Journal of consulting and clinical psychology, Jan 17, 2015
Spiritually integrated psychotherapy (SIP) is increasingly common, though systematic assessment o... more Spiritually integrated psychotherapy (SIP) is increasingly common, though systematic assessment of interest in such treatments, and predictors of such interest, has not yet been conducted among acute psychiatric patients. We conducted a survey with 253 acute psychiatric patients (95-99% response rate) at a private psychiatric hospital in Eastern Massachusetts to assess for interest in SIP, religious affiliation, and general spiritual or religious involvement alongside clinical and demographic factors. More than half (58.2%) of patients reported "fairly" or greater interest in SIP, and 17.4% reported "very much" interest. Demographic and clinical factors were not significant predictors except that current depression predicted greater interest. Religious affiliation and general spiritual or religious involvement were associated with more interest; however, many affiliated patients reported low or no interest (42%), and conversely many unaffiliated patients reported...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Jan 12, 2015
Major Depressive Disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A ... more Major Depressive Disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria (RDoC) initiative, we used source localization of scalp-recorded EEG resting data to examine the neural correlates of three emerging endophenotypes of depression: neuroticism, blunted reward learning and cognitive control deficits. Data were drawn from the ongoing multi-site EMBARC study. We estimated intracranial current density for standard EEG frequency bands in 82 unmedicated adults with MDD, using Low-Resolution Brain Electromagnetic Tomography (LORETA). Region-of-interest and whole-brain analyses tested associations between resting state EEG current density and endophenotypes of interest. Neuroticism was associated with increased resting gamma (36.5-44 Hz) current density in the ventral (subgenual) anterior cingulate cortex (ACC) and orbit...
Depression is characterized by poor executive function, but - counterintuitively - in some studie... more Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on i...
BackgroundStudies investigating structural brain abnormalities in depression have typically emplo... more BackgroundStudies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research.MethodTo examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxe...
The World Health Organization estimates that during a given 12-month period, approximately 34 mil... more The World Health Organization estimates that during a given 12-month period, approximately 34 million people suffering from major depressive disorder go untreated in Europe and the Americas alone. Barriers to treatment include geographic distance, lack of mental health insurance, prohibitive cost of treatment, long wait-lists, and perceived stigma. Over the past two decades, Internet-based cognitive-behavioral therapy (iCBT) programs have proliferated. A growing body of research supports the efficacy of iCBT for depression and other psychiatric conditions, and these programs may help address barriers that hinder access to effective treatment. The present review describes common iCBT programs along with the evidence base supporting their efficacy in reducing symptoms of depression, reviews research on moderators of treatment response, and provides suggestions for future directions in research and care.
Meditation apps are popular and may reduce psychological distress, including during the COVID-19 ... more Meditation apps are popular and may reduce psychological distress, including during the COVID-19 pandemic. However, it is not clear who is most likely to benefit. Using randomized controlled trial data comparing a 4-week meditation app (Healthy Minds Program; HMP) with an assessment-only control in school system employees (n=662), we developed an algorithm predicting who is most likely to benefit from HMP. Baseline clinical and demographic characteristics were submitted to a machine learning model to develop a “Personalized Advantage Index” (PAI) reflecting an individual’s expected reduction in distress (preregistered primary outcome) from HMP vs. control. Significant Group x PAI interactions emerged, indicating that PAI scores moderated group differences in outcome. A regression model including repetitive negative thinking as the sole predictor performed comparably well. Finally, we demonstrate the translation of predictive models to personalized recommendations of expected benefit...
