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Background: Family caregivers of persons living with dementia often experience increased depression and suicidal ideation (SI). However, the feasibility and impact of therapies on caregiver SI has remained largely unexplored. Mentalizing imagery therapy (MIT) helps reduce psychological symptoms through mindfulness and guided imagery. This pilot study examined the feasibility of participation by caregivers with SI in a randomized controlled trial (RCT) of MIT versus a psychosocial support group (SG), and the respective impact of group on SI, depression, and secondary outcomes. Methods: A secondary analysis of data from an RCT of 4-week MIT or SG for caregivers (n = 46) was performed, identifying SI (n = 23) and non-SI (n = 23) cohorts. Group attendance and home practice were compared between cohorts. In the SI cohort (total n = 23, MIT n = 11, SG n = 12), group differences in SI, depression, and secondary outcomes were evaluated post-group and at 4-month follow-up. Results: Attendance in both groups and home practice in MIT were similar between SI and non-SI cohorts. In the SI cohort, MIT evinced greater improvements relative to SG in SI (p=.02) and depression (p=.02) post-group, and other secondary outcomes at follow-up. Limitations: Limitations include small sample size and single-item assessments of SI from validated depression rating scales. Conclusions: Participation in an RCT was feasible for caregivers with SI. MIT resulted in important benefits for SI and depression, while SG showed no acute SI benefit. The role of MIT in improving SI should be confirmed with adequately powered trials, as effective therapies to address caregiver SI are critical.
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Objective: To evaluate feasibility, acceptability, and preliminary efficacy of heated yoga to treat moderate-to-severe depression.Design: An 8-week randomized controlled trial (RCT) of heated yoga versus waitlist control was conducted from March 2017 to August 2019.Methods: Participants in the yoga condition were asked to attend heated yoga classes at 2 community heated yoga studios at least twice weekly. We assessed acceptability and feasibility using exit interview and attendance data, respectively. The primary intervention efficacy outcome variable was change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) score from baseline to post-intervention (week 8).Results: We randomized 80 participants and included 65 (mean [± SD] age 32.7 [± 11.7] years; 81.5% female) in the analyses (yoga n = 33, waitlist n = 32). The mean IDS-CR score at baseline was 35.6 (± 7.9) for the full sample, 36.9 (± 8.8) for yoga participants, and 34.4 (± 6.7) for waitlist participants. Participants attended an average of 10.3 (± 7.1) total classes over the 8-week intervention period. Yoga participants had a significantly greater pre- to post-intervention reduction in IDS-CR scores than waitlist participants (Cohen d = 1.04, P < .001). More yoga participants (59.3%; n = 16) than waitlist participants (6.3%; n = 2) evidenced larger treatment responses (IDS-CR ≥ 50% decrease in symptoms). Participants rated the heated yoga and its aftereffects positively in exit interviews.Conclusions: Approximately 1 heated yoga session per week (mean of 10.3 classes over 8 weeks) was associated with significantly greater reduction in depression symptoms than a waitlist control. Participants rated heated yoga positively. Taken together, results suggest feasibility, acceptability, and preliminary efficacy for patients with depression and warrant further research using active control conditions.Trial Registration: ClinicalTrials.gov identifier: NCT02607514.
