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.

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.

Urban vs. rural differences in psychiatric diagnoses, symptom severity, and functioning in a psychiatric sample.

OBJECTIVE: Identifying whether certain groups of people experience elevated rates or severities of psychiatric symptoms provides information to guide healthcare allocation. People living in urban areas have higher rates of some psychiatric disorders relative to people living in rural settings, however, it is unclear if psychiatric severity is more elevated in urban vs. rural settings. This study investigates the urban vs. rural differences in rates of psychiatric disorders and severity of psychiatric symptoms. METHOD: A cohort of patients (63% women, 85% White) presenting to an outpatient psychiatric treatment center in the U.S. completed patient-reported outcomes at all clinic visits as part of standard care. Rurality was determined by municipality population density. Sociodemographic characteristics, psychiatric diagnoses, trauma exposure, psychiatric symptom severity, functioning, and suicidality were compared by rural vs. urban municipality. RESULTS: There were virtually no differences between patients living in rural vs. urban municipalities on rates of psychiatric disorders, severity of psychiatric symptoms, functional impairment, and suicidality (ps≥.09). The only difference was that patients living in rural municipalities had higher exposure to serious accidents than patients living in urban municipalities (p < .01); exposure to nine other traumatic events did not differ between groups (p≥.07). CONCLUSIONS: People living in urban and rural municipalities have a similar need for mental health treatment. Access to care may be one explanatory factor for the occasional rural-urban differences in rates of psychiatric disorders. In other words, if people living in rural areas can access care, their symptom presentations appear unlikely to differ from those of people living in urban areas.

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.

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.

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.

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.

Screening for ADHD in a general outpatient psychiatric sample of adults.

Adults (n = 805) seeking outpatient psychiatric care completed the Adult ADHD Self-Report Scale (ASRS) and measures of impairment and co-occurring psychopathology as part of a measurement-based care initiative. Diagnostic indicators of ADHD (i.e., formal diagnosis and/or medication treatment) were recorded from the electronic medical record (EMR). Agreement between screening positive for ADHD and EMR indicators for the diagnosis was explored, and clinical characteristics of adults identified with ADHD using these indicators were examined. Lastly, the contribution of ADHD to functional impairment was examined, controlling for the contribution of other demographic and psychiatric comorbidities. In the full sample, 54.78% of adults screened positive for ADHD based on the ASRS, and using EMR indicators, only 11.93% of adults were identified with ADHD. Agreement emerged between self-reported ADHD and ADHD EMR indicators, although adults screening positive for ADHD generally reported greater psychiatric complexity relative to adults identified with ADHD in the EMR. ADHD was associated with clinical impairment even when controlling for other psychiatric comorbidities. The considerable difference in prevalence of ADHD based on self-report screening versus EMR indicators suggests that ADHD may be overlooked in adult psychiatric care. Findings point to the importance of assessing adult ADHD in routine psychiatric care.

Microvascular ß-Adrenergic Receptor-Mediated Vasodilation Is Attenuated in Adults With Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is associated with sympathetic overactivity and alterations in peripheral adrenergic receptor function; however, no studies have directly assessed vasoconstrictor responsiveness in adults with MDD. We tested the hypotheses that ß-adrenergic receptor-mediated vasodilation would be blunted in adults with MDD compared with healthy nondepressed adults (HA) and would functionally contribute to exaggerated norepinephrine-induced vasoconstriction. METHODS: In 13 HA (8 female; 24±4 years) and in 12 adults with MDD (8 female; 22±3 yrs), red blood cell flux was measured during graded intradermal microdialysis perfusion of the ß-adrenergic receptor agonist isoproterenol (10-10 to 10-4 mol/L) and, separately, during the perfusion of norepinephrine (10-12 to 10-2 mol/L), alone and in combination with the ß-adrenergic receptor antagonist propranolol (2 mmol/L). Nonadrenergic vasoconstriction was assessed via perfusion of angiotensin II (10-12 to 10-4 mol/L). RESULTS: Isoproterenol-induced vasodilation was blunted in adults with MDD (188.9±70.1 HA versus 128.3±39.4 au MDD, P=0.025). Net norepinephrine-induced vasoconstriction was exaggerated in adults with MDD (-0.16±0.54 HA versus -0.75±0.56 au MDD, P=0.014); however, there were no group differences in angiotensin II-induced vasoconstriction. Propranolol potentiated norepinephrine-induced vasoconstriction in HA (-0.16±0.54 norepinephrine versus -1.60±1.40 au propranolol, P<0.01) but had no effect in adults with MDD (-0.75±0.56 norepinephrine versus -1.58±1.56 au propranolol, P=0.08). CONCLUSIONS: ß-adrenergic receptor-mediated microvascular vasodilation was blunted in adults with MDD and contributed to exaggerated adrenergic vasoconstriction. The relative loss of the vasoprotective effect of ß-adrenergic receptor-mediated vasodilation may contribute to increased peripheral resistance, thereby driving the development of hypertension in adults with MDD.

