The Impact of Adjustment on Workplace Attitudes and Behaviors Among Health Care Workers During the COVID-19 Pandemic.

OBJECTIVE: We examined the impact of health care workers' (HCWs) adjustment to the COVID-19 pandemic on their work-related attitudes and behaviors. METHODS: HCWs ( n = 1468) participated in an observational longitudinal study in which they completed surveys of anxiety and occupational health between 2020 and 2021. RESULTS: Most HCWs reported anxiety that was consistently below the diagnostic threshold (68%) or fell below the threshold within a year (16%). Others reported consistently high (14%) or increasing (2%) anxiety, especially women, younger HCWs, those with a weakened immune system, and allied health professionals. Consistently high or increasing anxiety was associated with poorer job satisfaction, work engagement, perceived supervisor support, burnout, and turnover intentions. CONCLUSIONS: Resources to support HCWs may be focused on those who report consistently high or increasing anxiety to minimize the effects of crises and disasters on the workforce.

Altered Reward Processing and Sex Differences in Chronic Pain.

Chronic pain and reward processing are understood to be reciprocally related to one another. Previous studies of reward processing in chronic pain patients have reported incongruent findings. While several factors likely contribute to these disparate findings, these previous studies did not stratify their analyses by sex-a factor previously shown to robustly impact reward-related responses. Thus, we examined sex as a factor of interest in level of striatal activation during anticipation of monetary incentives among patients with chronic non-specific back pain and healthy controls (HC). This study utilized functional magnetic resonance imaging during a monetary incentive delay task to evaluate reward and loss responsivity in the striatum among males and females with and without chronic pain (N = 90). Group, sex, and group-by-sex interactions were analyzed via repeated measures analysis of variance. Among HC, males exhibited significantly greater blood oxygen level dependent (BOLD) signal in the striatum during reward anticipation, particularly during large reward trials. By contrast, no significant sex differences were observed among patients. A significant group-by-sex interaction was also observed, revealing diminished BOLD responses among males with chronic pain relative to control males. These results provide novel evidence of sex-specific reductions in anticipatory responses to reward in patients with chronic pain. Altered striatal reward responsivity among males, but not females, suggests that the reward systems of males and females are uniquely disrupted by chronic pain, and highlights the value of including sex as a factor of interest in future studies of reward responsivity in the context of persistent pain.

Unique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function.

Major depressive disorder (MDD) and opioid use disorder (OUD) are common, potentially fatal, polygenic disorders that are moderately heritable and often co-occur. We examined the unique and shared associations of polygenic risk scores (PRS) for these disorders with µ-opioid receptor (MOR) concentration and endogenous opioid response during a stressful stimulus. Participants were 144 healthy European-ancestry (EA) subjects (88 females) who underwent MOR quantification scans with [11C]carfentanil and PET and provided DNA for genotyping. MOR non-displaceable binding potential (BPND) was measured in 5 regions of interest (ROIs) related to mood and addiction. We examined associations of PRS both at baseline and following opioid release calculated as the ratio of baseline and stress-challenge scans, first in the entire sample and then separately by sex. MOR availability at baseline was positively associated with MDD PRS in the amygdala and ventral pallidum. MDD and OUD PRS were significantly associated with stress-induced opioid system activation in multiple ROIs, accounting for up to 14.5% and 5.4%, respectively, of the variance in regional activation. The associations were most robust among females, where combined they accounted for up to 25.0% of the variance among the ROIs. We conclude that there is a pathophysiologic link between polygenic risk for MDD and OUD and opioid system activity, as evidenced by PRS with unique and overlapping regional associations with this neurotransmitter system. This link could help to explain the high rate of comorbidity of MDD and OUD and suggests that opioid-modulating interventions could be useful in treating MDD and OUD, both individually and jointly.

Social cognitive mechanisms in healthcare worker resilience across time during the pandemic.