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Depresión , Yoga , Adulto , Femenino , Humanos , Masculino , Depresión/terapiaRESUMEN
Spanish speaking family caregivers of people living with dementia have limited supportive resources in Spanish. There are few validated, culturally acceptable virtual interventions for reducing these caregivers' psychological distress. We investigated the feasibility of a Spanish language adaptation of a virtual Mentalizing Imagery Therapy (MIT) program, which provides guided imagery and mindfulness training to reduce depression, increase mentalizing, and promote well-being. 12 Spanish-speaking family dementia caregivers received a 4-week virtual MIT program. Follow-up was obtained post group and at 4 months post baseline assessment. Feasibility, acceptability, and satisfaction with MIT were assessed. The primary psychological outcome was depressive symptoms; secondary outcomes included caregiver burden, dispositional mindfulness, perceived stress, well-being, interpersonal support, and neurological quality of life. Statistical analysis was performed with mixed linear models. Caregivers were 52 ± 8 (mean ± SD) years of age. 60% had a high school education or less. Participation in weekly group meetings was 100%. Home practice was performed on average 4 ± 1 times per week [range 2-5]. Satisfaction with MIT reached 19 ± 2 of a possible 20 points. Reduction in depression from baseline was observed by week three (p = 0.01) and maintained at 4 month follow-up (p = 0.05). There were significant improvements in mindfulness post-group, and in caregiver burden and well-being at 4 months. MIT was successfully adapted for Latino Spanish language family dementia caregivers within a virtual group environment. MIT is feasible and acceptable and may help reduce depressive symptoms and improve subjective well-being. Larger, randomized controlled trials of MIT should determine durability of effects and validate efficacy in this population.
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Context: Self-compassion training involves the cultivation of feelings of warmth and safety, presence, and interconnectedness. Mindful Self-Compassion (MSC) training in a group setting has been found to increase self-compassion, mindfulness, and emotional well-being. Objective: The current study intended to examine the outcomes of live, online, videoconference-based MSC training with online peer-support for nonclinical populations in different cities in China. Design: The research team designed a pre-post pilot study. Setting: The study took place at Renmin University in Beijing, China. Participants: Participants were 253 Chinese individuals who were recruited from different regions in China through online advertisements. Intervention: Participants took part in online MSC training in a two-hour, group class each week for eight weeks and received support from online peer groups and through a half-day in-person retreat. Outcome Measures: Self-report outcomes were obtained at baseline and postintervention, using the Self Compassion Scale (SCS) and the Compassion for Others Scale (CS) for primary outcomes, and the Depression, Anxiety, and Stress Scale (DASS-21), the Fear of Compassion Scale (FOCS), the Satisfaction with Life Scale (SWLS), the Subjective Happiness Scale (SHS), and the Cognitive and Affective Mindfulness Scale (CAMS-R), for secondary outcomes. A fixed effects model was used to test for within-group changes in the scales. Results: The online MSC program yielded a high retention rate. Of the 206 first-time participants, 179 (86.9%) attended six or more of the eight MSC sessions, and 183 (88.8%) completed the assessments at both baseline and postintervention. Of the 183 retained participants, 97.8% were female, with an average age of 37.8 ± 7.9; 94% had college or higher education. For all scales, the within-person changes occurred in the expected direction; positive attributes and experiences increased, while negative attributes and experiences decreased. Conclusions: The study showed that first-time participants in China in an online MSC training that was supported by online peer groups had high attendance rates, high assessment completion, and favorable results. These preliminary outcomes suggest that future studies with more rigorous designs are warranted to further investigate online training with peer support as an effective and efficient approach to disseminate MSC training in China.
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Atención Plena , Autocompasión , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Proyectos Piloto , Emociones , Empatía , Atención Plena/métodosRESUMEN
Background: Family caregivers of dementia patients experience high levels of interpersonal stress that often results in elevated anxiety, and depression, and negative impacts on interpersonal relationships. Changes in behaviors and the structure of relationships with the care recipient (CR) and others in the social milieu challenge the caregivers' ability to mentalize, or understand the links between mental states and behaviors. This study investigates the experiences and perceived benefits of family dementia caregivers who underwent Mentalizing Imagery Therapy (MIT), a treatment aiming to improve balanced self-other mentalizing and reduce psychological symptoms. Methods: Purposeful sampling was used to select 11 family dementia caregivers who underwent a 4-week pilot trial of MIT. Semi-structured interviews were completed post-intervention to identify subjective benefits, putative psychological mediators and perceived active components. Results: Caregivers reported improvements in well-being, mood, anxiety, and sleep, and a majority stated MIT helped with forming and maintaining healthier relationships. Some participants noted benefits extending to how they reacted to their social environment and perceived themselves more objectively from others' perspectives. Specific elements of MIT, including self-compassion, self-care, and the ability to reflect on emotionally arousing challenges, might have mediated these improvements. Conclusion: Family dementia caregivers perceived salutary benefits of MIT on multiple domains of well-being. The self reports suggest MIT holds promise for improving well-being, reducing non-mentalizing patterns of thought, and facilitating improvements in balanced mentalization within the caregivers' relationships.