Augmented T-cell mitochondrial reactive oxygen species in adults with major depressive disorder.

The prevalence of major depressive disorder (MDD) is highest in young adulthood, an effect that has been magnified by the COVID-19 pandemic. Importantly, individuals with MDD are at a greater risk of developing cardiovascular disease (CVD). Accumulating evidence supports immune system dysregulation as a major contributor to the elevated CVD risk in older adults with MDD; however, whether this is present in young adults with MDD without comorbid disease remains unclear. Interestingly, recent data suggest augmented T-cell mitochondrial reactive oxygen species (T-cell mitoROS) as a potent driver of immune dysregulation in animal models of psychiatric disease. With this background in mind, we tested the hypothesis that young adults with MDD would have augmented T-cell mitoROS and circulating proinflammatory cytokines compared with healthy young adults without MDD (HA). Whole blood was drawn from 14 young adults with MDD (age: 23 ± 2 yr) and 11 HA (age: 22 ± 1 yr). T-cell mitoROS (MitoSOX red; total: CD3+, T-helper: CD4+, T cytotoxic: CD8+) and serum cytokines were assessed by flow cytometry. Total T-cell mitoROS was significantly greater in adults with MDD compared with HA [median: 14,089 arbitrary units (AU); median: 1,362 AU, P = 0.01]. Likewise, both T-helper and T-cytotoxic cell mitoROS were significantly greater in adults with MDD compared with HA (both: P < 0.05). There were no differences in circulating cytokines between groups (all cytokines: P > 0.05). Collectively, these findings suggest that elevated T-cell mitoROS may represent an early marker of immune system dysregulation in young, otherwise healthy, adults with MDD.NEW & NOTEWORTHY To our knowledge, we provide the first evidence of augmented T-cell mitochondrial reactive oxygen species (T-cell mitoROS) in young, otherwise healthy adults with MDD. Although the elevated T-cell mitoROS did not correspond to a proinflammatory profile, these findings suggest that elevated T-cell mitoROS may be an early marker of immune system dysregulation 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.

Transdiagnostic and functional predictors of depression severity and trajectory in the Penn state psychiatry clinical assessment and rating evaluation system (PCARES) registry.

BACKGROUND: Timely, accurate diagnosis and subsequent identification of risk factors for depression that is difficult-to-treat can aid in decreasing the burden of depressive illness and reducing probability of future disability. We aimed to identify sociodemographic, clinical, and functional factors that predict depression severity over one year in a real-world, naturalistic, transdiagnostic clinical sample. A subset sample with moderate depression was examined to determine the magnitude of improvement. METHODS: The Penn State Psychiatry Clinical Assessment and Rating System (PCARES) Registry houses data from systematically-structured patient-reported outcomes and clinical data from an Electronic Medical Record (EMR) gathered during routine clinical care of patients seeking mental health care at a mid-Atlantic clinic. Self-report symptom and functional measures were obtained, and sociodemographic features and clinical diagnoses were extracted from the EMR from 1,766 patients between 2/6/2016 to 9/30/2019. The Patient Health Questionnaire 9 (PHQ-9) depression scale was obtained at each visit. Using a discrete mixture clustering model, the study population was divided into five longitudinal trajectory groups, termed depression severity groups, based on intra-individual PHQ-9 score trajectories over one year. Multinomial logistic regression models were estimated to evaluate associations between characteristics and the likelihood of depression severity group membership. To determine the magnitude of improvement, predictors of the slope of the PHQ-9 trajectory were examined for patients with moderate depression. RESULTS: The strongest predictors of high depression severity over one year were poor functioning, high transdiagnostic DSM-5 Level 1 crosscutting symptom score, diagnosis of Post-Traumatic Stress Disorder (PTSD), public/self-pay insurance, female gender, and non-White race. Among the subset of patients with moderate depression, strong predictors of improvement were commercial insurance and exposure to trauma; the strongest predictors of worsening were high functional impairment, high transdiagnostic Level 1 symptom score, diagnosis of PTSD, diagnosis of bipolar disorder, and marital status of single or formerly married; depression-specific symptom measures were not predictive. LIMITATIONS: Limitations include inferring education and income status from zip code level-data, the non-random missingness of data, and the use of diagnoses collected from the electronic medical record. CONCLUSION: Functional impairment, transdiagnostic measures of symptom burden, and insurance status are strong predictors of depression severity and poor outcome.

