RESUMEN
BACKGROUND: The prevalence of major depressive disorder (MDD) poses significant global health challenges, with available treatments often insufficient in achieving remission for many patients. Digital health technologies, such as SMS text messaging-based cognitive behavioral therapy, offer accessible alternatives but may not reach all individuals. Email communication presents a secure avenue for health communication, yet its effectiveness compared to SMS text messaging in providing mental health support for patients with MDD remains uncertain. OBJECTIVE: This study aims to compare the efficacy of email versus SMS text messaging as delivery platforms for supporting patients with MDD, addressing a critical gap in understanding optimal digital interventions for mental health care. METHODS: A randomized noninferiority pilot trial was conducted, comparing outcomes for patients receiving 6-week daily supportive messages via email with those receiving messages via SMS text message. This duration corresponds to a minimum of 180 days of message delivery. The supportive messages maintained consistent length and structure across both delivery methods. Participants (N=66) were recruited from the Access 24/7 clinic in Edmonton, Alberta, among those who were diagnosed with MDD. The outcomes were measured at baseline and 6 months after enrollment using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the World Health Organization Well-Being Index (WHO-5). RESULTS: Most of the participants were females (n=43, 65%), aged between 26 and 40 years (n=34, 55%), had high school education (n=35, 58%), employed (n=33, 50%), and single (n=24, 36%). Again, most participants had had no history of any major physical illness (n=56, 85%) and (n=61, 92%) responded "No" to having a history of admission for treatment of mood disorders. There was no statistically significant difference in the mean changes in PHQ-9, GAD-7, and WHO-5 scores between the email and SMS text messaging groups (mean difference, 95% CI: -1.90, 95% CI -6.53 to 2.74; 5.78, 95% CI -1.94 to 13.50; and 11.85, 95% CI -3.81 to 27.51), respectively. Both supportive modalities showed potential in reducing depressive symptoms and improving quality of life. CONCLUSIONS: The study's findings suggest that both email and SMS text messaging interventions have equivalent effectiveness in reducing depression symptoms among individuals with MDD. As digital technology continues to evolve, harnessing the power of multiple digital platforms for mental health interventions can significantly contribute to bridging the existing treatment gaps and improving the overall well-being of individuals with depressive conditions. Further research is needed with a larger sample size to confirm and expand upon these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04638231; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552095/.
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Trastorno Depresivo Mayor , Correo Electrónico , Envío de Mensajes de Texto , Humanos , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/psicología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Since the birth of cognitive science, researchers have used reaction time and accuracy to measure cognitive ability. Although recognition of these two measures is often based on empirical observations, the underlying consensus is that most cognitive behaviors may be along two fundamental dimensions: cognitive processing speed (CPS) and cognitive processing accuracy (CPA). In this study, we used genomic-wide association studies (GWAS) data from 14 cognitive traits to show the presence of those two factors and revealed the specific neurobiological basis underlying them. We identified that CPS and CPA had distinct brain phenotypes (e.g. white matter microstructure), neurobiological bases (e.g. postsynaptic membrane), and developmental periods (i.e. late infancy). Moreover, those two factors showed differential associations with other health-related traits such as screen exposure and sleep status, and a significant causal relationship with psychiatric disorders such as major depressive disorder and schizophrenia. Utilizing an independent cohort from the Adolescent Brain Cognitive Development (ABCD) study, we also uncovered the distinct contributions of those two factors on the cognitive development of young adolescents. These findings reveal two fundamental factors underlying various cognitive abilities, elucidate the distinct brain structural fingerprint and genetic architecture of CPS and CPA, and hint at the complex interrelationship between cognitive ability, lifestyle, and mental health.