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Network psychometric models are often estimated using a single indicator for each node in the network, thus failing to consider potential measurement error. In this study, we investigate the impact of measurement error on cross-sectional network models. First, we conduct a simulation study to evaluate the performance of models based on single indicators as well as models that utilize information from multiple indicators per node, including average scores, factor scores, and latent variables. Our results demonstrate that measurement error impairs the reliability and performance of network models, especially when using single indicators. The reliability and performance of network models improves substantially with increasing sample size and when using methods that combine information from multiple indicators per node. Second, we use empirical data from the STAR*D trial (n = 3,731) to further evaluate the impact of measurement error. In the STAR*D trial, depression symptoms were assessed via three questionnaires, providing multiple indicators per symptom. Consistent with our simulation results, we find that when using sub-samples of this dataset, the discrepancy between the three single-indicator networks (one network per questionnaire) diminishes with increasing sample size. Together, our simulated and empirical findings provide evidence that measurement error can hinder network estimation when working with smaller samples and offers guidance on methods to mitigate measurement error.
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Reproducibilidad de los Resultados , Simulación por Computador , Estudios Transversales , Humanos , Psicometría/métodos , Encuestas y CuestionariosRESUMEN
More than 50 million people worldwide live with a dementia, and most are cared for by family members. Family caregivers often experience chronic stress and insomnia, resulting in decreased mental and physical health. Accessibility of in-person stress reduction therapy is limited due to caregiver time constraints and distance from therapy sites. Mentalizing imagery therapy (MIT) provides mindfulness and guided imagery tools to reduce stress, promote self and other understanding, and increase feelings of interconnectedness. Combining MIT with caregiver skills training might enable caregivers to both reduce stress and better utilize newly learned caregiving skills, but this has never been studied. Delivering MIT through a smartphone application (App) has the potential to overcome difficulties with scalability and dissemination and offers caregivers an easy-to-use format. Harnessing passive smartphone data provides an important opportunity to study behavioral changes continuously and with higher granularity than routine clinical assessments. This protocol describes a randomized, controlled, superiority trial in which 120 family dementia caregivers, aged 60 years or older, will be assigned to smartphone App delivery of caregiver skills with MIT (experimental condition) or without MIT (control condition). The primary objectives of the trial are to assess whether the experimental condition is superior to control on reducing family caregiver stress, insomnia and related outcomes and to demonstrate the feasibility of developing behavioral markers from passive smartphone data that predict health outcomes in older adults. Trial outcomes may inform the suitability of our intervention for caregivers and provide new methods for assessment of older adults.