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.

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.

Group-led creative writing and behavioural health in cancer: a randomised clinical trial.

BACKGROUND: Cancer diagnosis can adversely affect mental well-being and overall clinical outcome. We evaluated the efficacy of a group-led creative writing workshop (CWW) on mood in patients with cancer prospectively. METHODS: We conducted a single-institution phase II study. Sixty adult patients with cancer (any type or stage) were randomised 2:1 to CWW (4×CWW sessions, bimonthly over 8 weeks) versus active control (AC) (independent writing at home with the help of a book, four sessions, bimonthly over 8 weeks). The total study duration was 6 months with a follow-up of up to 3 months. PRIMARY OBJECTIVE: changes in overall mood, depression and anxiety symptoms before and after intervention in both arms. Emotional Thermometer Scale (ETS) was used to assess changes in patients' mood. Additionally, the Patient Health Questionnaire (PHQ)-9 and General Anxiety Disorder Scale (GAD)-7 were used to evaluate depression and anxiety symptoms. RESULTS: Of 50 evaluable patients (CWW 34, AC 17), 26 patients in the CWW arm attended at least one class and 19 attended at least four classes. Patients in CWW had significant immediate improvement in the overall ETS (post vs preclass scores; p<0.0001, 95% CI -4.31 to -2.47). Four of the five subscale ETS scores were significantly lower for the CWW arm: distress (p=0.0346, 95% CI -2.6 to -0.1), anxiety (p=0.0366, 95% CI -4.1 to -0.2), depression (p=0.0441, 95% CI -3.9 to -0.1) and anger (p=0.0494, 95% CI -3.3 to 0). No significant differences were seen in the AC arm. No significant differences were observed in the PHQ-9 or the GAD-7 scores. CONCLUSION: CWW had a positive effect on mood based on ETS scores, suggesting a potential therapeutic benefit among patients with cancer.

Cerebrovascular reactivity is blunted in young adults with major depressive disorder: The influence of current depressive symptomology.

BACKGROUND: In middle-aged adults with depression, cerebral vasodilatory reactivity is blunted; however, this has not been examined in treatment-naïve young adults with major depressive disorder (MDD). We tested the hypothesis that cerebrovascular reactivity would be blunted in young adults (18-30 yrs) with MDD compared to healthy non-depressed adults (HA) and would be attenuated to a greater extent in adults with symptomatic MDD (sMDD) compared to adults with MDD in remission (euthymic MDD; eMDD). METHODS: Sixteen adults with MDD [21±3yrs; n = 8 sMDD (6 women); n = 8 eMDD (5 women)] and 14 HA (22±3yrs; 9 women) participated. End-tidal carbon dioxide concentration (PETCO2; capnograph), beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), and internal carotid artery (ICA) diameter and blood velocity (Doppler ultrasound) were continuously measured during baseline and rebreathing-induced hypercapnia. Cerebrovascular reactivity was calculated as the relative increase in vascular conductance during hypercapnia. RESULTS: In adults with MDD, cerebrovascular reactivity in the MCA (∆39±9 HA vs. ∆31±13% MDD, p = 0.04), but not the ICA (∆36±24 HA vs. ∆34±18% MDD, p = 0.84), was blunted compared to HA. In the MCA, cerebrovascular reactivity was reduced in adults with sMDD compared to adults with eMDD (∆36±11 eMDD vs. ∆25±13% sMDD, p = 0.02). LIMITATIONS: The cross-sectional nature approach limits conclusions regarding the temporal nature of this link. CONCLUSION: These data indicate that MCA cerebrovascular reactivity is blunted in young adults with MDD and further modulated by current depressive symptomology, suggesting that the management of depressive symptomology may secondarily improve cerebrovascular health.

