Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40.746
Filtrar
1.
Biol Pharm Bull ; 47(3): 556-561, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432911

RESUMO

Mental illness poses a huge social burden, accounting for approximately 14% of all deaths. Depression, a major component of mental illness, affects approximately 300 million people worldwide, mainly in developed countries, and is not only a major social burden but also a cause of suicide. The social burden of depression is estimated to increase further in developing countries, and overcoming it is a pressing issue for all countries, including Japan. Although clinical evidence has demonstrated the efficacy of serotonergic neurotransmission enhancers in the treatment of depression, the full picture of their therapeutic effects has not yet been fully elucidated. In this review, we show that the hyperactivity of serotonin neurons, especially those in the dorsal raphe nucleus, is commonly induced by various antidepressants within a period corresponding to the onset of their clinical efficacy. We established quantitative prediction methods for pharmacological activity using only chemical structures to translate the biological understanding of mental disorders, including major depressive disorders, into clinically effective therapeutics. Our method exhibited better performance than the previously reported methods of quantitative prediction, while targeting a larger number of proteins. Our article suggests the importance of integrative neuropharmacology and informatics-based pharmacology studies to understand the biological basis of mental disorders and facilitate drug development for these disorders.


Assuntos
Transtorno Depressivo Maior , Transtornos Mentais , Transtornos Psicóticos , Humanos , Neurofarmacologia , Transtornos Mentais/tratamento farmacológico , Informática
2.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38436562

RESUMO

BACKGROUND: Depression has been linked to an increased risk of cardiovascular and respiratory diseases; however, its impact on cardiac and lung function remains unclear, especially when accounting for potential gene-environment interactions. METHODS: We developed a novel polygenic and gene-environment interaction risk score (PGIRS) integrating the major genetic effect and gene-environment interaction effect of depression-associated loci. The single nucleotide polymorphisms (SNPs) demonstrating major genetic effect or environmental interaction effect were obtained from genome-wide SNP association and SNP-environment interaction analyses of depression. We then calculated the depression PGIRS for non-depressed individuals, using smoking and alcohol consumption as environmental factors. Using linear regression analysis, we assessed the associations of PGIRS and conventional polygenic risk score (PRS) with lung function (N = 42 886) and cardiac function (N = 1791) in the subjects with or without exposing to smoking and alcohol drinking. RESULTS: We detected significant associations of depression PGIRS with cardiac and lung function, contrary to conventional depression PRS. Among smokers, forced vital capacity exhibited a negative association with PGIRS (ß = -0.037, FDR = 1.00 × 10-8), contrasting with no significant association with PRS (ß = -0.002, FDR = 0.943). In drinkers, we observed a positive association between cardiac index with PGIRS (ß = 0.088, FDR = 0.010), whereas no such association was found with PRS (ß = 0.040, FDR = 0.265). Notably, in individuals who both smoked and drank, forced expiratory volume in 1-second demonstrated a negative association with PGIRS (ß = -0.042, FDR = 6.30 × 10-9), but not with PRS (ß = -0.003, FDR = 0.857). CONCLUSIONS: Our findings underscore the profound impact of depression on cardiac and lung function, highlighting the enhanced efficacy of considering gene-environment interactions in PRS-based studies.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/genética , Interação Gene-Ambiente , Fumar/efeitos adversos , Pulmão
3.
J Obstet Gynaecol ; 44(1): 2321321, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38425012