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Demencia , Mentalización , Aplicaciones Móviles , Trastornos del Inicio y del Mantenimiento del Sueño , Anciano , Cuidadores/educación , Demencia/terapia , Humanos , Imágenes en Psicoterapia , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos del Inicio y del Mantenimiento del Sueño/terapiaRESUMEN
INTRODUCTION: Family caregivers of patients with dementia suffer a high burden of depression and reduced positive emotions. Mentalizing imagery therapy (MIT) provides mindfulness and guided imagery skills training to improve balanced mentalizing and emotion regulation. OBJECTIVE: Our aims were to test the hypotheses that MIT for family caregivers would reduce depression symptoms and improve positive psychological traits more than a support group (SG), and would increase dorsolateral prefrontal cortex (DLPFC) connectivity and reduce subgenual anterior cingulate cortex (sgACC) connectivity. METHODS: Forty-six caregivers participated in a randomized controlled trial comparing a 4-week MIT group (n = 24) versus an SG (n = 22). Resting state neuroimaging was obtained at baseline and post-group in 28 caregivers, and questionnaires completed by all participants. The primary outcome was change in depression; secondary measures included anxiety, mindfulness, self-compassion, and well-being. Brain networks with participation of DLPFC and sgACC were identified. Connectivity strengths of DLPFC and sgACC with respective networks were determined with dual regression. DLPFC connectivity was correlated with mindfulness and depression outcomes. RESULTS: MIT significantly outperformed SG in improving depression, anxiety, mindfulness, self-compassion, and well-being, with moderate to large effect sizes. Relative to SG, participants in MIT showed significant increases in DLPFC connectivity - exactly replicating pilot study results - but no change in sgACC. DLPFC connectivity change correlated positively with mindfulness and negatively with depression change. CONCLUSIONS: In this trial, MIT was superior to SG for reducing depression and anxiety symptoms and improving positive psychological traits. Neuroimaging results suggested that strengthening DLPFC connectivity with an emotion regulation network might be mechanistically related to MIT effects.
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Demencia , Mentalización , Atención Plena , Cuidadores , Humanos , Imágenes en Psicoterapia , Imagen por Resonancia Magnética , Atención Plena/métodos , Proyectos Piloto , Corteza Prefrontal/diagnóstico por imagenRESUMEN
A growing body of research suggests that meditative- and mindfulness-focused interventions may improve neuropsychiatric symptoms that commonly occur in a range of neurological disorders. In this article, the principles of meditation and mindfulness are first defined, as well as briefly describing the neurobiological mechanisms implicated in these interventions. Thereafter, a range of meditative- and mindfulness-focused interventions are detailed, along with their supporting evidence to treat neuropsychiatric symptoms in neurological conditions (e.g., headache, movement disorders, chronic pain, etc.). Overall, these interventions warrant further investigation among individuals with neurological conditions. When recommending these interventions, health care professionals must consider a combination of structural (e.g., insurance reimbursement) and patient factors (e.g., ability to tolerate a group setting).
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Meditación , Trastornos Mentales , Atención Plena , Neurología , Humanos , Selección de PacienteRESUMEN
BACKGROUND: Family dementia caregivers experience high rates of depression and anxiety that often go untreated due to time demands. We aimed to determine the feasibility of a brief, 4-week Mentalizing Imagery Therapy intervention, which couples mindfulness with guided imagery practices aimed at bolstering mentalizing capacity, to reduce caregiver psychological symptoms and to explore potential impact on dorsolateral prefrontal cortex connectivity. METHODS: Twenty-four family dementia caregivers with moderate depression symptoms (a score of 10 in Patient Health Questionnaire-9) were assigned to either group Mentalizing Imagery Therapy (MIT, n = 12) or a waitlist augmented by optional relaxation exercises (n = 12). Participants completed questionnaires to measure depression and anxiety at baseline and followup, and those eligible also underwent resting state functional magnetic resonance (fMRI) brain imaging at these time points. RESULTS: Eleven of 12 caregivers assigned to MIT completed the intervention and attended weekly groups 98% of the time. MIT home practice logs indicated average practice of 5 ± 2 sessions per week for 23 ± 8 min per session. All participants in waitlist completed the post-assessment. MIT participants exhibited significantly greater improvement than waitlist on self-reported depression and anxiety symptoms (p<.05) after 4 weeks. Neuroimaging results revealed increased dorsolateral prefrontal cortex connectivity with a putative emotion regulation network in the MIT group (p = .05) but not in waitlist (p = 1.0). LIMITATIONS: Sample size limitations necessitate validation of findings in larger, randomized controlled trials. CONCLUSIONS: A 4-week group MIT program was feasible for caregivers, with high levels of participation in weekly group meetings and home practice exercises.
