Transitions of care for adolescents with disorders of gut-brain interaction.

OBJECTIVES: Little is known about the experience of adolescents and young adults (AYA) with disorders of gut-brain interaction (DGBI) who transition from pediatric to adult gastroenterology care. In this two-part study, we used quantitative and qualitative methods to: (1) assess incidence of optimal versus suboptimal transitions of care for AYA with DGBI, (2) characterize health and quality of life effects of the transition, and (3) identify barriers and facilitators for optimal transition of care. METHODS: In Part 1, we conducted a retrospective review of AYA referrals to our adult neurogastroenterology clinic who had transitioned from pediatric gastroenterology care (N = 109, 17-23 years, 72% female). We collected demographic, psychosocial, and healthcare utilization data to determine rate and risk factors for suboptimal transitions. In Part 2, we recruited 24 AYA and parents (n = 19 AYA, n = 5 parents) for completion of a survey and semistructured interview, which was analyzed using validated rapid qualitative analysis method. RESULTS: In Part 1, 20% (22/109) of AYA met the criteria for suboptimal transition of care, which was associated with treatment adherence concern and functional impairment. In Part 2, we identified two principal themes: (1) AYA's health and quality of life are impacted during the transition, and (2) parental involvement and collaboration with pediatric gastrointestinal (GI) are facilitators to successful transitions, whereas access to care and practice style change are barriers. CONCLUSION: AYA with DGBI have high rates of suboptimal care transitions, affecting their health and quality of life. Our study highlights the need for a comprehensive approach that incorporates parents and pediatric providers.

Development of a brief cognitive-behavioral treatment for avoidant/restrictive food intake disorder in the context of disorders of gut-brain interaction: Initial feasibility, acceptability, and clinical outcomes.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) symptoms are common (up to 40%) among adults with disorders of gut-brain interaction (DGBI), but treatments for this population (DGBI + ARFID) have yet to be evaluated. We aimed to identify initial feasibility, acceptability, and clinical effects of an exposure-based cognitive-behavioral treatment (CBT) for adults with DGBI + ARFID. METHODS: Patients (N = 14) received CBT as part of routine care in an outpatient gastroenterology clinic. A two-part investigation of the CBT included a retrospective evaluation of patients who were offered a flexible (8-10) session length and an observational prospective study of patients who were offered eight sessions. Feasibility benchmarks were ≥75% completion of sessions, quantitative measures (for treatment completers), and qualitative interviews. Acceptability was assessed with a benchmark of ≥70% patients reporting a posttreatment satisfaction scores ≥3 on 1-4 scale and with posttreatment qualitative interviews. Mixed model analysis explored signals of improvement in clinical outcomes. RESULTS: All feasibility and acceptability benchmarks were achieved (and qualitative feedback revealed high satisfaction with the treatment and outcomes). There were improvements in clinical outcomes across treatment (all p's < .0001) with large effects for ARFID fear (-52%; Hedge's g = 1.5; 95% CI = 0.6, 2.5) and gastrointestinal-specific anxiety (-42%; Hedge's g = 1.0; 95% CI = 0.5, 16). Among those who needed to gain weight (n = 10), 94%-103% of expected weight gain goals were achieved. DISCUSSION: Initial development and testing of a brief 8-session CBT protocol for DGBI + ARFID showed high feasibility, acceptability, and promising clinical improvements. Findings will inform an NIH Stage 1B randomized control trial. PUBLIC SIGNIFICANCE: While cognitive-behavioral treatments (CBTs) for ARFID have been created in outpatient feeding and eating disorder clinics, they have yet to be developed and refined for other clinic settings or populations. In line with the recommendations for behavioral treatment development, we conducted a two-part investigation of an exposure-based CBT for a patient population with high rates of ARFID-adults with disorders of gut-brain interaction (also known as functional gastrointestinal disorders). We found patients had high satisfaction with treatment and there were promising improvements for both gastrointestinal and ARFID outcomes. The refined treatment includes eight sessions delivered by a behavioral health care provider and the findings reported in this article will be studied next in an NIH Stage 1B randomized controlled trial.

