Effects Of Major Depressive Disorder Research Articles

Mendelian randomization identifies causal effects of major depressive disorder on accelerated aging

BackgroundEvidence links major depressive disorder (MDD) with aging, but it's unclear if MDD accelerates aging and what factors mediate this transition. MethodsTwo-sample Mendelian randomization (MR) analyses were applied to estimate the causal association between MDD and frailty index (FI), telomere length (TL), and appendicular lean mass (ALM) from available genome-wide association studies in populations of European ancestry. Furthermore, we conducted mediation MR analyses to assess the mediating effects of 31 lifestyle factors or diseases on the causal relationship between MDD and aging. ResultsMDD was significantly causally associated with increased FI (βIVW = 0.23, 95 % CI = 0.18 to 0.28, p = 1.20 × 10−17), shorter TL (βIVW = −0.04, 95 % CI = −0.07 to −0.01, p = 0.01), and decreased ALM (βIVW = −0.07, 95 % CI = −0.11 to −0.03, p = 3.54 × 10−4). The mediation analysis through two-step MR revealed smoking initiation (9.09 %), hypertension (6.67 %) and heart failure (5.36 %) mediated the causal effect of MDD on FI. Additionally, alcohol use disorders and alcohol dependence on the causal relationship between MDD and TL were found to be 17.52 % and 17.13 % respectively. LimitationsConfounding, statistical power, and Euro-centric focus limit generalization. ConclusionOverall, individuals with MDD may be at a higher risk of experiencing premature aging, and this risk is partially influenced by the pathways involving smoking, alcohol use, and cardiovascular health. It underscores the importance of early intervention and comprehensive health management in individuals with MDD to promote healthy aging and overall well-being.

Major Depressive Disorder as a Driver of Dual Systems Model Development During Adolescence and Emerging Adulthood Among Justice-Involved Youth: Is Salience Age-Graded?

The dual systems model is a psychological framework centered on differential development of sensation-seeking and impulse control during adolescence and emerging adulthood with implications for understanding antisocial behavior. However, there is a dearth of research which has examined mental illness as a driver of differential development of these constructs. This study examined major depressive disorder as a risk factor for elevated sensation-seeking and diminished impulse control and tested to determine whether the salience differed by age. The Pathways to Desistance data were analyzed. Mixed effects models examined the direct effect of major depressive disorder on dual systems outcomes and test for moderation by age. Findings indicated that major depressive disorder at baseline was associated with increased sensation-seeking and diminished impulse control. Relationships did not differ in salience based on age. Results suggest that treatment effective for addressing depression may have relevance for mitigating the impact of the disorder on cognition.

Exploring the Effects of Major Depressive Disorder on Daily Occupations and the Impact of Psychotherapy: A Literature Review.

Major depressive disorder (MDD) is a prevalent psychological mood disorder that can disrupt one's functioning and result in decreased engagement in daily activities. Psychotherapy, in different approaches, is a common approach for individuals experiencing MDD. Nevertheless, a literaturereview of the research supporting the effectiveness of psychotherapeutic interventions in patients with MDD-impacted areas of their daily occupations, such as back to work, cognitive deficits, and well-being, has not been conducted. A literature review was carried out to evaluate the effectiveness of psychotherapy on daily occupations for individuals diagnosed with MDD. Due to variations in study design and outcome measures, a best evidence synthesis was carried out instead of a meta-analysis. Forty-one identified articles were fully assessed in total. These studies were conducted in various countries so that a global approach could be considered comprehensive. The findings showed strong evidence supporting the effectiveness of psychotherapy on return-to-work interventions in improving depressive symptoms. There was limited evidence for the effectiveness of psychotherapy on lifestyle interventions in reducing anxiety and suicidal ideation, as well as limited evidence for enhancing work participation. Notably, there were no studies evaluating individualized client-centered psychotherapy interactions with occupations, revealing a research gap. Challenges such as incomplete reporting within studies and study heterogeneity prevented a meta-analysis. While the overall evidence base for the effectiveness of psychotherapy for MDD in treating functionality is limited, the findings provide strong support for the efficacy of occupational therapy return-to-work interventions. This is particularly important given the economic costs associated with mental health issues and work-related absences. Further research is required to strengthen the existing evidence base.