RESUMO

BACKGROUND: The aim was to assess the causal relationship between depression and anxiety disorders and endometrial cancer. METHOD: We performed two-sample Mendelian randomisation analysis using summary statistics from genome-wide association studies to assess associations of major depressive disorder, anxiety and stress-related disorders with endometrial cancer. The genome-wide association studies(GWASs) data were derived from participants of predominantly European ancestry included in the Genome-wide Association Research Collaboration. Inverse variance-weighted, MR-Egger and weighted median MR analyses were performed, together with a range of sensitivity analyses. RESULTS: Mendelian randomisation analysis showed no statistically significant genetic responsibility effect of anxiety and stress-related disorders on any pathological type of endometrial cancer. Only the effect of major depressive disorder under the inverse variance weighting method increasing the risk of endometrial endometrial cancer (effect 0.004 p = 0.047) and the effect of major depressive disorder under the MR-Egger method decreasing endometrial cancer of all pathology types (effect -0.691 p = 0.015) were statistically significant. Other Mendelian randomisation analyses did not show a statistically significant effect. CONCLUSION: Major depressive disorder(MDD), anxiety and stress-related disorders(ASRD) are not genetically responsible for endometrial cancer. We consider that emotional disorders may affect endometrial cancer indirectly by affecting body mass index. This study provides us with new insights to better understand the aetiology of endometrial cancer and inform prevention strategies.


This study used public genomic data to analyse association between affective disorders, including depression and anxiety, and endometrial cancer. Genes treated as instrumental variables help us understand the causal link between affective disorders and endometrial cancer through bioinformatics. In addition to this, we added type 2 diabetes, body mass index, polycystic ovary syndrome, and age at menopause for multivariate Mendelian randomisation analyses with the aim of reducing confounding bias. Because we consider these factors may potentially influence the relationship between affective disorders and endometrial cancer. Ultimately we believe that the association between depression and endometrial cancer is not as strong as that of obesity, due to the genetic correlation between depression and obesity.


Assuntos
Carcinoma Endometrioide , Transtorno Depressivo Maior , Neoplasias do Endométrio , Humanos , Feminino , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Neoplasias do Endométrio/genética , Ansiedade , Polimorfismo de Nucleotídeo Único , Análise da Randomização Mendeliana
5.
Transl Psychiatry ; 14(1): 141, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461185

RESUMO

Major depressive disorder (MDD) is a common mental illness worldwide and is triggered by an intricate interplay between environmental and genetic factors. Although there are several studies on common variants in MDD, studies on rare variants are relatively limited. In addition, few studies have examined the genetic contributions to neurostructural alterations in MDD using whole-exome sequencing (WES). We performed WES in 367 patients with MDD and 161 healthy controls (HCs) to detect germline and copy number variations in the Korean population. Gene-based rare variants were analyzed to investigate the association between the genes and individuals, followed by neuroimaging-genetic analysis to explore the neural mechanisms underlying the genetic impact in 234 patients with MDD and 135 HCs using diffusion tensor imaging data. We identified 40 MDD-related genes and observed 95 recurrent regions of copy number variations. We also discovered a novel gene, FRMPD3, carrying rare variants that influence MDD. In addition, the single nucleotide polymorphism rs771995197 in the MUC6 gene was significantly associated with the integrity of widespread white matter tracts. Moreover, we identified 918 rare exonic missense variants in genes associated with MDD susceptibility. We postulate that rare variants of FRMPD3 may contribute significantly to MDD, with a mild penetration effect.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/genética , Imagem de Tensor de Difusão , Sequenciamento do Exoma , Variações do Número de Cópias de DNA , Neuroimagem
6.
PLoS One ; 19(3): e0299528, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38466739

RESUMO

BACKGROUND: Rates of depression and addiction have risen drastically over the past decade, but the lack of integrative techniques remains a barrier to accurate diagnoses of these mental illnesses. Changes in reward/aversion behavior and corresponding brain structures have been identified in those with major depressive disorder (MDD) and cocaine-dependence polysubstance abuse disorder (CD). Assessment of statistical interactions between computational behavior and brain structure may quantitatively segregate MDD and CD. METHODS: Here, 111 participants [40 controls (CTRL), 25 MDD, 46 CD] underwent structural brain MRI and completed an operant keypress task to produce computational judgment metrics. Three analyses were performed: (1) linear regression to evaluate groupwise (CTRL v. MDD v. CD) differences in structure-behavior associations, (2) qualitative and quantitative heatmap assessment of structure-behavior association patterns, and (3) the k-nearest neighbor machine learning approach using brain structure and keypress variable inputs to discriminate groups. RESULTS: This study yielded three primary findings. First, CTRL, MDD, and CD participants had distinct structure-behavior linear relationships, with only 7.8% of associations overlapping between any two groups. Second, the three groups had statistically distinct slopes and qualitatively distinct association patterns. Third, a machine learning approach could discriminate between CTRL and CD, but not MDD participants. CONCLUSIONS: These findings demonstrate that variable interactions between computational behavior and brain structure, and the patterns of these interactions, segregate MDD and CD. This work raises the hypothesis that analysis of interactions between operant tasks and structural neuroimaging might aide in the objective classification of MDD, CD and other mental health conditions.


