Early life stress impairs social function through AVP-dependent mechanisms

AbstractImpaired social function is a core feature of many psychiatric illnesses. Adverse experiences during childhood increase risk for mental illness, however it is currently unclear whether stress early in life plays a direct role in the development of social difficulties. Using an animal model of pre-pubertal stress (PPS), we investigated effects on social behaviour, oxytocin and arginine vasopressin (AVP). We also explored social performance and AVP expression in participants with borderline personality disorder (BPD) who experienced a high incidence of childhood stress. Social behaviour was impaired and AVP expression increased in animals experiencing PPS and participants with BPD. Behavioural deficits in animals were rescued through administration of the AVP receptor 1a antagonist Relcovaptan (SR49059). AVP levels and recognition of negative emotions were significantly correlated in BPD participants only. In conclusion, early life stress plays a profound role in the precipitation of social dysfunction, and AVP mediates at least part of this effect.

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Childhood stress impairs social function through AVP-dependent mechanisms

Translational Psychiatry ◽

10.1038/s41398-019-0678-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Nichola M. Brydges ◽

Jessica Hall ◽

Caroline Best ◽

Lowenna Rule ◽

Holly Watkin ◽

...

Keyword(s):

Social Behaviour ◽

Life Stress ◽

Social Performance ◽

Early Life Stress ◽

Social Function ◽

Childhood Stress ◽

Direct Role ◽

Adverse Experiences ◽

Increase Risk ◽

Social Difficulties

AbstractImpaired social function is a core feature of many psychiatric illnesses. Adverse experiences during childhood increase risk for mental illness, however it is currently unclear whether stress early in life plays a direct role in the development of social difficulties. Using a rat model of pre-pubertal stress (PPS), we investigated effects on social behaviour, oxytocin and arginine vasopressin (AVP) in the periphery (plasma) and centrally in the paraventricular and supraoptic hypothalamic nuclei. We also explored social performance and AVP expression (plasma) in participants with borderline personality disorder (BPD) who experienced a high incidence of childhood stress. Social behaviour was impaired and AVP expression increased in animals experiencing PPS and participants with BPD. Behavioural deficits in animals were rescued through administration of the AVPR1a antagonist Relcovaptan (SR49059). AVP levels and recognition of negative emotions were significantly correlated in BPD participants only. In conclusion, early life stress plays a role in the precipitation of social dysfunction, and AVP mediates at least part of this effect.

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Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

Nature Communications ◽

10.1038/s41467-019-13085-6 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 12

Author(s):

Catherine Jensen Peña ◽

Milo Smith ◽

Aarthi Ramakrishnan ◽

Hannah M. Cates ◽

Rosemary C. Bagot ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Cortical Plasticity ◽

Early Life Stress ◽

Stress Sensitivity ◽

Sensitive Period ◽

Male And Female ◽

Reward Circuitry ◽

Female Mice ◽

Increase Risk

Abstract Abuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain’s transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.

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Neurodevelopmental plasticity and psychiatric vulnerability

European Psychiatry ◽

10.1016/j.eurpsy.2015.09.331 ◽

2015 ◽

Vol 30 (S2) ◽

pp. S70-S70

Author(s):

A. Dayer

Keyword(s):

Life Stress ◽

Early Life ◽

Methylation Status ◽

Early Life Stress ◽

Childhood Adversity ◽

Cellular Level ◽

Special Focus ◽

Serotonin System ◽

Increase Risk

The early developmental period is characterized by a high degree of plasticity and, consequently, is very sensitive to environmental factors, such as early life stressors (ELS). Exposure to ELS is known to increase risk to psychopathologies such as depression and anxiety disorders later in life . At a cellular level, alterations in the migration and integration of GABAergic interneurons (INs) in cortical circuits have emerged as a key processes involved in the vulnerability to psychiatric disorders . In humans and rodents, ELS interacts with genes regulating the serotonin system to increase risk to stress-related disorders . In addition, ELS is associated to a variety of epigenetic methylation changes in blood DNA from patients displaying a high loading of ELS . Here, we aimed to investigate the role of the ionotropic serotonin 3A receptor (5-HT3AR) at a genetic and epigenetic level in rodent and human models of early-life stress. We will first present data indicating that the 5-HT3AR is specifically expressed in a subset of cortical INs derived from the caudal ganglionic eminence (CGE) and controls early steps of cortical circuit assembly . Interestingly, the migration, transcriptional programs and positioning of 5-HT3AR expressing interneuron subtypes were found to be dysregulated in pathological models of early-life serotonin dysregulation. At a behavioral level, we found that ELS interacts with the 5-HTR3A to modulate social behaviors. Finally, we will present human data indicating that childhood adversity significantly impacts the methylation status of the promoter region of the human 5-HT3AR in an allele-specific manner. Taken together, this presentation will highlight the importance of the serotonin system in early life development and psychopathology with a special focus on the role of the 5-HT3AR in cortical interneuron development.