Functional connectivity between the habenula and posterior default mode network contributes to the response of the duloxetine effect in major depressive disorder.

This study aims to investigate the functional connectivity (FC) changes of the habenula (Hb) among patients with major depressive disorder (MDD) after 12 weeks of duloxetine treatment (MDD12). Patients who were diagnosed with MDD for the first time and were drug-naïve were recruited at baseline as cases. Healthy controls (HCs) matched for sex, age, and education level were also recruited at the same time. At baseline, all participants underwent resting-state functional MRI. FC analyses were performed using the Hb seed region of interest, and three groups including HCs, MDD group and MDD12 group were compared using whole-brain voxel-wise comparisons. Compared to the HCs, the MDD group had decreased FC between the Hb and the right anterior cingulate cortex at baseline. Compared to the HCs, the FC between the Hb and the left medial superior frontal gyrus decreased in the MDD12 group. Additionally, the FC between the left precuneus, bilateral cuneus and Hb increased in the MDD12 group than that in the MDD group. No significant correlation was found between HDRS-17 and the FC between the Hb, bilateral cuneus, and the left precuneus in the MDD12 group. Our study suggests that the FC between the post-default mode network and Hb may be the treatment mechanism of duloxetine and the treatment mechanisms and the pathogenesis of depression may be independent of each other.

Causal relationship between affect disorders and endometrial cancer: a Mendelian randomisation study

Background The aim was to assess the causal relationship between depression and anxiety disorders and endometrial cancer. Method We performed two-sample Mendelian randomisation analysis using summary statistics from genome-wide association studies to assess associations of major depressive disorder, anxiety and stress-related disorders with endometrial cancer. The genome-wide association studies(GWASs) data were derived from participants of predominantly European ancestry included in the Genome-wide Association Research Collaboration. Inverse variance-weighted, MR-Egger and weighted median MR analyses were performed, together with a range of sensitivity analyses. Results Mendelian randomisation analysis showed no statistically significant genetic responsibility effect of anxiety and stress-related disorders on any pathological type of endometrial cancer. Only the effect of major depressive disorder under the inverse variance weighting method increasing the risk of endometrial endometrial cancer (effect 0.004 p = 0.047) and the effect of major depressive disorder under the MR-Egger method decreasing endometrial cancer of all pathology types (effect −0.691 p = 0.015) were statistically significant. Other Mendelian randomisation analyses did not show a statistically significant effect. Conclusion Major depressive disorder(MDD), anxiety and stress-related disorders(ASRD) are not genetically responsible for endometrial cancer. We consider that emotional disorders may affect endometrial cancer indirectly by affecting body mass index. This study provides us with new insights to better understand the aetiology of endometrial cancer and inform prevention strategies.

Distinct mechanisms of allopregnanolone and diazepam underlie neuronal oscillations and differential antidepressant effect.