Assuntos
Transtorno Depressivo Maior , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Transtornos Relacionados ao Uso de Substâncias/psicologia
7.
Photodermatol Photoimmunol Photomed ; 40(2): e12957, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38470033

RESUMO

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.


Assuntos
Transtorno Depressivo Maior , Terapia com Luz de Baixa Intensidade , Humanos , Transtorno Depressivo Maior/terapia , Projetos Piloto , Eletroencefalografia , Estimulação Magnética Transcraniana
8.
Mol Biol Rep ; 51(1): 415, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472517

RESUMO

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders.


Assuntos
Transtorno do Espectro Autista , Transtorno Depressivo Maior , Humanos , Feminino , Masculino , Transtorno do Espectro Autista/genética , Caracteres Sexuais , Transtorno Depressivo Maior/metabolismo , Estrogênios/metabolismo , Sinapses/metabolismo , Emoções
9.
Transl Psychiatry ; 14(1): 142, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38467624

RESUMO

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011-2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.


Assuntos
Depressão , Transtorno Depressivo Maior , Adulto , Humanos , Depressão/epidemiologia , Depressão/complicações , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Inquéritos Nutricionais , Estudos Longitudinais , Estudos Transversais , Cognição/fisiologia , Lipoproteínas , Predisposição Genética para Doença
10.
JAMA Netw Open ; 7(3): e241933, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38470418

RESUMO

Importance: Adolescent major depressive disorder (MDD) is associated with serious adverse implications for brain development and higher rates of self-injury and suicide, raising concerns about its neurobiological mechanisms in clinical neuroscience. However, most previous studies regarding the brain alterations in adolescent MDD focused on single-modal images or analyzed images of different modalities separately, ignoring the potential role of aberrant interactions between brain structure and function in the psychopathology. Objective: To examine alterations of structural and functional connectivity (SC-FC) coupling in adolescent MDD by integrating both diffusion magnetic resonance imaging (MRI) and resting-state functional MRI data. Design, Setting, and Participants: This cross-sectional study recruited participants aged 10 to 18 years from January 2, 2020, to December 28, 2021. Patients with first-episode MDD were recruited from the outpatient psychiatry clinics at The First Affiliated Hospital of Chongqing Medical University. Healthy controls were recruited by local media advertisement from the general population in Chongqing, China. The sample was divided into 5 subgroup pairs according to different environmental stressors and clinical characteristics. Data were analyzed from January 10, 2022, to February 20, 2023. Main Outcomes and Measures: The SC-FC coupling was calculated for each brain region of each participant using whole-brain SC and FC. Primary analyses included the group differences in SC-FC coupling and clinical symptom associations between SC-FC coupling and participants with adolescent MDD and healthy controls. Secondary analyses included differences among 5 types of MDD subgroups: with or without suicide attempt, with or without nonsuicidal self-injury behavior, with or without major life events, with or without childhood trauma, and with or without school bullying. Results: Final analyses examined SC-FC coupling of 168 participants with adolescent MDD (mean [mean absolute deviation (MAD)] age, 16.0 [1.7] years; 124 females [73.8%]) and 101 healthy controls (mean [MAD] age, 15.1 [2.4] years; 61 females [60.4%]). Adolescent MDD showed increased SC-FC coupling in the visual network, default mode network, and insula (Cohen d ranged from 0.365 to 0.581; false discovery rate [FDR]-corrected P < .05). Some subgroup-specific alterations were identified via subgroup analyses, particularly involving parahippocampal coupling decrease in participants with suicide attempt (partial η2 = 0.069; 90% CI, 0.025-0.121; FDR-corrected P = .007) and frontal-limbic coupling increase in participants with major life events (partial η2 ranged from 0.046 to 0.068; FDR-corrected P < .05). Conclusions and Relevance: Results of this cross-sectional study suggest increased SC-FC coupling in adolescent MDD, especially involving hub regions of the default mode network, visual network, and insula. The findings enrich knowledge of the aberrant brain SC-FC coupling in the psychopathology of adolescent MDD, underscoring the vulnerability of frontal-limbic SC-FC coupling to external stressors and the parahippocampal coupling in shaping future-minded behavior.


