Cardiac autonomic function is preserved in young adults with major depressive disorder.

The prevalence of major depressive disorder (MDD) is highest in young adults and contributes to an increased risk of developing future cardiovascular disease (CVD). However, the underlying mechanisms remain unclear. The studies examining cardiac autonomic function that have included young unmedicated adults with MDD report equivocal findings, and few have considered the potential influence of disease severity or duration. We hypothesized that heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) would be reduced in young unmedicated adults with MDD (18-30 yr old) compared with healthy nondepressed young adults (HA). We further hypothesized that greater symptom severity would be related to poorer cardiac autonomic function in young adults with MDD. Heart rate and beat-to-beat blood pressure were continuously recorded during 10 min of supine rest to assess HRV and cardiac BRS in 28 HA (17 female, 22 ± 3 yr old) and 37 adults with MDD experiencing current symptoms of mild-to-moderate severity (unmedicated; 28 female, 20 ± 3 yr old). Neither HRV [root mean square of successive differences between normal heartbeats (RMSSD): 63 ± 34 HA vs. 79 ± 36 ms MDD; P = 0.14] nor cardiac BRS (overall gain, 21 ± 10 HA vs. 23 ± 7 ms/mmHg MDD; P = 0.59) were different between groups. In young adults with MDD, there was no association between current depressive symptom severity and either HRV (RMSSD, R2 = 0.004, P = 0.73) or cardiac BRS (overall gain, R2 = 0.02, P = 0.85). Taken together, these data suggest that cardiac autonomic dysfunction may not contribute to elevated cardiovascular risk factor profiles in young unmedicated adults with MDD of mild-to-moderate severity.NEW & NOTEWORTHY This study investigated cardiac autonomic function in young unmedicated adults with major depressive disorder (MDD). The results demonstrated that both heart rate variability and cardiac baroreflex sensitivity were preserved in young unmedicated adults with MDD compared with healthy nondepressed young adults. Furthermore, in young adults with MDD, current depressive symptom severity was not associated with any indices of cardiac autonomic function.

Recovery at 30: Perspectives from Psychiatry Clinicians and Senior Faculty.

According to William Anthony's "Recovery from mental illness: the guiding vision of the mental health service system in the 1990s," mental health recovery means "changing one's attitudes, values, feelings, goals, and skills in order to live a satisfying life within the limitations caused by illness." This seminal work served as an overarching goal, a call to action, and a roadmap for the enhancement of psychiatric recovery. Unfortunately, from many viewpoints, the goals encouraged by Anthony have not been achieved. Through semi-structured interviews with psychiatry clinicians and senior faculty members, this article aims to elucidate the current status of psychiatric recovery, how the movement progressed to this point, and where we could go from here. The development of the recovery movement will be discussed, along with its assumptions and explicit goals. The interviews focus on the extent to which these goals have been achieved, barriers to progress, whether goals should be revised, and how to achieve these goals.

Daily Stress and Microvascular Dysfunction: The Buffering Effect of Physical Activity.

Although often short-lived, emotional responsiveness to daily stressors ( i.e. , routine and sometimes unexpected everyday hassles) is associated with increased cardiovascular disease (CVD), morbidity, and mortality. Here, we present the novel hypothesis that a disruption of microvascular homeostasis is a key antecedent. In addition, we postulate that physical activity may mitigate the psychobiological consequences of daily stress, thereby limiting pathophysiological CVD-related sequelae.

Gender differences in transdiagnostic domains and function of adults measured by DSM-5 assessment scales at the first clinical visit: a cohort study.