Can positive psychological interventions improve health behaviors? A systematic review of the literature.

Positive psychological interventions (PPIs), which aim to cultivate psychological well-being, have the potential to improve health behavior adherence. This systematic review summarized the existing literature on PPI studies with a health behavior outcome to examine study methodology, quality, and efficacy. Of the 27 identified studies, 20 measured physical activity, eight measured medication adherence, seven measured diet, and three measured smoking (eight targeted multiple behaviors). Twenty studies were randomized controlled trials (RCTs; 13 fully powered), and seven had a single-arm design. Study samples were usually adults (n = 21), majority non-Hispanic white (n = 15) and female (n = 14), and with a specific disease (e.g., diabetes, n = 16). Most interventions combined a PPI with health behavior-focused content (n = 17), used a remote delivery method (n = 17), and received a moderate or low study quality rating. Overall, 19/27 studies found a health behavior improvement of at least medium effect size, while six of the 13 studies powered to detect significant effects were statistically significant. Of the behaviors measured, physical activity was most likely to improve (14/20 studies). In summary, PPIs are being increasingly studied as a strategy to enhance health behavior adherence. The existing literature is limited by small sample size, low study quality and inconsistent intervention content and outcome measurement. Future research should establish the most effective components of PPIs that can be tailored to different populations, use objective health behavior measurement, and robustly examine the effects of PPIs on health behaviors in fully powered RCTs.

Relationships Between Life Stressors, Health Behaviors, and Chronic Medical Conditions in Mid-Life Adults: A Narrative Review.

OBJECTIVES: (1) To explore stressors affecting midlife adults and understand their impact on health behaviors and the development of chronic medical conditions; (2) To identify midlife-specific interventions that mitigate the impact of stressors on the health of this population. METHODS: We searched the PubMed database from inception to December 2017 using the search terms [mid-life] and [midlife] paired with related behaviors and conditions. Eligible articles provided data on: (1) sources of stress and effects on health behaviors, (2) development of chronic medical conditions, or (3) midlife interventions targeting health-related stressors or behaviors. We also reviewed the references of articles found in the initial search to identify additional articles. We included studies not focused on midlife for comparison. RESULTS: This review revealed that interpersonal stress (e.g., caregiving and loneliness), occupational stress, and financial stress are highly prevalent in midlife and have a substantial impact on the health and health behaviors of this population. Many of these stressors converge, intensifying associated distress and health impact. Although not always targeted specifically to this population, interventions focused on diminishing these stressors have showed promising results, particularly group interventions and those focused on positive psychological well-being and mindfulness. CONCLUSION: Midlife is a large and growing population at high risk for chronic medical conditions. Specific stressors during this period are negatively associated with health outcomes. Further research is needed on midlife-specific interventions focused on mitigating these stressors, as such interventions have the potential to improve quality of life and promote health in this significant and vulnerable segment of society.

Magnitude and sources of distress in mid-life adults with chronic medical illness: an exploratory mixed-methods analysis.

Most mid-life adults have at least one chronic medical condition (CMC) and are at risk for developing additional CMCs. Stressors specific to this life stage may contribute to CMC development by hindering healthy behaviors. The goal of this study was to compare sources and intensity of distress, as they relate to health behaviors, between mid-life and non-mid-life adults with CMCs. We utilized a mixed-methods approach by analyzing quantitative self-report measures of psychiatric symptoms and psychological well-being, with in-depth, semi-structured qualitative interviews to identify sources of stress in three cohorts of patients with CMCs (heart failure, type 2 diabetes, and coronary artery disease). Between-group differences on self-report measures were compared via independent samples t-tests and relevant themes from interview transcripts were compared via chi-square analysis. We found that mid-life participants (n = 30) reported greater psychological distress (depression/anxiety) than non-mid-life (n = 62) participants (Hospital Anxiety and Depression Scale scores 13.8 [SD 7.3] vs. 10.6 [SD 6.6]; t(90)=2.13; p = .035), and qualitative analysis revealed several specific sources of stress significantly more common (p < .001) in mid-life adults. Interventions targeting the needs of this population could reduce distress, improve health behaviors, and have a major impact on public health.