PURPOSE: Healthcare workers are at increased risk for mental health problems during disasters such as the COVID-19 pandemic. Identifying resilience mechanisms can inform development of interventions for this population. The current study examined pathways that may support healthcare worker resilience, specifically testing enabling (social support enabled self-efficacy) and cultivation (self-efficacy cultivating support) models. METHODS: Healthcare workers (N = 828) in the Rocky Mountain West completed self-report measures at four time points (once per month from April to July of 2020). We estimated structural equation models to explore the potential mediating effects that received social support and coping self-efficacy had (at time 2 and time 3) between traumatic stress symptom severity (at time 1 and time 4). Models included covariates gender, age, minority status, and time lagged co-variations between the proposed mediators (social support and coping self-efficacy). RESULTS: The full model fit the data well, CFI = .993, SRMR = .027, RMSEA = .036 [90% CIs (0.013, 0.057)]. Tests of sequential mediation supported enabling model dynamics. Specifically, the effects of time 1 traumatic stress severity were mediated through received social support at time 2 and time 3 coping self-efficacy, in sequential order to reduce time 4 traumatic stress severity. CONCLUSIONS: Findings show the importance of received social support and coping self-efficacy in mitigating psychopathology risk. Interventions can support mental health by focusing on social resource engagement that facilitates coping empowerment, which may decrease risk for mental health job-related problems among frontline healthcare workers exposed to highly stressful events.

Risk for opioid misuse in chronic pain patients is associated with endogenous opioid system dysregulation.

µ-Opioid receptors (MOR) are a major target of endogenous and exogenous opioids, including opioid pain medications. The µ-opioid neurotransmitter system is heavily implicated in the pathophysiology of chronic pain and opioid use disorder and, as such, central measures of µ-opioid system functioning are increasingly being considered as putative biomarkers for risk to misuse opioids. To explore the relationship between MOR system function and risk for opioid misuse, 28 subjects with chronic nonspecific back pain completed a clinically validated measure of opioid misuse risk, the Pain Medication Questionnaire (PMQ), and were subsequently separated into high (PMQ > 21) and low (PMQ ≤ 21) opioid misuse risk groups. Chronic pain patients along with 15 control participants underwent two separate [11C]-carfentanil positron emission tomography scans to explore MOR functional measures: one at baseline and one during a sustained pain-stress challenge, with the difference between the two providing an indirect measure of stress-induced endogenous opioid release. We found that chronic pain participants at high risk for opioid misuse displayed higher baseline MOR availability within the right amygdala relative to those at low risk. By contrast, patients at low risk for opioid misuse showed less pain-induced activation of MOR-mediated, endogenous opioid neurotransmission in the nucleus accumbens. This study links human in vivo MOR system functional measures to the development of addictive disorders and provides novel evidence that MORs and µ-opioid system responsivity may underlie risk to misuse opioids among chronic pain patients.

Using Network Parcels and Resting-State Networks to Estimate Correlates of Mood Disorder and Related Research Domain Criteria Constructs of Reward Responsiveness and Inhibitory Control.

BACKGROUND: Resting-state graph-based network edges can be powerful tools for identification of mood disorders. We address whether these edges can be integrated with Research Domain Criteria (RDoC) constructs for accurate identification of mood disorder-related markers, while minimizing active symptoms of disease. METHODS: We compared 132 individuals with currently remitted or euthymic mood disorder with 65 healthy comparison participants, ages 18-30 years. Subsets of smaller brain parcels, combined into three prominent networks and one network of parcels overlapping across these networks, were used to compare edge differences between groups. Consistent with the RDoC framework, we evaluated individual differences with performance measure regressors of inhibitory control and reward responsivity. Within an omnibus regression model, we predicted edges related to diagnostic group membership, performance within both RDoC domains, and relevant interactions. RESULTS: There were several edges of mood disorder group, predominantly of greater connectivity across networks, different than those related to individual differences in inhibitory control and reward responsivity. Edges related to diagnosis and inhibitory control did not align well with prior literature, whereas edges in relation to reward responsivity constructs showed greater alignment with prior literature. Those edges in interaction between RDoC constructs and diagnosis showed a divergence for inhibitory control (negative interactions in default mode) relative to reward (positive interactions with salience and emotion network). CONCLUSIONS: In conclusion, there is evidence that prior simple network models of mood disorders are currently of insufficient biological or diagnostic clarity or that parcel-based edges may be insufficiently sensitive for these purposes.

Mental health risks differentially associated with immunocompromised status among healthcare workers and family members at the pandemic outset.

