Early-life stress and antidepressants modulate peripheral biomarkers in a gene–environment rat model of depression

Abstract. The impact of the environment early in life on long-term outcomes is well known. Stressful experiences during pre- and postnatal development can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Furthermore, there is documented evidence for gene-environment interactions in the context of early-life stress. Identical gene variants can be associated with different phenotypes depending on environmental factors. DNA methylation, an enzymatically-catalyzed modification of the DNA, is the mechanism through which phenotypes are regulated. The dynamics and plasticity of epigenetic mechanisms can have short-term, long-term, or transgenerational consequences. In epigenetic research, rodent models have targeted several behavioral and emotional phenotypes. These models have contributed significantly to our understanding of the environmental regulation of the developmental brain in early life. This review will highlight studies with rats and mice on epigenetic processes in fetal programming of stress-related mental disorders.

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P.0065 Antidepressant-like effects of ketamine in a rat model of early-life stress: sex- and age-dependent efficacy

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2021.10.070 ◽

2021 ◽

Vol 53 ◽

pp. S47-S48

Author(s):

S. Ledesma-Corvi ◽

E. Hernández-Hernández ◽

M.J. García-Fuster

Keyword(s):

Rat Model ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Age Dependent

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Long-Term Treatment with Fluvoxamine Decreases Nonmotor Symptoms and Dopamine Depletion in a Postnatal Stress Rat Model of Parkinson’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1941480 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Ernest Dallé ◽

William M. U. Daniels ◽

Musa V. Mabandla

Keyword(s):

Rat Model ◽

Dopaminergic Neurons ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Term Treatment ◽

Nonmotor Symptoms ◽

Long Term Treatment ◽

6 Hydroxydopamine

Nonmotor symptoms (NMS) such as anxiety, depression, and cognitive deficits are frequently observed in Parkinson’s disease (PD) and precede the onset of motor symptoms by years. We have recently explored the short-term effects of Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) on dopaminergic neurons in a parkinsonian rat model. Here, we report the long-term effects of Fluvoxamine, on early-life stress-induced changes in the brain and behavior. We specifically evaluated the effects of Fluvoxamine on brain mechanisms that contribute to NMS associated with PD in a unilateral 6-hydroxydopamine-lesioned rat model. A 14-day early postnatal maternal separation protocol was applied to model early-life stress followed by unilateral intracerebral infusion of 6-hydroxydopamine (6-OHDA) to model aspects of parkinsonism in rats. The anxiolytic, antidepressant, and cognitive effects of Fluvoxamine were confirmed using the elevated plus-maze (EPM) test, sucrose preference test (SPT), and Morris water maze (MWM) test. Further to that, our results showed that animals exposed to early-life stress displayed increased plasma corticosterone and malondialdehyde (MDA) levels which were attenuated by Fluvoxamine treatment. A 6-OHDA lesion effect was evidenced by impairment in the limb-use asymmetry test as well as decreased dopamine (DA) and serotonin levels in the striatum, prefrontal cortex, and hippocampus. These effects were surprisingly attenuated by Fluvoxamine treatment in all treated rats. This study is the first to suggest that early and long-term treatment of neuropsychological diseases with Fluvoxamine may decrease the vulnerability of dopaminergic neurons that degenerate in the course of PD.

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EPA-1260 – Gene-environment interplay in the influence of early life stress on emotionality

European Psychiatry ◽

10.1016/s0924-9338(14)78497-4 ◽

2014 ◽

Vol 29 ◽

pp. 1

Author(s):

E. De Lana Meirelles ◽

R. Lopes ◽

J. Landeira-Fernandez ◽

P.F. Gardino

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Gene Environment

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Pharmacogenetic aspects of addictive behaviors

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2007.9.4/nhejazi ◽

2007 ◽

Vol 9 (4) ◽

pp. 447-454

Keyword(s):

Life Stress ◽

Early Life ◽

Drug Exposure ◽

Genetic Factors ◽

Early Life Stress ◽

Tissue Response ◽

Addictive Behaviors ◽

Gene Environment ◽

Treatment Responses ◽

Functional Alleles

Addictions are illnesses of complex causation, including inheritance and a role for gene/environment interactions. Functional alleles influencing pharmacodynamic (tissue response) and pharmacokinetic (absorption, distribution, and metabolism) play a role, but these interact with diverse environmental factors including early life stress, underage drug exposure, availability of addictive agents, and response to clinical interventions including pharmacotherapies. Identification of genetic factors in addiction thus plays an important role in the understanding of processes of addiction and origins of differential vulnerabilities and treatment responses.

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A Polygenic Score for Body Mass Index is Associated with Depressive Symptoms via Early Life Stress: Evidence for gene-environment correlation

10.1101/536938 ◽

2019 ◽

Cited By ~ 1

Author(s):

Reut Avinun ◽

Ahmad R. Hariri

Keyword(s):

Mental Health ◽

Body Mass Index ◽

Depressive Symptoms ◽

Body Mass ◽

Indirect Effect ◽

Genetic Risk ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Gene Environment

ABSTRACTBackgroundIncreasing childhood overweight and obesity rates are associated with not only adverse physical, but also mental health outcomes, including depression. These negative outcomes may be caused and/or exacerbated by the bullying and shaming overweight individuals experience. As body mass index (BMI) can be highly heritable, we hypothesized that a genetic risk toward higher BMI, will predict higher early life stress (ELS), which in turn will predict higher depressive symptoms in adulthood. Such a process will reflect an evocative gene-environment correlation (rGE) wherein an individual’s genetically influenced phenotype evokes a reaction from the environment that subsequently shapes the individual’s health.MethodsWe modeled genetic risk using a polygenic score of BMI derived from a recent large GWAS meta-analysis. Self-reports were used for the assessment of ELS and depressive symptoms in adulthood. The discovery sample consisted of 524 non-Hispanic Caucasian university students from the Duke Neurogenetics Study (DNS; 278 women, mean age 19.78±1.23 years) and the independent replication sample consisted of 5 930 white British individuals from the UK biobank (UKB; 3 128 women, mean age 62.66±7.38 years).ResultsA significant mediation effect was found in the DNS (indirect effect=.207, bootstrapped SE=.10, 95% CI: .014 to .421), and then replicated in the UKB (indirect effect=.04, bootstrapped SE=.01, 95% CI: .018 to .066). Higher BMI polygenic scores were associated with higher depressive symptoms through the experience of higher ELS.ConclusionsOur findings suggest that evocative rGE may contribute to weight-related mental health problems and stress the need for interventions that aim to reduce weight bias, specifically during childhood.

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