Genetic Correlates of Treatment-Resistant Depression: Insights from Polygenic Scores Across Cognitive, Temperamental, and Sleep Traits in the All of US cohort DOI
Bohan Xu, Katherine L. Forthman, Rayus Kuplicki

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 5, 2024

Abstract Background Treatment-resistant depression (TRD) is a major challenge in mental health, affecting significant number of patients and leading to considerable economic social burdens. The etiological factors contributing TRD are complex not fully understood. Objective To investigate the genetic associated with using polygenic scores (PGS) across various traits, explore their potential role etiology large-scale genomic data from All Us Research Program (AoU). Methods Data 292,663 participants AoU were analyzed case-cohort design. Treatment resistant (TRD), treatment responsive Major Depressive Disorder (trMDD), all others who have no formal diagnosis (non-MDD) identified through diagnostic codes prescription patterns. Polygenic for 61 unique traits seven domains used logistic regressions conducted assess associations between PGS TRD. Finally, Cox proportional hazard models predictive value progression rate event (MDD) Results In discovery set (104128 non-MDD, 16640 trMDD, 4177 TRD), 44 selected found be significantly MDD, regardless responsiveness. Eleven them stronger than encompassing education, cognition, personality, sleep, temperament. Genetic predisposition insomnia specific neuroticism increased risk (OR range 1.05 1.15), while higher education intelligence protective (ORs 0.88 0.91, respectively). These consistent two other independent sets within (n = 104,388 63,330). Among 28,964 individuals tracked over time, 3,854 developed an average 944 days (95% CI: 883 ∼ 992 days) after MDD diagnosis. eleven previously replicated modulating conversion Thus, those having would experiencing slower rates lower ratios 0.79 (80 th versus 20 percentile, 95% 0.74 0.85). Those had experience faster PGS, 1.21 1.13 1.30). Conclusions Our results indicate that related neuroticism, cognitive function, sleep patterns play development findings underscore importance considering psychosocial managing treating Future research should focus on integrating clinical outcomes enhance our understanding pathways resistance. Key Points Question What predisposing characteristics among develop treatment-resistant (TRD)? Findings Analysis revealed including depressive disorder and, particularly, studied, 11 showed compared linked which appeared protective, risk. Meaning when They suggest intervening tailored approach characteristics, reducing resistance depression. Personalized information measures underlying predispositions could eventually therapeutic strategies.

Language: Английский

Depression and Associated Factors Among Patients with Spinocerebellar Ataxia DOI Creative Commons

Sirivipa Jekpoo,

Nahathai Wongpakaran, Tinakon Wongpakaran

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(1), P. 160 - 160

Published: Jan. 19, 2025

Background and Objectives: Spinocerebellar ataxia (SCA) is a progressive neurodegenerative disease often accompanied by depression. This cross-sectional study investigated the prevalence of depression associated mental health factors in SCA patients. Material Methods: Eleven Thai patients completed questionnaires assessing depression, anxiety, inner strengths, perceived social support, personality traits stress. Results: Participants’ average age was 50.27 years old. The 27.27%. Depression scores were positively correlated with OI-anxiety score (r = 0.887, 95%CI 0.586 to 0.968), stress 0781, 0.305 0.936) including aggression 0.73, 95% CI 0.197 0.920), activity 0.651, 0.052 0.893) neuroticism 0.80, 0.351 0.942). Conversely, negatively strengths −0.70, −0.910 −0.139) particularly from family −0.88, −0.966 −0.564). Conclusions: These findings highlight need for comprehensive assessment intervention Strengthening promoting managing negative may improve quality life SCA.

Language: Английский

Citations

1
Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are all associated with neurotoxic immune networks and their intricate interactions with metabolic syndrome. DOI Creative Commons
Michaël Maes, Ketsupar Jirakran, Asara Vasupanrajit

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Abstract Background Major depressive disorder (MDD) is considered to be a neuroimmune disorder. However, there are no data regarding the association between comprehensive immune profiles and their interactions with metabolic syndrome (MetS) in predicting neuroticism, suicidal behaviors, severity of outpatient MDD (OMDD). Methods We assayed 48 serum cytokines, chemokines, growth factors using multiplex assay 67 healthy controls 66 OMDD patients. Around 50% control participants had diagnosis MetS. Results Ten differentially expressed proteins (DEPs) were upregulated (i.e., CXCL12, TNFB, PDGF, CCL11, IL9, IL4, CCL5, CCL2, CCL4, IL1RN), indicating an immune, defense stress response. Six DEPs downregulated (VEGFA, IL12, CCL3, CSF1, IL1B, NGF), lowered neurogenesis regulation neuron death. Significant MetS caused a) substantial increases TNF signaling, upregulation IL17, TNF, IL1RN; b) downregulation VEGFA FGF. A large part variance neuroticism (26.6%), behaviors (23.6%), phenome (31.4%) was predicted by immunological TNFB or VEGFA. Discussion characterized immunoneurotoxic profile which partly explains phenome’s severity. Lowered IL-10 increased neurotoxicity characteristics other depression phenotypes, including severe first-episode inpatient MDD. The presence considerably exacerbates immunoneurotoxicity. Consequently, studies should always performed subjects without