The mental health of healthcare workers (HCWs) is critical to their long-term well-being and future disaster preparedness. Goal 1 of this study was to identify rates of mental health problems experienced by HCWs. Goal 2 was to test a model of risk stemming from pandemic-related stressors and vulnerability factors. This cross-sectional study included HCWs (N â€‹= â€‹2,246 [1,573 clinical providers; 673 non-clinical staff]) in the Rocky Mountain West who voluntarily completed an online survey in April/May 2020. Respondents completed measures for traumatic stress symptoms, depression, anxiety, alcohol use, and sleep. Logistic regressions stratified by professional role (clinical versus non-clinical) were specified to predict clinical screening cutoff (positive/negative) as a function of five pandemic-related stressors (immunocompromised self; immunocompromised household member; care provision to infected patients; clinical management role; positive cases). Results showed that more than half of HCWs surveyed (52.5%) screened positive (above cutoff) for traumatic stress, depression, or anxiety, with ~20% reporting problematic alcohol use, and variable insufficient sleep from ~10% off shift to ~50% on shift. Clinical employees with an immunocompromised household member had increased odds of screening positive for a mental health problem. Non-clinical HCWs who were immunocompromised were at elevated risk for screening positive a mental health problem. Being female, minority status, and younger increased odds for mental health problems. Implications include alleviating a portion of the mental health burden of HCWs involved in response to the SARS-CoV-2 pandemic by considering policies to protect immunocompromised HCWs and their families (e.g., vaccine priorities, telework options).

Pandemic-related mental health risk among front line personnel.

The mental health of frontline workers is critical to a community's ability to manage crises and disasters. This study assessed risks for mental health problems (traumatic stress, depression, anxiety, alcohol use, insomnia) in association with pandemic-related stressors in a sample of emergency and hospital personnel (N = 571). Respondents completed self-report surveys online from April 1st to May 7th, 2020 in the Rocky Mountain region of the United States. Results showed that roughly fifteen to thirty percent of respondents screened positive for each disorder. Odds of screening positive were similar between groups for probable acute traumatic stress, depressive disorder, anxiety disorder, and alcohol use disorder; emergency personnel reported significantly higher rates of insufficient sleep than healthcare workers. Logistic regressions showed that respondents who reported having an immunocompromised condition had higher odds of acute traumatic stress, anxiety, and depression. Having an immunocompromised household member was associated with higher odds of insufficient sleep and anxiety. Being in a direct care provision role was associated with higher odds of screening positive for risky alcohol use. Being in a management role over direct care providers was associated with higher odds of screening positive for anxiety, risky alcohol use, and insufficient sleep. There was an inverse relationship between number of positive COVID-19 cases and anxiety, such that as positive cases went up, anxiety decreased. Overall, the mental health risks that we observed early in the COVID-19 pandemic are elevated above previous viral outbreaks (SARS) and comparable to rates shown in disasters (9/11 attacks; Hurricane Katrina).

Sex differences in the human reward system: convergent behavioral, autonomic and neural evidence.

Several studies have suggested that females and males differ in reward behaviors and their underlying neural circuitry. Whether human sex differences extend across neural and behavioral levels for both rewards and punishments remains unclear. We studied a community sample of 221 young women and men who performed a monetary incentive task known to engage the mesoaccumbal pathway and salience network. Both stimulus salience (behavioral relevance) and valence (win vs loss) varied during the task. In response to high- vs low-salience stimuli presented during the monetary incentive task, men showed greater subjective arousal ratings, behavioral accuracy and skin conductance responses (P < 0.006, Hedges' effect size g = 0.38 to 0.46). In a subsample studied with functional magnetic resonance imaging (n = 44), men exhibited greater responsiveness to stimulus salience in the nucleus accumbens, midbrain, anterior insula and dorsal anterior cingulate cortex (P < 0.02, g = 0.86 to 1.7). Behavioral, autonomic and neural sensitivity to the valence of stimuli did not differ by sex, indicating that responses to rewards vs punishments were similar in women and men. These results reveal novel and robust sex differences in reward- and punishment-related traits, behavior, autonomic activity and neural responses. These convergent results suggest a neurobehavioral basis for sexual dimorphism observed in the reward system, including reward-related disorders.

Common neural responses to romantic rejection and acceptance in healthy adults.