Objective: Rumination heightens risk for depression and anxiety, which increase substantially dur... more Objective: Rumination heightens risk for depression and anxiety, which increase substantially during adolescence. Smartphone apps offer a convenient and cost-effective means for adolescents to access mindfulness training, which may reduce rumination. Despite their increasing popularity, it is unclear which adolescents benefit from mindfulness apps.Methods: Adolescents (n = 152) with elevated trait rumination were randomly assigned to 3 weeks of app-based mindfulness training or a mood monitoring control. Multilevel models tested group differences in state rumination change, assessed via ecological momentary assessment. Baseline adolescent characteristics were submitted to elastic net regularization models to develop a “Personalized Advantage Index” indicating an individual’s expected outcome from the mindfulness app relative to the mood monitoring control. Finally, we translated a predictive model (developed in an external sample) for personalized recommendations of expected benefit...
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentat... more Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits. Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics. Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than pla...
One in three clinical trial patients with major depressive disorder report symptomatic improvemen... more One in three clinical trial patients with major depressive disorder report symptomatic improvement with placebo. Strategies to mitigate the effect of placebo responses have focused on modifying study design with variable success. Identifying and excluding or controlling for individuals with a high likelihood of responding to placebo may improve clinical trial efficiency and avoid unnecessary medication trials. Participants included those assigned to the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological variables to identify the most robust yet parsimonious features that predicted depression severity at the end of the double-blind 8-week trial. Variables retained in at least 50% of the 100 imputed data sets were used in a Bayesian multiple linear regression model to simultaneously predict the probab...
Major depressive disorder (MDD) remains challenging to treat. Although several clinical and demog... more Major depressive disorder (MDD) remains challenging to treat. Although several clinical and demographic variables have been found to predict poor antidepressant response, these markers have not been robustly replicated to warrant implementation in clinical care. Increased pretreatment rostral anterior cingulate cortex (rACC) theta activity has been linked to better antidepressant outcomes. However, no prior study has evaluated whether this marker has incremental predictive validity over clinical and demographic measures. To determine whether increased pretreatment rACC theta activity would predict symptom improvement regardless of randomization arm. A multicenter randomized clinical trial enrolled outpatients without psychosis and with chronic or recurrent MDD between July 29, 2011, and December 15, 2015 (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care [EMBARC]). Patients were consecutively recruited from 4 university hospitals: 634 patients we...
Journal of consulting and clinical psychology, Jan 17, 2015
Spiritually integrated psychotherapy (SIP) is increasingly common, though systematic assessment o... more Spiritually integrated psychotherapy (SIP) is increasingly common, though systematic assessment of interest in such treatments, and predictors of such interest, has not yet been conducted among acute psychiatric patients. We conducted a survey with 253 acute psychiatric patients (95-99% response rate) at a private psychiatric hospital in Eastern Massachusetts to assess for interest in SIP, religious affiliation, and general spiritual or religious involvement alongside clinical and demographic factors. More than half (58.2%) of patients reported "fairly" or greater interest in SIP, and 17.4% reported "very much" interest. Demographic and clinical factors were not significant predictors except that current depression predicted greater interest. Religious affiliation and general spiritual or religious involvement were associated with more interest; however, many affiliated patients reported low or no interest (42%), and conversely many unaffiliated patients reported...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Jan 12, 2015
Major Depressive Disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A ... more Major Depressive Disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria (RDoC) initiative, we used source localization of scalp-recorded EEG resting data to examine the neural correlates of three emerging endophenotypes of depression: neuroticism, blunted reward learning and cognitive control deficits. Data were drawn from the ongoing multi-site EMBARC study. We estimated intracranial current density for standard EEG frequency bands in 82 unmedicated adults with MDD, using Low-Resolution Brain Electromagnetic Tomography (LORETA). Region-of-interest and whole-brain analyses tested associations between resting state EEG current density and endophenotypes of interest. Neuroticism was associated with increased resting gamma (36.5-44 Hz) current density in the ventral (subgenual) anterior cingulate cortex (ACC) and orbit...
Depression is characterized by poor executive function, but - counterintuitively - in some studie... more Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on i...
BackgroundStudies investigating structural brain abnormalities in depression have typically emplo... more BackgroundStudies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research.MethodTo examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxe...