The rapid relief of depressive symptoms is a major medical requirement for effective treatments for major depressive disorder (MDD). A decrease in neuroactive steroids contributes to the pathophysiological mechanisms associated with the neurological symptoms of MDD. Zuranolone (SAGE-217), a neuroactive steroid that acts as a positive allosteric modulator of synaptic and extrasynaptic δ-subunit-containing GABAA receptors, has shown rapid-onset, clinically effective antidepressant action in patients with MDD or postpartum depression (PPD). Benzodiazepines, on the other hand, act as positive allosteric modulators of synaptic GABAA receptors but are not approved for the treatment of patients with MDD. It remains unclear how differences in molecular mechanisms contribute to the alleviation of depressive symptoms and the regulation of associated neuronal activity. Focusing on the antidepressant-like effects and neuronal activity of the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), we conducted a head-to-head comparison study of the neuroactive steroid allopregnanolone and the benzodiazepine diazepam using a mouse social defeat stress (SDS) model. Allopregnanolone but not diazepam exhibited antidepressant-like effects in a social interaction test in SDS mice. This antidepressant-like effect of allopregnanolone was abolished in extrasynaptic GABAA receptor δ-subunit knockout mice (δko mice) subjected to the same SDS protocol. Regarding the neurophysiological mechanism associated with these antidepressant-like effects, allopregnanolone but not diazepam increased theta oscillation in the BLA of SDS mice. This increase did not occur in δko mice. Consistent with this, allopregnanolone potentiated tonic inhibition in BLA interneurons via δ-subunit-containing extrasynaptic GABAA receptors. Theta oscillation in the mPFC of SDS mice was also increased by allopregnanolone but not by diazepam. Finally, allopregnanolone but not diazepam increased frontal theta activity in electroencephalography recordings in naïve and SDS mice. Neuronal network alterations associated with MDD showed decreased frontal theta and beta activity in depressed SDS mice. These results demonstrated that, unlike benzodiazepines, neuroactive steroids increased theta oscillation in the BLA and mPFC through the activation of δ-subunit-containing GABAA receptors, and this change was associated with antidepressant-like effects in the SDS model. Our findings support the notion that the distinctive mechanism of neuroactive steroids may contribute to the rapid antidepressant effects in MDD.

Plasma circRNA HIPK2 as a putative biomarker for the diagnosis and prediction of therapeutic effects in major depressive disorder

BackgroundCircular RNAs (circRNAs) are a prevalent type of non-coding RNAs exhibiting extensive expression in mammalian cells. Owing to their involvement in diverse pathophysiological mechanisms of major depressive disorder (MDD) and their inherent stability in peripheral blood, circRNAs have emerged as potential biomarkers of considerable significance. This study aimed to identify and validate circular RNA HIPK2 (circHIPK2) in MDD patients and to investigate its potential as a biomarker for the diagnosis and prognosis of MDD. MethodsPatients with MDD (n = 81) and healthy controls (HCs) (n = 48) were recruited for our study (October 2022 to June 2023). The expression of circHIPK2 in plasma was assessed using absolute quantitative polymerase chain reaction (qPCR). ResultsThe expression of circHIPK2 in plasma of patients with MDD exhibited a significant increase compared to HCs. The circHIPK2 levels showed an area under the curve (AUC) of 0.796, corresponding to a specificity of 97.9% and a sensitivity of 60.4% in diagnosing MDD. Additionally, the rate of change in circHIPK2 over a 14-day period exhibited an AUC curve of 0.819, indicating its predictive value for antidepressive effects. ConclusionsCircHIPK2 could serve as a potential biomarker for diagnosing MDD and predicting therapeutic effects of MDD.

Major Depressive Disorder Effects on Wound Healing in Peripheral Arterial Disease Patients Following Lower Extremity Amputation

Major Depressive Disorder Effects on Wound Healing in Peripheral Arterial Disease Patients Following Lower Extremity Amputation

Non-inferiority of intermittent theta burst stimulation over the left V1 vs. classical target for depression: A randomized, double-blind trial

BackgroundRepetitive transcranial magnetic stimulation (rTMS) targeting the visual cortex (VC) has shown antidepressant effects for major depressive disorder (MDD) in sham-controlled trials, but comparisons with rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) are lacking. We aimed to determine the non-inferiority of intermittent theta-burst stimulation (iTBS) over VC vs DLPFC for MDD. MethodsParticipants randomly received navigated iTBS over the left V1 or the left DLPFC twice daily for 14 days with a 3-month follow-up. The primary outcome was change in Hamilton Depression Rating Scale (HAMD-17) score from baseline to treatment end, with 2.5 points as the non-inferiority margin. Secondary outcomes included: improvement in Montgomery-Asberg Depression Rating Scale (MADRS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA); response and remission rates; suicidal ideation and adverse events. ResultsOf 75 randomized patients, 67 completed full treatment, including 52 first-episode patients and 15 relapsers. The primary outcome indicated the non-inferiority of VC (adjusted difference 1.14, lower 97.5 % CI −1.24; p = .002), confirmed by improvements in objective cognitive task and protein levels, as did most secondary outcomes. Reduced suicidal ideation after treatment, incidence of eye discomfort and pain score were lower in the VC group. ConclusionsLeft VC iTBS has the potential to be non-inferior to DLPFC iTBS in most first-episode MDD in improving depressive symptoms and cognitive function, with less suicidal ideation and adverse events. LimitationsGiven the limited sample size, the lack of a sham control and the use of antidepressants, the findings should be interpreted with caution.

