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Reduced brain derived neurotrophic factor (BDNF) concentration is reported to be associated with a cognitive decline in schizophrenia, depending on the stage of the disease. Aim of the study was to examine the possible association between plasma BDNF and cognitive decline in chronic stable schizophrenia and mild cognitive impairment (MCI). The study included 123 inpatients of both sexes with schizophrenia, 123 patients with MCI and 208 healthy control subjects. Cognitive abilities were assessed using mini mental state examination (MMSE), Clock Drawing test (CDT) and cognitive subscale of the Positive and Negative Syndrome Scale (PANSS). Plasma BDNF concentration was determined using ELISA. BDNF concentration was lower in patients with schizophrenia and MCI compared to age-matched healthy controls and was similar in carriers of different BDNF Val/66Met genotypes. The MMSE and CDT scores were lower in patients with schizophrenia compared to healthy controls and subjects with MCI. Reduced plasma BDNF was significantly associated with lower MMSE scores in all subjects. BDNF concentration in patients with schizophrenia was not affected by clinical and demographic factors. BDNF Val66Met polymorphism was not associated with the MMSE scores in all participants. Further studies should include longitudinal follow-up and other cognitive scales to confirm these results and offer cognition-improving strategies to prevent cognitive decline in chronic schizophrenia.
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Factor Neurotrófico Derivado del Encéfalo , Disfunción Cognitiva , Esquizofrenia , Humanos , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/genética , Masculino , Femenino , Disfunción Cognitiva/sangre , Disfunción Cognitiva/genética , Disfunción Cognitiva/diagnóstico , Esquizofrenia/sangre , Esquizofrenia/genética , Persona de Mediana Edad , Adulto , Psicología del Esquizofrénico , Enfermedad Crónica , Pruebas de Estado Mental y Demencia , Anciano , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Polimorfismo de Nucleótido SimpleRESUMEN
Dementia is a syndrome of global and progressive deterioration of cognitive skills, especially memory, learning, abstract thinking, and orientation, usually affecting the elderly. The most common forms are Alzheimer's disease, vascular dementia, and other (frontotemporal, Lewy body disease) dementias. The etiology of these multifactorial disorders involves complex interactions of various environmental and (epi)genetic factors and requires multiple forms of pharmacological intervention, including anti-dementia drugs for cognitive impairment, antidepressants, antipsychotics, anxiolytics and sedatives for behavioral and psychological symptoms of dementia, and other drugs for comorbid disorders. The pharmacotherapy of dementia patients has been characterized by a significant interindividual variability in drug response and the development of adverse drug effects. The therapeutic response to currently available drugs is partially effective in only some individuals, with side effects, drug interactions, intolerance, and non-compliance occurring in the majority of dementia patients. Therefore, understanding the genetic basis of a patient's response to pharmacotherapy might help clinicians select the most effective treatment for dementia while minimizing the likelihood of adverse reactions and drug interactions. Recent advances in pharmacogenomics may contribute to the individualization and optimization of dementia pharmacotherapy by increasing its efficacy and safety via a prediction of clinical outcomes. Thus, it can significantly improve the quality of life in dementia patients.
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Enfermedad de Alzheimer , Farmacogenética , Humanos , Anciano , Calidad de Vida , Enfermedad de Alzheimer/tratamiento farmacológico , Antidepresivos/uso terapéutico , CogniciónRESUMEN
Along with the typical biochemical alterations that occur during pregnancy, certain metabolic changes might be associated with the development of several psychiatric disorders, including postpartum depression (PPD), which is the most common type of psychiatric disorder during pregnancy or first postpartum year, and it develops in about 15% of women. Metabolomics is a rapidly developing discipline that deals with the metabolites as the final products of all genetically controlled biochemical pathways, highly influenced by external and internal changes. The aim of this paper was to review the published studies whose results suggest or deny a possible association between the fine regulation of the metabolome and PPD, enabling conclusions about whether metabolomics could be a useful tool in defining the biochemical pathways directly involved in the etiology, diagnosis and course of PPD. Beside numerous hormonal changes, a lot of different metabolic pathways have been discovered to be affected in women with PPD or associated with its development, including alterations in the energy metabolism, tryptophan and amino acid metabolism, steroid metabolism, purine cycle, as well as neurotransmitter metabolism. Additionally, metabolomics helped in defining the association between PPD and the exposure to various endocrine disrupting metabolites during pregnancy. Finally, metabolome reflects different PPD therapies and exposure of fetus or breastfed infants to pharmacotherapy prescribed to a mother suffering from PPD. This review can help in creating the picture about metabolomics' broad application in PPD studies, but it also implies that its potential is still not completely used.
