The relationship between alcohol consumption and amygdala volume in a community-based sample.

Most prior studies have reported decreased amygdala volume in those with a history of alcohol use disorder. Decreased amygdala volume associated with alcohol use disorder may be related to an increased risk of addiction and relapse. However, the relationship between amygdala volume and a broad range of alcohol consumption is largely unexplored. The present cross-sectional analysis investigates the relationship between amygdala volume and self-reported alcohol consumption in participants of the Dallas Heart Study, a community-based study of Dallas County, Texas residents. Brain imaging and survey data from participants (n = 2023) were obtained, and multiple linear regressions were performed with the average amygdala volume as the dependent variable and drinking status, drinking risk, drinks per week, and binge drinking as independent variables. Drinking risk was categorized such that low-risk constituted ≤ 14 drinks per week in men and ≤ 7 drinks per week in women, while > 14 drinks per week in men and > 7 drinks per week in women constituted high-risk. Age, sex, intracranial volume, body mass index, education, and Quick Inventory of Depressive Symptomatology-Self Report score were included in all models as covariates. No statistically significant (p ≤ .05) associations were observed between self-reported alcohol consumption and amygdala volume. The present study suggests non-significant relationships between self-reported alcohol consumption and amygdala volume when controlling for relevant demographic factors in a large, community-based sample.

Contribution of caregiver and child anxiety and depressive symptoms to child asthma-related quality of life.

BACKGROUND: Depression and anxiety negatively affect asthma-related quality of life (QoL). Yet, little is known regarding mood and asthma-related factors that best uniquely explain asthma-related QoL in children. OBJECTIVE: This cross-sectional study evaluated the unique variance explained by caregiver and child depressive and anxiety symptom severity in child asthma-related QoL, apart from that explained by demographics and asthma control. METHODS: Children aged 7 to 17 years with asthma (n = 205) and their caregivers with major depressive disorder were included. A 3-stage hierarchical linear regression analysis was conducted with the Pediatric Asthma Quality of Life Questionnaire total scores considered as the outcome. Predictors included demographic characteristics (stage 1); asthma control assessed by the Asthma Control Test (stage 2); and caregiver depression and anxiety (Hamilton Rating Scale for Depression and the Spielberger State/Trait Anxiety Scale) and child depression and anxiety (Children's Depression Inventory and the Screen for Child Anxiety-Related Disorders) (stage 3). RESULTS: Demographic characteristics accounted for only 5.5% of the Pediatric Asthma Quality of Life Questionnaire scores. Asthma control significantly increased variance explained in QoL to 32.6%, whereas caregiver and child depression and anxiety symptoms significantly increased variance explained to 42.6%. Child anxiety was found to uniquely explain the largest proportion of variance in QoL (rs2 = 0.584). CONCLUSION: After adjusting variance in QoL for demographic characteristics and asthma control, caregiver and child depression and anxiety measures significantly increased the proportion of variance explained in a child's asthma-related QoL. In addition to better asthma control, child and caregiver depression and anxiety should be addressed to increase child asthma-related QoL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02809677.

fMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.

The efficacy of citalopram or escitalopram in patients with asthma and major depressive disorder.

BACKGROUND: Major depressive disorder is common in people with asthma. Yet, few studies have evaluated depression treatment in those with asthma. OBJECTIVE: To explore the relationship between antidepressant use, depressive symptoms, and asthma control, pooled data from 3 randomized trials of either citalopram or escitalopram were assessed. METHODS: Linear fixed effects and binary logistic regression analyses were conducted with between-subject covariates including treatment group, (original) study, and demographics. The within-subject effect of visit, and a treatment group-visit (between-within) interaction effect, were also evaluated. Analyses were repeated in a high asthma exacerbation subgroup having at least 3 oral corticosteroid bursts in the previous 12 months. Outcomes included the Hamilton rating scale for depression (HAM-D17), the 7-item asthma control questionnaire (ACQ), and oral corticosteroid use (yes or no). RESULTS: In the pooled sample (n = 255), the antidepressant treatment group exhibited lower HAM-D17 overall (P ≤ .001) and a lower likelihood for oral corticosteroid use (P ≤ .001) relative to the placebo group. In the high-exacerbation subgroup (n = 96), treatment group participants had lower overall asthma control questionnaire (P = .004) and HAM-D17 scores (P ≤ .001), and a lower likelihood of oral corticosteroid use (P = .003), relative to placebo participants. All treatment group interaction effects were not significant. CONCLUSION: Citalopram or escitalopram exhibited efficacy in reducing depressive symptoms and the need for rescue oral corticosteroids in patients with asthma and major depressive disorder. Future work should determine whether selective serotonin reuptake inhibitors are effective at improving asthma outcomes in those with asthma who are not depressed. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00621946 and NCT01324700 (one study was conducted before ClinicalTrials.gov requirements).