Major Depressive Disorder Effects on Wound Healing in Peripheral Arterial Disease Patients Following Extremity Amputation

Major Depressive Disorder Effects on Wound Healing in Peripheral Arterial Disease Patients Following Extremity Amputation

Major depressive disorder as a moderator of the relationship between heavy-episodic drinking and anxiety symptoms

Background Major depressive disorder and heavy-episodic drinking are risk factors for the development of anxiety. However, the interactive effect between these constructs for predicting anxiety symptoms remains understudied. Aims This study sought to examine how major depressive disorder moderates the relationship between heavy-episodic drinking frequency and the development of anxiety symptoms in adolescence and emerging adulthood among a sample of justice-involved youth, with expectations that the salience of this relationship may differ based on life-course stage. Methods Several waves of the Pathways to Desistance study were analyzed. Poisson regression with robust standard errors was used to test the direct and interactive effects of major depressive disorder and heavy-episodic drinking frequency on anxiety symptoms at follow-up in adolescence and emerging adulthood separately. Results Results indicated that there was a significant negative interaction between major depressive disorder and heavy-episodic drinking frequency for predicting anxiety scores in both adolescence and emerging adulthood, though the results for adolescence were more robust. Conclusions These results suggest youth without major depressive disorder that engage in heavy-episodic drinking may be a priority population for treating anxiety issues, but that ceiling effects may limit the impact of the behavior on anxiety on youth with major depressive disorder.

Evidence for a causal effect of major depressive disorder, anxiety on prostatitis risk: A univariate and multivariate Mendelian randomization study.

Observational studies have shown an association between major depressive disorder (MDD), anxiety, and prostatitis. However, the causal relationship between MDD, anxiety, and prostatitis remains controversial. Therefore, we aimed to use two-sample Mendelian randomization (MR) to assess the causal effects of MDD and anxiety on prostatitis. We conducted univariable and multivariable MR analyses using summary statistics from publicly available genome-wide association studies to estimate the causal relationships between MDD, anxiety, and prostatitis risk. In the main MR analysis, the inverse-variance weighted (IVW) method was used, while secondary methods included the weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual and outlier (MR-PRESSO) tests to detect and correct for the presence of pleiotropy. MDD had 97 independent instrumental variables (IVs) and anxiety had 15 IVs. Univariable MR analysis showed that genetically determined MDD had a detrimental causal effect on prostatitis (IVW: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.005), while no causal relationship was found between anxiety and prostatitis (IVW: OR = 0.25, 95% CI = 0.02-2.82, p = 0.26). More convincingly, after adjusting for confounding factors such as body mass index, alcohol consumption, and smoking, the genetic liability for MDD remained associated with prostatitis risk, with no strong evidence of anxiety affecting prostatitis incidence. This study supports the notion that MDD has a detrimental effect on prostatitis risk, and strategies focused on addressing MDD may be one of the cornerstones for treating prostatitis. The potential preventive value of treating MDD for prostatitis should be further investigated in future research.

Effect of Major Depressive Disorder on Stroke Risk and Mortality: A Systematic Review.

This study aimed to systematically review the available data on major depressive disorder (MDD) and provide insight into how it may affect stroke risk and mortality. We conducted this systematic review drawing upon research published between July 2002 and July 2022 from the following databases: PubMed, ScienceDirect, and Google Scholar. After eliminating duplicates, screening the title and abstract, determining eligibility, and quality assessment, eight articles were left for utilization in this systematic review (one meta-analysis and seven non-randomized studies). There was a potentially significant association between MDD and stroke risk and mortality. The apparent connection between MDD and stroke has medical and public health relevance, given the high incidence, prevalence, and financial burden of MDD and stroke in the general populace. Therefore, it is imperative that further studies are conducted to confirm and validate this association between MDD and stroke while also elucidating the mechanism involved, investigating potential variables influencing this association, and contrasting MDD with conventional stroke risk factors to determine its predictive usefulness in comparison to traditional risk factors. This will have a significant effect on clinical practice since the information provided by such research will help guide essential targets for stroke prevention.