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OBJECTIVE: A growing body of scientific evidence suggests that meditation may slow brain aging. The amygdala-a heterogenous brain region known to decrease in volume with increasing age-seems to be involved in meditation and affected by meditation. Thus, we hypothesized that the age-related decline of the amygdala is diminished in meditation practitioners. METHODS: We investigated whether correlations between age and gray matter volumes of the amygdala are significantly reduced in 50 long-term meditators compared with 50 sex- and age-matched healthy controls. Both the meditator and control groups included 44% women. The age of the participants ranged between 24 and 77 years, with mean (standard deviation) ages of 50.4 (±11.8) years in meditators and 51.4 (±12.8) years in controls. In addition to studying the amygdala as a whole, we investigated its centromedial, laterobasal, and superficial subregions using a well-validated approach combining imaging-based signal intensities and cytoarchitectonically defined probabilities. RESULTS: We detected significant group-by-age interactions for the whole amygdala and for its subregions. Follow-up analyses indicated negative age-related correlations in both meditators and controls (the older the participants, the smaller the volumes) but with significantly steeper aging trajectories in controls. CONCLUSIONS: Altogether, these findings suggest that the age-related volume loss of the amygdala is less pronounced in long-term meditators. This effect was particularly evident for the laterobasal subregion, which has been functionally linked to aspects of self-focused reflection.
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Meditación , Adulto , Anciano , Amígdala del Cerebelo/diagnóstico por imagen , Encéfalo , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Facilitating mentalization, or the ability to understand mental states and their link to behavior, is increasingly viewed as a common mechanism of action across effective psychotherapies. Here we present an overview of a new set of contemplative psychotherapeutic techniques, Mentalizing Imagery Therapy (MIT), that uses guided imagery and mindfulness practices to facilitate mentalization. MIT aims to reduce negative psychological symptoms by stimulating an understanding of mental states and their links to behavior in self and others, including in challenging interpersonal situations. Case discussions of MIT in personality disordered and depressed patients are used to illustrate theoretical points and the specific practical benefits of MIT. We conclude that there are promising indications that the imagery and mindfulness practices of MIT, that are specifically targeted to facilitate insight in the context of attachment relationship challenges, may help to improve mentalization and reduce symptoms of depression and anxiety. Both in practice and with respect to its articulated goals, MIT promotes a distinct set of capacities from other mindfulness or compassion based therapies. Further research is required to determine the clinical efficacy of MIT in controlled trials.
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BACKGROUND: Studies testing the relationship between cortisol levels, depression, and antidepressant treatment response have yielded divergent results suggesting the possibility of moderators of a cortisol effect. Several studies indicate that age may moderate the relationship between cortisol and depression. In patients with Major Depressive Disorder (MDD), we studied the interactive effects of age and cortisol in association with MDD diagnostic status and mood and memory response to antidepressant treatment. METHODS: Serum cortisol levels in 66 unmedicated patients with MDD and 75 matched healthy controls (HC) were measured at baseline and retrospectively analyzed. Logistic regression was used to determine an association of age, cortisol and their interaction with MDD diagnosis in the pooled sample of MDD and HC participants. Thirty-four of the MDD participants (age range: 19-65 years; median: 36) underwent treatment with a selective serotonin reuptake inhibitor (SSRl) for 8 weeks. Clinician and self-ratings of depression symptoms, as well as tests of verbal and visual delayed recall were obtained at baseline and post treatment. Moderation analyses determined the effect of age on the relationship between baseline cortisol and treatment outcome. RESULTS: Cortisol, moderated by age, was associated with MDD diagnosis (pâ¯<â¯.05), treatment-associated reduction of depression symptoms (pâ¯<â¯.001) and improvement of delayed recall (pâ¯<â¯.001). Modeling the Cortisolâ¯×â¯Age interaction suggested that for participants below the median age of our sample, lower cortisol levels were associated with a lower rate of MDD diagnosis and higher antidepressant effects. On the contrary, in those above the median sample age, lower cortisol was associated with a higher rate of MDD and less improvement in depression symptoms and memory performance. CONCLUSIONS: Our results add to the body of literature suggesting that age might be an important factor in moderating the relationship between peripheral cortisol levels, depression, cognition, and prognosis. These results indicate that previous disparities in the literature linking peripheral cortisol levels with depression characteristics and treatment response may critically relate, at least in part, to the age of the participants studied.