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Depresión Posparto , Embarazo , Femenino , Humanos , Depresión Posparto/psicología , Periodo Posparto , Metabolómica , Triptófano/metabolismo , Metaboloma , Factores de RiesgoRESUMEN
Alzheimer's disease (AD) is often not recognized or is diagnosed very late, which significantly reduces the effectiveness of available pharmacological treatments. Metabolomic analyzes have great potential for improving existing knowledge about the pathogenesis and etiology of AD and represent a novel approach towards discovering biomarkers that could be used for diagnosis, prognosis, and therapy monitoring. In this study, we applied the untargeted metabolomic approach to investigate the changes in biochemical pathways related to AD pathology. We used gas chromatography and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively) to identify metabolites whose levels have changed in subjects with AD diagnosis (N = 40) compared to healthy controls (N = 40) and individuals with mild cognitive impairment (MCI, N = 40). The GC-MS identified significant differences between groups in levels of metabolites belonging to the classes of benzene and substituted derivatives, carboxylic acids and derivatives, fatty acyls, hydroxy acids and derivatives, keto acids and derivatives, and organooxygen compounds. Most of the compounds identified by the LC-MS were various fatty acyls, glycerolipids and glycerophospholipids. All of these compounds were decreased in AD patients and in subjects with MCI compared to healthy controls. The results of the study indicate disturbed metabolism of lipids and amino acids and an imbalance of metabolites involved in energy metabolism in individuals diagnosed with AD, compared to healthy controls and MCI subjects.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/metabolismo , Metabolómica , Metaboloma , Espectrometría de Masas , BiomarcadoresRESUMEN
Catechol-O-methyl transferase (COMT) gene variants are involved in different neuropsychiatric disorders and cognitive impairments, associated with altered dopamine function. This study investigated the genotypic and haplotypic association of COMT rs4680 and rs4618 polymorphisms with the severity of cognitive and other clinical symptoms in 544 male and 385 female subjects with schizophrenia. COMT rs4818 G carriers were more frequent in male patients with mild abstract thinking difficulties, compared to CC homozygotes or C allele carriers. Male carriers of COMT rs4680 A allele had worse abstract thinking (N5) scores than GG carriers, whereas AA homozygotes were more frequent in male subjects with lower scores on the intensity of the somatic concern (G1) item, compared to G carriers. Male carriers of COMT rs4818-rs4680 GA haplotype had the highest scores on the G1 item (somatic concern), whereas GG haplotype carriers had the lowest scores on G2 (anxiety) and G6 (depression) items. COMT GG haplotype was less frequent in female patients with severe disturbance of volition (G13 item) compared to the group with mild symptoms, while CG haplotype was more frequent in female patients with severe then mild symptoms. These findings suggest the sex-specific genotypic and haplotypic association of COMT variants with a severity of cognitive and other clinical symptoms of schizophrenia.