BACKGROUND: Measurement-based care has been called for as best practice in psychiatric care and learning health systems and use of transdiagnostic measures was suggested as part of the DSM-5. Our objective is to examine gender differences in first visit socioeconomic, transdiagnostic, and functional characteristics of a dynamic, real-world measurement-based care cohort. METHODS: Transdiagnostic, functional, and clinical measures were collected from 3,556 patients at first visit in an ambulatory psychiatric clinic. All patients were evaluated at the first visit by board-certified psychiatrists or licensed clinical psychologists. Demographic variables and clinical diagnoses were collected from the Electronic Medical Record. Self-report measures were collected that assessed transdiagnostic symptoms (DSM-5 Level 1 Cross-cutting Measure and Level 2 symptom scales), disability, alcohol use, attention deficit hyperactivity disorder (ADHD) symptoms, depression, anxiety, mania, suicidal thoughts and behaviors, and trauma exposure. RESULTS: Men and women did not differ in age, BMI, household income, high school graduation rate, race, or ethnicity, but women were more likely to be formerly married and less likely to have commercial insurance. Compared to men, women reported significantly higher overall psychopathology on the transdiagnostic Level 1 Cross-cutting measure and had higher depression, anxiety, sleep, anger, ADHD combined presentation, and suicidality severity. Women also had higher disability scores than men. However, men reported higher alcohol, tobacco and substance use, and more risky behavior than women. Trauma exposure differed significantly by gender; men reported more exposure to accidents, war-related trauma, serious accidents, and major disasters and women reported more unwanted sexual contact. CONCLUSIONS: This cross-sectional study of a transdiagnostic, ecologically-valid real-word measurement-based care cohort demonstrates gender differences in socioeconomic factors, trauma exposure, transdiagnostic symptoms, and functioning.

Short-term salicylate treatment improves microvascular endothelium-dependent dilation in young adults with major depressive disorder.

Reactive oxygen species (ROS)-mediated reductions in nitric oxide (NO)-dependent dilation are evident in adults with major depressive disorder (MDD); however, the upstream mechanisms remain unclear. Here, we hypothesized that nuclear factor-κB (NF-κB) activation-induced ROS production contributes to microvascular endothelial dysfunction in MDD. Thirteen treatment-naive adults with MDD (6 women; 19-23 yr) and 10 healthy nondepressed adults (HAs; 5 women; 20-25 yr) were tested before and after (open-label design) systemic NF-κB knockdown (nonacetylated salicylate; 3,000-4,500 mg/day × 4 days). Red cell flux (laser Doppler flowmetry) was measured during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine (ACh), alone and in combination with NO synthase inhibition [NG-nitro-l-arginine methyl ester (l-NAME)] or ROS scavenging (apocynin). Serum salicylate concentrations following treatment were not different between groups (22.8 ± 7.4 HAs vs. 20.8 ± 4.3 mg/dL MDD; P = 0.46). When compared with HAs, the NO-dependent component of ACh-induced dilation was blunted in adults with MDD before (P = 0.023), but not after (P = 0.27), salsalate treatment. In adults with MDD, the magnitude of improvement in endothelium-dependent dilation following salsalate treatment was inversely related to the degree of functional impairment at baseline (R2 = 0.43; P = 0.025). Localized ROS scavenging improved NO-dependent dilation before (P < 0.01), but not after (P > 0.05), salsalate treatment. Salsalate did not alter systemic concentrations of pro- or anti-inflammatory cytokines (all P > 0.05). These data suggest that NF-κB activation, via increased vascular ROS production, contributes to blunted NO-dependent dilation in young adults with MDD but otherwise free of clinical disease. These data provide the first direct evidence for a mechanistic role of vascular inflammation-associated endothelial dysfunction in human depression.NEW & NOTEWORTHY Our data indicate that short-term treatment with therapeutic doses of the nuclear factor-κB (NF-κB) inhibitor salsalate improved nitric oxide (NO)-mediated endothelium-dependent dilation in adults with major depressive disorder (MDD). In adults with MDD, acute localized scavenging of reactive oxygen species (ROS) with apocynin improved NO-dependent dilation before, but not after, salsalate administration. These data suggest that activation of NF-κB, in part via stimulation of vascular ROS production, contributes to blunted NO-mediated endothelium-dependent dilation in young adults with MDD.

Gender disparity in bipolar disorder diagnosis in the United States: A retrospective analysis of the 2005-2017 MarketScan Commercial Claims database.