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Encéfalo , Cognición , Estudio de Asociación del Genoma Completo , Fenotipo , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Cognición/fisiología , Adolescente , Femenino , Masculino , Tiempo de Reacción/genética , Niño , Esquizofrenia/genética , Trastorno Depresivo Mayor/genética , Polimorfismo de Nucleótido Simple , Velocidad de ProcesamientoRESUMEN
Following on from our pilot studies, this study aimed to test the efficacy of a combination of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus), magnesium orotate and coenzyme 10 for the treatment of major depressive disorder (MDD) through a double-blind placebo controlled clinical trial. The participants were 120 adults diagnosed with MDD randomised to daily oral administration, over 8 weeks, of either the intervention or placebo, with a 16-week follow-up period. Intent-to-treat analysis found a significantly lower frequency of the presence of a major depressive episode in the intervention group compared with placebo at the end of the 8-week treatment phase, with no difference between the two conditions at 8-week follow-up. Both the categorical and continuous measure of depressive symptoms showed a significant difference between the two conditions at 4 weeks, but not 8 and 16 weeks. The secondary end-point was demonstrated with an overall reduction in self-rated symptoms of anxiety and stress in the active treatment group compared with placebo. These findings suggest that the combination of probiotics, magnesium orotate and coenzyme 10 may be an effective treatment of MDD over an 8-week period.
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Trastorno Depresivo Mayor , Probióticos , Humanos , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/terapia , Masculino , Femenino , Adulto , Método Doble Ciego , Persona de Mediana Edad , Resultado del Tratamiento , Lactobacillus acidophilus , Bifidobacterium bifidum , Streptococcus thermophilusRESUMEN
BACKGROUND: Depression is widely recognized as a common non-motor symptom of Parkinson's disease (PD). Across different studies, the reported prevalence of depression in PD varies widely, ranging from 2.7% to 90%, but it is unclear whether this association is due to genetic or acquired factors. Whether there is a causal relationship remains unknown. The aim of this study was to use a two-sample Mendelian randomization (MR) approach to investigate the causal effect of PD on depression. METHODS: Analyses were conducted separately for individuals of European and East Asian ancestry using publicly available summary data from genome-wide association studies. Depression was divided into two categories: ever depressed for a whole week and major depressive disorder (MDD). PD data were used as the exposure and were obtained from the International Parkinson's Disease Genomics Consortium and the BioBank Japan PheWeb, while depression data were used as the outcome and were obtained from the ntegrative Epidemiology Unit (IEU) Open GWAS Project(A public GWAS databaseï¼ and the Psychiatric Genomics Consortium. The influence of PD on depression was assessed using inverse variance weighted (IVW), weighted median, MR-Egger, and weighted mode methods. Heterogeneity and pleiotropy were tested, and the results were validated using FinnGen GWAS data from version R9. RESULTS: In individuals of European ancestry, there was a causal relationship between PD and ever depressed for a whole week (IVW method, odds ratio [OR] = 0.990; 95% CI, 0.984-0.996; p = .002), but no causal relationship was observed between PD and MDD (IVW method, OR = 0.974; 95% CI, 0.942-1.009; p = .141). In individuals of East Asian ancestry, no causal relationship was observed between PD and ever depressed for a whole week (IVW method, OR = 1.001; 95% CI, 0.829-1.209; p = .990) and between PD and MDD (IVW method, OR = 1.017; 95% CI, 0.982-1.052; p = .342). The results of the three additional analysis methods were similar to those of the IVW method, and there was no heterogeneity according to Cochran's Q-test. There was no evidence of pleiotropy based on MR-Egger intercept test and MR-PRESSO. The FinnGen validation dataset supported these findings. The results are stable and reliable. CONCLUSION: The observed increase in depression among PD patients could potentially be attributed to modifiable acquired factors. Consequently, there is an urgent need to strengthen the management of PD patients in order to prevent the development of depression in the future.
