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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.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.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.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.

IntroductionThe psychological wellbeing of healthcare workers has been impacted by the high levels of stress many have experienced during the COVID-19 pandemic. This study aimed to examine the feasibility and acceptability of a brief online course focused on introducing skills that could increase resilience and decreases emotional distress in healthcare workers during the pandemic.Materials and MethodsEmployees of a large healthcare system completed a survey at baseline, one month, and two months later. The online course, called Resilience Training for Healthcare Workers, consists of three 12-20 minute videos focused on evidence-based skills that support aspects of emotional resilience: mindfulness, mentalization, and self-compassion.ResultsA total of 554 participants completed the baseline survey, endorsing moderate to high levels of emotional distress. Of those who completed all three assessments and participated in the course (n = 38), significant improvements in resilience and reductions in emotional distress were found across two months, in comparison to those who did not participate in the course.DiscussionThese findings suggest that a brief, online intervention can improve the mental health of healthcare workers during a crisis such as the COVID-19 pandemic.

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.

Background Little is known about the long-term outcomes of repeated ketamine infusions for depression. We conducted a retrospective chart review to investigate outcomes of maintenance intravenous ketamine treatment at Massachusetts General Hospital. Methods Eighty-five patients with treatment-resistant depression (TRD) who started intravenous ketamine from October 2018 to November 2019 were examined. Symptom severity was evaluated with the 16-item Quick Inventory of Depressive Symptomatology-Self Report scale (QIDS-SR16) at every visit prior to administration. The initial ketamine dose was usually 0.5 mg/kg infused over 40 min. Intravenous ketamine was administered twice-weekly for three weeks in an induction phase, followed by maintenance with a variable administration schedule and dose. Response was defined as a ≥50% reduction in total QIDS-SR16 score from baseline. Results Forty (47.1%) of the 85 patients who started treatment discontinued during or right after the induction phase; 3 (3.5%) were still on induction at the time of this report, and 42 (49.4%) transitioned to maintenance after completing induction. Among these patients, 14 (16.5%) discontinued during maintenance and 28 (32.9%) continued on maintenance. The mean ketamine dosage during maintenance was 0.91±0.28 mg/kg. Fifteen out of 82 patients (18.3%) responded to induction treatment and 6 (7.3%) remained in responder status at the time of data analysis during maintenance. Three patients discontinued ketamine due to side-effects. Conclusions Despite the apparently low response rate in QIDS-SR16 scores and considerable out-of-pocket costs, almost half of real-world outpatients with TRD decided to continue with maintenance ketamine treatment due to perceived significant improvement.

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 (1) to assess whether the experimental condition is superior to control on reducing family caregiver stress, insomnia and related outcomes and (2) 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.

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).

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.

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.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.The research team designed a pre-post pilot study.The study took place at Renmin University in Beijing, China.Participants were 253 Chinese individuals who were recruited from different regions in China through online advertisements.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.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.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.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.

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 follow-up, 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 52 sessions per week for 238 minutes 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

Background While riluzole has been investigated for the treatment of depression, little is known about its longer-term efficacy and optimal treatment duration in treatment-resistant depression (TRD). The objective of this study is to characterize the longer-term outcome of adjunctive riluzole therapy for TRD in an open-label extension of an 8-week acute treatment trial. Methods The data from 66 patients with TRD who received adjunctive riluzole in a 12-week open-label extension phase were analyzed. Response rates (⩾50% reduction in the Mongomery-Asberg Depression Rating Scale [MADRS] score), relapse rates (a MADRS score of ⩾22 in patients who had previously achieved response), and adverse events were examined in patients who had achieved response at the end of the acute phase and those who had not. Results Among acute phase responders, the maintained response rate was 66.7% (8/12) and the relapse rate was 8.3% (1/12). In acute phase non-responders, the response rate was 24.1% (13/54). The most commonly reported adverse event was fatigue (9.1%). Three cases were considered serious adverse events; vomiting (n = 1), shortness of breath (n = 1), and aborted suicide attempt (n = 1). Limitations This longer-term study was open-label and uncontrolled. The sample size was relatively small. Conclusions Longer-term adjunctive riluzole appears relatively well tolerated and beneficial for maintaining previous response. Additionally, approximately one fourth of patients who did not respond to 8-week antidepressant treatment might respond if treated with riluzole for 12 weeks. Those findings warrant further investigation because adjunctive riluzole could represent an option for treatment of depression when standard antidepressants have failed.