Language: Английский

Citations

4
Genetic Correlates of Treatment-Resistant Depression DOI
Bohan Xu, Katherine L. Forthman, Rayus Kuplicki

et al.

JAMA Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Importance Treatment-resistant depression (TRD) is a major challenge in mental health, affecting significant number of patients and leading to considerable burdens. The etiological factors contributing TRD are complex not fully understood. Objective To investigate the genetic associated with using polygenic scores (PGS) across various traits explore their potential role etiology large-scale genomic data from All Us (AoU) Research Program. Design, Setting, Participants This study was cohort design observational participants AoU Program who have both electronic health records data. Data analysis performed March 27 October 24, 2024. Exposures PGS for 61 unique 7 domains. Main Outcomes Measures Logistic regressions test if treatment-resistant compared treatment-responsive depressive disorder (trMDD). Cox proportional hazard model used determine progressions MDD were PGS. Results A total 292 663 (median [IQR] age, 57 (41-69) years; 175 981 female [60.1%]) included this analysis. In discovery set (124 945 participants), 11 selected found stronger associations than trMDD, encompassing domains education, cognition, personality, sleep, temperament. Genetic predisposition insomnia (odds ratio [OR], 1.11; 95% CI, 1.07-1.15) specific neuroticism (OR, 1.07-1.16) increased risk, whereas higher education 0.88; 0.85-0.91) intelligence 0.91; 0.88-0.94) protective. held different definitions (meta-analytic R 2 >83%) consistent other independent sets within (the whole-genome sequencing Diversity dataset, 104 388, Microarray 63 330). Among 28 964 individuals followed up over time, 3854 developed mean 944 days (95% 883-992 days). previously identified replicated be modulating conversion rate TRD. Conclusions Relevance suggest that related neuroticism, cognitive function, sleep patterns had association development These findings underscore importance considering psychosocial managing treating Future research should focus on integrating clinical outcomes enhance understanding pathways treatment resistance.

Language: Английский

Citations

0
The role of MED22 and its transcriptional interactions with childhood trauma and trauma-focused psychotherapy in patients with major depressive disorder DOI
Rosana Carvalho Silva, Elisabetta Maffioletti, Chiara Magri

et al.

Biological Psychology, Journal Year: 2025, Volume and Issue: unknown, P. 109039 - 109039

Published: April 1, 2025

Language: Английский

Citations

0
First-episode mild depression in young adults is a pre-proatherogenic condition even in the absence of subclinical metabolic syndrome: lowered lecithin-cholesterol acyltransferase as a key factor DOI Creative Commons

Michael Maes,

Asara Vasupanrajit, Ketsupar Jirakran

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 2, 2024

Major depression is classified into distinct subtypes: simple (SDMD) and major dysmood disorder (MDMD). MDMD patients exhibit elevated atherogenicity decreased reverse cholesterol transport (RCT). However, comprehensive data regarding lipid metabolism absent in first episode (FE)-SDMD.

Language: Английский

Citations

3
Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are all associated with neurotoxic immune networks and their intricate interactions with metabolic syndrome. DOI Creative Commons
Michaël Maes, Ketsupar Jirakran, Asara Vasupanrajit

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 21, 2024

Abstract Background Major depressive disorder (MDD) is considered to be a neuroimmune disorder. However, there are no data regarding the association between comprehensive immune profiles and their interactions with metabolic syndrome (MetS) in predicting neuroticism, suicidal behaviors, severity of outpatient MDD (OMDD). Methods We assayed 48 serum cytokines, chemokines, growth factors using multiplex assay 67 healthy controls 66 OMDD patients. Around 50% control participants had diagnosis MetS. Results Ten differentially expressed proteins (DEPs) were upregulated (i.e., CXCL12, TNFB, PDGF, CCL11, IL9, IL4, CCL5, CCL2, CCL4, IL1RN), indicating an immune, defense stress response. Six DEPs downregulated (VEGFA, IL12, CCL3, CSF1, IL1B, NGF), lowered neurogenesis regulation neuron death. Significant MetS caused a) substantial increases TNF signaling, upregulation IL17, TNF, IL1RN; b) downregulation VEGFA FGF. A large part variance neuroticism (26.6%), behaviors (23.6%), phenome (31.4%) was predicted by immunological TNFB or VEGFA. Discussion characterized immunoneurotoxic profile which partly explains phenome’s severity. Lowered IL-10 increased neurotoxicity characteristics other depression phenotypes, including severe first-episode inpatient MDD. The presence considerably exacerbates immunoneurotoxicity. Consequently, studies should always performed subjects without