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Pueblo Asiatico , Trastorno Depresivo Mayor , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/epidemiología , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Pueblo Asiatico/genética , Población Blanca/genética , Depresión/genética , Depresión/epidemiología , Predisposición Genética a la EnfermedadRESUMEN
Background: Extensive observational evidence has suggested an association between depression and type 2 diabetes (T2D). However, the causal relationships between these two diseases require further investigation. This study aimed to evaluate the bidirectional causal effect between two types of depression and T2D using two-sample Mendelian randomization (MR). Methods: We applied two-step MR techniques, using single-nucleotide polymorphisms (SNPs) as the genetic instruments for analysis. We utilized summary data from genome-wide association studies (GWASs) for major depression (MD), depressive status (frequency of depressed mood in the last two weeks), T2D, and other known T2D risk factors such as obesity, sedentary behavior (time spent watching television), and blood pressure. The analysis utilized inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, MR pleiotropy residual sum, and outlier methods to determine potential causal relationships. Results: The study found that MD was positively associated with T2D, with an odds ratio (OR) of 1.26 (95% CI: 1.10-1.43, p = 5.6×10-4) using the IVW method and an OR of 1.21 (95% CI: 1.04-1.41, p = 0.01) using the weighted median method. Depressive status was also positively associated with T2D, with an OR of 2.26 (95% CI: 1.03-4.94, p = 0.04) and an OR of 3.62 (95% CI: 1.33-9.90, p = 0.01) using the IVW and weighted median methods, respectively. No causal effects of MD and depressive status on T2D risk factors were observed, and T2D did not influence these factors. Conclusion: Our study demonstrates a causal relationship between depression and an increased risk of developing T2D, with both major depression and depressive status being positively associated with T2D.
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Diabetes Mellitus Tipo 2 , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiología , Factores de Riesgo , Depresión/genética , Depresión/epidemiología , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Predisposición Genética a la EnfermedadRESUMEN
Fibromyalgia (FM) affects 2% to 8% of the general population. FM patients often experience self-stigma and feel rejected by healthcare providers and families, resulting in isolation and distressing symptoms of pain, fatigue, and poor cognitive functioning, increasing the risk of depressive symptoms. Major Depressive Disorder (MDD) is the most common comorbidity in FM patients (Any depression: 43%; MDD: 32%). Genome-wide association studies (GWAS) have identified a common genetic risk loci for major depression and fibromyalgia. Given that even minor symptoms of depression worsen the outcomes of FM patients, clinicians are challenged to identify and manage depression in these patients. However, due to overlapping symptoms, limited screening, and contamination bias, MDD often goes undiagnosed and presents a critical challenge. Unrecognized and untreated MDD in FM patients can exacerbate fatigue, sleep disturbances, and pain, reduce physical functioning, and increase the risk of developing comorbid conditions, such as substance abuse and cardiovascular disease. These comorbidities are associated with a lower treatment response rate, a higher dropout rate, and a greater risk of relapse. Clinicians may effectively identify and treat MDD in FM patients with appropriate pharmacologic agents combined with aerobic exercise and cognitive-behavioral therapies for core FM symptoms, thus significantly reducing symptom severity for both MDD and FM. Such a comprehensive approach will result in a much-improved quality of life. MedLine content was searched via PubMed to identify eligible articles between 1995 and 2023 using search terms fibromyalgia, major depressive disorder, and treatment of depression in fibromyalgia, and the most current information is presented. In this primer for clinicians caring for FM patients, we describe clinically relevant pharmacologic and non-pharmacologic management approaches for treating MDD in FM patients.
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Trastorno Depresivo Mayor , Fibromialgia , Humanos , Fibromialgia/terapia , Fibromialgia/psicología , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/etiología , Terapia Cognitivo-Conductual/métodos , Comorbilidad , Antidepresivos/uso terapéuticoRESUMEN
BACKGROUND: Major depressive disorder (MDD) is characterized by hippocampal volume reduction, impacting cognitive function. Inflammation, particularly elevated tumor necrosis factor-alpha (TNF-α) levels, is consistently implicated in MDD pathophysiology. This study investigates the relationships between TNF-α levels, hippocampal volume, beta-amyloid (Aß) burden, and cognitive abilities in MDD patients, aiming to illuminate the complex interplay among inflammatory markers, pathology indicators, structural brain alterations, and cognitive performance in non-demented MDD individuals. METHOD: Fifty-two non-demented MDD patients, comprising 25 with mild cognitive impairment (MCI), were recruited along with 10 control subjects. Each participant underwent a thorough assessment encompassing TNF-α blood testing, 18F-florbetapir positron emission tomography, magnetic resonance imaging scans, and neuropsychological testing. Statistical analyses, adjusted for age and education, were performed to investigate the associations between TNF-α levels, adjusted hippocampal volume (HVa), global Aß burden, and cognitive performance. RESULTS: MCI MDD patients displayed elevated TNF-α levels and reduced HVa relative to controls. Correlation analyses demonstrated inverse relationships between TNF-α level and HVa in MCI MDD, all MDD, and all subjects groups. Both TNF-α level and HVa exhibited significant correlations with processing speed across all MDD and all subjects. Notably, global 18F-florbetapir standardized uptake value ratio did not exhibit significant correlations with TNF-α level, HVa, and cognitive measures. CONCLUSION: This study highlights elevated TNF-α levels and reduced hippocampal volume in MCI MDD patients, indicating a potential association between peripheral inflammation and structural brain alterations in depression. Furthermore, our results suggest that certain cases of MDD may be affected by non-amyloid-mediated process, which impacts their TNF-α and hippocampal volume. These findings emphasize the importance of further investigating the complex interplay among inflammation, neurodegeneration, and cognitive function in MDD.
