ArticleCells2022
Adverse Childhood Experiences Predict the Phenome of Affective Disorders and These Effects Are Mediated by Staging, Neuroimmunotoxic and Growth Factor Profiles.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 65 citations in OpenAlex.
- Unifying the hallmarks of major depression through neuroimmune-metabolic-oxidative (NIMETOX) dysregulation: a mechanistic systems framework.Cellular & molecular immunology · 2026Review
- Metabolic hormone and adipokine alterations in major depressive disorder in relation to the acute-phase inflammatory response and early-life adversity.Communications medicine · 2026Article
- Neuroimmune, metabolic and oxidative stress pathways in major depressive disorder.Nature reviews. Neurology · 2025Review
- Lipid profiles in major depression, both with and without metabolic syndrome: associations with suicidal behaviors and neuroticism.BMC psychiatry · 2025Article
- Five hypothesized biological mechanisms linking adverse childhood experiences with anxiety, depression, and PTSD: A scoping review.Neuroscience and biobehavioral reviews · 2025Article
- Impact of life adversity and gene expression on psychiatric symptoms in children and adolescents: findings from the Brazilian high risk cohort study.Frontiers in psychiatry · 2025Article
- T helper-1 activation via interleukin-16 is a key phenomenon in the acute phase of severe, first-episode major depressive disorder and suicidal behaviors.Journal of advanced research · 2024Article
- Early life adversity is associated with differential gene expression in immune cells: A cluster-based analysis across an acute psychosocial stressor.Brain, behavior, and immunity · 2024Article
- Cluster analysis exploring the impact of childhood neglect on cognitive function in patients with bipolar disorder.International journal of bipolar disorders · 2024Article
- In major dysmood disorder, physiosomatic, chronic fatigue and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity.Scientific reports · 2024Article
- Predictors of increased affective symptoms and suicidal ideation during the COVID-19 pandemic: results from a large-scale study of 14 271 Thai adults.BMJ mental health · 2024Article
- Childhood Maltreatment and Immune Cell Gene Regulation during Adolescence: Transcriptomics Highlight Non-Classical Monocytes.Biomolecules · 2024Article
- Application of trauma-focused cognitive behavioral therapy among children and adolescents with childhood household dysfunction.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Complex Intersections Between Adverse Childhood Experiences and Negative Life Events Impact the Phenome of Major Depression.Psychology research and behavior management · 2024Article
- Association of childhood adversities with psychosocial difficulties among Chinese children and adolescents.International journal of epidemiology · 2023Article
- Methamphetamine (MA) use and MA-induced psychosis are associated with increasing aberrations in the compensatory immunoregulatory system, interleukin-1α, and CCL5 levels.Translational psychiatry · 2023Article
- Lower Nerve Growth Factor Levels in Major Depression and Suicidal Behaviors: Effects of Adverse Childhood Experiences and Recurrence of Illness.Brain sciences · 2023Article
- The Cytokine, Chemokine, and Growth Factor Network of Prenatal Depression.Brain sciences · 2023Article
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Corrections and comments
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Authors and funding
10 authors at 4 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adverse childhood experiences (ACEs) enhance pro-inflammatory and pro-oxidant responses. In affective disorders, recent precision nomothetic psychiatry studies disclosed new pathway phenotypes, including an ROI-reoccurrence of illness (ROI)-oxidative stress latent construct. The aim of the present study is to delineate a) whether ACEs sensitize the M1 macrophage, the T helper cells (Th)1, Th2, and Th17, the IRS (immune-inflammatory-responses system), the CIRS (compensatory immunoregulatory system), and the neuroimmunotoxic and growth factor (GF) profiles and whether they are associated with ROI and the phenome of affective disorders and b) the molecular pathways underpinning the effects of the ACEs. We collected supernatants of stimulated (5 μg/mL of PHA and 25 μg/mL of LPS) and unstimulated diluted whole blood in 20 healthy controls and 30 depressed patients and measured a panel of 27 cytokines/GF using a Luminex method. ACEs (comprising mental and physical trauma, mental neglect, domestic violence, family history of mental disease, and parent loss) are accompanied by the increased stimulated, but not unstimulated, production of M1, Th1, Th2, Th17, IRS, neuroimmunotoxic, and GF profiles and are strongly correlated with ROI and the phenome. A latent vector extracted from the ROI features (recurrent episodes and suicidal behaviors) and the IRS/neuroimmunotoxic/GF profiles explains 66.8% of the variance in the phenome and completely mediates the effects of ACEs on the phenome. Enrichment analysis showed that the ACE-associated sensitization of immune/GF profiles involves JAK-STAT, nuclear factor-κB, tumor necrosis factor-α, G-protein coupled receptor, PI3K/Akt/RAS/MAPK, and hypoxia signaling. In summary, the ACE-induced sensitization of immune pathways and secondary immune hits predicts the phenome of affective disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.