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.

Mind–body therapies that include meditation (e.g., mindfulness-based therapies, transcendental meditation, mantra meditation, and yoga) have demonstrated efficacy for enhancing mental health in a range of clinical and healthy populations. Of the forms of meditation, empirical research has most commonly focused on mindfulness-based approaches. Existing evidence suggests that, on average, both meditative movement (e.g., yoga) and multicomponent mindfulness-based interventions (e.g., mindfulness-based cognitive therapy and mindfulness-based relapse prevention) appear at least as effective as other active treatments for disorders such as major depression and substance use disorder. Results of studies with healthy adults suggest that multicomponent interventions such as mindfulness-based stress reduction have potential to increase empathy, self-control, self-compassion, relationship quality, and spirituality as well as decrease rumination. Translational neuroscience of mind–body therapies has also begun to evaluate the neurobiological mechanisms by which meditative therapies enhance resilience to mental health disorders, and several promising mechanistic domains (neural, hormonal, immune, cellular, and cardiovascular) have been identified. Directions for future research and implications for clinical practice are discussed.

Objective Both cognitive behavioral therapy for depression (CBT-D) combined with brief motivational interviewing (CBT-D+BMI) and alone are associated with symptom improvement among college students with co-occurring depression and heavy episodic drinking (HED). However, little is known about change processes underlying these different treatments.The current study uses a network approach to examine change process that may differentially underlie CBT-D + BMI relative to CBT alone. Methods Participants included 94 college students with depression and HED who were randomized to either eight weeks of CBT-D + BMI or CBT alone. A network approach was adopted to examine how treatment condition influenced changes in the network structure of depression symptoms, heavy drinking, drinking motives, and consequences of alcohol. Network analyses were conducted using change scores representing the eight-week difference from pre-treatment to post-treatment assessments. Results Relative to CBT-D alone, the combined CBT-D + BMI treatment influenced the symptom network structure by preferentially targeting reductions in drinking to cope motives and in the depression symptom ‘loss of interest’. Conclusion The current study revealed that combined CBT-D + BMI may confer therapeutic benefit through different network structure pathways than CBT-D alone. Specifically, augmenting CBT-D with BMI may influence change processes related to drinking motives, such as drinking to cope.

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.

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.

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.

BackgroundFamily caregivers of patients with dementia experience high levels of interpersonal stress that often results in elevated anxiety, depression and negative impacts on social networks. 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 perceived benefits for family dementia caregivers of Mentalizing Imagery Therapy (MIT), which aims to improve balanced mentalizing of both self and others and reduce psychological symptoms. Methods11 family members who identified as the primary caregiver of a relative with dementia underwent a 4-week pilot trial of MIT and completed semi-structured interviews post-intervention to identify subjective benefits, putative psychological mediators and perceived active components. ResultsCaregivers reported improvements in general well-being, mood, anxiety, and sleep, and a majority stated the intervention 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 the intervention, including self-compassion, self-care, and the ability to reflect on emotionally arousing challenges, might have mediated these improvements. The combination of instructor, meditations, homework, group sessions, and educational sessions was well received by participants.ConclusionOur results show that family dementia caregivers described perceived salutary benefits of MIT on multiple domains of well-being. The self reports suggest MIT holds promise for reducing non-mentalizing patterns of thought, and facilitating improvements in balanced mentalization within the caregivers’ relationships. These results should be further extended in larger samples.

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: 23 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 9 subjects, post fMRI scans were also obtained after four weeks of either guided imagery or relaxation. Robust regression was used to predict changes in symptoms with longitudinal brain activation changes as the dependent variable. Results: Grief and depression symptoms were correlated (r = 0.50, p = .01), and both were negatively correlated with mindfulness (r = -.70, p = .0002; r = -.52, p = .01). Relative to viewing strangers, caregivers shown 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 brain activation 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 grief evoked brain activity in regions previously identified with bereavement grief. These activation foci might be useful as biomarkers of treatment response.

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.