Assuntos
Experiências Adversas da Infância , Transtorno Depressivo Maior , Feminino , Humanos , Adolescente , Transtorno Depressivo Maior/diagnóstico por imagem , Estudos Transversais , Depressão , Encéfalo/diagnóstico por imagem
11.
Cells ; 13(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474387

RESUMO

The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Doenças Neuroinflamatórias , Disbiose/tratamento farmacológico , Antidepressivos/farmacologia , Inflamação/metabolismo , Anti-Inflamatórios/uso terapêutico
12.
Molecules ; 29(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38474476

RESUMO

Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and severe side effects. Recently, two categories of fast-acting antidepressant compounds have surfaced, dissociative anesthetics S-ketamine and its metabolites, as well as psychedelics such as lysergic acid diethylamide (LSD). This has led to structural research and drug development of the receptors that they target. This review provides breakthroughs and achievements in the structure of depression-related receptors and novel ADs based on these. Cryo-electron microscopy (cryo-EM) has enabled researchers to identify the structures of membrane receptors, including the N-methyl-D-aspartate receptor (NMDAR) and the 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution structures can be used for the development of novel ADs using virtual drug screening (VDS). Moreover, the unique antidepressant effects of 5-HT1A receptors in various brain regions, and the pivotal roles of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and tyrosine kinase receptor 2 (TrkB) in regulating synaptic plasticity, emphasize their potential as therapeutic targets. Using structural information, a series of highly selective ADs were designed based on the different role of receptors in MDD. These molecules have the favorable characteristics of rapid onset and low adverse drug reactions. This review offers researchers guidance and a methodological framework for the structure-based design of ADs.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Serotonina , Estrutura Molecular , Microscopia Crioeletrônica , Antidepressivos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
13.
J Child Psychol Psychiatry ; 65(4): 538-567, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38426610

RESUMO

Depression is a serious public health problem, and adolescence is an 'age of risk' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico-amygdala circuit, lowers sensitivity to rewards in the cortico-striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self-medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress-related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a 'next generation' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents.


Assuntos
Depressão , Transtorno Depressivo Maior , Adolescente , Humanos , Encéfalo/metabolismo , Emoções , Inflamação/metabolismo
14.
Transl Psychiatry ; 14(1): 136, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443354

RESUMO

Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) correlation analysis to explore the association between subcortical FC and mood symptom profiles. FC score, reflecting the weighted representation of each individual in this association, was computed. Replication analysis was undertaken in an independent sample (n = 74). We also investigated the relationship between FC score and treatment outcome in the main sample. A distinctive subcortical connectivity pattern was found to be associated with negative affect. In general, higher FC between the caudate, putamen and thalamus was associated with greater negative affect. This association was partly replicated in the independent sample (similarity between the two samples: r = 0.66 for subcortical connectivity, r = 0.75 for mood symptom profile). Lower FC score predicted both remission and response to treatment after 8 weeks of antidepressant monotherapy. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical FC with negative affect. However, while the FC score significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.


