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Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients (N = 3012) using fixed- and random-effects inverse variance-weighted meta-analyses. Suicidal ideations were more likely to be reported by patients with higher neuroticism and lower extraversion phenotypic scores, but showed no significant association with polygenic load for these personality traits. Our findings provide new insights into the association between personality and suicidal behavior across mental illnesses and suggest that the genetic component of personality traits is unlikely to have strong causal effects on suicidal behavior.
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Transtorno Depressivo Maior , Ideação Suicida , Humanos , Transtorno Depressivo Maior/psicologia , Saúde Mental , Personalidade/genética , FenótipoRESUMO
INTRODUCTION: This study aimed to find the expression biomarkers of pharmacological treatment response in a naturalistic hospital setting. Through gene expression profiling, we were able to find differentially-expressed genes (DEGs) in unipolar (UD) and bipolar (BD) depressed women. METHODS: We performed gene expression profiling in hospitalized women with unipolar (n=24) and bipolar depression (n=32) who achieved clinical improvement after pharmacological treatment (without any restriction). To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. RESULTS: After pharmacological treatment, UD and BD varied in the number of regulated genes and ontological pathways. Also, the pathways of neurogenesis and synaptic transmission were significantly up-regulated. Our research focused on DEGs with a minimum fold change (FC) of more than 2. For both types of depression, 2 up-regulated genes, OPRM1 and CELF4 (p=0.013), were significantly associated with treatment response (defined as a 50% reduction on the Hamilton Depression Rating Scale [HDRS]). We also uncovered the SHANK3 (p=0.001) gene that is unique for UD and found that the RASGRF1 (p=0.010) gene may be a potential specific biomarker of treatment response for BD. CONCLUSION: Based on transcriptomic profiling, we identified potential expression biomarkers of treatment outcomes for UD and BD. We also proved that the Ras-GEF pathway associated with long-term memory, female stress response, and treatment response modulation in animal studies impacts treatment efficacy in patients with BD. Further studies focused on the outlined genes may help provide predictive markers of treatment outcomes in UD and BD.
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Transtorno Bipolar , Transtorno Depressivo , Biomarcadores , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Feminino , Humanos , Leucócitos Mononucleares , Resultado do TratamentoRESUMO
BACKGROUND: Neurotrophin-3 (NTF3) and neurotrophin-4 (NTF4) play a crucial role in the neurodevelopment, differentiation, survival, and protection of neurons in different brain regions. Schizophrenia and depression are highly associated with metabolic abnormalities. Longitudinal and cross-sectional comparisons of NTF3 and NTF4 levels, as well as clinical and metabolic parameters, were studied in schizophrenia, first-episode depression, and control groups. MATERIALS AND METHODS: Serum NTF3 and NTF4 levels, body mass index (BMI), fasting serum glucose and lipid profile: cholesterol, triglyceride, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were measured at baseline and week 8 in 133 women: 55 patients with schizophrenia (19 with first-episode and 36 chronic), 30 patients with a first-episode depression and 48 healthy controls. The severity of the symptoms was evaluated with the Positive and Negative Syndrome Scale, 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory. RESULTS: Longitudinal and cross-sectional comparisons did not detect any differences in the serum levels of NTF3 and NTF4 between studied groups. NTF3 and NTF4 levels were strongly correlated. Correlation of NTF3 and HDL-C levels at baseline was observed. Significant changes in cholesterol and fasting serum glucose levels in first-episode depression patients during 8 weeks of treatment were detected. Significant differences in BMI and LDL-C levels between schizophrenia and first-episode depression patients were discovered. CONCLUSIONS: To our knowledge, this is the first research which correlates NTF3 and NTF4 with metabolic parameters. Our study does not support the theory that the peripheral levels of NTF3 and NTF4 are disturbed in schizophrenia or first-episode depression.