BACKGROUND Family caregivers of patients with Alzheimer disease and related dementias (AD and ADRD) often experience high stress and are at high risk for depression. Technologically delivered therapy is attractive for AD and ADRD caregivers because of the time demands associated with in-person participation. OBJECTIVE We aimed to study the feasibility and conduct limited efficacy testing of a mobile app intervention delivering mentalizing imagery therapy (MIT) for family caregivers. METHODS A 4-week trial of the MIT app for family AD and ADRD caregivers was conducted to assess the feasibility of use and investigate changes in depression symptoms, mood, and caregiving experience. Semistructured interviews were conducted to characterize participants’ perceived feasibility and benefits. RESULTS A total of 17 of the 21 (80%) consented participants (mean age 67 years, range 54-79) utilized the app at least once and were further analyzed. Average usage of audio recordings was on 14 (SD 10) days out of 28 possible and comprised 29 (SD 28) individual sessions. There were improvements in depression with a large effect size for those who used the app at least moderately (P=.008), increases in positive mood postintervention (P CONCLUSIONS App delivery of MIT is feasible for family AD and ADRD caregivers, including aging seniors. Results showed moderate to high usage of the app for a majority of users. Limited efficacy testing provides justification for studying the MIT app for AD and ADRD caregivers to improve mood and reduce depression in larger, controlled trials.

Background: Family caregivers of patients with Alzheimer disease and related dementias (AD and ADRD) often experience high stress and are at high risk for depression. Technologically delivered therapy is attractive for AD and ADRD caregivers because of the time demands associated with in-person participation. Objective: We aimed to study the feasibility and conduct limited efficacy testing of a mobile app intervention delivering mentalizing imagery therapy (MIT) for family caregivers. Methods: A 4-week trial of the MIT app for family AD and ADRD caregivers was conducted to assess the feasibility of use and investigate changes in depression symptoms, mood, and caregiving experience. Semistructured interviews were conducted to characterize participants’ perceived feasibility and benefits. Results: A total of 17 of the 21 (80%) consented participants (mean age 67 years, range 54-79) utilized the app at least once and were further analyzed. Average usage of audio recordings was on 14 (SD 10) days out of 28 possible and comprised 29 (SD 28) individual sessions. There were improvements in depression with a large effect size for those who used the app at least moderately (P=.008), increases in positive mood postintervention (P

BackgroundStudies 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 psychopathology. In patients with Major Depressive Disorder (MDD), we studied the interactive effects of age and cortisol on predicting diagnostic status, improvement in mood and memory function with antidepressant treatment, and brain response to negative emotional stimuli.Methods66 unmedicated patients with MDD and 75 matched healthy controls had serum assayed at pre-treatment baseline for cortisol. Logistic regression was used to determine an association of age, cortisol and their interaction with MDD diagnosis. 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. A separate sample of 8 MDD participants prospectively underwent fMRI neuroimaging and cortisol collection while viewing negative emotional faces.ResultsAge moderated the effects of cortisol on predicting MDD diagnosis (pConclusionsOur results indicate that age moderates the relationship between peripheral cortisol levels and (1) MDD diagnosis, (2) brain reactivity to emotional stimuli, and (3) antidepressant-associated improvement in depression and memory symptoms. 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 patients studied.

Objectives: Due to psychological and physical strain, family caregivers of patients with Alzheimer’s disease and related dementias are at high risk for depression and stress related disorders. We investigated the feasibility of a mobile application (App) intervention delivering Mentalizing Imagery Therapy (MIT), which incorporates guided imagery and mindfulness, to facilitate self-regulation and increase perspective on the mental life of self and others. Method: A 4-week pilot trial of an MIT App for family caregivers of people with dementia was conducted to assess feasibility of use, mood and depression symptom benefit, and relationship changes. Semi-structured interviews were conducted at the study’s conclusion to characterize participants’ perceived benefits. Results: 80% of 21 consented participants downloaded the App, utilized it at least once, and were further analyzed. Of these participants, average usage of audio recordings was 14 ± 10 (SD) days out of 28 possible, and 29 ± 28 individual sessions. Acute improvement in mood from before to after completion of exercises was uniformly observed (p < .001), and after four weeks there was a significant increase in positive affect and a reduction in negative affect. Participants with severe levels of depression (n=3) at baseline exhibited an improvement in symptoms at 4 weeks averaging 30% (p < .05). Semi-structured interviews revealed an increase in the ability to remain “centered" despite caregiving challenges, take the perspective of the loved one, and positively reframe the caregiver experience.Conclusion: App delivery of MIT is feasible for family dementia caregivers. Results showed moderate to high usage of the app for a majority of the users, and promising improvements in mood and depression. These data provide justification for larger, controlled trials.