Ketamine Augmentation of Electroconvulsive Therapy: A Scoping Review of Dose-Dependent Effects in Major Depressive Disorder.

Intravenous ketamine infusions in subanesthetic doses have been shown to rapidly alleviate depressive symptoms. However, the efficacy of ketamine as an anesthetic duringelectroconvulsive therapy (ECT) for major depression has not yet been answered by a large randomized control trial (RCT). This scoping review aims to examine the available literature to determine whether the dose of ketamine used during ECT influences the response to treatment. A literature search was conducted on PubMed to identify all published RCTs within the last 10 years which compared ketamine anesthesia during ECT for major depression with another anesthetic. Studies using low (<0.8 mg/kg) versus high (≥0.8 mg/kg) doses of ketamine during ECT were evaluated for the differences in outcomes using depression rating scales. Studies that examined ketamine as a standalone treatment for depressionor focused primarily on the anesthetic benefits of ketamine were excluded from our review. Fifteen studies were utilized for this literature review. Overall, the studies showed inconsistent results in terms of the speed and magnitude of response to ketamine-assisted ECT in patients with major depression. Limitations of the available literature are discussed, including the lack of head-to-head comparisons, differences in methodology, inclusion/exclusion criteria, and primary and secondary endpoints.

Abstract P3-03-08: Depression and breast cancer recurrence among female veterans in the United States: a retrospective cohort study

Abstract Background: The importance of mental health to improve the quality of cancer survivorship and outcomes is gaining increased attention. Major depressive disorder (MDD) has been associated with higher breast cancer (BC) incidence, BC-specific and all-cause mortality. The effect of MDD on BC recurrence remains under-studied. The Veterans Health Administration (VHA) provides a unique opportunity to examine this relationship as it mandates annual MDD screening in the primary care setting and reports national screening rates of 96%. Objective: To examine the relationship between pre-existing MDD and BC recurrence among a diverse cohort of women in the United States. Methods: We established a retrospective cohort of women (age ≥ 18 years) diagnosed with early-stage incident BC from 2010 through 2019 using the VHA’s electronic medical record database. We used a two-year window to identify women with clinically diagnosed MDD prior to their BC diagnosis. Our outcome of interest was BC recurrence (local recurrence/second primary and distant recurrence). We used multivariable proportional hazards regression to examine the association between MDD and BC recurrence, accounting for competing risk of death. Our analyses were adjusted for age, race, ethnicity, marital status, priority group rating (proxy for socioeconomic status), rurality of primary residence, geographical region, cancer stage, year of BC diagnosis, and comorbidity burden. Priority group rating is a metric that incorporates patients’ income, receipt of VHA assistance benefits, capacity for gainful employment, and severity of service-connected conditions. We conducted subgroup analyses by tumor subtype. RESULTS: Our cohort consists of 6,045 women with BC, of whom 1,750 (29.0%) had a pre-existing MDD diagnosis. The median length of follow-up from BC diagnosis was 4.5 years (IQR=4.8 years). The average age at BC diagnosis was 57 years (SD=11 years) overall and 56 years (SD=10 years) among women with MDD. Sixty-one percent of women were white, 29% were black, 27% were married, and 28% were rural dwelling. Forty-four percent of invasive carcinomas were localized and 21% were regional. Thirty-five percent of patients had ductal carcinoma in situ. Women with MDD had a higher average Charlson Comorbidity Index score (mean=0.75, SD=1.13 vs. mean=0.58, SD=1.03) and proportion with a priority group rating between 1-4 (40% vs. 32%). The distribution of other described patient characteristics among women with MDD were similar to the overall cohort. On multivariable analysis, women with MDD had a 31% (95% CI: 1.11, 1.56) higher risk of BC recurrence compared to women without MDD. MDD was associated with a 29% (95% CI: 1.01, 1.66) and 33% (95% CI: 1.05, 1.67) higher risk of local recurrence/second primary and distant recurrence, respectively. The relationship between MDD and BC recurrence remained significant after adjusting for tumor subtype (HR=1.40, 95% CI: 1.07, 1.83). In subgroup analyses stratified by tumor subtype, MDD was associated with a higher risk of BC recurrence among women with estrogen receptor positive versus negative tumors (HR=1.65, 95% CI: 1.27, 2.14 vs. HR=0.71, 95% CI: 0.34, 1.46) and HER2/neu negative versus positive tumors (HR=1.53, 95% CI: 1.16, 2.00 vs. HR=1.24, 95% CI: 0.51, 2.96). The interaction between estrogen receptor status and MDD was statistically significant (p-interaction=0.02). CONCLUSION: Women with incident BC should be screened for MDD early in the cancer care continuum given the prevalence of MDD and association with increased risk of local recurrence/second primary and distant BC recurrence. Further research is needed to understand the interplay between these two diseases and their treatments. Citation Format: Maya Aboumrad, Brian Shiner, Avonne Connor, Bradley V. Watts, Kala Visvanathan. Depression and breast cancer recurrence among female veterans in the United States: a retrospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-08.