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Péptidos beta-Amiloides , Atrofia , Disfunción Cognitiva , Trastorno Depresivo Mayor , Hipocampo , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Factor de Necrosis Tumoral alfa , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/patología , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/metabolismo , Masculino , Femenino , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Anciano , Péptidos beta-Amiloides/metabolismo , Atrofia/patología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Persona de Mediana Edad , Pruebas Neuropsicológicas , Compuestos de Anilina , Glicoles de EtilenoRESUMEN
Objective: Major depressive disorder (MDD) is a common psychiatric disorder for which pharmacologic standard-of-care treatments have limited efficacy, particularly among individuals with cognitive dysfunction. Cognitive dysfunction is observed in approximately 25%-50% of those with MDD, wherein response to standard-of-care medications is reduced. Vortioxetine is an approved antidepressant that has shown evidence of procognitive effects in patients. It is not known if it has greater clinical efficacy in MDD patients with cognitive dysfunction, a more difficult to treat population, than other antidepressants.Methods: This study was a reanalysis of 1,812 subjects with MDD across 4 placebo controlled trials. Baseline cognition was measured by the Digit Symbol Substitution Test (DSST), the primary measure used to demonstrate vortioxetine's procognitive effects in clinical studies. Analyses examined whether baseline cognitive function was associated with differences in treatment outcomes.Results: Baseline DSST did not predict placebo-adjusted treatment effects of vortioxetine on depressive symptoms (pooled Cohen d = -0.02, 95% CI = -0.12 to 0.07). Analyses of additional cognitive measures similarly did not predict placebo-adjusted treatment effects on depression (all 95% CI contained zero). Finally, analyses of trials with selective serotonin reuptake inhibitors (SSRIs)/serotonin and norepinephrine reuptake inhibitors (SNRIs) as active comparators also revealed no prediction of SSRI/SNRI adjusted treatment effects of vortioxetine on depression.Conclusions: These findings, taken together, suggest that cognitive function does not moderate depression outcomes in vortioxetine, with results comparable to other antidepressants.
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Trastorno Depresivo Mayor , Vortioxetina , Humanos , Vortioxetina/uso terapéutico , Vortioxetina/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico , Adulto , Masculino , Femenino , Persona de Mediana Edad , Antidepresivos/uso terapéutico , Resultado del Tratamiento , Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
BACKGROUND: Non-suicidal self-injury (NSSI) is a significant public health concern among adolescents with major depressive disorders (MDD). Although previous research has linked child maltreatment (CM) to NSSI, the precise mechanisms remain unclear. This study aims to investigate the association between CM, cognitive reappraisal (CR), negative coping styles (NC) and NSSI in adolescents with MDD, from the perspectives of both Latent Variable Theory and the Network Theory of Mental Disorder. METHODS: A sample of 651 adolescents with MDD was recruited from January to December 2023. Data on CM, CR, NC, and NSSI were collected through paper-based self-reported questionnaires. Data analysis primarily involved structural equation modeling and network analysis. RESULTS: The reporting rate of NSSI among adolescents with MDD was 48.2%. CM showed a significant positive correlation with NSSI. NSSI was affected by CM through three paths: the mediating role of CR, the mediating role of NC, and the chain mediating role of both CR and NC. Emotional abuse (EA) was the central node, while NSSI, EA, and "The urge to cry quietly when faced with troubles"(NC10) were the key bridge nodes. CONCLUSIONS: This study is the first to use both structural equation modeling and network analysis to explore the explore the relationship between CM, CR, NC, and NSSI in adolescents with MDD, providing a theoretical basis for future early prevention and targeted interventions for adolescents with MDD.