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Índice de Massa Corporal , Depressão/sangue , Fatores de Crescimento Neural/sangue , Esquizofrenia/sangue , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Jejum/metabolismo , Jejum/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neurotrofina 3 , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuron differentiation during development, as well as the synaptic plasticity and neuron survival in adulthood. BDNF has been implicated in the pathogenesis of psychiatric disorders and its serum level is a potential biomarker for depression. The aim of this study was to examine serum levels of BDNF in first-episode depression and its correlation with clinical and metabolic parameters. MATERIALS AND METHODS: The study was performed on a group of 60 women: 30 diagnosed with a first-episode of depression and 30 healthy controls. 17-Item Hamilton Depression Rating Scale (HDRS-17) was used to assess the severity of depression. Patients were randomly chosen for treatment with sertraline or venlafaxine. BDNF serum levels and metabolic parameters: fasting serum glucose, cholesterol, triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) were measured at baseline and week 8 of treatment. RESULTS: There were no differences between BDNF level in depressed patients compared with the healthy controls. Lack of differences in medication effect of sertraline or venlafaxine on HDRS-17 scores during 8 weeks of treatment was observed. Correlation of BDNF at baseline and fasting serum glucose at baseline and week 8 was detected. CONCLUSIONS: Correlations of BDNF serum levels with metabolic parameters were observed.
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Fator Neurotrófico Derivado do Encéfalo/sangue , Depressão/sangue , Depressão/diagnóstico , Adulto , Biomarcadores/sangue , Estudos Transversais , Depressão/tratamento farmacológico , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Sertralina/uso terapêutico , Cloridrato de Venlafaxina/uso terapêuticoRESUMO
Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.
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Transtorno Bipolar/psicologia , Depressão/psicologia , Esquizofrenia , Psicologia do Esquizofrênico , Estresse Psicológico/psicologia , Ideação Suicida , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Análise de Regressão , Fatores Sexuais , Adulto JovemRESUMO
(1) Background: Schizophrenia is a chronic and progressive neuropsychiatric illness. Apart from positive and negative symptoms, 98% of the population diagnosed with schizophrenia have impaired cognitive functioning, which significantly influences the quality of life. The correlation between lipids and cognitive functioning has been well established. Our study aimed to investigate correlations between cognitive functions, the severity of schizophrenia symptoms, and lipid profiles. (2) Methods: Fifty-two women diagnosed with schizophrenia participated in this study. Cognitive functioning was measured using the Wisconsin Card Sorting Test (WCST). The Positive and Negative Symptom Scale (PANSS) was used. The serum lipid profile, including low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and triglycerides was measured. (3) Results: Better cognitive functions were associated with normal HDL levels, while low HDL levels correlated with worse WSCT scores. Only the PANSS negative subscale showed a correlation with HDL levels. Correlations with chronicity of schizophrenia and the patient's age with poorer cognitive functions, but not with symptom severity, were detected. Early/late age at onset did not influence WSCT scores. (4) Conclusions: Our results suggest high HDL levels might be a protective factor against cognitive impairment. The influences of age and illness duration also play a vital role in cognitive performance.
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PURPOSE: Bipolar affective disorder (BP) causes major functional impairment and reduced quality of life not only for patients, but also for many close relatives. We aimed to investigate mRNA levels in BP patients to find differentially expressed genes linked to specific clinical course variants; assuming that several gene expression alterations might indicate vulnerability pathways for specific course and severity of the disease. MATERIALS: We searched for up- and down-regulated genes comparing patients with diagnosis of BP type I (BPI) vs type II (BPII), history of suicide attempts, psychotic symptoms, predominance of manic/hypomanic episodes, and history of numerous episodes and comorbidity of substance use disorders or anxiety disorders. RNA was extracted from peripheral blood mononuclear cells and analyzed with use of microarray slides. RESULTS: Differentially expressed genes (DEGs) were found in all disease characteristics compared. The lowest number of DEGs were revealed when comparing BPI and BPII patients (18 genes), and the highest number when comparing patients with and without psychotic symptoms (3223 genes). Down-regulated genes identified here with the use of the DAVID database were among others linked to cell migration, defense response, and inflammatory response. CONCLUSIONS: The most specific transcriptome profile was revealed in BP with psychotic symptoms. Differentially expressed genes in this variant include, among others, genes involved in inflammatory and immune processes. It might suggest the overlap of biological background between BP with a history of psychotic features and schizophrenia.
