methods , PregnancyABSTRACT
BACKGROUND: Glycogen synthase kinase-3ß (GSK3ß), cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) play critical roles in neuronal survival, synaptic plasticity and memory and participate in the pathophysiology of both depressive disorder and Alzheimer's disease (AD). METHODS: This study was designed to determine the association of GSK3ß activity, CREB activity and BDNF concentration in peripheral blood of patients with AD with or without depressive symptoms and in depressive patients without AD. GSK3ß activity in platelets, CREB activity in lymphocytes and BDNF concentration in plasma, platelet-rich plasma or platelets were measured in 85 AD patients (36 of whom displayed co-morbid depressive symptoms), 65 non-AD patients with depressive disorder and 96 healthy controls. AD patients were clinically assessed for stage of dementia, cognitive impairment and severity of depressive symptoms. Depressive patients were clinically assessed for severity of depression. RESULTS: We observed increased CREB activity and GSK3ß activity in AD with depressive symptoms or in AD at mild stage of dementia. Decreased BDNF concentration was found in platelet-rich plasma of AD patients at moderate to severe stages of dementia or in AD without depressive symptoms. An association was revealed of the severity of cognitive impairment with the increase of GSK3ß in the platelets of AD patients with mild dementia. In depressive patients, a lower concentration of phosphorylated GSK3ß was associated with a higher severity of depression. Association was confirmed between severity of depression, CREB activation, and BDNF concentration in drug-naïve depressive patients. CONCLUSION: Our data demonstrated that AD is accompanied by increased CREB activity in lymphocytes and a decreased concentration of BDNF in platelet-rich plasma. The decreased BDNF concentration appears to correlate with moderate to severe stages of dementia in AD. Observation of decreased phosphorylation of GSK3ß in platelets of both AD patients with depressive symptoms and depressive patients after treatment confirms the role of increased GSK3ß activity in the pathophysiology of both AD and depressive disorder. Associations were confirmed between AD and platelet GSK3ß activity, lymphocyte CREB activity and plasma BDNF. CREB activity and platelet BDNF concentration seems to be related to depressive disorder.
Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/complications , Brain-Derived Neurotrophic Factor/blood , CREB-Binding Protein/blood , Depression/blood , Depression/complications , Glycogen Synthase Kinase 3/blood , Aged , Alzheimer Disease/psychology , Case-Control Studies , Depression/psychology , Female , Glycogen Synthase Kinase 3 beta , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating ScalesABSTRACT
BACKGROUND: Cortisol is presumed to be a risk factor for stress- and age-related disorders, such as depressive disorder and Alzheimer's disease (AD). The aim of this study was to investigate the association of plasma cortisol concentration with AD in presence or absence of comorbid depressive symptoms. MATERIAL AND METHODS: Plasma cortisol concentration was measured in 80 AD patients (35 of them with depressive symptoms), 27 elderly depressive patients without AD, and 37 elderly controls. RESULTS: Compared to controls, a significant increase of mean plasma cortisol was found in AD patients but not in depressive patients. Plasma cortisol was positively correlated with cognitive impairment in AD patients. We confirmed a U-shaped association between plasma cortisol and major depression and a linear association between plasma cortisol and AD without depressive symptoms. Significantly increased relative risk of disease in people with high plasma cortisol was found for AD with depressive symptoms and for AD with mild dementia. CONCLUSIONS: Plasma cortisol reflects the degree of cognitive impairment in AD rather than the severity of comorbid depression. We confirmed that both hypercortisolemia and hypocortisolemia are associated with depressive disorder. Significant association between high plasma cortisol and AD was found, supporting the use of high plasma cortisol as a component of a panel of biochemical markers for AD with depressive symptoms as well as AD in the early stage of dementia development.
Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/complications , Depression/blood , Depression/complications , Hydrocortisone/blood , Aged , Aged, 80 and over , Dementia/blood , Dementia/complications , Demography , Humans , Linear Models , Middle Aged , Neuropsychological TestsABSTRACT
BACKGROUND: Depressive disorder is related to an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). Insulin resistance (IR), connected with altered fatty acid (FA) composition, namely with decreased proportion of polyunsaturated FA could participate in these associations. The aim of the study was to investigate the composition of FA in plasma cholesterol esters (CE) and phosphatidylcholine (PC) as well as indices of insulin resistance and oxidative stress in the patients with depressive disorder. MATERIALS AND METHODS: Parameters of lipid and glucose homeostasis, concentrations of FA in plasma cholesteryl esters (CE) and phosphatidylcholine (PC) and conjugated dienes in LDL were investigated in a group of 47 patients (9M/38F) with depression and compared with 47 control persons (16M/31F). Delta-9 desaturase (D9D) and D6D desaturase were estimated as product to precursor fatty acid ratios. RESULTS: In depressive patients increased concentrations of palmitoleic acid and total monounsaturated FA with decreased proportion of total polyunsaturated FA n-6 (PUFA n-6) (all p<0.05) in CE were found, while in PC increased proportion of saturated FA was observed (p<0.05). Moreover, index of D6D activity was significantly increased in PC and CE (p<0.05). Concomitantly, in depressive patients higher levels of plasma triacylglycerols (p<0.05), conjugated dienes in LDL (p<0.001) and HOMA index of IR (p<0.05) were found. CONCLUSIONS: Esterified FA composition of depressive patients revealed changes, similar to those, usually observed in insulin resistance. Dysregulation of FA could participate in the pathogenesis of depression and be associated with an increased risk of CVD and DM2.