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Catecol O-Metiltransferasa , Esquizofrenia , Humanos , Masculino , Femenino , Haplotipos , Catecol O-Metiltransferasa/genética , Esquizofrenia/genética , Polimorfismo de Nucleótido Simple , GenotipoRESUMEN
The complex role of the serotonin system in respiratory function and inflammatory diseases such as asthma is unclear. Our study investigated platelet serotonin (5-HT) levels and platelet monoamine oxidase B (MAO-B) activity, as well as associations with HTR2A (rs6314; rs6313), HTR2C (rs3813929; rs518147), and MAOB (rs1799836; rs6651806) gene polymorphisms in 120 healthy individuals and 120 asthma patients of different severity and phenotypes. Platelet 5-HT concentration was significantly lower, while platelet MAO-B activity was considerably higher in asthma patients; however, they did not differ between patients with different asthma severity or phenotypes. Only the healthy subjects, but not the asthma patients, carrying the MAOB rs1799836 TT genotype had significantly lower platelet MAO-B activity than the C allele carriers. No significant differences in the frequency of the genotypes, alleles, or haplotypes for any of the investigated HTR2A, HTR2C and MAOB gene polymorphisms have been observed between asthma patients and healthy subjects or between patients with various asthma phenotypes. However, the carriers of the HTR2C rs518147 CC genotype or C allele were significantly less frequent in severe asthma patients than in the G allele carriers. Further studies are necessary to elucidate the involvement of the serotonergic system in asthma pathophysiology.
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Asma , Monoaminooxidasa , Receptor de Serotonina 5-HT2A , Receptor de Serotonina 5-HT2C , Alelos , Genotipo , Monoaminooxidasa/genética , Polimorfismo Genético , Serotonina , Humanos , Receptor de Serotonina 5-HT2A/genética , Receptor de Serotonina 5-HT2C/genética , Asma/genéticaRESUMEN
INTRODUCTION: Recent evidence from the studies evaluating the association between brain-derived neurotrophic factor (BDNF) concentration/levels, BDNF Val66Met (rs6265) polymorphism, and major depressive disorders, referred as depression, and the association between BDNF levels and/or BDNF Val66Met with the treatment response in depression is presented. AREAS COVERED: This mini review focuses on the changes in the peripheral BDNF levels in blood (serum, plasma, platelets) in patients with depression before or after treatment with antidepressant drugs or different therapeutic strategies. In addition, this review describes the recent data on the possible association between different antidepressants/therapeutic strategies and the particular BDNF Val66Met genotypes, evaluating the risk alleles associated with the response in patients with depression. EXPERT OPINION: BDNF has an important role in the pathophysiology and treatment response in depression. Most data reveal that peripheral BDNF levels are lower before than after antidepressant treatment and might be used as potential biomarkers of therapeutic response. Novel therapeutic strategies should target restoring/increasing BDNF levels.
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Trastorno Depresivo Mayor , Humanos , Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/uso terapéutico , Depresión/diagnóstico , Depresión/tratamiento farmacológico , Depresión/etiología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Genotipo , Polimorfismo de Nucleótido SimpleRESUMEN
Posttraumatic stress disorder (PTSD) is a severe trauma and stress-related disorder associated with different somatic comorbidities, especially cardiovascular and metabolic disorders, and with chronic low-grade inflammation. Altered balance of the hypothalamic-pituitary-adrenal (HPA) axis, cytokines and chemokines, C-reactive protein, oxidative stress markers, kynurenine pathways, and gut microbiota might be involved in the alterations of certain brain regions regulating fear conditioning and memory processes, that are all altered in PTSD. In addition to the HPA axis, the gut microbiota maintains the balance and interaction of the immune, CNS, and endocrine pathways forming the gut-brain axis. Disbalance in the HPA axis, gut-brain axis, oxidative stress pathways and kynurenine pathways, altered immune signaling and disrupted homeostasis, as well as the association of the PTSD with the inflammation and disrupted cognition support the search for novel strategies for treatment of PTSD. Besides potential anti-inflammatory treatment, dietary interventions or the use of beneficial bacteria, such as probiotics, can potentially improve the composition and the function of the bacterial community in the gut. Therefore, bacterial supplements and controlled dietary changes, with exercise, might have beneficial effects on the psychological and cognitive functions in patients with PTSD. These new treatments should be aimed to attenuate inflammatory processes and consequently to reduce PTSD symptoms but also to improve cognition and reduce cardio-metabolic disorders associated so frequently with PTSD.