Assuntos
Transtorno Depressivo Maior , Humanos , Afeto , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Estudos Prospectivos , Resultado do Tratamento
15.
BMC Neurosci ; 25(1): 12, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438989

RESUMO

BACKGROUND: Mutations in the gene DISC1 are associated with increased risk for schizophrenia, bipolar disorder and major depression. The study of mutated DISC1 represents a well-known and comprehensively characterized approach to understand neuropsychiatric disease mechanisms. However, previous studies have mainly used animal models or rather heterogeneous populations of iPSC-derived neurons, generated by undirected differentiation, to study the effects of DISC1 disruption. Since major hypotheses to explain neurodevelopmental, psychiatric disorders rely on altered neuronal connectivity observed in patients, an ideal iPSC-based model requires accurate representation of the structure and complexity of neuronal circuitries. In this study, we made use of an isogenic cell line with a mutation in DISC1 to study neuronal synaptic phenotypes in a culture system comprising a defined ratio of NGN2 and ASCL1/DLX2 (AD2)-transduced neurons, enriched for glutamatergic and GABAergic neurons, respectively, to mimic properties of the cortical microcircuitry. RESULTS: In heterozygous DISC1 mutant neurons, we replicated the expected phenotypes including altered neural progenitor proliferation as well as neurite outgrowth, deregulated DISC1-associated signaling pathways, and reduced synaptic densities in cultures composed of glutamatergic neurons. Cultures comprising a defined ratio of NGN2 and AD2 neurons then revealed considerably increased GABAergic synapse densities, which have not been observed in any iPSC-derived model so far. Increased inhibitory synapse densities could be associated with an increased efficiency of GABAergic differentiation, which we observed in AD2-transduced cultures of mutant neurons. Additionally, we found increased neuronal activity in GABAergic neurons through calcium imaging while the activity pattern of glutamatergic neurons remained unchanged. CONCLUSIONS: In conclusion, our results demonstrate phenotypic differences in a co-culture comprising a defined ratio of DISC1 mutant NGN2 and AD2 neurons, as compared to culture models comprising only one neuronal cell type. Altered synapse numbers and neuronal activity imply that DISC1 impacts the excitatory/inhibitory balance in NGN2/AD2 co-cultures, mainly through increased GABAergic input.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Animais , Humanos , Técnicas de Cocultura , Neurônios GABAérgicos , Mutação , Proteínas do Tecido Nervoso/genética
16.
Mol Genet Genomic Med ; 12(3): e2413, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38439604

RESUMO

BACKGROUND: The association between major depressive disorder (MDD) and irritable bowel syndrome (IBS) has been found in observational research; however, the causative relationship between MDD and IBS remains uncertain. Using the two-sample Mendelian randomization (MR) approach, we attempted to examine the causal effect of MDD on IBS. METHODS: Independent genetic variants for MDD identified by Howard et al. based on a genome-wide meta-analysis were selected for this study. Gene-Outcome associations for IBS were gathered from UK Biobank and FinnGen databases. The MR analysis included inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-PRESSO sensitivity analyses. RESULTS: FinnGen database subjected to inverse variance weighted (IVW) analysis revealed that MDD may be a risk factor for the development of IBS (OR = 1.356, 95% CI: 1.125-1.632, p = 0.0013). The same finding was reached in UK Biobank for IVW (OR = 1.011, 95% CI: 1.006-1.015, p = 3.18 × 10-7 ), MR-Egger progression (OR = 1.030, 95% CI: 1.008-1.051, p = 0.007), and weighted median (OR = 1.011, 95% CI: 1.005-1.016, p = 0.0001). CONCLUSION: Our findings supported a causal relationship between MDD and IBS, which may have implications for the clinical management of IBS in individuals with MDD.