Association of serotonin reuptake inhibitors with asthma control.

Background: Clinical trials demonstrated that selective serotonin reuptake inhibitors (SSRI) can improve asthma control in patients with comorbid major depressive disorder (MDD) and that this effect may be greater than the effect of SSRIs on depression. These findings suggest that SSRIs may improve asthma control in patients without MDD. Objective: The current retrospective study examined the effect of SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRI) on asthma control in adult patients. We hypothesized that patients would have fewer asthma exacerbations after treatment with an SSRI or SNRI. Methods: Electronic health record data of adult patients (N = 592) who were seen at a University of Texas Southwestern (UTSW) hospital or clinic and had (1) an SSRI or SNRI prescription, (2) a previous asthma diagnosis, and (3) no mood disorder diagnosis were extracted by using the UTSW Clinical Data Exchange Network. Wilcoxon signed rank tests were used to compare oral corticosteroid prescriptions and asthma-related emergency department (ED) visits and hospitalizations in the 12 months before and after the start of an SSRI/SNRI. Results: Therapy with SSRIs/SNRIs was associated with a significant decrease in oral corticosteroid use (p = 0.003), ED visits (p = 0.002), and hospitalizations (p < 0.001). Conclusion: Results from the current study add to the existing literature by demonstrating a reduced rate of severe exacerbations in patients with asthma by using an SSRI/SNRI without limiting the analytic sample to a high-illness-severity subgroup defined by symptoms of asthma or depression. Future work should include a prospective, placebo controlled study with individuals who have asthma and no comorbid mental health condition, verified by a mental health professional.

The cross-sectional relationship among omega-3 fatty acid levels, cardiorespiratory fitness, and depressive symptoms from the Cooper Center Longitudinal Study.

OBJECTIVE: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are implicated in numerous illnesses including depression. The literature is mixed regarding the relationship between n-3 PUFA levels and depression, and studies based on self-reported dietary n-3 PUFA intake may not accurately reflect in vivo levels. METHOD: The current cross-sectional analysis examined the relationship between erythrocyte levels (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CESD), adjusting for health-related factors and omega-3 supplement use in 16,398 adults assessed at the Cooper Clinic in Dallas, Texas for preventative medical examinations between April 6, 2009, and September 1, 2020. A three-stage hierarchical linear regression was conducted to examine the EPA and DHA levels on CES-D before and after inclusion of cardiorespiratory fitness (CRF) and high sensitivity C-reactive protein (hs-CRP) in the model. RESULTS: DHA level, but not EPA level, was significantly associated with CES-D scores. Taking omega-3 supplements was associated with lower CES-D scores even when adjusting for CRF, while hs-CRP was non-significantly associated with CES-D scores. These findings suggest that DHA levels are related to depressive symptom severity. Omega-3 PUFA supplement use was associated with lower CES-D scores when controlling for EPA and DHA levels. CONCLUSION: The findings from this cross-sectional study suggest that lifestyle and/or other contextual factors unrelated to EPA and DHA levels may also be associated with depressive symptom severity. Longitudinal studies are needed to evaluate the role of health-related mediators among these relationships.

The Relationship Between Coronary Artery Calcification and Carotid Intima Media Thickness and Hippocampal Volume: An Analysis From the Dallas Heart Study.

BACKGROUND: Higher rates of dementia are reported in people with a history of coronary artery disease. Smaller hippocampal volume (HV) is a risk factor for the development of dementia. OBJECTIVE: This study assessed whether coronary artery calcification (CAC) and carotid intima media thickness (CIMT) are associated with HV in participants from the Dallas Heart Study, a community-based study of Dallas County, Texas, residents. METHODS: Data from a total of n = 1821 participants in the Dallas Heart Study with brain magnetic resonance imaging, CAC, and CIMT information were included in the present study, after excluding those with a history of myocardial infarction or stroke. To evaluate the effect of CAC and CIMT on total HV, 4 linear regression analyses were conducted in which the primary predictor was (1) CAC as a continuous metric; (2) CAC as a binary metric (CAC = 0 vs. CAC ≥ 1); (3) CAC as a continuous metric but only for those with CAC >0; and (4) CIMT as a continuous metric. Demographic and cardiovascular disease risk factors, as well as intracranial volume, were entered into the model as covariates. RESULTS: Participants were largely women (58.2%) with a mean age of 49.7 ± 10.3 years. Forty-six percent of the sample reported being Black, and approximately 14% reported being Hispanic. All 3 variations of the CAC effect were nonsignificant predictors of total HV (ß = -0.013, P = 0.602; ß = -0.011, P = 0.650; ß = 0.036, P = 0.354, respectively), as was the effect of CIMT (ß = 0.009, P = 0.686). CONCLUSIONS: Current findings suggest nonsignificant relationships between both CAC and CIMT and between CAC and total HV, while controlling for other related factors in a large, diverse, community-based sample of people without a history of myocardial infarction or stroke. In the context of existing evidence that both coronary artery disease and smaller HV are associated with the development of dementia, the present findings suggest that neither marker of the cardiovascular disease examined here is associated with a reduction in HV in the population studied. Longitudinal studies are needed to assess relationships between CAC and CIMT and between CAC and HV over time.