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Transtorno Bipolar , Perfilação da Expressão Gênica , Humanos , Transtorno Bipolar/genética , Biomarcadores/metabolismo , Feminino , Masculino , Transcriptoma , Adulto , Fenótipo , Pessoa de Meia-IdadeRESUMO
AIM: There have been limited prospective investigations of early clinical markers involved in mood regulation and diagnosis change in young patients. This study aimed to evaluate the changes in impulsivity and defence mechanisms in patients with major depressive disorder (MDD) and bipolar disorder (BD) with acute symptoms and remission compared to healthy controls (HC), and possible psychological predictors of diagnosis conversion. METHODS: Seventy-nine young MDD or BD patients and 40 HC were enrolled in a two-year prospective study. A comprehensive clinical interview focused on clinical and psychological evaluation during follow-up visits. The severity of depressive symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS-17), whilst the Young Mania Rating Scale (YMRS) was used for hypo/manic symptoms during each control visit. All patients completed the Defence Style Questionnaire (DSQ-40) and Barratt Impulsiveness Scale (BIS-11). RESULTS: Patients used more immature defences, and had significantly higher total impulsivity scores than controls. BD patients had elevated motor and non-planning impulsivity compared with HC and MDD subjects. Total and non-planning impulsiveness remained elevated in euthymia in BD and MDD compared to HC. There were no statistically significant differences in total defence styles and impulsiveness scores at baseline vs. euthymia in MDD or BD patients groups. Significantly higher dissociation scores at baseline discriminated depressive patients who convert to BD in their diagnosis. CONCLUSIONS: Patients with acute mood symptoms used more frequent immature defences and had significantly higher total impulsivity scores than healthy persons. A lack of differences in total defence styles and impulsiveness between patients with acute symptoms and after reaching euthymia in both MDD and BD groups indicates that they are independent of disease status. Dissociation defence mechanisms may be an early diagnostic indicator of BD.
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Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Transtornos do Humor , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Estudos Prospectivos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Comportamento ImpulsivoRESUMO
Disturbances of melatonin secretion alter the circadian rhythm and sleep-wake cycle, which is observed among patients with depression. Melatonin acts via melatonin receptors MT1 and MT2, which are present in many tissues, including peripheral blood mononuclear cells (PBMC). We assume that disturbances of the melatonin pathway in the brain may be reflected by molecular changes in peripheral organs. The study objective was to evaluate the methylation profile of CpG island in the promoter region of melatonin receptor genes MTNR1A and MTNR1B in PBMC of patients with depression and compare it with healthy volunteers. The study group comprised 85 patients with unipolar (UP) and bipolar disorders (BP) and 83 controls. The methylation pattern of CpG island in the promoter region was analyzed using the quantitative methylation-specific real-time PCR (qMSP-PCR) method. We found that the methylation profile of the patients with depression varied in comparison to the control group. The methylation level of MTNR1A was significantly lower among depressed patients compared to controls. Additionally, melatonin concentration was negatively correlated with MTNR1B methylation level among the UP patients. The study may suggest that the methylation profile of melatonin receptors in PBMC may be used as a complementary molecular marker in depression diagnosis.
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Transtorno Bipolar , Melatonina , Humanos , Receptores de Melatonina/genética , Receptores de Melatonina/metabolismo , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Leucócitos Mononucleares/metabolismo , Melatonina/genética , MetilaçãoRESUMO
The heterogeneity of symptoms in young patients with major depression disorder makes it difficult to properly identify and diagnose. Therefore, the appropriate evaluation of mood symptoms is important in early intervention. The aim of this study was to (a) establish dimensions of the Hamilton Depression Rating Scale (HDRS-17) in adolescents and young adults and (b) perform correlations between the identified dimensions and psychological variables (impulsivity, personality traits). This study enrolled 52 young patients with major depression disorder (MDD). The severity of the depressive symptoms was established using the HDRS-17. The factor structure of the scale was studied using the principal component analysis (PCA) with varimax rotation. The patients completed the self-reported Barratt Impulsiveness Scale (BIS-11) and Temperament and Character Inventory (TCI). The three dimensions of the HDRS-17 identified as core in adolescent and young patients with MDD were (1) psychic depression/motor retardation, (2) disturbed thinking, and (3) sleep disturbances/anxiety. In our study, dimension 1 correlated with reward dependence and cooperativeness; dimension 2 correlated with non-planning impulsivity, harm avoidance, and self-directedness; and dimension 3 correlated with reward dependence. Conclusions: Our study supports the previous findings, which indicate that a certain set of clinical features (including the HDRS-17 dimensions, not only total score) may represent a vulnerability pattern that characterizes patients with depression.