Subject(s)
Depressive Disorder/epidemiology , Depressive Disorder/metabolism , Fatty Acids, Unsaturated/blood , Insulin Resistance/physiology , Adult , Aged , Cardiovascular Diseases/epidemiology , Cholesterol Esters/blood , Diabetes Mellitus, Type 2/epidemiology , Fatty Acids, Monounsaturated/blood , Female , Humans , Linoleoyl-CoA Desaturase/blood , Male , Middle Aged , Oxidative Stress/physiology , Phosphatidylcholines/blood , Risk Factors , Stearoyl-CoA Desaturase/bloodABSTRACT
As an improvement on currently used methods of molecular spectroscopy, we used chiroptical techniques (electronic circular dichroism, fluorescence detected circular dichroism, and Raman optical activity [ROA]) to investigate the human blood plasma. To avoid the degradation of plasma samples, we measured them directly without any further preparation. We also tested cutoff weight filters (Amicon Ultra 100, 30, 10, and 3 kDa by Merck Millipore) to reduce undesirable fluorescence in the ROA and Raman spectra and also to remove the most abundant protein in the plasma-human serum albumin. The obtained spectra show that the ultrafiltration has a positive effect on undesirable fluorescence in ROA and Raman and also could reduce the amount of albumin in the plasma. Our results suggest that blood plasma can be successfully measured by the aforementioned methods. Therefore, these methods can potentially be useful for following research in the development of new, noninvasive, and reliable screening methods of clinical diagnostics.
Subject(s)
Blood Chemical Analysis/methods , Spectrum Analysis/methods , Humans , StereoisomerismABSTRACT
The lipids constitute majority of dry weight of mature human brain. From lipids, 35% is comprised of PUFA with long chain (LC-PUFA), especially docosahexaenoic acid (DHA) of n-3 family and arachidonic acid (AA) of n-6 family. Humans are dependent on dietary intake of both AA and DHA. Interestingly, the dietary n-6/n-3 ratio increased considerably during last century. LC-PUFAs play numerous roles in the brain, including structural (forming the physico-chemical properties in the lipid bilayer of cellular membranes) and signaling ones. Moreover, they influence neurogenesis and neurotransmission within the nervous tissue. The metabolites of PUFA modulate immune and inflammatory processes in the brain, oxidative stress as well as its consequences. Of high importance is also their connection with several metabolic factors involved in the proper function of the brain and/or were discovered to play a role in the pathogenesis of neuropsychiatric diseases - melatonin, homocysteine, leptin, and adiponectin. This review gives short view of the metabolism and possible mechanisms of PUFA n-3 action in the brain, and their role in the pathogenesis of psychiatric diseases.
Subject(s)
Brain/metabolism , Fatty Acids, Omega-3/metabolism , Mental Disorders/metabolism , Neuroimmunomodulation/physiology , Oxidative Stress/physiology , Animals , Brain/immunology , Humans , Mental Disorders/immunologyABSTRACT
BACKGROUND: Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS. AIM: The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder. MATERIALS AND METHODS: The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age. RESULTS: Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p <0.05), insulin (p <0.01), C-peptide (p <0.01), value of HOMA-IR (p <0.01), and the leptin-to-adiponectin ratio (p <0.05).The QUICKI index of insulin sensitivity was lower (p <0.01). HAM-D score of DD cases correlated negatively with adiponectin (r = - 0.3505; p < 0.05), independently of HOMA-IR. We have not found in DD group any differences between the drug free patients and those treated either with escitaloprame alone or in the combination with mirtazapine. CONCLUSIONS: The results of the pilot study presented support the hypothesis that at least part of DD cases has increased leptin serum levels and certain features of MetS. It could be the factor connecting depression with an increased risk of either DM2 or CVD.