Although romantic rejection and acceptance have a strong impact on mood in adults, their neural response patterns are relatively unexplored. The present study used functional magnetic resonance imaging (fMRI) to examine neural responses to romantic rejection and acceptance in 36 healthy men and women, ages 18-53 years. Activations during rejection showed extensive anatomical overlap with activations during acceptance in the ventrolateral prefrontal cortex (vlPFC) and anterior insula (AI). In an analysis of sex differences, men and women did not differ in behavioral responses; however, men showed greater activation to romantic rejection and acceptance in the left vlPFC and AI compared to women. The vlPFC and AI may play a role in social cognition, tuned to detect the intentions and feelings of others whether they are positive or negative. In the context of romantic rejection and acceptance, this activation may signal the intent of others who are desired by the individual, leading to changes in mood, self-esteem, and social motivation.

Dissociable Neural Responses to Monetary and Social Gain and Loss in Women With Major Depressive Disorder.

Neuroimaging studies have revealed aberrant reward and loss processing in patients with major depressive disorder (MDD). While most studies use monetary stimuli to study these processes, it is important to consider social stimuli given that the social environment plays a significant role in the development and maintenance of MDD. In the present study, we examined whether monetary gain/loss and social acceptance/rejection would elicit dissociable salience-related neural responses in women diagnosed with MDD compared to healthy control (HC) women. Twenty women diagnosed with MDD and 20 matched HC women performed the monetary incentive delay task (MID) and the social feedback task (SFT) during functional magnetic resonance imaging (fMRI). This study focused on women since women have a higher rate of MDD, higher frequency of relapse, and are more likely to develop MDD as a consequence of negative interpersonal relationships compared to men. We found that during the MID, HCs but not MDD patients demonstrated strong overlapping activations in the right anterior insula (AI) in response to both monetary gain and loss. During the SFT, MDD patients but not HCs showed overlapping activations in the AI in response to social acceptance and rejection. Our results may suggest a dissociation such that MDD patients show decreased sensitivity to monetary stimuli whether gain or loss, and increased sensitivity to social stimuli whether acceptance or rejection, although this will need to be verified in larger samples with direct comparisons between groups and stimuli. These data demonstrate distinct abnormalities in reward and loss processing that converge within the AI. Our findings also highlight the critical need to assess across both non-social and social domains when examining reward and loss systems in MDD to broaden our understanding of the disorder and identify novel targets for treatment.

Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder.

Heterogeneity within Major Depressive Disorder (MDD) has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A [(11C)WAY-100635], as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets.

Postmenopausal hormone treatment alters neural pathways but does not improve verbal cognitive function.

OBJECTIVE: Cognitive outcomes in trials of postmenopausal hormone treatment have been inconsistent. Differing outcomes may be attributed to hormone formulation, treatment duration and timing, and differential cognitive domain effects. We previously demonstrated treatment benefits on visual cognitive function. In the present study, we describe the effects of hormone treatment on verbal outcomes in the same women, seeking to understand the effects of prior versus current hormone treatment on verbal function. METHODS: This is a cross-sectional evaluation of 57 women (38 hormone users [25 prior long-term users and 13 current users] and 19 never-users). Hormone users took identical formulations of estrogen or estrogen + progestin (0.625 mg/d conjugated equine estrogens with or without medroxyprogesterone acetate) for at least 10 years, beginning within 2 years of menopause. Women were evaluated with tests of verbal function and functional magnetic resonance imaging (fMRI) of a verbal discrimination task. RESULTS: All women scored similarly on assessments of verbal function (Hopkins Verbal Learning Test and a verbal discrimination task performed during the fMRI scanning session); however, women ever treated with hormones had more left inferior frontal (T = 3.72; P < 0.001) and right prefrontal cortex (T = 3.53; P < 0.001) activation during the verbal task. Hormone-treated women performed slightly worse on the verbal discrimination task (mean accuracy 81.72 ±â€Š11.57 ever-treated, 85.30 ±â€Š5.87 never-treated, P = 0.14), took longer to respond (mean reaction time 1.10 ±â€Š0.17 s ever-treated, 1.02 ±â€Š0.11 never-treated, P = 0.03), and remembered fewer previously viewed words (mean accuracy 62.21 ±â€Š8.73 ever-treated, 65.45 ±â€Š7.49 never-treated, P = 0.18). Increased posterior cingulate activity was associated with longer response times (R = 0.323, P = 0.015) and worse delayed verbal recall (R = -0.328, P = 0.048), suggesting that increased activation was associated with less efficient cognitive processing. We did not detect between group differences in activation in the left prefrontal cortex, superior frontal cortex, thalamus, or occipital/parietal junction. CONCLUSIONS: Although current and past hormone treatment was associated with differences in neural pathways used during verbal discrimination, verbal function was not higher than never-users.