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Both depression and rheumatoid arthritis (RA) have a very high comorbidity rate. A bilateral association is estimated to increase the mutual risk and the common denominator is inflammation being observed in both diseases. Previous studies have mainly focused on assessing peripheral blood's inflammatory and pro-inflammatory cytokines levels. We aimed to extend insights into the molecular mechanisms of depression based on hub RA genes. To do so, we prioritized RA-related genes using in-silico tools. We then investigated whether RA-related genes undergo altered expression in patients with unipolar and bipolar depression without a concurrent RA diagnosis and any exponents of active inflammation. In addition, we selected a homogeneous group of patients treated with lithium (Li), which has immunomodulatory properties. The study was performed on patients with bipolar depression (BD, n = 45; Li, n = 20), unipolar depression (UD, n = 27), and healthy controls (HC, n = 22) of both sexes. To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. We selected a list of 180 hub genes whose altered expression we analyzed using the expression microarray results. In the entire study group, we identified altered expression of 93 of the 180 genes, including 35 down-regulated (OPRM1 gene with highest FC > 3) and 58 up-regulated (TLR4 gene with highest FC > 3). In UD patients, we observed maximally up-regulated expression of the TEK gene (FC > 3), and in BD of the CXCL8 gene (FC > 5). On the other hand, in lithium-treated patients, the gene with the most reduced expression was the TRPV1 gene. The study proved that depression and RA are produced by a partially shared "inflammatory interactome" in which the opioid and angiogenesis pathways are important.
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Artrite Reumatoide , Transtorno Depressivo Maior , Masculino , Feminino , Humanos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Leucócitos Mononucleares/metabolismo , Depressão/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Inflamação/metabolismoRESUMO
BACKGROUND: Prolactin in schizophrenia is considered in the context of antipsychotic drug-induced hyperprolactinemia. However, the European First Episode Schizophrenia Trial showed that hyperprolacti nemia occurred in a significant proportion of drug-naïve first-episode schizophrenia patients, which shows that it may also be caused by other factors, including genetic predisposition. Therefore, we investigated the functional polymorphism of the prolactin gene in schizophrenic patients compared with control subjects. METHOD: The experimental group consisted of 403 patients with schizophrenia: 202 females and 201 males. The control group consisted of 653 subjects: 377 females and 276 males. The functional polymorphism -1149 G/T (rs1341239) of the prolactin gene was genotyped using the TaqMan single-nucleotide polymorphism allelic discrimination method. RESULTS: The distribution of genotypes in schizophrenic patients was significantly different from those of the control subjects (p=0.031). After breaking down by gender, for male patients, the difference versus control males was significant for both genotypes and alleles (p=0.031 and p=0.002, respectively), with allele G being observed more frequently in schizophrenic patients. CONCLUSION: The results may suggest a possible abnormality of the functional -1149 G/T polymorphism of the prolactin gene in schizophrenia, especially in male patients, similar to that found in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. This could also correspond with an autoimmune pathogenesis of schizophrenia.
