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Prolonged Grief Disorder: Course, Diagnosis, Assessment, and Treatment

Szuhany, Kristin L; Malgaroli, Matteo; Miron, Carly D; Simon, Naomi M
Losing a loved one is one of life's greatest stressors. Although most bereaved individuals navigate through a period of intense acute grief that lessens with time, approximately 10% will develop a prolonged grief condition. This review provides an overview of the course of grief and describes risk factors for developing prolonged grief disorder. The evolution of the prolonged grief disorder diagnosis, including the latest criteria sets for ICD-11 and DSM-5, as well as common comorbid conditions and differential diagnosis are discussed. Clinically useful self-report and clinician-rated measures for assessing symptom constructs and overall prolonged grief disorder severity, evidence-based psychotherapies (such as complicated grief treatment), as well as evidence about pharmacologic approaches are presented. Finally, the authors discuss important future directions, including a potential increase in prolonged grief disorder cases due to the COVID-19 pandemic.
PMCID:8475918
PMID: 34690579
ISSN: 1541-4094
CID: 5042182

Randomized, Placebo-Controlled Trial of the Angiotensin Receptor Antagonist Losartan for Posttraumatic Stress Disorder

Stein, Murray B; Jain, Sonia; Simon, Naomi M; West, James C; Marvar, Paul J; Bui, Eric; He, Feng; Benedek, David M; Cassano, Paolo; Griffith, James L; Howlett, Jonathan; Malgaroli, Matteo; Melaragno, Andrew; Seligowski, Antonia V; Shu, I-Wei; Song, Suzan; Szuhany, Kristin; Taylor, Charles T; Ressler, Kerry J
BACKGROUND:Evidence-based pharmacological treatments for posttraumatic stress disorder (PTSD) are few and of limited efficacy. Previous work suggests that angiotensin type 1 receptor inhibition facilitates fear inhibition and extinction, important for recovery from PTSD. This study tests the efficacy of the angiotensin type 1 receptor antagonist losartan, an antihypertensive drug, repurposed for the treatment of PTSD. METHODS:A randomized controlled trial was conducted for 10 weeks in 149 men and women meeting DSM-5 PTSD criteria. Losartan (vs. placebo) was flexibly titrated from 25 to 100 mg/day by week 6 and held at highest tolerated dose until week 10. Primary outcome was the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) change score at 10 weeks from baseline. A key secondary outcome was change in CAPS-5 associated with a single nucleotide polymorphism of the ACE gene. Additional secondary outcomes included changes in the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9, and proportion of responders with a Clinical Global Impressions-Improvement scale of "much improved" or "very much improved." RESULTS:Both groups had robust improvement in PTSD symptoms, but there was no significant difference on the primary end point, CAPS-5 measured as week 10 change from baseline, between losartan and placebo (mean change difference, 0.9, 95% confidence interval, -3.2 to 5.0). There was no significant difference in the proportion of Clinical Global Impressions-Improvement scale responders for losartan (58.6%) versus placebo (57.9%), no significant differences in changes in PTSD Checklist for DSM-5 or Patient Health Questionnaire-9, and no association between ACE genotype and CAPS-5 improvement on losartan. CONCLUSIONS:At these doses and durations, there was no significant benefit of losartan compared with placebo for the treatment of PTSD. We discuss implications for failure to determine the benefit of a repurposed drug with strong a priori expectations of success based on preclinical and epidemiological data.
PMID: 34275593
ISSN: 1873-2402
CID: 4947782

Machine yearning: How advances in computational methods lead to new insights about reactions to loss

Malgaroli, Matteo; Maccallum, Fiona; Bonanno, George A
The loss of a loved one is a potentially traumatic event that can result in disparate outcomes and symptom patterns. Machine learning methods offer computational tools to probe this heterogeneity and understand grief psychopathology in its complexity. In this article, we examine the latest contributions to the scientific study of bereavement reactions garnered through the use of computational methods. We focus on findings originating from trajectory modeling studies, as well as the recent insights originating from the network analysis of prolonged grief symptoms. We also discuss applications of artificial intelligence for the accurate identification of major depression and post-traumatic stress, as examples for their potential applications to the study of loss reactions.
PMID: 34261030
ISSN: 2352-2518
CID: 4938662