Assuntos
Transtorno Depressivo Maior , Síndrome do Intestino Irritável , Humanos , Transtorno Depressivo Maior/genética , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/genética , Análise da Randomização Mendeliana , Bases de Dados Factuais , Fatores de Risco
17.
Lancet ; 403(10430): 969-983, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38458216

RESUMO

The potential risk for mental health conditions over the menopause transition shapes women's expectations and informs putative physiological mechanisms regulating women's mental health. We review evidence from prospective studies reporting on associations between mental health conditions and the menopause transition. Major depressive disorder and the more prevalent subthreshold depressive symptoms are the most common conditions studied. We reviewed 12 prospective studies reporting depressive symptoms, major depressive disorder, or both over the menopause transition and found no compelling evidence for a universal increased risk for either condition. However, specific subgroups of participants, primarily defined by menopause-related risk factors (ie, vasomotor symptoms that are severe or disturb sleep, a long duration of the transition, or reproductive hormone dynamics) and psychosocial risk factors (eg, stressful life events), were vulnerable to depressive symptoms. The increased risk of major depressive disorder over the menopause transition appears predominantly in individuals with previous major depressive disorder. Greater focus on recognising risk factors in primary care is warranted. On the basis of scarce data, we found no compelling evidence that risk of anxiety, bipolar disorder, or psychosis is universally elevated over the menopause transition. Potential misattribution of psychological distress and psychiatric disorders to menopause could harm women by delaying accurate diagnosis and the initiation of effective psychotropic treatments, and by creating negative expectations for people approaching menopause. A paradigm shift is needed. We conclude with recommendations for the detection and treatment of depressive symptoms or major depressive disorder and strategies to promote good mental health over the menopause transition, while responsibly preparing and supporting those at risk.


Assuntos
Transtorno Depressivo Maior , Saúde Mental , Feminino , Humanos , Transtorno Depressivo Maior/epidemiologia , Estudos Prospectivos , Menopausa/psicologia , Saúde da Mulher , Depressão/epidemiologia , Depressão/psicologia
18.
Transl Psychiatry ; 14(1): 134, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443348

RESUMO

Suicidal behavior and non-suicidal self-injury (NSSI) are common in adolescent patients with major depressive disorder (MDD). Thus, delineating the unique characteristics of suicide attempters having adolescent MDD with NSSI is important for suicide prediction in the clinical setting. Here, we performed psychological and biochemical assessments of 130 youths having MDD with NSSI. Participants were divided into two groups according to the presence/absence of suicide attempts (SAs). Our results demonstrated that the age of suicide attempters is lower than that of non-attempters in participants having adolescent MDD with NSSI; suicide attempters had higher Barratt Impulsiveness Scale (BIS-11) impulsivity scores and lower serum CRP and cortisol levels than those having MDD with NSSI alone, suggesting levels of cortisol and CRP were inversely correlated with SAs in patients with adolescent MDD with NSSI. Furthermore, multivariate regression analysis revealed that NSSI frequency in the last month and CRP levels were suicidal ideation predictors in adolescent MDD with NSSI, which may indicate that the increased frequency of NSSI behavior is a potential risk factor for suicide. Additionally, we explored the correlation between psychological and blood biochemical indicators to distinguish suicide attempters among participants having adolescent MDD with NSSI and identified a unique correlation network that could serve as a marker for suicide attempters. Our research data further suggested a complex correlation between the psychological and behavioral indicators of impulsivity and anger. Therefore, our study findings may provide clues to identify good clinical warning signs for SA in patients with adolescent MDD with NSSI.