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Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/terapia , Sistema Hipófiso-Suprarrenal , Sistema Hipotálamo-Hipofisario , Quinurenina/metabolismo , Inflamación/metabolismo , Sistema Inmunológico/metabolismoRESUMEN
In the last decade, increasing evidence has emerged linking alterations in the brain-derived neurotrophic factor (BDNF) expression with the development of Alzheimer's disease (AD). Because of the important role of BDNF in cognition and its association with AD pathogenesis, the aim of this study was to evaluate the potential difference in plasma BDNF concentrations between subjects with mild cognitive impairment (MCI; N = 209) and AD patients (N = 295) and to determine the possible association between BDNF plasma levels and the degree of cognitive decline in these individuals. The results showed a significantly higher (p < 0.001) concentration of plasma BDNF in subjects with AD (1.16; 0.13-21.34) compared with individuals with MCI (0.68; 0.02-19.14). The results of the present study additionally indicated a negative correlation between cognitive functions and BDNF plasma concentrations, suggesting higher BDNF levels in subjects with more pronounced cognitive decline. The correlation analysis revealed a significant negative correlation between BDNF plasma levels and both Mini-Mental State Examination (p < 0.001) and Clock Drawing test (p < 0.001) scores. In conclusion, the results of our study point towards elevated plasma BDNF levels in AD patients compared with MCI subjects, which may be due to the body's attempt to counteract the early and middle stages of neurodegeneration.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Factor Neurotrófico Derivado del Encéfalo , Biomarcadores , Enfermedad de Alzheimer/diagnóstico , CogniciónRESUMEN
The molecular underpinnings of post-traumatic stress disorder (PTSD) are still unclear due to the complex interactions of genetic, psychological, and environmental factors. Glycosylation is a common post-translational modification of proteins, and different pathophysiological states, such as inflammation, autoimmune diseases, and mental disorders including PTSD, show altered N-glycome. Fucosyltransferase 8 (FUT8) is the enzyme that catalyzes the addition of core fucose on glycoproteins, and mutations in the FUT8 gene are associated with defects in glycosylation and functional abnormalities. This is the first study that investigated the associations of plasma N-glycan levels with FUT8-related rs6573604, rs11621121, rs10483776, and rs4073416 polymorphisms and their haplotypes in 541 PTSD patients and control participants. The results demonstrated that the rs6573604 T allele was more frequent in the PTSD than in the control participants. Significant associations of plasma N-glycan levels with PTSD and FUT8-related polymorphisms were observed. We also detected associations of rs11621121 and rs10483776 polymorphisms and their haplotypes with plasma levels of specific N-glycan species in both the control and PTSD groups. In carriers of different rs6573604 and rs4073416 genotypes and alleles, differences in plasma N-glycan levels were only found in the control group. These molecular findings suggest a possible regulatory role of FUT8-related polymorphisms in glycosylation, the alternations of which could partially explain the development and clinical manifestation of PTSD.
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Fucosiltransferasas , Trastornos por Estrés Postraumático , Humanos , Fucosa/metabolismo , Fucosiltransferasas/genética , Fucosiltransferasas/metabolismo , Glicoproteínas/metabolismo , Glicosilación , Polisacáridos/metabolismo , Trastornos por Estrés Postraumático/genéticaRESUMEN
Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII index) are increasingly used as indicators of inflammation in different conditions, including schizophrenia. However, their relationship with negative symptoms, including anhedonia, is largely unknown. Included were 200 patients with schizophrenia and 134 healthy controls (HC), assessed for physical anhedonia (PA), using the Revised Physical Anhedonia Scale (RPAS), and social anhedonia (SA) by the Revised Social Anhedonia Scale (RSAS). Patients were rated by the Positive and Negative Syndrome Scale (PANSS), the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Most of the negative symptoms were in a weak to moderate positive correlations with blood cell inflammatory ratios, namely, between NLR and MLR with PANSS negative scale, CAINS, and BNSS, and in male patients, between PLR and PANSS negative scale and CAINS. Fewer correlations were detected in females, but also in a positive direction. An exception was SA, given the negative correlation between its severity and the SII index in females, and its presence and higher PLR in males. While different negative symptoms were associated with subclinical inflammation, the relationship between SA and lower inflammatory markers deserves further exploration.