You've made the diagnosis of functional neurological disorder: now what?

Patients with functional neurological disorders (FND)/conversion disorder commonly present to outpatient clinics. FND is now a 'rule in' diagnosis based on neurological examination findings and semiological features. While neurologists may be more comfortable diagnosing patients with FND, there is only limited guidance as to how to conduct follow-up outpatient visits. Using clinical vignettes, we provide practical suggestions that may help guide clinical encounters including how to: (1) explore illness beliefs openly; (2) enquire longitudinally about predisposing vulnerabilities, acute precipitants and perpetuating factors that may be further elucidated over time; (3) facilitate psychotherapy engagement by actively listening for potentially unhelpful or maladaptive patterns of thoughts, behaviours, fears or psychosocial stressors that can be reflected back to the patient and (4) enquire about the fidelity of individual treatments and educate other providers who may be less familiar with FND. These suggestions, while important to individualise, provide a blueprint for follow-up FND clinical care.

Non-cardiac Chest Pain: A Review for the Consultation-Liaison Psychiatrist.

BACKGROUND: Patients presenting with chest pain to general practice or emergency providers represent a unique challenge, as the differential is broad and varies widely in acuity. Importantly, most cases of chest pain in both acute and general practice settings are ultimately found to be non-cardiac in origin, and a substantial proportion of patients experiencing non-cardiac chest pain (NCCP) suffer significant disability. In light of emerging evidence that mental health providers can serve a key role in the care of patients with NCCP, knowledge of the differential diagnosis, psychiatric co-morbidities, and therapeutic techniques for NCCP would be of great use to both consultation-liaison (C-L) psychiatrists and other mental health providers. METHODS: We reviewed prior published work on (1) the appropriate medical workup of the acute presentation of chest pain, (2) the relevant medical and psychiatric differential diagnosis for chest pain determined to be non-cardiac in origin, (3) the management of related conditions in psychosomatic medicine, and (4) management strategies for patients with NCCP. RESULTS: We identified key differential diagnostic and therapeutic considerations for psychosomatic medicine providers in 3 different clinical contexts: acute care in the emergency department, inpatient C-L psychiatry, and outpatient C-L psychiatry. We also identified several gaps in the literature surrounding the short-term and long-term management of NCCP in patients with psychiatric etiologies or co-morbid psychiatric conditions. CONCLUSIONS: Though some approaches to the care of patients with NCCP have been developed, more work is needed to determine the most effective management techniques for this unique and high-morbidity population.

Nerve-derived transmitters including peptides influence cutaneous immunology.

Clinical observations suggest that the nervous and immune systems are closely related. For example, inflammatory skin disorders; such as psoriasis, atopic dermatitis, rosacea and acne; are widely believed to be exacerbated by stress. A growing body of research now suggests that neuropeptides and neurotransmitters serve as a link between these two systems. Neuropeptides and neurotransmitters are released by nerves innervating the skin to influence important actors of the immune system, such as Langerhans cells and mast cells, which are located within close anatomic proximity. Catecholamines and other sympathetic transmitters that are released in response to activation of the sympathetic nervous system are also able to reach the skin and affect immune cells. Neuropeptides appear to direct the outcome of Langerhans cell antigen presentation with regard to the subtypes of Th cells generated and neuropeptides induce the degranulation of mast cells, among other effects. Additionally, endothelial cells, which release many inflammatory mediators and express cell surface molecules that allow leukocytes to exit the bloodstream, appear to be regulated by certain neuropeptides and transmitters. This review focuses on the evidence that products of nerves have important regulatory activities on antigen presentation, mast cell function and endothelial cell biology. These activities are highly likely to have clinical and therapeutic relevance.

Nurse practitioner-delivered cognitive-behavioral treatment as a novel implementation route for irritable bowel syndrome: A proof of concept.