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Prolactina/genética , Esquizofrenia/genética , Adolescente , Adulto , Idoso , Alelos , Doenças Autoimunes/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Hiperprolactinemia/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prolactina/imunologia , Esquizofrenia/imunologia , Fatores SexuaisRESUMO
Bipolar disorder (BD) is one of the most disabling psychiatric illnesses. Over half of BD patients experienced early onset of the disease, and in most cases, it begins with a depressed mood episode. Up to 50% of adolescents initially diagnosed with major depressive disorder (MDD) convert to bipolar spectrum disorder. Diagnostic tools or biomarkers to facilitate the prediction of diagnosis conversion from MDD to BD are still lacking. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a 2-year follow-up study on 69 adolescent patients diagnosed with MDD or BD. The control group consisted of 31 healthy youths. We monitored diagnosis change from MDD to BD. Impulsiveness was assessed using Barratt Impulsiveness Scale (BIS-11) and defense mechanisms using Defense Style Questionnaire (DSQ-40). According to the immunological hypothesis of mood disorders, we investigated baseline cytokines levels either in depressive or hypomanic/manic episodes. We correlated interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-alpha) levels with clinical factors. We detected higher IL-8 and TNF-alpha in patients in hypomanic/manic compared to depressed episodes. We found correlations of cytokine levels with immature defense style. We did not discover predictors of diagnosis conversion from MDD to BD.
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AIM: Cognitive deficits are the core factors impacting quality of life among patients diagnosed with schizophrenia. Effective method of treatment for this domain of symptoms remains lacking. Recent evidence suggests the link between impaired cognition and aberrant inflammatory response. Severity of symptoms might be linked to individual genetic predispositions and single-nucleotide polymorphisms (SNPs) in genes encoding interleukins and their receptors. Current genetic association studies include anti-inflammatory interleukins, such as IL10. Functional polymorphisms of IL10 (rs1800871, rs18008729) have been indicated to affect information processing in schizophrenia. MATERIALS AND METHODS: In this study, we analyzed the potential impact of 27 functional SNPs in 8 cytokine genes on cognitive parameters measured by Wisconsin card-sorting test (WCST) in schizophrenia group (n = 150) and healthy controls (n = 152). RESULTS: We found significant associations of two functional polymorphisms of IL10 (rs1800871, rs1800872) and WCST results. Allele A carriers in rs1800871 performed significantly better in Percent of Conceptual Level Responses (CLR%). Allele A carriers in rs1800871 and allele T carriers in rs1800872 obtained better results in Completed Categories (CC). The impact of illness duration was observed, with better performance of recent-onset patients. CONCLUSIONS: Results of this study indicate that genetic variants of inflammatory response are associated with cognitive deficits in schizophrenia. The role of cytokines in schizophrenia need to be investigated in the aspect of pro-/anti-inflammatory imbalance. Altered inflammatory response promote chronic mild inflammation in the brain and aberrant synaptic plasticity.
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Disfunção Cognitiva/genética , Disfunção Cognitiva/fisiopatologia , Inflamação/genética , Interleucina-10/genética , Esquizofrenia/genética , Adulto , Disfunção Cognitiva/etiologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Esquizofrenia/complicações , Adulto JovemRESUMO
BACKGROUND: An increasing incidence of mood disorders in adolescents and young adults is being observed. The assessment of personality traits seems to be an interesting tool in identifying early markers of major depression (MD) or bipolar disorder (BD) as well as predictors of the course of the disease. The aim of this study was to compare the personality profiles in young patients with MD and BD in acute and remitted mood states. METHODS: Seventy-nine adolescents and young adults with mood disorder diagnoses (MD or BD) were included in the study. The participants were assessed based on structured diagnostic interviews and completed the Temperament and Character Inventory (TCI). The clinical evaluation was conducted during the acute episodes and after reaching the stabilized mood in the course of follow-up visits in a 2-year study observation. RESULTS: At baseline, MD patients had higher scores on the harm avoidance (HA) with more pronounced anticipatory worry and fatigability subscale than BD patients. Conversely, BD patients reached higher scores in the total self-directedness (SD) character dimension and its sub-dimensions. MD patients with acute depressive symptoms had higher scores in the HA dimension and its subscale: anticipatory worry, shyness, and fatigability compared with their euthymic states. No significant differences in TCI dimensions between baseline and euthymia in the BD subgroup were found, and no differences between euthymic MD and BD patients. CONCLUSIONS: Higher ST and SD sub-dimensions may constitute a personality profile specific to BD, while high HA seems to be related to major depression in both acute and remitted states in young patients.