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Neutrófilos , Esquizofrenia , Femenino , Humanos , Masculino , Monocitos , Anhedonia , Estudios Retrospectivos , Linfocitos , InflamaciónRESUMEN
Due to the increasing number of progressive dementias in the population, numerous studies are being conducted that seek to determine risk factors, biomarkers and pathological mechanisms that could help to differentiate between normal symptoms of aging, mild cognitive impairment (MCI) and dementia. The aim of this study was to investigate the possible association of levels of BDNF and COMT gene expression and methylation in peripheral blood cells with the development of Alzheimer's disease (AD). Our results revealed higher expression levels of BDNF (p < 0.001) in MCI subjects compared to individuals diagnosed with AD. However, no difference in COMT gene expression (p = 0.366) was detected. DNA methylation of the CpG islands and other sequences with potential effects on gene expression regulation revealed just one region (BDNF_9) in the BDNF gene (p = 0.078) with marginally lower levels of methylation in the AD compared to MCI subjects. Here, we show that the level of BDNF expression in the periphery is decreased in subjects with AD compared to individuals with MCI. The combined results from the gene expression analysis and DNA methylation analysis point to the potential of BDNF as a marker that could help distinguish between MCI and AD patients.
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Some of the most prevalent neurodegenerative disorders, including Alzheimer's and Parkinson's disease, are proteinopathies characterized by the accumulation of specific protein aggregates in the brain. Such misfolded protein aggregates can trigger modulation of the innate and adaptive immune systems and subsequently lead to chronic neuroinflammation that drives the onset and progression of neurodegenerative diseases. Since there is still no effective disease-modifying treatment, new therapeutic targets for neurodegenerative proteinopathies have been sought. The endocannabinoid system, and in particular the cannabinoid CB2 receptors, have been extensively studied, due to their important role in neuroinflammation, especially in microglial cells. Several studies have shown promising effects of CB2 receptor activation on reducing protein aggregation-based pathology as well as on attenuating inflammation and several dementia-related symptoms. In this review, we discuss the available data on the role of CB2 receptors in neuroinflammation and the potential benefits and limitations of specific agonists of these receptors in the therapy of neurodegenerative proteinopathies.
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A decrease in serotonergic transmission throughout the brain is among the earliest pathological changes in Alzheimer's disease (AD). Serotonergic receptors are also affected in AD. Polymorphisms in genes of serotonin (5HT) receptors have been mostly associated with behavioral and psychological symptoms of dementia (BPSD). In this study, we examined if AD patients carrying different genotypes in 5HTR1B rs13212041, 5HTR2A rs6313 (T102C), 5HTR2C rs3813929 (-759C/T), and 5HTR6 rs1805054 (C267T) polymorphisms have a higher risk of faster disease progression (assessed by neuropsychological testing), are more prone to develop AD-related pathology (reflected by levels of cerebrospinal fluid [CSF] AD biomarkers), or have an association with an apolipoprotein E (APOE) haplotype. This study included 115 patients with AD, 53 patients with mild cognitive impairment (MCI), and 2701 healthy controls. AD biomarkers were determined in the CSF of AD and MCI patients using enzyme-linked immunosorbent assays (ELISA), while polymorphisms were determined using either TaqMan SNP Genotyping Assays or Illumina genotyping platforms. We detected a significant decrease in the CSF amyloid ß1-42 (Aß1-42) and an increase in p-tau181/Aß1-42 ratio in carriers of the T allele in the 5HTR2C rs3813929 (-759C/T) polymorphism. A significantly higher number of APOE ε4 allele carriers was observed among individuals carrying a TT genotype within the 5HTR2A T102C polymorphism, a C allele within the 5HTR1B rs13212041 polymorphism, and a T allele within the 5HTR6 rs1805054 (C267T) polymorphism. Additionally, individuals carrying the C allele within the 5HTR1B rs13212041 polymorphism were significantly more represented among AD patients and had poorer performances on the Rey-Osterrieth test. Carriers of the T allele within the 5HTR6 rs1805054 had poorer performances on the MMSE and ADAS-Cog. As all four analyzed polymorphisms of serotonin receptor genes showed an association with either genetic, CSF, or neuropsychological biomarkers of AD, they deserve further investigation as potential early genetic biomarkers of AD.