The World Health Organization estimates that during a given 12-month period, approximately 34 mil... more The World Health Organization estimates that during a given 12-month period, approximately 34 million people suffering from major depressive disorder go untreated in Europe and the Americas alone. Barriers to treatment include geographic distance, lack of mental health insurance, prohibitive cost of treatment, long wait-lists, and perceived stigma. Over the past two decades, Internet-based cognitive-behavioral therapy (iCBT) programs have proliferated. A growing body of research supports the efficacy of iCBT for depression and other psychiatric conditions, and these programs may help address barriers that hinder access to effective treatment. The present review describes common iCBT programs along with the evidence base supporting their efficacy in reducing symptoms of depression, reviews research on moderators of treatment response, and provides suggestions for future directions in research and care.
Meditation apps are popular and may reduce psychological distress, including during the COVID-19 ... more Meditation apps are popular and may reduce psychological distress, including during the COVID-19 pandemic. However, it is not clear who is most likely to benefit. Using randomized controlled trial data comparing a 4-week meditation app (Healthy Minds Program; HMP) with an assessment-only control in school system employees (n=662), we developed an algorithm predicting who is most likely to benefit from HMP. Baseline clinical and demographic characteristics were submitted to a machine learning model to develop a “Personalized Advantage Index” (PAI) reflecting an individual’s expected reduction in distress (preregistered primary outcome) from HMP vs. control. Significant Group x PAI interactions emerged, indicating that PAI scores moderated group differences in outcome. A regression model including repetitive negative thinking as the sole predictor performed comparably well. Finally, we demonstrate the translation of predictive models to personalized recommendations of expected benefit...
Objective: Rumination heightens risk for depression and anxiety, which increase substantially dur... more Objective: Rumination heightens risk for depression and anxiety, which increase substantially during adolescence. Smartphone apps offer a convenient and cost-effective means for adolescents to access mindfulness training, which may reduce rumination. Despite their increasing popularity, it is unclear which adolescents benefit from mindfulness apps.Methods: Adolescents (n = 152) with elevated trait rumination were randomly assigned to 3 weeks of app-based mindfulness training or a mood monitoring control. Multilevel models tested group differences in state rumination change, assessed via ecological momentary assessment. Baseline adolescent characteristics were submitted to elastic net regularization models to develop a “Personalized Advantage Index” indicating an individual’s expected outcome from the mindfulness app relative to the mood monitoring control. Finally, we translated a predictive model (developed in an external sample) for personalized recommendations of expected benefit...
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentat... more Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits. Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics. Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than pla...
One in three clinical trial patients with major depressive disorder report symptomatic improvemen... more One in three clinical trial patients with major depressive disorder report symptomatic improvement with placebo. Strategies to mitigate the effect of placebo responses have focused on modifying study design with variable success. Identifying and excluding or controlling for individuals with a high likelihood of responding to placebo may improve clinical trial efficiency and avoid unnecessary medication trials. Participants included those assigned to the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological variables to identify the most robust yet parsimonious features that predicted depression severity at the end of the double-blind 8-week trial. Variables retained in at least 50% of the 100 imputed data sets were used in a Bayesian multiple linear regression model to simultaneously predict the probab...
Major depressive disorder (MDD) remains challenging to treat. Although several clinical and demog... more Major depressive disorder (MDD) remains challenging to treat. Although several clinical and demographic variables have been found to predict poor antidepressant response, these markers have not been robustly replicated to warrant implementation in clinical care. Increased pretreatment rostral anterior cingulate cortex (rACC) theta activity has been linked to better antidepressant outcomes. However, no prior study has evaluated whether this marker has incremental predictive validity over clinical and demographic measures. To determine whether increased pretreatment rACC theta activity would predict symptom improvement regardless of randomization arm. A multicenter randomized clinical trial enrolled outpatients without psychosis and with chronic or recurrent MDD between July 29, 2011, and December 15, 2015 (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care [EMBARC]). Patients were consecutively recruited from 4 university hospitals: 634 patients we...
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