Barriers and engagement in breast cancer survivorship wellness activities

Szuhany, Kristin L; Malgaroli, Matteo; Riley, Gabriella; Miron, Carly D; Suzuki, Rebecca; Park, Jae Hyung; Rosenthal, Jane; Chachoua, Abraham; Meyers, Marleen; Simon, Naomi M
PURPOSE/OBJECTIVE:Breast cancer survivors may be at risk for increased rates of emotional distress and poorer quality of life. Survivorship care plans (SCPs) promoting wellness activities may support well-being; however, survivors may not receive or engage in their SCPs. This study aimed to assess receipt and participation in SCP activities as well as barriers to engagement amongst breast cancer survivors. METHODS:Breast cancer survivors (n = 187; 99% female, Mean age = 57.7) consented and completed self-reported assessments of SCP recommendations, engagement and interest in wellness activities, and potential barriers to engagement. RESULTS:A minority of participants recalled receiving an SCP (21%). The most physician recommended (62%) and completed (53%) activity was exercise. Interest in adding other wellness activities to the SCP was high, with reported interest levels of approximately 50% for several activities (e.g., mind body, nutrition, psychotherapy interventions). Fully half reported that having a physician-designed plan would influence participation in activities. The most common reported barriers to SCP activity engagement were lack of time (82%), work/school (65%), and lack of information (65%). CONCLUSION/CONCLUSIONS:Few survivors recalled receiving a formal SCP, and lack of information about wellness activities was a commonly reported barrier to participation. Interest in wellness activities was generally high and may indicate the need for more formal prescription or motivation enhancement techniques to promote SCP engagement. There may be a clinical need to emphasize SCP recommendations to enhance recall and increase engagement in wellness activities that may reduce psychological distress and improve quality of life.
PMID: 34095986
ISSN: 1573-7217
CID: 4899592

Posttraumatic Distress Symptoms and Their Response to Treatment in Adults With Prolonged Grief Disorder

Na, Peter J; Adhikari, Samrachana; Szuhany, Kristin L; Chen, Alan Z; Suzuki, Rebecca R; Malgaroli, Matteo; Robinaugh, Donald J; Bui, Eric; Mauro, Christine; Skritskaya, Natalia A; Lebowitz, Barry D; Zisook, Sidney; Reynolds, Charles F; Shear, M Katherine; Simon, Naomi M
OBJECTIVE:Posttraumatic stress disorder and prolonged grief disorder (PGD) arise following major life stressors and may share some overlapping symptomatology. This study aimed to examine the presence and response to treatment of posttraumatic stress symptoms (PTSS) in bereaved adults with a primary diagnosis of PGD. METHODS:A randomized controlled trial of 395 adults with PGD (defined as an Inventory of Complicated Grief score ≥ 30 plus confirmation on structured clinical interview) randomly assigned participants to either complicated grief treatment (CGT) with citalopram, CGT plus placebo, citalopram, or placebo between March 2010 and September 2014. This secondary analysis examined the presence of PTSS (per the Davidson Trauma Scale) at baseline and change in PTSS with treatment using longitudinal mixed-effects regression and examined the role of violent compared to nonviolent deaths (loss type). RESULTS:High levels of PTSS were present at baseline, regardless of loss type, and were associated with increased functional impairment (P < .001). CGT with placebo demonstrated efficacy for PTSS compared to placebo in both threshold (OR = 2.71; 95% CI, 1.13-6.52; P = .026) and continuous (P < .001; effect size d = 0.47) analyses, and analyses were suggestive of a greater effect for CGT plus citalopram compared to citalopram alone (threshold analysis: OR = 2.84; 95% CI, 1.20-6.70; P = .017; continuous analysis: P = .053; d = 0.25). In contrast, citalopram did not differ from placebo, and CGT plus citalopram did not differ from CGT plus placebo. CONCLUSIONS:Bereavement-related PTSS are common in bereaved adults with PGD in the context of both violent and nonviolent death and are associated with poorer functioning. CGT shows efficacy for PTSS, while the antidepressant citalopram does not. TRIAL REGISTRATION:: ClinicalTrials.gov identifier: NCT01179568.
PMID: 34000119
ISSN: 1555-2101
CID: 4876702

Digital Health and Artificial Intelligence for PTSD: Improving Treatment Delivery Through Personalization

Malgaroli, Matteo; Hull, Thomas Derrick; Schultebraucks, Katharina
ISI:000623376600005
ISSN: 0048-5713
CID: 4820412