Treatment with the second-generation antipsychotic quetiapine is associated with increased subgenual ACC activation during reward processing in major depressive disorder

BackgroundThe second-generation antipsychotic (SGA) quetiapine is an essential option for antidepressant augmentation therapy in major depressive disorder (MDD), yet neurobiological mechanisms behind its antidepressant properties remain unclear. As SGAs interfere with activity in reward-related brain areas, including the anterior cingulate cortex (ACC) — a key brain region in antidepressant interventions, this study examined whether quetiapine treatment affects ACC activity during reward processing in MDD patients. MethodsUsing the ACC as region of interest, an independent t-test comparing reward-related BOLD response of 51 quetiapine-taking and 51 antipsychotic-free MDD patients was conducted. Monetary reward outcome feedback was measured in a card-guessing paradigm using pseudorandom blocks. Participants were matched for age, sex, and depression severity and analyses were controlled for confounding variables, including total antidepressant medication load, illness chronicity and acute depression severity. Potential dosage effects were examined in a 3 × 1 ANOVA. Differences in ACC-related functional connectivity were assessed in psycho-physiological interaction (PPI) analyses. ResultsLeft subgenual ACC activity was significantly higher in the quetiapine group compared to antipsychotic-free participants and dependent on high-dose quetiapine intake. Results remained significant after controlling for confounding variables. The PPI analysis did not yield significant group differences in ACC-related functional connectivity. LimitationsCausal interpretation is limited due to cross-sectional findings. ConclusionElevated subgenual ACC activity to rewarding stimuli may represent a neurobiological marker and potential key interface of quetiapine's antidepressant effects in MDD. These results underline ACC activity during reward processing as an investigative avenue for future research and therapeutic interventions to improve MDD treatment outcomes.

An electric field modeling study with meta-analysis to understand the antidepressant effects of transcranial direct current stimulation (tDCS).

Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect. A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated. A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed. Our results highlight the need for a standardized tDCS protocol in MDD clinical trials.

Effects of Major Depressive Disorder on Monocytes, High-Density Lipoprotein (HDL) and Monocyte to HDL Ratio: A Case-Control Study.

In this study, we investigated the effects of Major Depressive Disorder (MDD) on monocyte counts, High-Density Lipoprotein (HDL) levels, and Monocyte to HDL ratios (MHR) among inflammatory markers. This is a retrospective case-control study. The case group of our study included 120 major depressive patients. The control group included 124 healthy individuals. The data were collected using a Personal Information Form, the Clinical Global Impression Scale, and the Hamilton Depression Rating Scale. The lipid profiles and complete blood count parameters of the case and control groups were tested and compared. The collected data were analyzed using the Kruskal-Wallis test, Mann-Whitney U test and independent-samples t-test. A significant increase in the monocyte and MHR values and a decrease in the HDL values of the case group were observed with older ages (p<0.01). In the case group, the MHR and monocyte count values were higher, and the HDL levels were lower in the MDD patients who had never received treatment in comparison to those who had received treatment. As the severity of depression increased, MHR levels also increased. Our study is the first study to show that MHR is significantly higher in MDD patients than healthy controls. It was also shown that depression severity and MHR are positively correlated. Consequently, MHR might be a simple, practical, and low-cost parameter which shows inflammation in MDD patients.

Mendelian randomization investigation highlights different roles of selenium status in mental disorders

Observational studies have suggested a relationship between selenium status and mental disorders (MDs). However, it remains unclear whether selenium status was causally associated with MDs. Thus, we performed a two-sample Mendelian randomization analysis using genome-wide association studies (GWAS) summary statistics to investigate the causal effects of selenium levels on seven MDs, including schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), bipolar disorder (BD), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and panic disorder (PD). Strong genetic instruments of blood selenium (n = 9) and blood-toenail selenium (n = 12) were applied to the above seven MDs GWAS datasets from Psychiatric Genomics Consortium, which were further replicated in the FinnGen Biobank. The inverse-variance weighted method was employed to calculate the causal effects. The results showed that genetically predicted blood selenium levels were associated with a decreased risk of schizophrenia (odds ratio [OR] = 0.90, 95% CI: 0.87–0.95) and AN (OR = 0.87, 95% CI: 0.77–0.97). However, both blood and blood-toenail selenium levels were linked to an increased risk of MDD (blood: OR = 1.08, 95% CI: 1.05–1.12; blood-toenail: OR = 1.08, 95% CI: 1.04–1.13) and ASD (blood: OR = 1.11, 95% CI: 1.05–1.17; blood-toenail: OR = 1.13, 95% CI: 1.05–1.21), respectively. No obvious associations were found between selenium levels and BD as well as ADHD. Our findings highlighted a protective role of selenium in SZ and AN, while a risk effect in MDD and ASD. Further studies are required to verify the underlying mechanism mediating the unequal effects of Se on different MDs, which will pave a new path for the intervention of MDs.

Abstract 9993: Effect of Major Depressive Disorder on Inpatient Outcomes of Hypertensive Emergency: Analysis From National Inpatient Sample

Objective: Our aim was to determine if co-diagnosis of major depressive disorder (MDD) influenced inpatient outcomes of hypertensive emergency (HTNE) admissions. Methods: We analyzed the national inpatient sample (2012-2019) for HTNE admissions of ages &gt;18 years. The primary outcomes were hospital length of stay (LOS), costs (adjusted for inflation), adverse hospital events (need for mechanical circulatory support and intubation) and in-hospital mortality. Secondary outcomes included predictors of mortality in HTNE patients with MDD. Demographic (age, sex, race) and clinical (history of hypertension, hyperlipidemia, stroke, chronic kidney disease, myocardial infarction, obesity, smoking) factors were adjusted for. Data was analyzed in STATA 16.0, and adjusted odds ratios (AOR) were calculated using linear and logistic regression method. Results: Our study included 149,366 weighted discharges for HTNE. Prevalence of MDD was 9.6% (n=14,339). Average age of the patients were 48 years. 65% were Caucasians, 57% were females and average LOS was 5.5 days. Patients with MDD had longer LOS (6.4 vs 5.1 p&lt;0.001). The adjusted hospital cost was $25,923 higher in patients with MDD (p&lt;0.001), and they also had higher odds of inpatient mortality (AOR 1.76, [1.53 -1.83], P &lt; 0.001). The odds for requiring mechanical circulatory support were higher in patients with MDD (AOR 1.44, P &lt; 0.001). African American men had the highest inpatient costs and LOS. Several conditions increased mortality in HTNE patients with MDD including obesity, cerebrovascular disease (CVD) and end-stage renal disease (ESRD). (Figure 1) Conclusion: Major depressive disorder has an important and unexplored association with hypertension. Our study demonstrates that patients admitted with hypertensive emergency have increased hospital LOS, cost, adverse hospital events and mortality when they have concomitant depression.