Language: Английский

Citations

2
Complex Intersections Between Adverse Childhood Experiences and Negative Life Events Impact the Phenome of Major Depression DOI Creative Commons
Asara Vasupanrajit, Michaël Maes, Ketsupar Jirakran

et al.

Psychology Research and Behavior Management, Journal Year: 2024, Volume and Issue: Volume 17, P. 2161 - 2178

Published: May 1, 2024

There is evidence that adverse childhood experiences (ACEs) and negative life events (NLEs) are associated with major depression (MDD).

Language: Английский

Citations

1
The recurrence of illness (ROI) index is a key factor in major depression that indicates increasing immune-linked neurotoxicity and vulnerability to suicidal behaviors DOI Creative Commons

Michael Maes,

Ketsupar Jirakran, Asara Vasupanrajit

et al.

Psychiatry Research, Journal Year: 2024, Volume and Issue: 339, P. 116085 - 116085

Published: July 16, 2024

In this study, we aimed to investigate the associations between recurrence of illness (ROI) and biomarkers related an activated immune network, immune-linked neurotoxicity (INT), a combined INT atherogenicity index (METAMMUNE). The study involved 67 healthy controls 66 outpatient MDD (OMDD) participants. We utilized Multiplex method measure 48 cytokines examined METAMMUNE composite scores in association with different ROI indices. Our findings revealed that was successfully created by extracting validated principal component, from physician-rated or self-declared number depressive episodes, frequency lifetime suicidal ideation attempts. significantly associated indices, neuroticism, current behaviors, phenome. analysis also significant portion variance OMDD phenome, which includes anxiety, depression, can be accounted for regression on INT, ROI, emotional neglect abuse. A latent construct extracted three components, results indicate increasing indicates heightened immune-metabolic abnormalities, increased risk elevated severity phenome features.

Language: Английский

Citations

1
The chain mediating role of social support and positive coping between neuroticism and depressive symptoms among graduate students DOI Creative Commons
Peng Wan, Jinsheng Hu,

Qingshuo Yang

et al.

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 25, 2024

Introduction Graduate students face unprecedented levels of neuroticism and pressure compared to their peers. Despite existing research examining the connection between depressive symptoms, a gap in current understanding mediating mechanisms that act on this relationship, especially among specific student population. Methods This study investigated potential chain-mediating roles social support positive coping relationship symptoms graduate students. The participants were 1845 who provided demographic information complete assessments including Eysenck Personality Questionnaire (EPQ), Depression Rating Scale (BDI-II), Social Support (SSRS), Coping Style (SCSQ). analysis involved correlational chain mediation model was used investigate associations neuroticism, support, mechanisms, symptoms. Results results show significant correlations coping. Moreover, our findings verify affects through three pathways: effect coping, Discussion Overall, hypothesized conclusively fits data: Neuroticism directly influences effects as well these two variables.

Language: Английский

Citations

1
In major depression, complex intersections between adverse childhood experiences and negative life events impact neuroticism, brooding, suicidal tendencies, insomnia, and cognitive interference DOI Creative Commons
Asara Vasupanrajit, Michaël Maes, Ketsupar Jirakran

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 7, 2024

Abstract Background There is evidence that adverse childhood experiences (ACEs) and negative life events (NLEs) are associated with major depression (MDD). Purpose To determine whether ACEs affect all features of mild MDD, including suicidal tendencies, brooding, neuroticism, insomnia, cognitive deficits, severity anxiety, NLEs mediate these effects. Patients methods This study examines a cohort 118 academic students, namely 74 students who satisfied the DSM-5-TR criteria for MDD 44 normal control students. We assessed ideation attempts, depression, Stroop tests. Results One validated factor could be extracted from current behaviors, labeled phenome depression. A large part variance in (55.0%) was explained by combined effects self-, relationships, academic-related conjunction ACEs, family dysfunction abuse neglect (both physical emotional). The latter significantly interacted (moderating effect) to impact phenome. Although sexual did not have direct on phenome, its were mediated NLEs. discovered increased abuse, emotional neglect, related predicted 22.5% Up 18.5% test scores scores. Conclusion Complex intersections between which comprises while together other may interference inhibition.

Language: Английский

Citations

0