© 2017 Elsevier B.V. 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 (β=.26, p=.042) and GSSG (β=.25, p=.049), but not GSH (β=.05, p=.711). Core anxiety severity was positively associated with F2-isoprostanes (β=.34, p=.012) and GSSG, although this did not reach significance (β=.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.

Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N=26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N=16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R2>.43 and p

Objectives: Family dementia caregivers are at high risk of depression and burnout. We assessed the feasibility of Central Meditation and Imagery Therapy for Caregivers (CMIT-C), a novel 8-week group meditation and guided imagery group therapy program, for dementia caregivers reporting stress because of caregiving responsibilities. Methods: Twelve family dementia caregivers enrolled in CMIT-C. Primary outcomes included depression and anxiety, and secondary outcomes included insomnia, quality of life, and mindfulness. Changes over the study and 3month followup were analyzed with non-parametric related samples tests. Correlations of feeling state changes from meditation diaries at 1week were made with symptom changes post meditation training. Results: Ten participants completed the study. Completers came to an average of 7±1 sessions out of a possible 8 sessions, and turned in home practice logs of 90±10% of the time. Anxiety, depression, and insomnia symptoms decreased, and mindfulness ratings improved with large effects (all p

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 (SSRI) 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 (p

Background There are many prognostic factors for treatment outcome in major depressive disorder (MDD). The predictive power of any single factor, however, is limited. We aimed to develop profiles of antidepressant response and remission based upon hierarchical combinations of baseline clinical and demographic factors. Methods Using data from Level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D), in which 2,876 participants with MDD were treated with citalopram, a signal-detection analysis was performed to identify hierarchical predictive profiles for patients with different treatment outcome. An automated algorithm was used to determine the optimal predictive variables by evaluating sensitivity, specificity, positive and negative predictive value, and test efficiency. Results Hierarchical combinations of baseline clinical and demographic factors yielded profiles that significantly predicted treatment outcome. In contrast to an overall 47% response rate in STAR*D Level 1, response rates of profiled patient subgroups ranged from 31 to 63%. In contrast to an overall remission rate of 28%, identified subsets of patients had a 12 to 55% probability of remission. The predictors of antidepressant treatment outcome most commonly incorporated into profiles were related to socioeconomic status (e.g., income, education), whereas indicators of depressive symptom type and severity, as well as comorbid clinical conditions, were useful but less powerful predictors. Conclusions Hierarchical profiles of demographic and clinical baseline variables categorized patients according to the likelihood they would benefit from a single antidepressant trial. Socioeconomic factors had greater predictive power than symptoms or other clinical factors, and profiles combining multiple factors were stronger predictors than individual factors alone.

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.

The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD were compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated - most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity.

Background Despite therapeutic advances for major depression, a subset of patients with this disorder does not respond to conventional treatment. Stereotactic ablative procedures such as anterior cingulotomy have been performed in severely affected, treatment-resistant patients, but the long-term results of such procedures are not fully understood. Methods Findings are reported for 33 patients with severe treatment-resistant major depression who underwent ablative stereotactic procedures (dorsal anterior cingulotomy followed if necessary by subcaudate tractotomy). Preoperative and long-term postoperative Beck Depression Inventory scores were obtained along with postoperative Clinical Global Improvement values. Both were analyzed to evaluate patients' responses to the surgical procedure(s). Results At mean follow-up of 30 months after one or more stereotactic ablative procedures, 11 patients (33.3%) were classified as responders, 14 (42.4%) were partial responders, and 8 (24.2%) did not respond to the surgical procedure(s). Among those (17) who underwent only one procedure, seven (41.2%) responded, whereas six (35.3%) and four (23.5%) showed partial or no response, respectively. Among patients who required multiple surgical procedures, four patients (25%) responded, whereas eight (50%) and four (25%) patients demonstrated partial or no responses, respectively, at long-term follow-up evaluations. Conclusions Approximately 75% of depression patients previously resistant to antidepressant therapies received partial or substantial benefit from stereotactic ablative procedures. Those requiring only a single anterior cingulotomy tended to demonstrate more pronounced responses than patients who underwent multiple surgical procedures.