Subject(s)
Adiponectin/blood , Blood Glucose/metabolism , Depression/blood , Insulin Resistance , Leptin/blood , Adult , Aged , Antidepressive Agents/therapeutic use , Body Mass Index , Chi-Square Distribution , Citalopram/therapeutic use , Depression/drug therapy , Diagnostic and Statistical Manual of Mental Disorders , Drug Therapy, Combination , Female , Humans , Insulin/blood , Mianserin/analogs & derivatives , Mianserin/therapeutic use , Middle Aged , Mirtazapine , Patient Selection , Pilot Projects , Waist CircumferenceABSTRACT
OBJECTIVES: To investigate the activities of the main antioxidative enzymes and oxidative stress in women with depressive disorder (DD). METHODS: In 35 drug-naive women with DD and 35 age matched healthy women enzymes superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPX1), glutathione reductase (GR) and paraoxonase (PON1), concentrations of conjugated dienes (CD), reduced glutathione (GSH) and anthropometric and clinical data were investigated. RESULTS: Women with DD were found to have decreased activities of GPX1 (p<0.05), decreased concentrations of GSH (p<0.05), and increased activities of GR (p<0.05), CuZnSOD (p<0.001), and concentrations of CD (p<0.05). Activity of GPX1 was positively correlated with concentration of GSH (p<0.05). Concentrations of CD were positively correlated with TG (p<0.01). CONCLUSION: Our set of depressive women was characterized by changes indicating an increased oxidative stress, as well as by certain features of metabolic syndrome.
Subject(s)
Depressive Disorder/enzymology , Enzymes/metabolism , Oxidative Stress , Aged , Alkadienes/blood , Alkadienes/chemistry , Aryldialkylphosphatase/blood , Aryldialkylphosphatase/metabolism , Catalase/blood , Catalase/metabolism , Depressive Disorder/blood , Depressive Disorder/pathology , Enzymes/blood , Female , Glutathione/blood , Glutathione/metabolism , Glutathione Peroxidase/blood , Glutathione Peroxidase/metabolism , Glutathione Reductase/blood , Glutathione Reductase/metabolism , Humans , Middle Aged , Oxidation-Reduction , Spectrophotometry , Superoxide Dismutase/blood , Superoxide Dismutase/metabolism , Triglycerides/bloodABSTRACT
The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54 Males/59 Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P < 0.05) and lower content of arachidonic acid in plasma phosphatidylcholine (PC) (P = 0.052), lower index of Delta5 desaturation (P < 0.01) and unsaturation index (UI) (P < 0.001). In contrast, DD patients had higher concentrations of plasma glucose, insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.
Subject(s)
Coenzyme A Ligases/genetics , Depression/metabolism , Fatty Acids/metabolism , Metabolic Syndrome/metabolism , 8,11,14-Eicosatrienoic Acid/blood , Arachidonic Acid/blood , Blood Glucose , Chromatography, Gas , Female , Humans , Insulin/blood , Male , Phosphatidylcholines/blood , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide/genetics , RadioimmunoassayABSTRACT
OBJECTIVE: The early differential diagnosis of Alzheimer's disease (AD) remains still problematic. We developed a laboratory test enabling us to distinguish patients with AD from those with vascular dementia (VD) and healthy subjects. METHODS: The AD group consisted of 22 women and 18 men. The VD group consisted of 16 women and 8 men. Age-matched controls consisted of 12 women and 9 men. Plasma pregnenolone sulfate (PregS), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) were determined by radioimmunoassay. 17-Hydroxypregnenolone (17Preg) and 7-hydroxylated metabolites of DHEA (7alphaDHEA, 7betaDHEA) were determined by radioimmunoassay after separation by high performance liquid chromatography (HPLC). Homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cysgly) and glutathione (GSH) were measured by HPLC. RESULTS: The ANOVA results of significant between-group differences were as follows: The PregS and the 17-Preg and DHEAS levels were independent from the diagnosis. The 7alphaDHEA levels significantly depended on the sex (p < 0.05) and diagnosis (p < 0.01). Amino-thiols were influenced by the diagnosis (p < 0.01, p = 0.0541, p < 0.01 and p = 0.0536 for Cys, Hcy, Cysgly and GSH, respectively). Using a stepwise backward regression analysis, the following parameters were obtained: X = 11.5 + 4.03 x sex +1.09 x Hcy + 0.190 x PregS - 4.76 x DHEAS + 3.00 x DHEA - 34.3 x 77alphaDHEA - 0.885 x Cysgly from which P-value as a discriminator was calculated according to the formula: P = 1/(1 + e(-x)). Then, for P > 0.5, a subject was considered as AD-positive (with 89% correct prediction). DISCUSSION: The opportunity of early differential diagnosis of AD should help physicians to use suitable treatment for retardation of pathological processes.