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Understanding behavioral effects of early life stress using the reactive scope and allostatic load models

Development and Psychopathology ◽

10.1017/s0954579411000460 ◽

2011 ◽

Vol 23 (4) ◽

pp. 1001-1016 ◽

Cited By ~ 33

Author(s):

Brittany R. Howell ◽

Mar M. Sanchez

Keyword(s):

Energy Balance ◽

Life Stress ◽

Early Life ◽

Allostatic Load ◽

Early Life Stress ◽

Load Model ◽

Load Models ◽

Adverse Experiences ◽

Wear And Tear ◽

Prolonged Stress

AbstractThe mechanisms through which early life stress leads to psychopathology are thought to involve allostatic load, the “wear and tear” an organism is subjected to as a consequence of sustained elevated levels of glucocorticoids caused by repeated/prolonged stress activations. The allostatic load model described this phenomenon, but has been criticized as inadequate to explain alterations associated with early adverse experience in some systems, including behavior, which cannot be entirely explained from an energy balance perspective. The reactive scope model has been more recently proposed and focuses less on energy balance and more on dynamic ranges of physiological and behavioral mediators. In this review we examine the mechanisms underlying the behavioral consequences of early life stress in the context of both these models. We focus on adverse experiences that involve mother–infant relationship disruption, and dissect those mechanisms involving maternal care as a regulator of development of neural circuits that control emotional and social behaviors in the offspring. We also discuss the evolutionary purpose of the plasticity in behavioral development, which has a clear adaptive value in a changing environment.

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Developmental stress and social phenotypes: integrating neuroendocrine, behavioural and evolutionary perspectives

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0242 ◽

2017 ◽

Vol 372 (1727) ◽

pp. 20160242 ◽

Cited By ~ 18

Author(s):

Karen A. Spencer

Keyword(s):

Hpa Axis ◽

Social Behaviour ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Developmental Stress ◽

Positive Effects ◽

Neuroendocrine Axis ◽

Complex Relationships ◽

Social Behaviours

The social world is filled with different types of interactions, and social experience interacts with stress on several different levels. Activation of the neuroendocrine axis that regulates the response to stress can have consequences for innumerable behavioural responses, including social decision-making and aspects of sociality, such as gregariousness and aggression. This is especially true for stress experienced during early life, when physiological systems are developing and highly sensitive to perturbation. Stress at this time can have persistent effects on social behaviours into adulthood. One important question remaining is to what extent these effects are adaptive. This paper initially reviews the current literature investigating the complex relationships between the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems and several aspects of social behaviour in vertebrates. In addition, the review explores the evidence surrounding the potential for ‘social programming’ via differential development and activation of the HPA axis, providing an insight into the potential for positive effects on fitness following early life stress. Finally, the paper provides a framework from which novel investigations could work to fully understand the adaptive significance of early life effects on social behaviours. This article is part of the themed issue ‘Physiological determinants of social behaviour in animals'.

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Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

10.1101/624353 ◽

2019 ◽

Author(s):

Catherine Jensen Peña ◽

Milo Smith ◽

Aarthi Ramakrishnan ◽

Hannah M. Cates ◽

Rosemary C. Bagot ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Cortical Plasticity ◽

Early Life Stress ◽

Stress Sensitivity ◽

Sensitive Period ◽

Male And Female ◽

Reward Circuitry ◽

Female Mice ◽

Increase Risk

ABSTRACTAbuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain’s transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.

Download Full-text