Pulmonary lymphohistiocytic inflammation and fibrosis characterize bleomycin (BLM) lung injury. IL-12, a p70 cytokine produced primarily by macrophages and dendritic cells, promotes T-helper-1-mediated inflammation. IL-12 production by blood monocytes and bronchoalveolar large mononuclear cells (BAMC) was investigated at Days 1-14 following intratracheal administration of BLM. In the lung, BAMC showed a large peak of IL-12 expression at Day 5 that returned rapidly toward baseline. IL-12p40(-/-) mice treated with BLM intratracheally showed less pulmonary mononuclear cell inflammation at Day 7 than wild-type controls, whereas pulmonary fibrosis and hydroxyproline content were increased in IL-12p40(-/-) mice at Day 14. The expression of IP-10, RANTES, and eotaxin were decreased in IL-12p40(-/-) mice and lung IL-6 expression was increased, all compared to controls. We conclude that IL-12 promotes the lymphohistiocytic response to BLM and may inhibit the late development of pulmonary fibrosis.

© 2015 The Academy of Psychosomatic Medicine. Background: Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, owing to a lower side-effect burden, potential reduction of polypharmacy, and theoretical considerations that such interventions may target some of the cognitive roots of depression. Objective: We aimed to determine the state of the evidence supporting this application. Methods: Randomized controlled trials of techniques meeting the Agency for Healthcare Research and Quality definition of meditation, for participants having clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e., how they were applied) components, and trial outcomes were reviewed. Results: 18 studies meeting the inclusion criteria were identified, encompassing 7 distinct techniques and 1173 patients. Mindfulness-Based Cognitive Therapy comprised the largest proportion of studies. Studies including patients having acute major depressive episodes (. n = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (. n = 8), demonstrated moderate to large reductions in depression symptoms within the group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. Conclusions: A substantial body of evidence indicates that meditation therapies may have salutary effects on patients having clinical depressive disorders during the acute and subacute phases of treatment. Owing to methodologic deficiencies and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium.

Family dementia caregivers are at high risk of depression and burnout. We assessed the feasibility of Central Meditation and Imagery Therapy for Caregivers (CMIT-C), a novel 8-week group meditation and guided imagery group therapy program, for dementia caregivers reporting stress because of caregiving responsibilities.Twelve family dementia caregivers enrolled in CMIT-C. Primary outcomes included depression and anxiety, and secondary outcomes included insomnia, quality of life, and mindfulness. Changes over the study and 3 month follow-up were analyzed with non-parametric related samples tests. Correlations of feeling state changes from meditation diaries at 1 week were made with symptom changes post meditation training.Ten participants completed the study. Completers came to an average of 7 ± 1 sessions out of a possible 8 sessions, and turned in home practice logs of 90 ± 10% of the time. Anxiety, depression, and insomnia symptoms decreased, and mindfulness ratings improved with large effects (all p 0.05 and Cohen's d ≥ 0.7). Gains were stable at 3 months. Early response during the first week of meditation practice was associated with subsequent home meditation practice, anxiety change at 8 weeks, and endpoint satisfaction with CMIT-C.Central Meditation and Imagery Therapy for Caregivers is a feasible intervention for dementia caregivers. Results suggest that this therapeutic technique can reduce symptoms of anxiety, depression, and insomnia, and increase levels of mindfulness. Early response to meditation practice predicted those with the greatest short-term benefits, and this may inform future studies of meditation. Larger controlled efficacy studies of CMIT-C for dementia caregivers are warranted.