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Antipsychotic-induced parkinsonism (AIP) is the most common type of extrapyramidal side effect (EPS), caused by the blockage of dopamine receptors. Since dopamine availability might influence the AIP risk, the dopamine transporter (DAT) and serotonin receptors (5-HTRs), which modulate the dopamine release, may be also involved in the AIP development. As some of the individual differences in the susceptibility to AIP might be due to the genetic background, this study aimed to examine the associations of SLC6A3, HTR2C and HTR6 gene polymorphisms with AIP in haloperidol-treated schizophrenia patients. The Extrapyramidal Symptom Rating Scale (ESRS) was used to evaluate AIP as a separate entity. Genotyping was performed using a PCR, following the extraction of blood DNA. The results revealed significant associations between HTR6 rs1805054 polymorphism and haloperidol-induced tremor and rigidity. Additionally, the findings indicated a combined effect of HTR6 T and SLC6A3 9R alleles on AIP, with their combination associated with significantly lower scores of ESRS subscale II for parkinsonism, ESRS-based tremor or hyperkinesia and ESRS subscales VI and VIII. These genetic predictors of AIP could be helpful in better understanding its pathophysiology, recognizing the individuals at risk of developing AIP and offering personalized therapeutic strategies for the patients suffering from this EPS.
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INTRODUCTION: Behavioral and psychological symptoms of dementia (BPSD) are symptoms of non-cognitive nature, which frequently develop during the course and different stages of dementia. The diagnosis of BPSD is complex due to symptom variety, and relies on detailed clinical evaluation and medical history. Accurate assessment of BPSD is crucial in order to tailor therapeutic intervention (non-pharmacological and pharmacological) for each individual and monitor patient response to therapy. AREAS COVERED: This review encompasses the epidemiology, classification, assessment and etiology of BPSD, as well as their impact on caregiver distress, and gives an overview of current and emerging non-pharmacological and pharmacological therapeutic options, as well as potential BPSD biomarkers, in order to provide a framework for improving BPSD diagnosis and developing novel, targeted and specific therapeutic strategies for BPSD. EXPERT OPINION: Due to the large heterogeneity of BPSD and of the fact that drugs available only alleviate symptoms, finding an adequate treatment is very challenging and often involves a polytherapeutic approach. Non-pharmacologic interventions have shown promising results in improving BPSD, however further research is needed to confirm their beneficial effects. Thus, the modification of pre-existancing as well as the development of novel pharmacologic and non-pharmacologic solutions should be considered for BPSD therapy.