Assuntos
Transtorno Depressivo Maior , Comportamento Autodestrutivo , Adolescente , Humanos , Tentativa de Suicídio , Hidrocortisona , Ira
19.
PLoS One ; 19(3): e0295224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451991

RESUMO

BACKGROUND: We conducted a clinic-based cross-sectional survey among 710 people living with HIV/AIDS in stable 'sexual' relationships in central and southwestern Uganda. Although sexual function is rarely discussed due to the private nature of sexual life. Yet, sexual problems may predispose to negative health and social outcomes including marital conflict. Among individuals living with HIV/AIDS, sexual function and dysfunction have hardly been studied especially in sub-Saharan Africa. In this study, we aimed to determine the nature, prevalence and factors associated with sexual dysfunction (SD) among people living with HIV/AIDS (PLWHA) in Uganda. METHODS: We conducted a clinic based cross sectional survey among 710 PLWHA in stable 'sexual' relationships in central region and southwestern Uganda. We collected data on socio-demographic characteristics (age, highest educational attainment, religion, food security, employment, income level, marital status and socio-economic status); psychiatric problems (major depressive disorder, suicidality and HIV-related neurocognitive impairment); psychosocial factors (maladaptive coping styles, negative life events, social support, resilience, HIV stigma); and clinical factors (CD4 counts, body weight, height, HIV clinical stage, treatment adherence). RESULTS: Sexual dysfunction (SD) was more prevalent in women (38.7%) than men (17.6%) and majority (89.3% of men and 66.3% of women) did not seek help for the SD. Among men, being of a religion other than Christianity was significantly associated with SD (OR = 5.30, 95%CI 1.60-17.51, p = 0.006). Among women, older age (> 45 years) (OR = 2.96, 95%CI 1.82-4.79, p<0.01), being widowed (OR = 1.80, 95%CI 1.03-3.12, p = 0.051) or being separated from the spouse (OR = 1.69, 95% CI 1.09-2.59, p = 0.051) were significantly associated with SD. Depressive symptoms were significantly associated with SD in both men (OR = 0.27, 95%CI 0.74-0.99) and women (OR = 1.61, 95%CI 1.04-2.48, p = 0.032). In women, high CD4 count (OR = 1.42, 95% CI 1-2.01, p = 0.05) was associated with SD. CONCLUSION: Sexual dysfunction has considerable prevalence among PLWHA in Uganda. It is associated with socio-demographic, psychiatric and clinical illness factors. To further improve the quality of life of PLWHA, they should be screened for sexual dysfunction as part of routine assessment.


Assuntos
Síndrome de Imunodeficiência Adquirida , Transtorno Depressivo Maior , Infecções por HIV , Masculino , Humanos , Feminino , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Uganda/epidemiologia , Prevalência , Qualidade de Vida
20.
BMC Med Inform Decis Mak ; 24(1): 68, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459459

RESUMO

BACKGROUND: To discover pharmacotherapy prescription patterns and their statistical associations with outcomes through a clinical pathway inference framework applied to real-world data. METHODS: We apply machine learning steps in our framework using a 2006 to 2020 cohort of veterans with major depressive disorder (MDD). Outpatient antidepressant pharmacy fills, dispensed inpatient antidepressant medications, emergency department visits, self-harm, and all-cause mortality data were extracted from the Department of Veterans Affairs Corporate Data Warehouse. RESULTS: Our MDD cohort consisted of 252,179 individuals. During the study period there were 98,417 emergency department visits, 1,016 cases of self-harm, and 1,507 deaths from all causes. The top ten prescription patterns accounted for 69.3% of the data for individuals starting antidepressants at the fluoxetine equivalent of 20-39 mg. Additionally, we found associations between outcomes and dosage change. CONCLUSIONS: For 252,179 Veterans who served in Iraq and Afghanistan with subsequent MDD noted in their electronic medical records, we documented and described the major pharmacotherapy prescription patterns implemented by Veterans Health Administration providers. Ten patterns accounted for almost 70% of the data. Associations between antidepressant usage and outcomes in observational data may be confounded. The low numbers of adverse events, especially those associated with all-cause mortality, make our calculations imprecise. Furthermore, our outcomes are also indications for both disease and treatment. Despite these limitations, we demonstrate the usefulness of our framework in providing operational insight into clinical practice, and our results underscore the need for increased monitoring during critical points of treatment.


Assuntos
Transtorno Depressivo Maior , Veteranos , Humanos , Transtorno Depressivo Maior/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...