There are many prognostic factors for treatment outcome in major depressive disorder (MDD). The predictive power of any single factor, however, is limited. We aimed to develop profiles of antidepressant response and remission based upon hierarchical combinations of baseline clinical and demographic factors.Using data from Level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D), in which 2,876 participants with MDD were treated with citalopram, a signal-detection analysis was performed to identify hierarchical predictive profiles for patients with different treatment outcome. An automated algorithm was used to determine the optimal predictive variables by evaluating sensitivity, specificity, positive and negative predictive value, and test efficiency.Hierarchical combinations of baseline clinical and demographic factors yielded profiles that significantly predicted treatment outcome. In contrast to an overall 47% response rate in STAR*D Level 1, response rates of profiled patient subgroups ranged from 31 to 63%. In contrast to an overall remission rate of 28%, identified subsets of patients had a 12 to 55% probability of remission. The predictors of antidepressant treatment outcome most commonly incorporated into profiles were related to socioeconomic status (e.g., income, education), whereas indicators of depressive symptom type and severity, as well as comorbid clinical conditions, were useful but less powerful predictors.Hierarchical profiles of demographic and clinical baseline variables categorized patients according to the likelihood they would benefit from a single antidepressant trial. Socioeconomic factors had greater predictive power than symptoms or other clinical factors, and profiles combining multiple factors were stronger predictors than individual factors alone.

Anterior cervical arachnoid cysts are rare in the pediatric population, with only 16 cases reported. We present the first case of an anterior cervical arachnoid cyst in a neonate and review the literature on pediatric cervical arachnoid cysts. A 16-day-old baby girl with a history of myelomeningocele repair progressively developed symptoms of upper extremity weakness over the course of 2 weeks. Magnetic resonance imaging (MRI) demonstrated a compressive arachnoid cyst extending from C2 to C7. The child was taken for posterior cervical laminoplasty and cyst fenestration. Intraoperatively, diffuse cervical arachnoiditis was noted. Rapid improvement in upper extremity paresis was noted within 24 h of surgery, and MRI confirmed decompression of the cyst. However, flaccid upper extremity paresis recurred within 2 weeks. MRI confirmed recurrence of the anterior cervical arachnoid cyst. The child was taken for a secondary fenestration and stenting of the cyst. Only partial improvement in arm function was noted by 1 month following reoperation. Arachnoid cysts can be effectively treated with surgical fenestration, shunting, and complete or partial excision. Rapid identification and treatment results in improvement in myelopathic symptoms; however, the most efficacious treatment modality remains unknown. Of the 17 cases of anterior cervical arachnoid cysts reported in the literature, 11 (65%) have had either prior myelomeningocele repair or a history of spinal trauma. Anterior cervical arachnoid cysts should be considered in the differential diagnosis of acute onset myelopathy in the pediatric population especially in cases with a history of spinal trauma or myelomeningocele repair.

To the Editor: In their recent article "Prognostic Subgroups for Citalopram Response in the STAR*D Trial," Jakubovski and Bloch conclude that baseline socioeconomic variables "are likely to be more informative than routine clinical variables such as past medication response, duration and severity of illness, and comorbid psychiatric illnesses" in the prediction of citalopram treatment outcome. In particular, their assertion carries the curious implication that demographic factors are more strongly related to treatment response than patient-specific ones. However, their findings are not in agreement with an earlier study we published using the same data and analysis methods.

Bleomycin yields pulmonary injury characterized by inflammation that proceeds to fibrosis. The production of IL-10 by pulmonary macrophages is increased in the inflammation that accompanies bleomycin lung injury. In the present study, IL-10 deficient and wildtype mice received 0.075 units of bleomycin intratracheally at day 0 and were sacrificed at day 7 or day 14. At day 7, pulmonary inflammation was increased in IL-10-deficient mice as reflected by increased representation of CD3+ and CD4+ lymphocytes and GR-1+ pulmonary granulocytes in the bronchoalveolar lavage (BAL) fluid. Pulmonary interstitial CD80+ and CD86+ mononuclear cells were increased in situ. At day 14, mononuclear cell inflammation was comparable between groups but pulmonary eosinophils were increased in the wildtype. There was no difference in the degree of pulmonary fibrosis, as judged by histology or lung hydroxyproline content. Lung chemokine expression of MIP-1alpha/beta, MIP-2, and eotaxin was increased at days 7 and 14 with a trend towards increased MCP-1 expression at day 14. The findings suggest an immunomodulatory role for IL-10 in the inflammatory response but not in the pulmonary fibrosis yielded by bleomycin.