BACKGROUND: Exposure-based cognitive-behavioral therapy (exposure-CBT) is efficacious for irritable bowel syndrome (IBS). However, few patients receive exposure-CBT due to a lack of behavioral health providers trained in brain-gut behavior therapies. Nurse practitioners (NPs) could fill a critical need for scalable delivery methods. In a pragmatic investigation of a 5-session NP-delivered exposure-CBT for adults with Rome IV-defined IBS, we evaluated treatment feasibility and acceptability and explored changes clinical outcomes. METHODS: Exposure-CBT was delivered as part of routine care involving four sessions every other week and a 2-month booster session. Patients could electively participate in an observational study including pre-, mid-, and post-treatment surveys and a post-treatment qualitative interview. Independently coded ratings of NP treatment protocol adherence and competence ratings were completed from audio recordings, rated on a 1 (not at all) to 5 (completely) scale. RESULTS: Twenty-five patients consented (ages 22-67 years; 76% female; 48% IBS-diarrhea predominant). There was high feasibility-adherence average = 4.1, NP competence average = 4.8, 72% treatment completion, 93% satisfaction scores ≥3. Treatment satisfaction was high (rated as 4/4 "very satisfied" by n = 9 and as 3/4 "mostly satisfied" by n = 5). There were improvements in clinical outcomes across treatment with large effects for IBS-symptom severity (-53%; Hedge's g = 1.0; 95% confidence interval [CI] = 0.5, 1.5) and IBS quality of life (+31%; Hedge's g = 0.8; 95% CI = 0.4, 1.2). CONCLUSIONS: NP-delivered exposure-CBT for IBS was initially feasible and acceptable with promising clinical improvements. Findings will inform a future NIH Stage 1B/ORBIT Phase IIB pilot randomized control trial.

History of trying exclusion diets and association with avoidant/restrictive food intake disorder in neurogastroenterology patients: A retrospective chart review.

BACKGROUND: Exclusion diets for gastrointestinal symptom management have been hypothesized to be a risk factor for avoidant/restrictive food intake disorder (ARFID; a non-body image-based eating disorder). In a retrospective study of pediatric and adult neurogastroenterology patients, we aimed to (1) identify the prevalence and characteristics of an exclusion diet history and (2) evaluate if an exclusion diet history was concurrently associated with the presence of ARFID symptoms. METHODS: We conducted a chart review of 539 consecutive referrals (ages 6-90, 69% female) to adult (n = 410; January-December 2016) and pediatric (n = 129; January 2016-December 2018) neurogastroenterology clinics. Masked coders (n = 4) retrospectively applied DSM-5 criteria for ARFID and a separate coder assessed documentation of exclusion diet history. We excluded patients with no documentation of diet in the chart (n = 35) or who were not orally fed (n = 9). RESULTS: Of 495 patients included, 194 (39%) had an exclusion diet history, and 118 (24%) had symptoms of ARFID. Of reported diets, dairy-free was the most frequent (45%), followed by gluten-free (36%). Where documented, exclusion diets were self-initiated by patients/parents in 66% of cases, and recommended by gastroenterology providers in 30%. Exclusion diet history was significantly associated with the presence of ARFID symptoms (OR = 3.12[95% CI 1.92-5.14], p < 0.001). CONCLUSIONS: History of following an exclusion diet was common and was most often patient-initiated among pediatric and adult neurogastroenterology patients. As patients with self-reported exclusion diet history were over three times as likely to have ARFID symptoms, providers should be cognizant of this potential association when considering dietary interventions.

An Adaptive, Algorithm-based Text Message Intervention to Promote Health Behavior Adherence in Type 2 Diabetes: Treatment Development and Proof-of-Concept Trial.