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Demencia , Síntomas Conductuales/tratamiento farmacológico , Cuidadores/psicología , Demencia/tratamiento farmacológico , HumanosRESUMEN
Post-traumatic stress disorder (PTSD) is a trauma and stress related disorder frequently associated with cognitive decline. War veterans with PTSD have a higher risk of developing dementia than healthy subjects. Brain derived neurotrophic factor (BDNF) is an important protein that modulates plasticity, memory consolidation and cognitive processes. Lower circulating BDNF levels were related to memory impairment and cognitive deterioration. The aim of this study was to evaluate cognitive deterioration and plasma BDNF concentration in 120 veterans with combat related PTSD, 120 healthy controls, 47 subjects with mild cognitive impairment (MCI) and 76 patients with Alzheimer's disease (AD), and to assess if plasma BDNF concentration might be used as biomarker of cognitive deterioration. Veterans with PTSD had significantly decreased plasma BDNF concentration and worse cognitive performances (assessed using the Mini Mental State Examination, Clock Drawing test and Montreal Cognitive Assessment scores/categories) than healthy subjects, and similarly reduced plasma BDNF and cognitive decline as MCI subjects. Reduced plasma BDNF was found in cognitively impaired subjects. These results suggest that veterans with PTSD should be closely monitored in order to early detect and predict cognitive worsening and promote interventions that might help restore blood BDNF levels and cognitive functions.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Trastornos por Estrés Postraumático , Veteranos , Enfermedad de Alzheimer/psicología , Factor Neurotrófico Derivado del Encéfalo , Disfunción Cognitiva/etiología , Humanos , Trastornos por Estrés Postraumático/complicacionesRESUMEN
Posttraumatic stress disorder (PTSD) is complex neuropsychiatric disorder triggered by a traumatic event and characterized by the symptoms that represent large burden to patients, as well as to society. Lipidomic approach can be applied as a useful tool for discovery of novel diagnostic, prognostic and therapeutic lipid biomarkers of various disorders, whose etiology is complex and still unknown, including PTSD. Since changes in the levels of lipid metabolites might indicate impairments in various metabolic pathways and cellular processes, the aim of this lipidomic study was to determine altered levels of lipid compounds in PTSD. The study enrolled 235 male patients with combat PTSD and 241 healthy male control subjects. Targeted lipidomic analysis of plasma samples was conducted using reverse-phase liquid chromatography coupled with mass spectrometry. Lipids that have been analyzed belong to the group of ceramides, cholesterol esters, diacylglycerols, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylethanolamines, sphingomyelins and triglycerides. The levels of fifteen lipid compounds were found to be significantly different between PTSD patients and healthy control subjects, including four phosphatidylcholines, two phosphatidylethanolamines, five sphingomyelins, two cholesterol esters and two ceramides. The lipid metabolites whose levels significantly differed between patients with PTSD and control subjects are associated with various biological processes, including impairments of membrane integrity and function, mitochondrial dysfunction, inflammation and oxidative stress. As these processes might be associated with development and progression of PTSD, altered lipid compounds represent potential biomarkers that could facilitate the diagnosis of PTSD, prediction of the disease, as well as identification of novel treatment approaches in PTSD.
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Lipidómica , Trastornos por Estrés Postraumático , Biomarcadores , Ceramidas , Ésteres del Colesterol , Humanos , Masculino , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas , Esfingomielinas , Trastornos por Estrés Postraumático/diagnósticoRESUMEN
Post-traumatic stress disorder (PTSD) is a complex trauma-related disorder, the etiology and underlying molecular mechanisms of which are still unclear and probably involve different (epi)genetic and environmental factors. Protein N-glycosylation is a common post-translational modification that has been associated with several pathophysiological states, including inflammation and PTSD. Hepatocyte nuclear factor-1α (HNF1A) is a transcriptional regulator of many genes involved in the inflammatory processes, and it has been identified as master regulator of plasma protein glycosylation. The aim of this study was to determine the association between N-glycan levels in plasma and immunoglobulin G, methylation at four CpG positions in the HNF1A gene, HNF1A antisense RNA 1 (HNF1A-AS1), rs7953249 and HNF1A rs735396 polymorphisms in a total of 555 PTSD and control subjects. We found significant association of rs7953249 and rs735396 polymorphisms, as well as HNF1A gene methylation at the CpG3 site, with highly branched, galactosylated and sialyated plasma N-glycans, mostly in patients with PTSD. HNF1A-AS1 rs7953249 polymorphism was also associated with PTSD; however, none of the polymorphisms were associated with HNF1A gene methylation. These results indicate a possible regulatory role of the investigated HNF1A polymorphisms with respect to the abundance of complex plasma N-glycans previously associated with proinflammatory response, which could contribute to the clinical manifestation of PTSD and its comorbidities.