ArticleTranslational psychiatry2014
Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis.
Article in Translational psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 51 citations in OpenAlex.
- Childhood Abuse, Social Support, and Long-Term Pharmacological Treatment Outcomes in Patients With Depressive Disorders.Frontiers in psychiatry · 2022Article
- The effectiveness of mindfulness-based cognitive therapy combined with medication therapy in preventing recurrence of major depressive disorder in convalescent patients.Frontiers in psychology · 2022Article
- BDNF Overexpression in the Ventral Hippocampus Promotes Antidepressant- and Anxiolytic-Like Activity in Serotonin Transporter Knockout Rats.International journal of molecular sciences · 2021Article
- Mechanisms underlying remediation of depression-associated anxiety by chronic N-acetyl cysteine treatment.Psychopharmacology · 2020Article
- Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link.International journal of molecular sciences · 2020Review
- Metabolic, Molecular, and Behavioral Effects of Western Diet in Serotonin Transporter-Deficient Mice: Rescue by Heterozygosity?Frontiers in neuroscience · 2020Article
- Animal models of PTSD: a challenge to be met.Molecular psychiatry · 2019Review
- Maternal Deprivation Induces Memory Deficits That Are Reduced by One Aerobic Exercise Shot Performed after the Learning Session.Neural plasticity · 2019Article
- Transcriptome Analysis on Maternal Separation Rats With Depression-Related Manifestations Ameliorated by Electroacupuncture.Frontiers in neuroscience · 2019Article
- The 5-HTTLPR genotype, early life adversity and cortisol responsivity to psychosocial stress in women.BJPsych open · 2018Article
- Comparative studies of social buffering: A consideration of approaches, terminology, and pitfalls.Neuroscience and biobehavioral reviews · 2018Review
- The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Developmental plasticity: Bridging research in evolution and human health.Evolution, medicine, and public health · 2017Review
- The Serotonin Transporter and Early Life Stress: Translational Perspectives.Frontiers in cellular neuroscience · 2017Review
- A translational approach to clinical practice via stress-responsive glucocorticoid receptor signaling.Stem cell investigation · 2017Article
- Overfeeding during a critical postnatal period exacerbates hypothalamic-pituitary-adrenal axis responses to immune challenge: a role for adrenal melanocortin 2 receptors.Scientific reports · 2016Article
- Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype.PloS one · 2015Article
- Early life stress and serotonin transporter gene variation interact to affect the transcription of the glucocorticoid and mineralocorticoid receptors, and the co-chaperone FKBP5, in the adult rat brain.Frontiers in behavioral neuroscience · 2014Article
- Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa.Harvard review of psychiatryReview
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). Furthermore, 5-HTTLPR has been associated with abnormal functioning of the stress-responsive hypothalamo-pituitary-adrenal (HPA) axis. Here, we examined if, and at what level, the HPA-axis is affected in an animal model for ELS × 5-HTTLPR interactions. Heterozygous and homozygous 5-HTT knockout rats and their wild-type littermates were exposed daily at postnatal days 2-14 to 3 h of maternal separation. When grown to adulthood, plasma levels of adrenocorticotropic hormone (ACTH), and the major rat glucocorticoid, corticosterone (CORT), were measured. Furthermore, the gene expression of key HPA-axis players at the level of the hypothalamus, pituitary and adrenal glands was assessed. No 5-HTT genotype × ELS interaction effects on gene expression were observed at the level of the hypothalamus or pituitary. However, we found significant 5-HTT genotype × ELS interaction effects for plasma CORT levels and adrenal mRNA levels of the ACTH receptor, such that 5-HTT deficiency was associated under control conditions with increased, but after ELS with decreased basal HPA-axis activity. With the use of an in vitro adrenal assay, naïve 5-HTT knockout rats were furthermore shown to display increased adrenal ACTH sensitivity. Therefore, we conclude that basal HPA-axis activity is affected by the interaction of 5-HTT genotype and ELS, and is programmed, within the axis itself, predominantly at the level of the adrenal gland. This study therefore emphasizes the importance of the adrenal gland for HPA-related psychiatric disorders.
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