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Transtorno Depressivo Maior , Temperamento , Humanos , Adolescente , Adulto Jovem , Transtornos do Humor/epidemiologia , Estudos Prospectivos , Polônia/epidemiologia , Inventário de Personalidade , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologiaRESUMO
AIM: MMP-9 is a candidate gene related to the neurodevelopment hypothesis of schizophrenia. The aim of this research was TDT analysis of polymorphism -1562C>T MMP-9 gene in schizophrenia. METHODS: Research was carried out on 147 trios (patient and his/hers both healthy parents). Genetic material was isolated from leukocytes using the salting out method. Polymorphism was studied with PCR-RFLP, statistic analysis was made using transmission disquilibrium test by Haploview 4.2. RESULTS: There was no significant association between analyzed polymorphism of MMP-9 (-1562 C>T) and schizophrenia. CONCLUSIONS: Insignificant association doesn't exclude the possible contribution of MMP-9 to pathogenesis of schizophrenia. Further research is needed to be carried out on bigger groups and other populations.
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Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético , Esquizofrenia/genética , Adulto , Estudos de Coortes , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Polônia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Esquizofrenia/metabolismo , Adulto JovemRESUMO
Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the periphery of depressed patients. This study aimed to comprehensively analyze the differences between healthy control subjects (n = 84) and unipolar and bipolar depression patients (n = 94), including an analysis of the melatonin pathway at the level of the genes and serum biomarkers. An innovative approach is a pilot study based on gene expression profiling carried out on clinical and cell culture models using agomelatine and melatonin. We confirmed the melatonin biosynthesis pathway's molecular regulation dysfunctions, with a specific pattern for unipolar and bipolar depression, at the AANAT gene, its polymorphisms (rs8150 and rs3760138), and examined the serum biomarkers (serotonin, AANAT, ASMT, and melatonin). The biological pathway analysis uncovered pathways and genes that were uniquely altered after agomelatine treatment in a clinical model and melatonin treatment in a cell culture model. In both models, we confirmed the immunomodulatory effect of melatonin agents in depression.
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Mood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14-24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.
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Biomarcadores/sangue , Transtornos do Humor/diagnóstico , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Adolescente , Biomarcadores/metabolismo , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Fatores Sexuais , Adulto JovemRESUMO
Bipolar disorder (BD) is a chronic mental disorder that affects more than 1% of the population worldwide. Over 65% of patients experience early onset of the disease. Most cases of juvenile bipolar disorder begin with a depressed mood episode, and up to 50% of youth initially diagnosed with major depression go onto developing a BD. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a two-year follow-up study on 79 adolescent patients diagnosed with MDD or BD, with a detailed clinical assessment at five visits. We monitored diagnosis change from MDD to BD. The control group consisted of 31 healthy youths. According to the neurodevelopmental and neuroimmunological hypotheses of mood disorders, we analyzed serum levels of brain-derived neurotrophic factor (BDNF), proBDNF, epidermal growth factor (EGF), migration inhibitory factor (MIF), stem cell factor (SCF), and correlations with clinical factors. We detected a significant disease-dependent increase in EGF level in MDD and BP patients at baseline exacerbation of depressive or hypomanic/manic episodes as well as in euthymic state compared to healthy controls. No potential biological predictors of disease conversion were found. Replication studies on a larger cohort of patients are needed.
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Due to current depression prevalence, it is crucial to make the correct diagnosis as soon as possible. The study aimed to identify commonly available, easy to apply, and quick to interpret tools allowing for a differential diagnosis between unipolar and bipolar disorder. The study group includes women with long duration of unipolar (UP, N = 34) and bipolar (BP, N = 43) affective disorder. The diagnosis was established according to the DSM criteria using SCID questionnaire. Additional questionnaires were used to differentiate between UP and BP. BP patients had an earlier age of onset, were hospitalized more times, and more often had a family history of psychiatric disorders than UP (p-value < 0.05). Moreover, BP achieved a higher impulsiveness score and more frequently had experienced severe problems with close individuals. To our knowledge, this is the first publication presenting results of numerous questionnaires applied simultaneously in patients on clinical group. Several of them suggest the direction of clinical assessment, such as: the age of onset, family psychiatric burdens, history of stressful life events, learning problems, social and job relations. Further studies are necessary to confirm the utility of this approach.