BACKGROUND: Most individuals with type 2 diabetes (T2D) struggle to adhere to one or more health behaviors. Text message interventions (TMIs) have the potential to improve adherence but have had mixed effects on diet and activity in T2D. We developed an eight-week, adaptive, algorithm-driven TMI to promote physical activity, diet, self-care, and well-being. Then, in a single-arm trial, we assessed its feasibility, acceptability, and preliminary efficacy in 15 individuals with T2D and suboptimal adherence. METHODS: Participants received daily text messages and were asked to rate the utility of each message (0=not helpful, 10=very helpful). These ratings were used by an algorithm to select subsequent messages based on each participant's prior ratings. We assessed intervention feasibility by rates of message transmission/response and acceptability through ratings of message utility and burden. Finally, we examined pre-post changes in diabetes self-care, diet, physical activity, and psychological outcomes and calculated effect sizes (Cohen's d). RESULTS: All text messages were delivered, and participants provided ratings for 79% of messages, above our a priori thresholds for feasibility. Participants rated the individual messages and overall TMI as subjectively useful (utility: 8.1 [SD=2.1] and 7.8 [SD=2.0], respectively) and not burdensome (burden: 0.8 [SD=1.8]). The intervention led to significant, medium- to large-sized improvements in self-care (d=0.77), diet (d=0.99), and activity (d=0.61) but minimal change in psychological outcomes. CONCLUSIONS: The TMI was feasible and well-accepted, and it led to promising improvements in adherence-related outcomes. These findings should be confirmed in a larger randomized controlled trial.

Psychiatric comorbidities among adult patients with disorders of gut-brain interaction: Prevalence and relationships to treatment outcomes.

BACKGROUND: Little is known about the impact of psychiatric comorbidity on pharmacologic treatment outcomes, including neuromodulators (medications targeting the gut-brain axis), among adult patients with disorders of gut-brain interaction (DGBI). Accordingly, we aimed to examine associations between psychiatric comorbidity and DGBI pharmacologic treatment outcomes. METHODS: In a retrospective study of consecutively referred new patients (N = 410; ages 18-90; 73% female) to a tertiary neurogastroenterology clinic in 2016 with follow-up through 2018, relationships between psychiatric illness (any psychiatric illness, anxiety disorders, depressive disorders) and pharmacologic treatment selection (any medication, neuromodulating medication) and treatment outcomes, respectively, were examined using multivariable logistic regression, adjusting for demographics, gastrointestinal (GI) diagnoses, and pre-existing neuromodulator use. KEY RESULTS: Anxiety disorders (35%) were the most common psychiatric comorbidity, followed by depressive disorders (29%). Patients with anxiety disorders were more likely to be prescribed a neuromodulator by their gastroenterologist (OR = 1.72 [95% CI 1.10-2.75]) yet less likely to respond to neuromodulators (OR = 0.43 [0.21-0.90]) or any GI medication (OR = 0.24 [0.12-0.50]) in fully adjusted analyses. In contrast, depressive disorders were not associated with neuromodulator prescription or response. CONCLUSIONS AND INFERENCES: Anxiety disorders are common among patients with DGBI and significantly reduce the likelihood of GI pharmacologic treatment response to any medication prescribed, including neuromodulators.

Positive psychological well-being: A novel concept for improving symptoms, quality of life, and health behaviors in irritable bowel syndrome.

BACKGROUND: Though a growing body of research suggests that greater positive psychological well-being in irritable bowel syndrome (IBS) may be protective, existing brain-gut behavior therapies primarily target negative psychological factors. Little is known about how positive psychological factors in IBS relate to IBS symptoms, health-related quality of life (HRQoL), or adherence to key health behaviors, such as physical activity and diet modification. Accordingly, per the ORBIT model of behavioral treatment development for chronic diseases, we explored potential connections between psychological constructs and IBS symptoms, health behavior engagement (physical activity and dietary modification), and HRQoL in a qualitative study to inform the development of a novel brain-gut behavior therapy. METHODS: Participants with IBS completed self-report assessments and semi-structured phone interviews about relationships between positive and negative psychological constructs, IBS symptoms, health behavior engagement, and HRQoL. KEY RESULTS: Participants (n = 23; 57% female) ranged in age from 25 to 79 (mean age = 54). IBS subtypes were similarly represented (IBS-diarrhea [n = 8], IBS-constipation [n = 7], and IBS-mixed [n = 8]). Participants described opposing relationships between positive and negative psychological constructs, IBS symptoms, health behavior engagement, and HRQoL, respectively, such that experiencing positive constructs largely mitigated IBS symptoms, boosted health behavior participation, and improved HRQoL, and negative constructs exacerbated symptoms, reduced health behavior participation, and worsened HRQoL. CONCLUSIONS AND INFERENCES: Participants with IBS linked greater positive psychological well-being to moderated IBS symptoms and better HRQoL and health behavior participation. An intervention to cultivate greater well-being may be a novel way to mitigate IBS symptoms, boost health behavior participation, and improve HRQoL in IBS.