OBJECTIVE: To examine gender disparities in the diagnosis of bipolar disorder (BD) within a privately insured population in the United States and investigate potential contributing factors for these gender differences. METHODS: This retrospective cohort study utilized 2005-2017 claims data from the MarketScan® Commercial Claims and Encounters database. The study cohort included subjects, aged 10-64 years, who had a minimum of 1-year continuous insurance coverage and no record of a BD diagnosis before cohort entry. We examined the gender difference in BD diagnosis rate, overall and by subgroups. We then used Cox regression models to evaluate the gender effect on time to first BD diagnosis, and the potential moderators of gender effect. RESULTS: The study cohort consisted of 97,193,443 subjects; 0.45% of subjects were diagnosed with BDs after cohort entry with males having a lower diagnosis rate than females (0.36% vs. 0.54%). The Cox regression analysis indicated that males were less likely to be diagnosed with BDs (unadjusted Hazard Ratio, HR [95% CI]: 0.69 [0.68-0.69]) and gender difference remained significant after adjusting for demographics, comorbidity and healthcare utilizations (adjusted HR [95% CI]: 0.77 [0.76-0.77]). Gender disparity was consistently strong among most age groups, but varied in other demographic subgroups. CONCLUSIONS: Even though the prevalence of BDs is approximately equal between genders in the general population, our study found a much lower diagnosis rate in men compared to women for a privately insured U.S. POPULATION: Future studies aimed at identifying and understanding the barriers to diagnosis of BDs in men are warranted.

Adjunctive dietary intervention for bipolar disorder: a randomized, controlled, parallel-group, modified double-blinded trial of a high n-3 plus low n-6 diet.

OBJECTIVE: To investigate the preliminary efficacy of a high n-3 plus low n-6 (H3-L6) dietary intervention in improving mood stability in Bipolar Disorder (BD) when compared to dietary intervention with usual U.S. levels of n-6 and n-3 polyunsaturated fatty acid (PUFA) intakes (control diet, CD). METHODS: This 2-arm, parallel-group, randomized, modified double-blind, controlled 48-week study of 12-week intensive diet intervention in subjects with BD was conducted at a single suburban-rural site in the mid-Atlantic region. Participants with DSM-IV TR BD I or II with hypomanic or depressive symptoms were randomized, stratified on gender (N = 82). The intervention included the provision of group-specific study foods and dietary counseling. Variability of mood symptoms was measured by a twice-daily, 12-week ecological momentary analysis (EMA) paradigm, and group differences were analyzed using multilevel models. Circulating n-3 and n-6 fatty acids were measured at baseline and after 4, 8, and 12 weeks of diet exposure. RESULTS: All 82 randomized participants were included in biochemical analyses. Seventy participants completed at least 2 EMA surveys and were included in primary EMA analyses. Variability in mood, energy, irritability, and pain as measured using EMA was reduced in the H3-L6 group compared to the CD group. No significant differences in mean ratings of mood symptoms, or any other symptom measures, were detected. The dietary intervention effect on target PUFAs significantly differed by the group over time. CONCLUSIONS: A dietary intervention adjunctive to usual care showed preliminary efficacy in improving variability in mood symptoms in participants with BD. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02272010.

Dysregulated Diurnal Cortisol Pattern and Heightened Night-Time Cortisol in Individuals with Bipolar Disorder.

INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may contribute to the symptom burden in bipolar disorder (BD). Further characterization of cortisol secretion is needed to improve understanding of the connection between mood, sleep, and the HPA axis. Here, we observe diurnal cortisol patterns in individuals with BD and healthy controls (HCs) to determine time points where differences may occur. METHODS: Salivary cortisol was measured at 6 time points (wake, 15, 30, and 45 min after wake, between 2:00 and 4:00 p.m. and 10:00 p.m.) for 3 consecutive days in individuals with symptomatic BD (N = 27) and HC participants (N = 31). A general linear model with correlated errors was utilized to determine if salivary cortisol changed differently throughout the day between the 2 study groups. RESULTS: A significant interaction (F = 2.74, df = 5, and p = 0.02) was observed between the time of day and the study group (BD vs. HC) when modeling salivary cortisol over time, indicating that salivary cortisol levels throughout the day significantly differed between the study groups. Specifically, salivary cortisol in BD was elevated compared to HCs at the 10:00 p.m. time point (p = 0.01). CONCLUSION: Significantly higher levels of cortisol in participants with BD in the night-time suggest that the attenuation of cortisol observed in healthy individuals may be impaired in those with BD. Reregulation of cortisol levels may be a target of further study and treatment intervention for individuals with BD.