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Trastorno Depresivo Mayor/metabolismo , Hidrocortisona/metabolismo , Memoria/fisiología , Resultado del Tratamiento , Adulto , Factores de Edad , Antidepresivos/uso terapéutico , Estudios de Casos y Controles , Cognición/efectos de los fármacos , Depresión/metabolismo , Trastorno Depresivo Mayor/fisiopatología , Femenino , Humanos , Hidrocortisona/análisis , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Estudios Retrospectivos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacologíaRESUMEN
Background: Family dementia caregivers often suffer from an immense toll of grief while caring for their loved ones. We sought to identify the clinical relationship between grief, depression and mindfulness and identify neural predictors of symptomatology and improvement. Methods: Twenty three family dementia caregivers were assessed at baseline for grief, mindfulness and depression, of which 17 underwent functional magnetic resonance imaging (fMRI). During fMRI, caregivers were shown faces of either their dementia-stricken relative or that of a stranger, paired with grief-related or neutral words. In nine subjects, post fMRI scans were also obtained after 4 weeks of either guided imagery or relaxation. Robust regression was used to predict changes in symptoms with longitudinal brain activation (BA) changes as the dependent variable. Results: Grief and depression symptoms were correlated (r = 0.50, p = 0.01), and both were negatively correlated with mindfulness (r = -0.70, p = 0.0002; r = -0.52, p = 0.01). Relative to viewing strangers, caregivers showed pictures of their loved ones (picture factor) exhibited increased activation in the dorsal anterior cingulate gyrus and precuneus. Improvement in grief but not mindfulness or depression was predicted by increased relative BA in the precuneus and anterior cingulate (different subregions from baseline). Viewing grief-related vs. neutral words elicited activity in the medial prefrontal cortex and precuneus. Conclusions: Caregiver grief, depression and mindfulness are interrelated but have at least partially nonoverlapping neural mechanisms. Picture and word stimuli related to caregiver grief evoked brain activity in regions previously identified with bereavement grief. These activation foci might be useful as biomarkers of treatment response.
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BACKGROUND: Oxidative stress is implicated in both depression and anxiety, but it is currently unclear whether this relates to syndromal diagnoses or trans-diagnostic dimensional symptoms. We examined the relationship between oxidative stress and severity of depression and anxiety symptoms in individuals with Major Depressive Disorder (MDD). METHODS: Plasma oxidative stress markers F2-isoprostanes and oxidized glutathione (GSSG), and the antioxidant reduced glutathione (GSH), were assessed in 69 physically healthy, medication-free MDD subjects. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. Total HAM-A and HAM-D scores, along with "core" anxiety and depression subscales, and individual HAM-D items "psychic anxiety" and "depressed mood," were related to oxidative stress markers. Analyses controlled for age, sex, BMI, and smoking. RESULTS: Total HAM-A ratings were positively associated with F2-isoprostanes (ß=.26, p=.042) and GSSG (ß=.25, p=.049), but not GSH (ß=.05, p=.711). Core anxiety severity was positively associated with F2-isoprostanes (ß=.34, p=.012) and GSSG, although this did not reach significance (ß=.24, p=.074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p>.13). Subjects scoring high on "psychic anxiety" had elevated F2-isoprostanes (p=.030) and GSSG (p=.020). This was not seen with "depressed mood" scores (all p>.12). LIMITATIONS: We assessed peripheral oxidative markers, but their relationship to the brain is unclear. CONCLUSIONS: Oxidative stress is more closely related to anxiety than depression symptoms in MDD. This highlights the importance of relating oxidative stress to specific symptoms and could provide new insights into the biological correlates of affective disorders.