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Adaptación Psicológica , Maltrato a los Niños , Trastorno Depresivo Mayor , Conducta Autodestructiva , Humanos , Adolescente , Trastorno Depresivo Mayor/psicología , Conducta Autodestructiva/psicología , Maltrato a los Niños/psicología , Masculino , Femenino , Niño , Cognición/fisiologíaRESUMEN
OBJECTIVE: To collect evidence on the possibility that patients with depression experience self-stigmatization based on label information for medications. METHODS: We developed a discrete-choice experiment (DCE) survey instrument that asked respondents to make choices between hypothetical treatments for major depressive disorder (MDD). We also included treatment type (antidepressants versus antipsychotics) and approved indications for the medication. The choice questions mimicked the information presented in product inserts and required systematic tradeoffs between treatment efficacy, treatment type, and indication. We calculated how many patients were willing to forgo efficacy to avoid treatments with information associated with self-stigmatization, and how much efficacy they were willing to forgo. We also evaluated the impact of contextualizing the treatment information to reduce self-stigmatization by randomizing respondents who received additional context. RESULTS: A total of 501 patients with MDD were recruited to complete the DCE survey. Respondents had well-defined preferences for treatment outcomes. Over 60% (63.4%) of respondents were found to be significantly affected by treatment indication. These respondents were willing to forgo about 2.5 percentage points in the chance of treatment efficacy to avoid treatments indicated for schizophrenia. We also find that some level of contextualization of the treatment details could help reduce the negative impact of treatment type and indications. CONCLUSIONS: Product-label treatment indication can potentially lead to patient self-stigmatization as shown by patients' avoidance of treatments that are also used to treat schizophrenia. While the effect appears to be relatively small, results suggests that the issue is likely pervasive.
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Antidepresivos , Conducta de Elección , Trastorno Depresivo Mayor , Prioridad del Paciente , Humanos , Masculino , Femenino , Antidepresivos/uso terapéutico , Adulto , Persona de Mediana Edad , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Prioridad del Paciente/psicología , Encuestas y Cuestionarios , Etiquetado de Medicamentos , Estereotipo , Antipsicóticos/uso terapéutico , Resultado del Tratamiento , Anciano , Estigma SocialRESUMEN
Major depressive disorder (MDD) is a severe psychiatric condition that significantly impacts the overall quality of life. Although MDD can occur across all age groups, it is notably prevalent among older individuals, with the aggravating circumstance that the clinical condition is frequently overlooked and undertreated. Furthermore, older adults often encounter resistance to standard treatments, experience adverse events, and face challenges associated with polypharmacy. Given that late-life MDD is associated with heightened rates of disability and mortality, as well as imposing a significant economic and logistical burden on healthcare systems, it becomes imperative to explore novel therapeutic approaches. These could serve as either supplements to standard guidelines or alternatives for non-responsive patients, potentially enhancing the management of geriatric MDD patients. This review aims to delve into the potential of microRNAs targeting Brain-Derived Neurotrophic Factor (BDNF). In MDD, a significant decrease in both central and peripheral BDNF has been well-documented, raising implications for therapy response. Notably, BDNF appears to be a key player in the intricate interplay between microRNA-induced neuroplasticity deficits and neuroinflammation, both processes deeply implicated in the onset and progression of the disease. Special emphasis is placed on delivery methods, with a comprehensive comparison of the strengths and weaknesses of each proposed approach. Our hypothesis proposes that employing multiple microRNAs concurrently, with the ability to directly influence BDNF and activate closely associated pathways, may represent the most promising strategy. Regarding vehicles, although the perfect nanoparticle remains elusive, considering the trade-offs, liposomes emerge as the most suitable option.