Inflammation and the dimensions of depression: A review.

Patients with depressive disorders show a wide range of clinical manifestations including cognitive and neurovegetative symptoms. Importantly, these symptoms can differ in terms of biological etiology, and deconstructing depression into specific symptoms may provide valuable insight into the underlying neurobiology. Little research has examined inflammation in the context of depressive dimensions. Here we conduct a narrative review of the existing literature (21 studies) to elucidate whether the depression-inflammation link is symptom specific. Overall, there is evidence that an association exists between neurovegetative symptoms of depression and inflammation, independent of cognitive symptoms. The same cannot be said of cognitive symptoms and inflammation. There is also some evidence of gender differences in the directionality of the relationship between depression and inflammation. Potential explanations for these findings, limitations of the existing literature and recommendations for future research design are discussed.

Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive Disorder.

RATIONALE: In rodent models of depression, oxidative stress-induced reductions in NO bioavailability contribute to impaired endothelium-dependent dilation. Endothelial dysfunction is evident in major depressive disorder (MDD); however, the molecular mediators remain undefined. OBJECTIVE: We sought to translate preclinical findings to humans by testing the role of oxidative stress in mediating microvascular endothelial dysfunction, including potential modulatory influences of sex, in MDD. METHODS AND RESULTS: Twenty-four treatment-naive, otherwise healthy, young adults with MDD (14 women; 18-23 years) and 20 healthy adults (10 women; 19-30 years) participated. Red blood cell flux (laser Doppler flowmetry) was measured during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine, alone and in combination with an NO synthase inhibitor (L-NAME), a superoxide scavenger (Tempol), and an NADPH oxidase inhibitor (apocynin), as well as during perfusion of the endothelium-independent agonist sodium nitroprusside. Tissue oxidative stress markers (eg, nitrotyrosine abundance, superoxide production) were also quantified. Endothelium-dependent dilation was blunted in MDD and mediated by reductions in NO-dependent dilation. Endothelium-independent dilation was likewise attenuated in MDD. In MDD, there were no sex differences in either NO-mediated endothelium-dependent dilation or endothelium-independent dilation. Acute scavenging of superoxide or inhibition of NADPH oxidase improved NO-dependent dilation in MDD. Expression and activity of oxidative stress markers were increased in MDD. In a subset of adults with MDD treated with a selective serotonin reuptake inhibitor for their depressive symptoms and in remission (n=8; 7 women; 19-37 years), NO-mediated endothelium-dependent dilation was preserved, but endothelium-independent dilation was impaired, compared with healthy adults. CONCLUSIONS: Oxidative stress-induced reductions in NO-dependent dilation, as well as alterations in vascular smooth muscle function, directly contribute to microvascular dysfunction in MDD. Strategies targeting vascular oxidative stress may be viable therapeutic options for improving NO-mediated endothelial function and reducing cardiovascular risk in MDD.

Predictors of diagnostic delay: Assessment of psychiatric disorders in the clinic.