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Ansiedad/sangre , Depresión/sangre , Trastorno Depresivo Mayor/sangre , Estrés Oxidativo/fisiología , Adulto , Biomarcadores/sangre , F2-Isoprostanos/sangre , Femenino , Glutatión/sangre , Disulfuro de Glutatión/sangre , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Hispanics are the largest minority group in the United States, approximately 7% of the population older than 65. They often encounter challenges related to health care access and quality of care. The prevalence of dementia among Hispanics is higher than that of non-Hispanic whites and they frequently present at a more advanced stage of illness. Cognitive evaluation should take into account sociodemographic information and cultural factors to avoid misdiagnosis and guide management. A provider who has knowledge of Hispanic culture should conduct the neuropsychological assessment, and tests used to measure cognitive functioning should be developed for Hispanics in the United States.
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Envejecimiento , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etnología , Demencia/diagnóstico , Hispánicos o Latinos , Pruebas Neuropsicológicas , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/epidemiología , HumanosRESUMEN
BACKGROUND: Headache pain is often comorbid with major depressive disorder (MDD) and is associated with greater symptom burden, disability, and suicidality. The biological correlates of headache pain in MDD, however, remain obscure. The purpose of this study was to examine the association between brain oscillatory activity and headache pain in MDD subjects. METHODS: A total of 64 subjects with MDD who were free of psychoactive medications were evaluated for severity of headache pain in the past week. Brain function was assessed using resting-state quantitative electroencephalography (qEEG). We derived cordance in the theta (4-8 Hz) and alpha (8-12 Hz) frequency bands at each electrode, and examined correlations with headache pain in regions of interest while controlling for depression severity. Frontal and posterior asymmetry in alpha power was calculated in regions of interest. RESULTS: Headache pain severity was associated with depression severity ( r = 0.447, P < .001). In bilateral frontal and right posterior regions, alpha cordance was significantly associated with headache intensity, including when controlling for depression severity. The direction of the correlation was positive anteriorly and negative posteriorly. Frontal left dominant alpha asymmetry correlated with severity of headache but not depression symptoms. CONCLUSION: Alterations in brain oscillations identified by alpha cordance and alpha asymmetry may be associated with the pathophysiology of headache pain in depression. These findings should be prospectively confirmed.
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Encéfalo/fisiopatología , Depresión/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Electroencefalografía , Cefalea/fisiopatología , Dolor/fisiopatología , Adulto , Depresión/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Electroencefalografía/métodos , Femenino , Cefalea/diagnóstico , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Neurofisiología/métodos , Dolor/diagnóstico , Adulto JovenRESUMEN
OBJECTIVE: Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects. METHODS: Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment "response" was defined as ≥50% decrease in HDRS ratings over 8 weeks of treatment. RESULTS: After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p<0.001), TNF-α (p<0.001), 8-OHdG (p=0.018), and F2-isoprostanes (p=0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p=0.006), and after eight weeks of treatment (p=0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p=0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p=0.019). CONCLUSION: Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.
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Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/fisiopatología , Inflamación/sangre , Evaluación de Resultado en la Atención de Salud , Estrés Oxidativo/fisiología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificaciónRESUMEN
Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5-8 Hz) and the alpha (8-12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms. Prefrontal delta-theta and alpha power were calculated for 194 subjects with moderate MDD prior to and one week after start of treatment. Changes at one week in delta-theta and alpha power, as well as the delta-theta/alpha ratio, were examined in three cohorts: initial (N = 70) and replication (N = 76) cohorts treated with escitalopram, and a cohort treated with placebo (N = 48). Mean delta-theta power significantly increased and alpha power decreased after one week of escitalopram treatment, but did not significantly change with placebo treatment. The delta-theta/alpha ratio change was a specific predictor of the likelihood of remission after seven weeks of medication treatment: a large increase in this ratio was associated with non-remission in escitalopram-treated subjects, but not placebo-treated subjects. Escitalopram and placebo treatment have differential effects on delta-theta and alpha frequency oscillations. Early increase in delta-theta/alpha may constitute a replicable biomarker for non-remission during SSRI treatment of MDD.