Positive psychological well-being and clinical characteristics in IBS: A systematic review.

OBJECTIVE: Psychological factors (e.g., depression, anxiety) are known to contribute to the development and maintenance of irritable bowel syndrome (IBS). Less is known, however, about the role of positive psychological well-being (PPWB) in IBS. Accordingly, we completed a systematic review of the literature examining relationships between PPWB and clinical characteristics in IBS. METHOD: A systematic review using search terms related to PPWB and IBS from inception through July 28, 2022, was completed. Quality was assessed with the NIH Quality Assessment Tool. A narrative synthesis of findings, rather than meta-analysis, was completed due to study heterogeneity. RESULTS: 22 articles with a total of 4285 participants with IBS met inclusion criteria. Individuals with IBS had lower levels of PPWB (e.g., resilience, positive affect, self-efficacy, emotion regulation) compared to healthy populations, which in turn was associated with reduced physical and mental health and health-related quality of life (HRQoL). Limited exploration of potential biological mechanisms underlying these relationships has been described. CONCLUSIONS: PPWB is diminished in individuals with IBS compared to other populations, and greater PPWB is linked to superior physical, psychological, and HRQoL outcomes. Interventions to increase PPWB may have the potential to improve IBS-related outcomes. REGISTRATION: Prospective Register of Systematic Reviews CRD42022304767.

Pharmacologic treatment of delirium symptoms: A systematic review.

OBJECTIVE: We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium symptoms among hospitalized adults. METHODS: Searches of PubMed, Scopus, Embase, and Cochrane Library databases from inception to May 2021 were performed to identify studies investigating efficacy of pharmacologic agents for management of delirium. RESULTS: Of 11,424 articles obtained from searches, a total of 33 articles (N = 3030 participants) of randomized or non-randomized trials, in which pharmacologic treatment was compared to active comparator, placebo, or no treatment, met all criteria and were included in this review. Medications used for management of delirium symptoms included antipsychotic medications (N = 27), alpha-2 agonists (N = 5), benzodiazepines (N = 2), antidepressants (n = 1), acetylcholinesterase inhibitors (N = 2), melatonin (N = 2), opioids (N = 1), and antiemetics (N = 2). Despite somewhat mixed findings and a relative lack of high-quality trials, it appears that antipsychotic medications (e.g., haloperidol, olanzapine, risperidone, or quetiapine) and dexmedetomidine have the potential to improve delirium outcomes. CONCLUSIONS: Pharmacologic agents can reduce delirium symptoms (e.g., agitation) in some hospitalized patients. Additional double-blinded, randomized, placebo-controlled clinical trials are critically needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations (e.g., post-surgical patients, patients at the end-of-life, or in intensive care units).

A Care Management Intervention for Noncardiac Chest Pain: Treatment Development and Feasibility Assessment.