COVID-19-Related Daily Stress Processes in College-Aged Adults: Examining the Role of Depressive Symptom Severity.

Exposure to daily stressors specific to the COVID-19 pandemic (e.g., threat of infection) is associated with emotional distress, heightened stress reactivity, and increased depressive symptomology. Herein, we examined whether current depressive symptomology modulates the association between COVID-19-related daily stressor exposure and negative affective reactivity in young, otherwise healthy, college-aged adults. Fifty-eight adults (21 men; 22±3years) completed a daily web-based interview for eight consecutive days to assess COVID-19-related daily stress exposure and emotional responsiveness (September-November 2020). Depressive symptom severity was assessed using the Patient Health Questionnaire-9 (PHQ-9), and a score of ≥10 (range: 0-27) was used to define adults with a depressive episode (n=20). Participants reported at least one COVID-19-related stressor on 35.8% of interview days. Depressive symptomology did not predict the likelihood of exposure to a COVID-19-related stressor (p=0.46; OR=1.52; 95% CI: 0.492-4.718). However, negative affect (NA) was greater on days with an exposure to any COVID-19-specific daily stressor in adults with moderate-to-severe depressive symptoms (b=0.28, SE=0.093, p=0.003) but not in those without (b=0.009, SE=0.074, p=0.90), such that negative affective reactivity to COVID-19-related stressors was amplified in adults with a current depressive episode (p=0.019). Depressive symptomology did not moderate positive affective reactivity (p=0.686). Taken together, these data suggest that exposure to daily stressors related to COVID-19 further worsens NA in adults with a current depressive episode, potentially rendering them more susceptible to adverse mental health outcomes during the pandemic.

Prolonged functional cerebral asymmetry as a consequence of dysfunctional parvocellular paraventricular hypothalamic nucleus signaling: An integrative model for the pathophysiology of bipolar disorder.

Approximately 45 million people worldwide are diagnosed with bipolar disorder (BD). While there are many known risk factors and models of the pathologic processes influencing BD, the exact neurologic underpinnings of BD are unknown. We attempt to integrate the existing literature and create a unifying hypothesis regarding the pathophysiology of BD with the hope that a concrete model may potentially facilitate more specific diagnosis, prevention, and treatment of BD in the future. We hypothesize that dysfunctional signaling from the parvocellular neurons of the paraventricular hypothalamic nucleus (PVN) results in the clinical presentation of BD. Functional damage to this nucleus and its signaling pathways may be mediated by myriad factors (e.g. immune dysregulation and auto-immune processes, polygenetic variation, dysfunctional interhemispheric connections, and impaired or overactivated hypothalamic axes) which could help explain the wide variety of clinical presentations along the BD spectrum. The neurons of the PVN regulate ultradian rhythms, which are observed in cyclic variations in healthy individuals, and mediate changes in functional hemispheric lateralization. Theoretically, dysfunctional PVN signaling results in prolonged functional hemispheric dominance. In this model, prolonged right hemispheric dominance leads to depressive symptoms, whereas left hemispheric dominance correlated to the clinical picture of mania. Subsequently, physiologic processes that increase signaling through the PVN (hypothalamic-pituitaryadrenal axis, hypothalamic- pituitary-gonadal axis, and hypothalamic-pituitary-thyroid axis activity, suprachiasmatic nucleus pathways) as well as, neuro-endocrine induced excito-toxicity, auto-immune and inflammatory flairs may induce mood episodes in susceptible individuals. Potentially, ultradian rhythms slowing with age, in combination with changes in hypothalamic axes and maturation of neural circuitry, accounts for BD clinically presenting more frequently in young adulthood than later in life.