Abnormal emotional and neural responses to romantic rejection and acceptance in depressed women.

INTRODUCTION: Responding adaptively to one's social environment is a key factor predicting the course of major depressive disorder (MDD). Socially rejecting events can exacerbate, whereas socially accepting events can ameliorate depressive symptoms. The neural responses to rejection and acceptance in MDD are relatively unexplored. METHODS: We used functional magnetic resonance imaging (fMRI) to measure neural responses to romantic rejection and acceptance in women diagnosed with current MDD (n = 19) and a matched group of healthy controls (HCs) (n = 19). During fMRI, participants received rejecting, accepting, and neutral feedback from self-selected potential romantic partners. RESULTS: In women with MDD but not HCs, rejection significantly increased activity in the right anterior insula relative to neutral feedback. Greater activation during rejection was found in the dorsal anterior cingulate cortex in MDD compared to HCs. Women with MDD reported stronger emotional responses than HCs to both rejection and acceptance. In addition, left and right nucleus accumbens (NAcc) activity mediated the relationship between trait reward responsiveness and increased ratings of feeling "happy and accepted" following acceptance in HCs, but not the MDD group. DISCUSSION: Women with MDD were behaviorally and neurally hyperresponsive to rejection. Although both groups were behaviorally responsive to acceptance, in MDD this was dissociated from NAcc activity. These findings highlight abnormal behavioral and neural responses to social cues in MDD, with implications for disease prognosis and the development of novel and sensitive biomarkers for MDD focused on neural pathways for social-affective processing. LIMITATIONS: Conclusions may be limited to depressed women in a romantic context.

The impact of oxytocin on stress: the role of sex.

Accumulating research indicates oxytocin plays a significant role in regulating the behavioral and neurobiological responses to stress. Evidence from preclinical models suggests the effect of oxytocin on stress-responsivity appears to be dependent on individual characteristics, including sex. Although the interaction between oxytocinergic and stress systems has been widely studied in rodents, recent efforts have been made to examine the interface between these two systems in humans. This brief review examines how administration of oxytocin can influence the neuroendocrine, behavioral, and neural responses to stress, explores how sex may impact these effects, and provides considerations for future work.

Oxytocin Genotype Moderates the Impact of Social Support on Psychiatric Distress in Alcohol-Dependent Patients.

AIMS: The social environment strongly influences individual mental health. Individuals with strong social support systems tend to experience higher levels of well-being, lower levels of psychological distress and exhibit fewer psychiatric symptoms. However, there is a significant degree of individual variability as to the extent to which social support is beneficial to overall mental health. From a neurobiological perspective, it is suggested that the social hormone, oxytocin, may moderate the favorable effects of social interaction. To explore this possibility, we evaluated oxytocin genotype, social support and psychological health in a group of individuals diagnosed with DSM-IV alcohol dependence. METHODS: The associations between OXT genotype, social support and psychological health were analyzed in data from 269 adults diagnosed with DSM-IV alcohol dependence (25% female) admitted into residential treatment programs and outpatient centers in Warsaw, Poland. RESULTS: In line with past observations, we noted that psychiatric distress scores were negatively correlated with social support. Extending these observations, we uncovered a significant moderating effect of OXT genotype (rs2740210) on the relationship between social support and psychiatric distress. While G carriers displayed the predicted negative relationship between social support and psychiatric distress, T homozygotes failed to exhibit such a relationship. CONCLUSION: Genetically driven variation in oxytocin system functioning may influence the degree to which the beneficial effects of social support are felt in this population. These results have direct clinical relevance as enhancing social engagement to improve mental health may prove to be a less effective strategy in some patients owing to intrinsic factors. SHORT SUMMARY: The associations between oxytocin genotype, social support, and psychological health were analyzed in data from 269 adults diagnosed with DSM-IV alcohol dependence. A significant moderating effect of OXT genotype (rs2740210) on the relationship between social support and psychiatric distress was detected.

Oxytocin modulates hemodynamic responses to monetary incentives in humans.

RATIONALE: Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. OBJECTIVES: We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. METHODS: The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. RESULTS: We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. CONCLUSIONS: Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans-even in a non-social context-and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.