ABSTRACT.Objective: Noncardiac chest pain is common and can cause distress, impair quality of life, and lead to recurrent evaluation. It is often multifactorial in etiology and influenced by psychological factors. The objective of this study was to describe the development, implementation, and preliminary feasibility of an 8-week multicomponent care management intervention.Methods: Participants with noncardiac chest pain were recruited from primary care clinics, ambulatory cardiac stress testing, and the emergency department (ED) at an urban academic hospital from March 2019 to November 2019. The care management team consisted of a nurse, cardiologist, and psychiatrist. Following a 1-time consultation visit with the cardiologist and nurse, evaluation and treatment recommendations were conveyed to the participant's primary care physician. The nurse completed 8 weekly phone calls with the participant to provide support, introduce therapeutic principles, and assist with care coordination under the supervision of a psychiatrist. Intervention feasibility was assessed on 7 domains. To examine preliminary efficacy, the number of ED visits was recorded, and participants completed pre-post measures of psychological health and health-related quality of life and Likert scales of chest pain symptom severity, frequency, and impact.Results: The intervention was developed and implemented in 3 patients who completed 100% of the consultation visits and a mean of 95.8% of study phone calls. There were no adverse events or ED visits. Mean scores for chest pain severity, chest pain frequency, chest pain impact, depression, anxiety, and somatization all improved. No other trends were observed.Conclusions: The findings suggest that a care management intervention may be feasible with potential to improve chest pain symptoms and psychological outcomes. A larger, randomized trial is needed to explore the efficacy of this intervention.Trial Registration: ClinicalTrials.gov identifier: NCT04904198.

Recurrent versus new-onset depressive symptoms: Relationships with biomarkers of cardiovascular health following acute coronary syndrome.

OBJECTIVE: New-onset depressive symptoms commonly arise among persons without a history of major depressive disorder (MDD) in the setting of acute medical illness. Although depressive symptoms in general are associated with alterations in prognostic biomarkers following acute coronary syndrome (ACS), the nature of specifically new-onset depressive symptoms is less well-characterized. It is unclear whether such symptoms neurobiologically resemble recurrent symptoms of MDD or instead represent a distinct condition. In this exploratory analysis, we aimed to examine the effects of prior MDD history on the relationships between post-ACS depressive symptoms and cardiovascular biomarkers. METHODS: One-hundred sixty-four participants attended study visits 2 weeks and 6 months after ACS to complete self-report measures and provide biomarker samples. MDD history was identified by a psychiatrist through systematic electronic medical record review. Generalized estimating equations were performed to examine the moderating effects of MDD history on concurrent relationships between depressive symptoms and several biomarkers (endothelin-1, soluble intercellular adhesion molecule-1, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha). RESULTS: Twenty percent (n = 33) of participants had a history of MDD. Depressive symptoms were more strongly associated with levels of endothelin-1 in patients with prior MDD compared to those without (B = 0.024, 95% CI [0.005, 0.043], p = .012), adjusting for age, sex, medical factors, and anxiety. MDD history did not moderate relationships between depressive symptoms and other biomarkers. CONCLUSION: Recurrent post-ACS depressive symptoms are more strongly associated with elevated endothelin-1 levels than new-onset symptoms. Further work is needed to clarify the mechanism and clinical implications of this relationship.

The nucleus accumbens is involved in both the pursuit of social reward and the avoidance of social punishment.

Human social motivation is characterized by the pursuit of social reward and the avoidance of social punishment. The ventral striatum/nucleus accumbens (VS/Nacc), in particular, has been implicated in the reward component of social motivation, i.e., the 'wanting' of social incentives like approval. However, it is unclear to what extent the VS/Nacc is involved in avoiding social punishment like disapproval, an intrinsically pleasant outcome. Thus, we conducted an event-related functional magnetic resonance imaging (fMRI) study using a social incentive delay task with dynamic video stimuli instead of static pictures as social incentives in order to examine participants' motivation for social reward gain and social punishment avoidance. As predicted, the anticipation of avoidable social punishment (i.e., disapproval) recruited the VS/Nacc in a manner that was similar to VS/Nacc activation observed during the anticipation of social reward gain (i.e., approval). Stronger VS/Nacc activity was accompanied by faster reaction times of the participants to obtain those desired outcomes. This data support the assumption that dynamic social incentives elicit robust VS/Nacc activity, which likely reflects motivation to obtain social reward and to avoid social punishment. Clinical implications regarding the involvement of the VS/Nacc in social motivation dysfunction in autism and social phobia are discussed.