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Factor Neurotrófico Derivado del Encéfalo , Trastorno Depresivo Mayor , MicroARNs , Humanos , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/metabolismo , MicroARNs/genética , Anciano , Encéfalo/metabolismo , Edad de InicioRESUMEN
Real-time fMRI neurofeedback (rtfMRI-NF) has emerged as a promising intervention for psychiatric disorders, yet its clinical efficacy remains underexplored due to an incomplete mechanistic understanding. This study aimed to delineate the whole-brain mechanisms underpinning the effects of rtfMRI-NF on repetitive negative thinking in depression. In a double-blind randomized controlled trial, forty-three depressed individuals underwent NF training targeting the functional connectivity (FC) between the posterior cingulate cortex and the right temporoparietal junction, linked to rumination severity. Participants were randomly assigned to active or sham groups, with the sham group receiving synthesized feedback mimicking real NF signal patterns. The active group demonstrated a significant reduction in brooding rumination scores (d = -1.52, p < 0.001), whereas the sham group did not (d = -0.23, p = 0.503). While the target FC did not show discernible training effects or group differences, connectome-based predictive modeling (CPM) analysis revealed that the interaction between brain activity during regulation and brain response to the feedback signal was the critical factor in explaining treatment outcomes. The model incorporating this interaction successfully predicted rumination changes across both groups. The FCs significantly contributing to the prediction were distributed across brain regions, notably the frontal control, salience network, and subcortical reward processing areas. These results underscore the importance of considering the interplay between brain regulation activities and brain response to the feedback signal in understanding the therapeutic mechanisms of rtfMRI-NF. The study affirms rtfMRI-NF's potential as a therapeutic intervention for repetitive negative thinking and highlights the need for a nuanced understanding of the whole-brain mechanisms contributing to its efficacy.
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Conectoma , Imagen por Resonancia Magnética , Neurorretroalimentación , Humanos , Neurorretroalimentación/métodos , Femenino , Masculino , Adulto , Método Doble Ciego , Rumiación Cognitiva/fisiología , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/diagnóstico por imagen , Adulto Joven , Persona de Mediana Edad , Pesimismo , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Resultado del TratamientoRESUMEN
BACKGROUND: Increasing evidences suggest that nonalcoholic fatty liver disease (NAFLD) is associated with neuropsychiatric disorders. Nevertheless, whether there were causal associations between them remained vague. A causal association between neuropsychiatric disorders and NAFLD was investigated in this study. METHODS: We assessed the published genome-wide association study summary statistics for NAFLD, seven mental disorder-related diseases and six central nervous system dysfunction-related diseases. The causal relationships were first assessed using two-sample and multivariable Mendelian randomization (MR). Then, sensitivity analyses were performed, followed by a reverse MR analysis to determine whether reverse causality is possible. Finally, we performed replication analyses and combined the findings from the above studies. RESULTS: Our meta-analysis results showed NAFLD significantly increased the risk of anxiety disorders (OR = 1.016, 95% CI = 1.010-1.021, P value < 0.0001). In addition, major depressive disorder was the potential risk factor for NAFLD (OR = 1.233, 95% CI = 1.063-1.430, P value = 0.006). Multivariable MR analysis showed that the causal effect of major depressive disorder on NAFLD remained significant after considering body mass index, but the association disappeared after adjusting for the effect of waist circumference. Furthermore, other neuropsychiatric disorders and NAFLD were not found to be causally related. CONCLUSIONS: These results implied causal relationships of NAFLD with anxiety disorders and Major Depressive Disorder. This study highlighted the need to recognize and understand the connection between neuropsychiatric disorders and NAFLD to prevent the development of related diseases.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Mentales , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Trastornos Mentales/genética , Trastornos Mentales/epidemiología , Factores de Riesgo , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Causalidad , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/genéticaRESUMEN
BACKGROUND: Depression is a highly prevalent and often recurrent condition; however, treatment is not always accessible or effective in addressing abnormalities in emotional processing. Given the high prevalence of depression worldwide, identifying and mapping out effective and sustainable interventions is crucial. Emotion dysregulation in depression is not readily amenable to improvement due to the complex, time-dynamic nature of emotion; however, systematic planning frameworks for programs addressing behavioral changes can provide guidelines for the development of a rational intervention that tackles these difficulties. This study proposes an empirical and theoretical art-based emotion regulation (ER) intervention using an integrated approach that combines intervention mapping (IM) with participatory action research (PAR). METHODS: We used the IM protocol to identify strategies and develop an intervention for patients with major depressive disorder (MDD). As applied in this study, IM comprises six steps: (a) determining the need for new treatments and determinants of risk; (b) identifying changeable determinants and assigning specific intervention targets; (c) selecting strategies to improve ER across relevant theories and research disciplines; (d) creating a treatment program and refining it based on consultations with an advisory group; (e) developing the implementation plan and conducting a PAR study to pilot-test it; and (f) planning evaluation strategies and conducting a PAR study for feedback on the initial testing. RESULTS: Following the steps of IM, we developed two frameworks for an art-based ER intervention: an individual and an integrative framework. The programs include four theory- and evidence-based ER strategies aimed mainly at decreasing depressive symptoms and improving ER in patients with MDD. We also developed a plan for evaluating the proposed intervention. Based on our preliminary PAR studies, the intervention was feasible and acceptable for adoption and implementation in primary care settings. CONCLUSION: The application of IM incorporated with PAR has resulted in an intervention for improving ER in depression. While changing behavior is perceived as a challenging and elaborate task, this method can be useful in offering a clear structure for developing rational interventions. Further refinement is necessary through rigorous research.