BACKGROUND: Diagnostic delay contributes to morbidity in psychiatric disorders. METHODS: Patients in an ambulatory psychiatry clinic were given patient-reported outcome measures at an initial visit, and a subset (N = 493) were given a structured interview (MINI International Neuropsychiatric Interview, MINI), in addition to the clinical encounter (CLIN). Diagnostic agreement between MINI and CLIN was assessed at an initial and follow-up visit. Diagnostic delay was identified if diagnostic disagreement between MINI and CLIN occurred at the initial visit and changed to an agreement at a follow-up visit. Registry data was compiled by an honest broker. RESULTS: Significant agreement occurred between MINI and CLIN diagnoses for major depressive disorder (MDD), bipolar disorder (BD), generalized anxiety disorder, and panic disorder. Diagnostic agreement for MDD occurred at initial visit for 63% of patients, and at follow-up for 87% of those with initial diagnostic disagreement; for BD, 75% at initial visit and 28% at follow-up. No demographic, socioeconomic, symptom severity or functioning measures predicted diagnostic agreement for the MDD group at the first visit, however initial psychopathological symptom complexity predicted diagnostic agreement in the diagnostic delay group. Initial diagnostic agreement for BD was predicted by lower symptom burden and better social, physical, and occupational functioning. No factors predicted additional diagnostic agreement at the second visit in the diagnostic delay group. CONCLUSION: Initial assessment by a structured interview aided physicians in identifying MDD by the second visit in patients with complex psychopathology. Patients with high complexity/severity of symptoms and more difficulty with functioning were less commonly identified with BD even with the assistance of a structured interview. Use of structured assessment tools may improve the detection of psychiatric illness by clinicians at the first visit.

Total sleep time and kynurenine metabolism associated with mood symptom severity in bipolar disorder.

OBJECTIVE: Chronic, low-level inflammation is associated with symptomatic bipolar disorder (BD) and with chronic insomnia. Disrupted sleep is a feature of episodes of both mania and depression. We examined the effect of neopterin, a marker of cellular immune activation, and kynurenine (KYN), an inflammatory byproduct of the serotonin pathway, on the association between total sleep time and depression severity in BD. METHOD: Twenty-one symptomatic BD participants and 28 healthy controls (HC) were recruited and followed during usual clinical care. At baseline and after symptomatic recovery, total sleep time was objectively measured with actigraphy for 1 week and blood plasma was collected to measure the serotonin precursor tryptophan (TRP), KYN, the KYN/TRP ratio, and neopterin levels. Statistical analyses were conducted using chi-square, independent t tests and hierarchical linear multiple regression models. RESULTS: Total sleep time was correlated positively with depressive severity and negatively with manic severity. TRP was significantly reduced in BD participants compared to HC. KYN, TRP, and the KYN/TRP ratio were associated with depressive severity when total sleep time and body mass index (BMI) were included in the model. The KYN/TRP ratio trended towards a negative association with mania symptoms, controlling for BMI and total sleep time, in acutely symptomatic BD participants. Neopterin was not associated with sleep or mood severity. After usual clinical care, BD participants showed significantly decreased clinical symptoms but no significant differences in sleep phenotype or biomarkers. CONCLUSION: Inflammation, sleep, and mood are closely intertwined. Future research into the effect of inflammation on sleep in BD may lead to clinical markers of outcome.

Seasonality of blood neopterin levels in the Old Order Amish.

Seasonal changes in non-human animals and seasonal affective disorder (SAD) in humans are associated with immune activation in winter relative to summer. We intended to measure seasonal variation in neopterin, a marker of cellular immunity, and its interactions with gender and seasonality of mood. We studied 320 Amish from Lancaster, PA, USA (men = 128; 40%) with an average age [Standard deviation (SD)] of 56.7 (13.9) years. Blood neopterin level was measured with enzyme-linked immunosorbent assay (ELISA). Seasonality was measured with Seasonal Pattern Assessment Questionnaire (SPAQ). Statistical analysis included analysis of covariance (ANCOVAs) and multivariate linear regression. We also investigated interactions of seasonal differences in neopterin with gender, seasonality scores and estimation of SAD diagnosis. We found a significantly higher neopterin level in winter than in summer (p = 0.006). There were no significant gender or seasonality interactions. Our study confirmed the hypothesized higher neopterin level in winter. A cross sectional design was our major limitation. If this finding will be replicated by longitudinal studies in multiple groups, neopterin could be used to monitor immune status across seasons in demographically diverse samples, even if heterogeneous in gender distribution, and degree of seasonality of mood.

Anxiety and depression in adults with primary immunodeficiency: How much do these patients experience and how much do they attribute to their primary immunodeficiency?