The Impact of Caregiver Depression on Child Asthma Outcomes: Pathways and Mechanisms.

BACKGROUND: Depression is common in caregivers of children with asthma and is associated with poor outcomes in their child. No prior studies have longitudinally examined caregiver depression remission as a predictor of improvement in child asthma control. OBJECTIVE: This 2-site study examined whether the proportion of time a caregiver was in depression remission predicted subsequent child asthma control at exit. METHOD: Caregivers (n = 205) with current major depressive disorder and their children, ages 7 to 17, with persistent asthma were observed every 4 weeks for 52 weeks. Caregiver depressive symptoms were measured using the 17-item Hamilton Rating Scale for Depression (HRSD). Child asthma was assessed with the (Childhood) Asthma Control Test (cACT/ACT) and spirometry, and depression with the Children's Depression Inventory (CDI). Linear regression analyses were conducted with change in cACT/ACT, CDI, and forced expiratory volume in 1 second (FEV1)% predicted as outcomes and proportion of time the caregiver was in remission (HRSD score ≤ 7) as the predictor. Multilevel mediation analyses examined the role of child depressive symptoms and asthma controller medication adherence. RESULTS: Children were, on average, 54.1% female and 11 years old. Caregiver proportion of time in HRSD-assessed remission of depression was a significant predictor of improvement in cACT/ACT, CDI, and FEV1% predicted. Child CDI score, but not medication adherence, mediated the relationship between caregiver HRSD scores and child asthma control scores. CONCLUSIONS: Improvement in caregiver depression positively influences child asthma outcomes partially through improvement in child depressive symptom severity. Caregiver depression screening and treatment might lead to improvement in child asthma outcomes.

Relationship between chronic obstructive pulmonary disease and cognition in an aging population.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a common and severe respiratory illness. Prior research suggests that COPD may be associated with depression as well as cognitive impairment and increased risk of dementia. Many studies to date have been relatively small, have largely relied on global screening measures to identify cognitive impairment, and have not examined the potential role of comorbid depression on cognition. This cross-sectional study examined the relationship between COPD and multiple cognitive domains at two time points using data from a large longitudinal population database. METHODS: Linear multivariate analyses were conducted using secondary data from the Wisconsin Longitudinal Study to determine the effect of lifetime COPD and depressive symptom severity, assessed with the Center for Epidemiological Studies Depression Scale (CESD), on multiple cognitive outcomes. RESULTS: In both 2004 (n = 1608) and 2011 (n = 1743), lifetime COPD was found to be a non-significant predictor of all cognitive outcomes, while depressive symptom severity predicted significantly lower scores on the immediate recall and digit ordering tasks in 2004 and on all outcomes in 2011. Exploratory analyses in only those with lifetime COPD revealed COPD severity to be a non-significant factor for all outcomes in 2004 and 2011. CONCLUSION: COPD was not significantly associated with cognition. Conversely, higher depressive symptom severity was significantly associated with poorer performance on additional cognitive tasks in 2011 compared to 2004, suggesting that depression may contribute to cognitive decline, dependent upon the context of aging.

Association between headache and suicidality: An analysis of universal suicide screening data at a large urban county hospital.

BACKGROUND: Identifying individuals at increased risk of suicide is important, particularly those who present for treatment for nonpsychiatric chief complaints who may go undetected. It has been found that pain symptoms, such as headache, are associated with suicide, although this association requires further characterization. This study examined specific components of suicidality in relation to headache subtypes. METHODS: This study retrospectively reviewed 2,832,835 nonpsychiatric adult clinical encounters at a large county hospital, where a standardized suicide risk screening tool, the Columbia-Suicide Severity Rating Scale (C-SSRS), was universally implemented. The C-SSRS assesses specific components of suicidality: wish to be dead and suicidal ideation, method, intent, plan, and action. Multivariate logistic regressions were performed to assess the association between headache, as well as headache subtype (migraine, tension, or cluster), and each component of suicidality. RESULTS: There were significant positive associations between presenting with a headache and 2 specific components of suicidality: wish to be dead and suicidal action. Individuals with tension headache may have a lower risk of wishing to be dead compared to those with migraine and cluster headaches. CONCLUSIONS: The association of headaches with specific elements of sui-cidality demonstrates the potential yield of identification of suicide risk among individuals with nonpsychiatric presentations.