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Trastorno Depresivo Mayor , Regulación Emocional , Humanos , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/psicología , Investigación sobre Servicios de Salud , Investigación Participativa Basada en la ComunidadRESUMEN
OBJECTIVE: Whether selective serotonin reuptake inhibitors (SSRI) increase suicide risk, especially in young adults, is still a controversial issue. This study aimed to examine the change in impulsivity characteristics and to evaluate the relationship between impulsivity and suicidality in young adults with major depression who were started on SSRIs. METHOD: The study included 50 patients between the ages of 18-24 years with a diagnosis of major depression who were planned to start SSRIs. Participants were evaluated with the Beck Depression Scale, Beck Anxiety Scale, Young Mania Rating Scale, Columbia Suicide Severity Rating Scale, Barratt Impulsivity Scale, Daily Impulsivity Scale (DIS), and Go/ No-Go Task (GNG) before and at the end of the first week of treatment. RESULTS: Seventy percent of the patients (n: 35) completed the assessments at baseline and at the end of the first week. At the end of one-week there was a statistically significant decrease in the DIS (t=2.283, p=0.029) and commission errors in GNG (t=3.19, p=0.003). In addition, 7 out of 11 patients who had suicidal ideation at the first evaluation did not continue to have suicidal ideation at the end of the first week and there was a significant decrease in the severity of suicidal ideation at the end of the follow-up (W:132.0, p<0.001). CONCLUSION: One-week SSRI use in young adults resulted in a decrease in impulsivity in self-report scales assessing state impulsivity and in the GNG. It was observed that the severity of suicidal ideation decreased at the end of the one-week treatment period.
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Trastorno Depresivo Mayor , Conducta Impulsiva , Escalas de Valoración Psiquiátrica , Inhibidores Selectivos de la Recaptación de Serotonina , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Masculino , Conducta Impulsiva/efectos de los fármacos , Femenino , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Adulto Joven , Adolescente , Ideación Suicida , AdultoRESUMEN
Purpose: To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels. Patients and Methods: Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs. Results: After false discovery rate correction, patients with MDD exhibited higher CD81 levels (P FDR = 0.040) and lower BDNF levels (P FDR = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 (P FDR = 0.002) and Alix (P FDR = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased (P FDR = 0.046), while BDNF levels normalized to CD81 increased (P FDR = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma (ρ=0.117, P = 0.334). Conclusion: This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers.
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Astrocitos , Biomarcadores , Factor Neurotrófico Derivado del Encéfalo , Trastorno Depresivo Mayor , Vesículas Extracelulares , Plasticidad Neuronal , Humanos , Factor Neurotrófico Derivado del Encéfalo/sangre , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Masculino , Femenino , Plasticidad Neuronal/fisiología , Adulto , Persona de Mediana Edad , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/metabolismo , Biomarcadores/sangre , Astrocitos/metabolismo , Tetraspanina 28/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Estudios de Casos y Controles , Proteínas de Unión al Calcio , Proteínas de Ciclo Celular , Complejos de Clasificación Endosomal Requeridos para el TransporteRESUMEN
BACKGROUND: Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. METHODS: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. RESULTS: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. CONCLUSIONS: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.