INTRODUCTION: Primary immunodeficiency (PID) is a rare group of disorders that manifest similarly with infection, neoplasms, allergic, and autoimmune diseases, and are treated with injectable medications. Often the burden of disease and cost of management is excessive, and premature death is not uncommon. In light of these features of PID, it was our objective to survey our cohort to assess for factors that can influence depression and anxiety. METHODS: We used an investigator-developed survey, in addition to the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale, after institutional review board approval of our pilot study, to determine the extent of anxiety and depression that our patients with PID experienced and variables that may have affected the difference of expression. The differences among groups were tested by using Wilcoxon rank sum tests, Kruskal-Wallis tests, and chi-square tests. RESULTS: The patients with PID had similar depression compared with the U.S. population, as assessed by the HAM-D scale. Risk factors associated with elevated HAM-D scores included the following: not driving, intravenous immunoglobulin therapy (versus subcutaneous), nurse-administered therapy (versus self-administered), having unpleasant adverse effects from therapy, previously attempted suicide, and family members with reported anxiety and/or depression. Anxiety was not significantly increased in our cohort. Risk factors for significantly elevated Hamilton Anxiety Rating Scale scores included the following: having poor health, an unhealthy diet, lack of refreshing sleep, and family members with reported anxiety and/or depression. CONCLUSION: Many factors influence depression and anxiety, and may add to the morbidity of PID. Patients should be assessed for our identified factors for depression and anxiety. Treatment or referrals should be initiated as it is hoped to improve our patients' quality of life and outcomes.

Depression and anxiety in patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is characterized by edematous swelling attacks of the face, extremities, abdomen, genitalia, and upper airway. The potential for laryngeal swelling makes the disease life-threatening, and the swelling elsewhere contributes to the significant burden of illness. The increased risk for mental health disorders in HAE is due to the burden of disease and possibly associated activation of the immune system. OBJECTIVE: To determine the prevalence of depression and anxiety in HAE patients and the most high-yield features of depression to target in a clinical encounter. METHODS: Depression and anxiety symptoms were evaluated using the 29 items of the Hamilton Depression Rating Scale along with the 14-item Hamilton Anxiety Rating Scale. The sample size was 26 participants with a diagnosis of type 1 or 2 HAE drawn from a cohort of 60 adult patients. In addition, a literature search was performed regarding how immune modulation affects depression and anxiety. RESULTS: A total of 39% of participants were identified as experiencing depression of mild (50%), moderate (40%), or severe (10%) levels. Fifteen percent of participants displayed prominent anxiety, half of whom had mild anxiety, 25% moderate anxiety, and 25% severe anxiety. The literature on inflammation and depression suggests a possible link between HAE and depression. CONCLUSION: Our data and the literature support that depression and anxiety symptoms are common in patients with HAE and may be secondary to chronic disease burden, associated pathophysiologic features, or both. Treatment that addresses the psychosocial and mental health of HAE patients is critical for best practice.

Sympathetic and blood pressure reactivity in young adults with major depressive disorder.

BACKGROUND: Sympathetic and blood pressure (BP) hyper-reactivity to stress may contribute to increased cardiovascular disease (CVD) risk in adults with major depressive disorder (MDD); however, whether this is evident in young adults with MDD without comorbid disease remains unclear. We hypothesized that acute stress-induced increases in muscle sympathetic nerve activity (MSNA) and BP would be exaggerated in young adults with MDD compared to healthy non-depressed young adults (HA) and that, in adults with MDD, greater symptom severity would be positively related to MSNA and BP reactivity. METHODS: In 28 HA (17 female) and 39 young adults with MDD of mild-to-moderate severity (unmedicated; 31 female), MSNA (microneurography) and beat-to-beat BP (finger photoplethysmography) were measured at rest and during the cold pressor test (CPT) and Stroop color word test (SCWT). RESULTS: There were no group differences in resting MSNA (p = 0.24). Neither MSNA nor BP reactivity to either the CPT [MSNA: ∆24 ±â€¯10 HA vs. ∆21 ±â€¯11 bursts/min MDD, p = 0.67; mean arterial pressure (MAP): ∆22 ±â€¯7 HA vs. ∆21 ±â€¯10 mmHg MDD, p = 0.46)] or the SCWT (MSNA: ∆-4 ±â€¯6 HA vs. ∆-5 ±â€¯8 bursts/min MDD, p = 0.99; MAP: ∆7 ±â€¯8 HA vs ∆9 ±â€¯5 mmHg MDD; p = 0.82) were different between groups. In adults with MDD, symptom severity predicted MAP reactivity to the CPT (ß = 0.78, SE = 0.26, p = 0.006), but not MSNA (p = 0.42). LIMITATIONS: The mild-to-moderate symptom severity reflects only part of the MDD spectrum. CONCLUSIONS: Neither sympathetic nor BP stress reactivity are exaggerated in young adults with MDD; however, greater symptom severity may amplify BP reactivity to stress, thereby increasing CVD risk.