Desmosterol and 7-dehydrocholesterol concentrations in post mortem brains of depressed people: The role of trazodone.

Major depressive disorder (MDD) is a common, disabling, and heterogeneous condition that responds unpredictably to current treatments. We previously showed an association between depressive symptoms and plasma concentrations of two cholesterol precursors, desmosterol and 7-dehydrocholesterol (7DHC). Here, we measured total cholesterol and sterol concentrations with mass spectrometry in postmortem brain samples from depressed and control subjects. Mean (±SEM) desmosterol concentration was 8.9 ± 0.97 ng/mg in the depressed versus 10.7 ± 0.72 ng/mg in the control group. The mean of the posterior probability distribution for the difference in desmosterol concentration between the two groups was 2.36 (95% highest density interval [HDI] 0.59-4.17). Mean 7DHC concentrations, 12.5 ± 4.1 ng/mg in the depressed versus 5.4 ± 0.74 ng/mg in the control group, were unlikely to be different (95% HDI, [-1.37-0.34]). We found that presence of trazodone in the peri-mortem toxicology screen accounted for the observed difference in desmosterol concentrations. We also observed extremely high 7DHC levels in all 4 subjects who had taken trazodone. Trazodone has been recently found to inhibit 7-dehydrocholesterol reductase and alter sterol concentrations in rodents, cell culture, human fibroblasts, and blood. In this study, we demonstrate for the first time that trazodone alters human brain sterol composition. Given congenital deficiency of 7-dehydrocholesterol reductase results in Smith-Lemli-Opitz syndrome, our findings support the hypothesis that this commonly used medication may have previously unappreciated risks.

The relative importance of reputation and pride as predictors of employee turnover in an academic medical center.

BACKGROUND: Past research shows a dual role of organizational reputation in an employment context. Prospective and current employees are affected by public perceptions of their employer, as affiliation with an employer widely known for its positive achievements boosts organization-based self-esteem whereas a poor reputation leads to decreased self-esteem and disassociation. Another key construct is engagement, which relates to employee enthusiasm and their attitude toward the organization and their interest in finding employment elsewhere. PURPOSE: The current study examined relationships between engagement, organizational pride, perceived departmental and institutional reputation, and turnover intentions in employees at an academic medical center. METHODS: Participants were 241 faculty, staff, and trainees (63.9% women) in a clinical department at an academic medical center who completed an anonymous online survey that contained the Utrecht Work Engagement Scale, as well as questions about pride, reputation, and turnover intentions. Relationships between engagement, organizational pride, perceived departmental and institutional reputation, and turnover intentions were explored. RESULTS: To determine whether employee engagement mediates the relationship between various predictors and turnover intentions, exploratory mediation models were examined. All of the variables were significantly correlated with each other. Perception of departmental reputation was more strongly associated with engagement, pride, and turnover intentions than was institutional reputation. Engagement fully mediated the relationship between perceived institutional reputation and turnover intentions and partially mediated relationships between departmental reputation and turnover intentions and between pride and turnover intentions. PRACTICE IMPLICATIONS: The findings suggest that perception of one's department may be more important to engagement and pride than perception of the larger institution. Furthermore, relationships between pride and reputation and turnover intentions in an academic medical center appear to be, at least partially, mediated through engagement. In contrast to common practice, turnover reduction efforts might be more effective if they enhance perceived departmental, rather than institutional, reputation.

Glucocorticoids for therapeutic immunosuppression: Clinical pearls for the practicing neurologist.

Given widespread use of glucocorticoid therapy in neurologic disease, understanding glucocorticoid pharmacology and risk is paramount for the practicing neurologist. While dosing and tapering regimens vary depending on the neurological disease and indication being treated, there are important general principles of glucocorticoid prescribing and monitoring that can guide clinical decision-making. Glucocorticoid-related toxicities can occur across multiple organ systems, including hypertension; dyslipidemia; weight gain; hyperglycemia; osteoporosis and avascular necrosis; myopathy; gastrointestinal bleeding; infection; and neuropsychiatric effects with sleep, mood disturbance and cognition. This narrative review provides a practical framework for safe and responsible prescribing of this therapeutic class of medications, including appreciation of immunosuppressive consequences, risk mitigation strategies, dosing and tapering, and recognition of adrenal insufficiency and glucocorticoid withdrawal.