Networks of major depressive disorder: A systematic review

Malgaroli, Matteo; Calderon, Adam; Bonanno, George A
There has been a marked increase of network studies of Major Depressive Disorder (MDD). Despite rapidly growing contributions, their findings have yet to be systematically aggregated and examined. We therefore conducted a systematic review of depression network studies using PRISMA guidelines. A total of 254 clinical and population studies were collected from ISI's Web of Science and PsycINFO, between January 2010 to May 2020. A total of 23 between-subject studies were included for review, resulting in 58 cross-sectional networks. To determine their most critical symptoms and their connections, we analyzed strength centrality rankings, and aggregated the most robust symptoms connections into a summary network. Results indicated substantial variability between study samples, depression measures, and network features. Fatigue and Depressed Mood were the most central symptoms, while Weight changes tended to have the weakest centrality. Depressed Mood and Fatigue formed two separated symptoms communities characterized by recurrent connections, with Mood-Anhedonia as the most frequent edge of MDD. Network analysis informed our understanding of MDD, suggesting the critical role of Fatigue and Depressed Mood. The study's findings are discussed in their clinical and methodological implications, including future directions for network studies of MDD.
PMID: 33721606
ISSN: 1873-7811
CID: 4809732

Just in time crisis response: suicide alert system for telemedicine psychotherapy settings

Bantilan, Niels; Malgaroli, Matteo; Ray, Bonnie; Hull, Thomas D
AbstractObjective: To design a Natural Language Processing (NLP) algorithm capable of detecting suicide content from patients' written communication to their therapists, to support rapid response and clinical decision making in telehealth settings. Method: A training dataset of therapy transcripts for 1,864 patients was established by detecting patient content endorsing suicidality using a proxy-model anchored on therapists' suicide prevention interventions; human expert raters then assessed the level of suicide risk endorsed by patients identified by the proxy-model (i.e., no risk, risk factors, ideation, method, or plan). A bag-of-words classification model was then iteratively built using the annotations from the expert raters to detect suicide risk level in 85,216 labeled patients' sentences from the training dataset. Results: The final NLP model identified risk-related content from non-risk content with good accuracy (AUC = 82.78). Conclusions: Risk for suicide could be reliably identified by the NLP algorithm. The risk detection model could assist telehealth clinicians in providing crisis resources in a timely manner. This modeling approach could also be applied to other psychotherapy research tasks to assist in the understanding of how the psychotherapy process unfolds for each patient and therapist.
PMID: 32558625
ISSN: 1468-4381
CID: 4780692

Trajectories of grief: Comparing symptoms from the DSM-5 and ICD-11 diagnoses

Bonanno, George A; Malgaroli, Matteo
BACKGROUND:Diagnostic criteria for prolonged grief have appeared in the Diagnostic and Statistical Manual of Mental Disorders ( DSM-5; persistent complex bereavement disorder, PCBD) and in the ICD-11 (prolonged grief disorder, PGD), and the question of which diagnosis is most clinically useful has been hotly debated. This study provides the first longitudinal comparison of PCBD and PGD in their ability to capture symptom change over time and their relation to long-term outcomes. METHODS:A community sample was recruited consisting of 282 individuals who had recently lost a spouse. Structured clinical interviews were conducted at 3, 14, and 25 months postloss for symptoms corresponding to PCBD and PGD criteria. Outcomes at 25 months included PCBD and PGD caseness, depression, global functioning, and interviewer ratings of participant suffering. RESULTS:PCBD and PGD trajectories determined by growth mixture modeling, each captured three primary outcomes: resilience, moderate-improving symptoms, and prolonged-stable symptoms. The PGD solution also identified trajectories of increasing and decreasing distress: prolonged-worsening and acute-recovering symptoms. Prediction of 25-month outcomes indicated differences conforming to the severity of PGD symptoms, and the prolonged-worsening trajectory was associated with the worst adjustment. CONCLUSIONS:PGD symptoms were more differentiated, better-captured psychopathology, and other outcomes and were more sensitive to change over time compared to PCBD.
PMID: 31012187
ISSN: 1520-6394
CID: 4780672

The Context Sensitivity Index (CSI): Measuring the Ability to Identify the Presence and Absence of Stressor Context Cues

Bonanno, George A; Maccallum, Fiona; Malgaroli, Matteo; Hou, Wai Kai
The ability to accurately perceive cues to contextual demands across different situations has been identified as a crucial component of successful self-regulation. However, previous attempts to measure context sensitivity have suffered from serious methodological limitations, most notably the possibility that respondents may not possess sufficient knowledge of their own abilities, the confounding of perception of context with response to context, the use of only one or two contextual variations, and the failure to consider the abilities to both accurately detect contextual cues and accurately determine cue absence. This article reports a new, easy-to-administer scenario-based questionnaire measure, the Context Sensitivity Index (CSI), that addressed each of these limitations. The 20-item CSI was iteratively developed and normed using data from five studies to create separate indices to capture sensitivity to the presence of contextual cues (Cue Presence index) and to the relative absence of cues (Cue Absence index). We validated these indices against measures of flexibility, psychopathology, and other scales. Results are discussed in terms of the CSI's implications, limitations, and future applications.
PMID: 30577707
ISSN: 1552-3489
CID: 4780662