Cardiovascular disease burden is associated with worsened depression symptoms in the U.S. general population.

BACKGROUND: Cardiovascular disease (CVD) and depression are the leading causes of disability in the U.S. Using five cycles (2009-2018) of the U.S. National Health and Nutrition Examination Survey, we examined the cross-sectional association between CVD risk factor burden and depression severity in nonpregnant adults with no history of CVD events. METHODS: With at least 3000 participants per cycle, the overall N was 18,175. CVD risk factors were ascertained through self-report, lab tests, or medications. The sum of hypertension, diabetes, dyslipidemia, and current smoking represented a CVD risk score variable (range: 0-4). Depression severity was assessed using scores on the 9-item patient health questionnaire: 0-9 (none-mild) and 10-27 (moderate-to-severe). Logistic regression models were performed to investigate the association between CVD risk score categories and moderate-to-severe depression. Cycle-specific odds ratios (OR) were meta-analyzed to obtain a pooled OR (95 % CI) (Q-statistic p > 0.05). RESULTS: Compared to participants with no CVD risk factors, participants with risk scores of 1, 2, 3, and 4, had 1.28 (0.92-1.77), 2.18 (1.62-2.94), 2.53 (1.86-3.49), 2.97 (1.67-5.31) times higher odds of moderate-to-severe depression, respectively, after adjusting for socio-demographics and antidepressant use (linear trend p < 0.0001). This relationship persisted after additionally adjusting for lifestyle variables. LIMITATIONS: NHANES data is cross-sectional and self-reported, thus preventing causal assessments and leading to potential recall bias. CONCLUSIONS: Among U.S. adults, CVD risk factor burden was associated with worsened depression symptoms. Integrated mental and physical healthcare services could improve risk stratification among persons with CVD and depression, possibly reducing long-term disability and healthcare costs.

Heightened inflammation in bipolar disorder occurs independent of symptom severity and is explained by body mass index.

Inflammation is hypothesized to be a key component of bipolar disorder (BP) development and progression. However, findings linking BP prevalence and symptomology to immune functioning have been mixed, with some work suggesting that obesity may play an important role in BP-relevant inflammation. Here we investigate differences in biomarkers of inflammation [C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, IL-8, IL-10] between healthy controls (HC) and individuals with BP or other mental illness (MI). Adults with BP, MI, or HC (n = 545, 70% BP, 21% HC, 9% MI) self-reported depressive and manic symptoms close to a blood draw and physical exam that included measurement of height and weight. A composite score was calculated from the four cytokines measured in plasma; follow-up analyses explored a pro-inflammatory composite and IL-10, individually. BP individuals had elevated cytokine concentrations compared to HC (B = 0.197, [0.062, 0.333], t (542) = 2.855, p = .004); this difference was also evident for the pro-inflammatory composite and for IL-10. Cytokine concentrations were not associated with BP mood states. Body mass index (BMI), an indicator of obesity, was significantly higher in BP compared to HC (B = 3.780, [2.118, 5.443], t (479) = 4.457, p < .001) and differences in cytokines between the two groups was no longer significant after controlling for BMI. No differences in CRP were evident between BP and HC. These results suggest that cytokine concentrations are elevated in BP and this difference from HC is associated with obesity. Interventions targeting immune modulators in BP must carefully consider the complex relationships within the BP-inflammation-obesity triangle.