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Contaminación del Aire , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Estudios Transversales , Contaminación del Aire/efectos adversos , Adulto , Adulto Joven , Predisposición Genética a la Enfermedad , Material Particulado/efectos adversos , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/fisiopatología , Lóbulo Parietal/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Beijing , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/fisiopatología , Velocidad de ProcesamientoRESUMEN
BACKGROUND: Current models of major depressive disorder (MDD) primarily focus on the structural and functional changes in key prefrontal areas responsible for emotional regulation. Among these regions some sections such as the dorsal prefrontal area, has received limited attention regarding its structural abnormalities in MDD. This study aims to evaluate volumetric abnormalities in brain regions associated with markers of depression severity and episode frequency. METHODS: The study included 33 MDD patients and 33 healthy subjects. Using an atlas-based method, we measured the volumes of several key brain regions based on MRI data. The regions of interest included prefrontal and posterior sections of the middle frontal gyrus (MFG) and superior frontal gyrus (SFG). Additionally, we evaluated the volumes of the dorsal anterior cingulate cortex (dACC), perigenual (rostral) anterior cingulate cortex (pgACC), subgenual cingulate cortex (sgACC), posterior cingulate cortex (PCC), hippocampus (HPC), and parahippocampus (paraHPC). Hamilton Depression Scale (HAM-D) scores and count of the depressive episodes of patients were also obtained. A regression analysis with sex as the confounding factor has been made. RESULTS: Analysis of covariances, controlling for sex, showed significant atrophy in the sgACC in the depression group: F(1, 63) = 4.013, p = 0.049 (left) and F(1, 63) = 8.786, p < 0.004 (right). Poisson regression, also controlling for sex, found that each additional depressive episode was associated with a significant reduction in left posterior MFG volume (0.952 times, 95 % CI, 0.906 to 1.000; p = 0.049). CONCLUSIONS: Findings in this study highlight the structural abnormalities in MDD patients in correlation to either current depression severity or chronicity of the disease.
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Atrofia , Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Corteza Prefrontal , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Trastorno Depresivo Mayor/psicología , Masculino , Femenino , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Adulto , Atrofia/patología , Persona de Mediana Edad , Atlas como Asunto , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Major Depressive Disorder (MDD), as a chronic mental disorder, causes changes in mood, thoughts, and behavior. The pathophysiology of the disorder and its treatment are still unknown. One of the most notable changes observed in patients with MDD through fMRI is abnormal functional brain connectivity. METHODS: Preprocessed data from 60 MDD patients and 60 normal controls (NCs) were selected, which has been performed using the DPARSF toolbox. The whole-brain functional networks and topologies were extracted using graph theory-based methods. A two-sample, two-tailed t-test was used to compare the topological features of functional brain networks between the MDD and NCs groups using the DPABI-Net/Statistical Analysis toolbox. RESULTS: The obtained results showed a decrease in both global and local efficiency in MDD patients compared to NCs, and specifically, MDD patients showed significantly higher path length values. Acceptable p-values were obtained with a small sample size and less computational volume compared to the other studies on large datasets. At the node level, MDD patients showed decreased and relatively decreased node degrees in the sensorimotor network (SMN) and the dorsal attention network (DAN), respectively, as well as decreased node efficiency in the SMN, default mode network (DMN), and DAN. Also, MDD patients showed slightly decreased node efficiency in the visual networks (VN) and the ventral attention network (VAN), which were reported after FDR correction with Q < 0.05. LIMITATIONS: All participants were Chinese. CONCLUSIONS: Collectively, increased path length, decreased global and local efficiency, and also decreased nodal degree and efficiency in the SMN, DAN, DAN, VN, and VAN were found in patients compared to NCs.
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Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Red Nerviosa , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/fisiopatología , Imagen por Resonancia Magnética/métodos , Femenino , Adulto , Masculino , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Persona de Mediana Edad , Conectoma/métodos , Adulto JovenRESUMEN
Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD.