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Database : the Journal of Biological... Jun 2024Major depressive disorder (MDD) is a pressing global health issue. Its pathogenesis remains elusive, but numerous studies have revealed its intricate associations with...
Major depressive disorder (MDD) is a pressing global health issue. Its pathogenesis remains elusive, but numerous studies have revealed its intricate associations with various biological factors. Consequently, there is an urgent need for a comprehensive multi-omics resource to help researchers in conducting multi-omics data analysis for MDD. To address this issue, we constructed the MDDOmics database (Major Depressive Disorder Omics, (https://www.csuligroup.com/MDDOmics/), which integrates an extensive collection of published multi-omics data related to MDD. The database contains 41 222 entries of MDD research results and several original datasets, including Single Nucleotide Polymorphisms, genes, non-coding RNAs, DNA methylations, metabolites and proteins, and offers various interfaces for searching and visualization. We also provide extensive downstream analyses of the collected MDD data, including differential analysis, enrichment analysis and disease-gene prediction. Moreover, the database also incorporates multi-omics data for bipolar disorder, schizophrenia and anxiety disorder, due to the challenge in differentiating MDD from similar psychiatric disorders. In conclusion, by leveraging the rich content and online interfaces from MDDOmics, researchers can conduct more comprehensive analyses of MDD and its similar disorders from various perspectives, thereby gaining a deeper understanding of potential MDD biomarkers and intricate disease pathogenesis. Database URL: https://www.csuligroup.com/MDDOmics/.
Topics: Depressive Disorder, Major; Humans; Databases, Genetic; Polymorphism, Single Nucleotide; Genomics; DNA Methylation; Multiomics
PubMed: 38917209
DOI: 10.1093/database/baae042 -
JAMA Network Open Jun 2024The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD.
OBJECTIVE
To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT.
DESIGN, SETTING, AND PARTICIPANTS
This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians.
EXPOSURES
Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks.
MAIN OUTCOMES AND MEASURES
Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses.
RESULTS
Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment.
CONCLUSIONS AND RELEVANCE
In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.
Topics: Humans; Ketamine; Electroconvulsive Therapy; Female; Male; Middle Aged; Depressive Disorder, Treatment-Resistant; Adult; Aged; Treatment Outcome
PubMed: 38916891
DOI: 10.1001/jamanetworkopen.2024.17786 -
BioRxiv : the Preprint Server For... Jun 2024has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2 transmembrane (TM) helix of in rats, and...
OBJECTIVE
has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2 transmembrane (TM) helix of in rats, and similar obesity variants have been identified in humans. The current study investigates the role of a TM variant in adiposity and behavior.
METHODS
We used CRISPR-SpCas9 to mutate the TM domain of in WKY rats (Adcy3 ). We also created a heterozygous knockout rat in the same strain (Adcy3 ). Wild-type (WT), Adcy3 , and Adcy3 rats were fed a high-fat diet for 12 weeks. We measured body weight, fat mass, glucose tolerance, food intake, metabolism, emotion-like behaviors, and memory.
RESULTS
Adcy3 and Adcy3 rats weighed more than WT rats due to increased fat mass. There were key sex differences: adiposity was driven by increased food intake in males but by decreased energy expenditure in females. Adcy3 males displayed increased passive coping and decreased memory while Adcy3 females displayed increased anxiety-like behavior.
CONCLUSIONS
These studies show that the ADCY3 TM domain plays a role in protein function, that may contribute to the relationship between obesity and MDD, and that sex influences the relationships between , metabolism, and behavior.
STUDY IMPORTANCE QUESTIONS
has been linked to both obesity and depression in humans, with protein-coding variants in the transmembrane domain leading to increased obesity. Yet the underlying mechanisms are unknown, and it is unknown if the same variants can cause both obesity and depression. Rodent knockout models show increased adiposity and altered emotional behaviors, but no rodent models have assessed the role of protein-coding variants in Very few studies have assessed sex differences. This is the first study to assess the role of a protein-coding variant in the transmembrane domain of , showing increases in both obesity and emotion-like behaviors in a rat model. We observed striking sex differences, where male and female rats had different factors driving their adiposity and different patterns of altered behavior. Understanding the role of in obesity and MDD may lead to improved treatments for both diseases. Improving our understanding of the sex differences caused by the same mutation emphasizes the importance of studying both sexes and paves the way for personalized medicine approaches.
PubMed: 38916175
DOI: 10.1101/2024.06.16.598846 -
BMC Geriatrics Jun 2024Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults...
BACKGROUND
Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD.
METHODS
We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups.
RESULTS
LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes.
CONCLUSIONS
The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.
Topics: Humans; Male; Aged; Female; Blinking; Reflex, Pupillary; Depression; Aged, 80 and over; Middle Aged; Adult; Pupil; Darkness; Young Adult; Light
PubMed: 38914987
DOI: 10.1186/s12877-024-05034-w -
Journal of Medical Internet Research Jun 2024Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for...
BACKGROUND
Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for the assessment and prediction of disease progression. Our study proposes a novel methodology, the Multimorbidity-Adjusted Disability Score (MADS), which integrates disease trajectory methodologies with advanced techniques for assessing interdependencies among concurrent diseases. This approach is designed to better assess the clinical burden of clusters of interrelated diseases and enhance our ability to anticipate disease progression, thereby potentially informing targeted preventive care interventions.
OBJECTIVE
This study aims to evaluate the effectiveness of the MADS in stratifying patients into clinically relevant risk groups based on their multimorbidity profiles, which accurately reflect their clinical complexity and the probabilities of developing new associated disease conditions.
METHODS
In a retrospective multicentric cohort study, we developed the MADS by analyzing disease trajectories and applying Bayesian statistics to determine disease-disease probabilities combined with well-established disability weights. We used major depressive disorder (MDD) as a primary case study for this evaluation. We stratified patients into different risk levels corresponding to different percentiles of MADS distribution. We statistically assessed the association of MADS risk strata with mortality, health care resource use, and disease progression across 1 million individuals from Spain, the United Kingdom, and Finland.
RESULTS
The results revealed significantly different distributions of the assessed outcomes across the MADS risk tiers, including mortality rates; primary care visits; specialized care outpatient consultations; visits in mental health specialized centers; emergency room visits; hospitalizations; pharmacological and nonpharmacological expenditures; and dispensation of antipsychotics, anxiolytics, sedatives, and antidepressants (P<.001 in all cases). Moreover, the results of the pairwise comparisons between adjacent risk tiers illustrate a substantial and gradual pattern of increased mortality rate, heightened health care use, increased health care expenditures, and a raised pharmacological burden as individuals progress from lower MADS risk tiers to higher-risk tiers. The analysis also revealed an augmented risk of multimorbidity progression within the high-risk groups, aligned with a higher incidence of new onsets of MDD-related diseases.
CONCLUSIONS
The MADS seems to be a promising approach for predicting health risks associated with multimorbidity. It might complement current risk assessment state-of-the-art tools by providing valuable insights for tailored epidemiological impact analyses of clusters of interrelated diseases and by accurately assessing multimorbidity progression risks. This study paves the way for innovative digital developments to support advanced health risk assessment strategies. Further validation is required to generalize its use beyond the initial case study of MDD.
Topics: Humans; Retrospective Studies; Multimorbidity; Female; Male; Middle Aged; Risk Assessment; Adult; Aged; Spain; Depressive Disorder, Major; Bayes Theorem; Disease Progression; United Kingdom; Depression; Finland
PubMed: 38913991
DOI: 10.2196/53162 -
JMIR MHealth and UHealth Jun 2024Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health... (Observational Study)
Observational Study
BACKGROUND
Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health care. Stratified care models, in particular, offer personalized care recommendations that can offer clinically effective interventions while conserving resources. Nonetheless, clinical evaluation is needed to understand their benefits for mental health and their use in a real-world setting.
OBJECTIVE
This study aimed to examine the changes in clinical outcomes (ie, depressive and anxiety symptoms and well-being) and to evaluate the use of stratified blended care among members of an employer-sponsored digital mental health benefit.
METHODS
In a large prospective observational study, we examined the changes in depressive symptoms (9-item Patient Health Questionnaire), anxiety symptoms (7-item Generalized Anxiety Disorder scale), and well-being (5-item World Health Organization Well-Being Index) for 3 months in 509 participants (mean age 33.9, SD 8.7 years; women: n=312, 61.3%; men: n=175, 34.4%; nonbinary: n=22, 4.3%) who were newly enrolled and engaged in care with an employer-sponsored digital mental health platform (Modern Health Inc). We also investigated the extent to which participants followed the recommendations provided to them through a stratified blended care model.
RESULTS
Participants with elevated baseline symptoms of depression and anxiety exhibited significant symptom improvements, with a 37% score improvement in depression and a 29% score improvement in anxiety (P values <.001). Participants with baseline scores indicative of poorer well-being also improved over the study period (90% score improvement; P=.002). Furthermore, over half exhibited clinical improvement or recovery for depressive symptoms (n=122, 65.2%), anxiety symptoms (n=127, 59.1%), and low well-being (n=82, 64.6%). Among participants with mild or no baseline symptoms, we found high rates of maintenance for low depressive (n=297, 92.2%) and anxiety (n=255, 86.7%) symptoms and high well-being (n=344, 90.1%). In total, two-thirds of the participants (n=343, 67.4%) used their recommended care, 16.9% (n=86) intensified their care beyond their initial recommendation, and 15.7% (n=80) of participants underused care by not engaging with the highest level of care recommended to them.
CONCLUSIONS
Participants with elevated baseline depressive or anxiety symptoms improved their mental health significantly from baseline to follow-up, and most participants without symptoms or with mild symptoms at baseline maintained their mental health over time. In addition, engagement patterns indicate that the stratified blended care model was efficient in matching individuals with the most effective and least costly care while also allowing them to self-determine their care and use combinations of services that best fit their needs. Overall, the results of this study support the clinical effectiveness of the platform for improving and preserving mental health and support the utility and effectiveness of stratified blended care models to improve access to and use of digitally delivered mental health services.
Topics: Humans; Female; Male; Adult; Prospective Studies; Longitudinal Studies; Mental Health Services; Middle Aged; Surveys and Questionnaires; Depression; Telemedicine
PubMed: 38913405
DOI: 10.2196/48298 -
General Psychiatry 2024Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as...
Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.
BACKGROUND
Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression (TRD).
AIMS
The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.
METHODS
Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS. White matter (WM) properties were extracted and compared between the response/non-response and remission/non-remission groups. Structural connectome was constructed and analysed using graph theory. Distances of the volume of activated tissue (VAT) to the main modulating tracts were also estimated to evaluate the correlations.
RESULTS
Differences in fibre bundle properties of tracts, including superior thalamic radiation and reticulospinal tract, were observed between the remission and non-remission groups. Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups (p=0.010, t=3.07). The normalised clustering coefficient (γ) and the small-world property (σ) in graph analysis correlated with the symptom improvement after the correction of age.
CONCLUSIONS
Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions, as well as the distance of the VAT to the modulating tracts, may influence the clinical outcome of BNST-NAc DBS. These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.
PubMed: 38912307
DOI: 10.1136/gpsych-2023-101210 -
Frontiers in Psychiatry 2024The psychic structure of people with psychosis has been the subject of theoretical and qualitative considerations. However, it has not been sufficiently studied...
INTRODUCTION
The psychic structure of people with psychosis has been the subject of theoretical and qualitative considerations. However, it has not been sufficiently studied quantitatively. Therefore, the aim of this study was to explore the structural abilities of people diagnosed with schizophrenia and schizoaffective psychosis using the Levels of Structural Integration Axis of the Operationalized Psychodynamic Diagnosis System (OPD-2-LSIA). The study aimed to determine possible associations between the OPD-2-LSIA and central parameters of illness. Additionally, possible structural differences between people diagnosed with schizophrenia and schizoaffective psychosis were tested.
METHODS
This cross-sectional study included 129 outpatients with schizophrenia or schizoaffective disorders. Measures of structural integration, symptom load, severity of illness, cognition, and social functioning were obtained. Descriptive statistics were used to analyze the overall structural level and the structural dimensions. Correlation coefficients were computed to measure the associations between OPD-2-LSIA and variables regarding the severity of illness and psychosocial functioning. Regression models were used to measure the influence of illness-related variables on OPD-2-LSIA, and the influence of OPD-2-LSIA on psychosocial functioning. Participants diagnosed with schizophrenia and schizoaffective disorders were examined with regard to possible group differences.
RESULTS
The results of the OPD-2-LSIA showed that the overall structural level was between 'moderate to low' and 'low level of structural integration'. Significant correlations were found between OPD-2-LSIA and psychotic symptoms (but not depressive symptoms), as well as between OPD-2-LSIA and psychosocial functioning. It was found that variables related to severity of illness had a significant impact on OPD-2-LSIA, with psychotic, but not depressive symptoms being significant predictors. OPD-2-LSIA was found to predict psychosocial functioning beyond symptoms and cognition. No significant differences were found between participants with schizophrenia and schizoaffective psychosis. There was also no correlation found between OPD-2-LSIA and depressive symptomatology (except for the subdimension Internal communication).
DISCUSSION
Contrary to theoretical assumptions, the results of the study show a heterogenous picture of the psychic structure of people with psychosis. The associations between OPD-2-LSIA and severity of illness, particularly psychotic symptomatology, as well as the influence of OPD-2-LSIA on psychosocial functioning, are discussed.
PubMed: 38911709
DOI: 10.3389/fpsyt.2024.1388478 -
Frontiers in Psychiatry 2024Internalizing symptoms associated with anxiety and depression have been correlated with harmful alcohol use among Latino/as, but little attention has been paid to...
Internalizing symptoms associated with anxiety and depression have been correlated with harmful alcohol use among Latino/as, but little attention has been paid to assessing the association between perceived discrimination and harmful alcohol use. The present study was designed to investigate the association between perceived discrimination, internalizing symptoms associated with anxiety and depression, and harmful alcohol use among Latino/a immigrants living in the United States (US). Our sample included 426 Latino/a immigrants. Their mean age was 40.05 years ( = 6.50), 65.50% were women, 80.00% had a partner, 54.20% lived on less than $2,000 a month, and 41.50% reported having attained a college degree. Perceived discrimination was assessed using the Perceived Discrimination Scale, anxious symptoms were assessed using the GAD-7, depressive symptoms were assessed using the CES-D short form, and harmful alcohol use was assessed using AUDIT. We estimated a linear regression model using cross-sectional, self-reported data. The model was statistically significant, = 0.38, (8, 425) = 32.09, < 0.01. Discrimination was significantly associated with AUDIT scores, (β = 0.21, < 0.01) after accounting for covariates and for symptoms of anxiety and depression. Our results indicate that experiences of discrimination in the US are associated with increased harmful alcohol use even after controlling for other variables. These findings may be useful in designing coping interventions specifically for Latino/a immigrants to reduce the risk of alcohol use disorder. This study also has political and public health implications for acknowledging the detrimental health consequences of experiencing discrimination, providing support to the position that reducing racism and discrimination represent important public health priorities.
PubMed: 38911705
DOI: 10.3389/fpsyt.2024.1358648 -
Scientific Reports Jun 2024Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with...
Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with prefrontal hypofunction and subcortical hyperactivity. The aim of this study was to determine the effect of vortioxetine on heart rate variability (HRV), a parameter of cardiac autonomic regulation, in depressed hospitalized paediatric patients and assess the clinical effectiveness of the drug in this population. We performed repeated polysomnography analyses at admission and after a short treatment in hospital (15.2 days on average) and measured various HRV parameters (RRi, pNN50, RMSSD, LF-HRV, HF-HRV) during wakefulness, N3 and REM sleep stages. Out of 27 study subjects, 67% have improved depression symptoms as well as anxiety and subjective sleep quality after short vortioxetine treatment. We have found a significant decrease in parasympathetic parameters pNN50, RMSSD and HF-HRV during N3 sleep phase, though not exclusively among vortioxetine responders. The anticipated increase in cardiovagal regulation after vortioxetine treatment was not demonstrated in this pilot study, possibly due to the drug's multimodal mechanism and impact on the nucleus tractus solitarii, particularly its antagonism on 5HT-3 receptors. Application of selective drugs could further explain the effect of vortioxetine on HRV in depressed patients.
Topics: Humans; Vortioxetine; Heart Rate; Child; Adolescent; Male; Female; Autonomic Nervous System; Antidepressive Agents; Polysomnography; Depression; Pilot Projects
PubMed: 38910177
DOI: 10.1038/s41598-024-65278-9