Early life experience alters response of adult neurogenesis to stress

Mirescu, Christian; Peters, Jennifer D.; Gould, Elizabeth

doi:10.1038/nn1290

Cited by 556 publications

(415 citation statements)

References 42 publications

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“…Early life traumatic events occurring during a period of neuronal plasticity have been shown in both humans and animal models to determine long-lasting neuroendocrine changes that induce hypersensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to new stressors. [38][39][40] In humans, CSA appears to cause persistent hyperreactivity of both the HPA axis and autonomic system. 38 Furthermore, adverse experiences early in life cause structural changes in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…38 Furthermore, adverse experiences early in life cause structural changes in the brain. 40 Rats exposed to maternal deprivation have long-lasting suppression of adult neurogenesis in the hippocampus, a brain region that is involved in the processing of emotional experience. 40 The effect of MAOA on the hippocampus may underlie the interaction between MAOA and childhood trauma.…”

Section: Discussionmentioning

confidence: 99%

“…40 Rats exposed to maternal deprivation have long-lasting suppression of adult neurogenesis in the hippocampus, a brain region that is involved in the processing of emotional experience. 40 The effect of MAOA on the hippocampus may underlie the interaction between MAOA and childhood trauma. Carriers of the low activity variant of MAOA-LPR display hyperactivation of the hippocampus and amygdala during the retrieval of negatively valenced emotional material.…”

Section: Discussionmentioning

confidence: 99%

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Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

et al. 2007

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Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior. Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone. Participants included 168 alcoholics (39 with ASPD (antisocial alcoholics) and 123 controls (no alcoholics, no ASPD). Antisocial behavior was also modeled as a continuous trait: ASPD symptoms count. The MAOA-LPR low activity allele was associated with alcoholism (P = 0.005), particularly antisocial alcoholism (P = 0.00009), only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women. The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P = 0.008) and antisocial alcoholics (P = 0.001). Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism (P = 0.006), and to a lesser extent with antisocial alcoholism (P = 0.03). In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone. A MAOB haplotype was associated with alcoholism independently from ASPD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

et al. 2007

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“…145,204 Early adverse experience inhibits structural plasticity via hypersensitivity to glucocorticoids and diminishes the ability of the hippocampus to respond to stress in adulthood. 205 Immune system and cytokines Psychological, physical and systemic stressors, the latter including infection, chronic inflammation and tissue injury, have been reported to influence cytokine production. [206][207][208][209][210] Cytokines are the signaling molecules of the immune system, and may also act to signal the CNS about the presence of an immunological challenge.…”

Section: Stressmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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“…It is also now apparent that neonatal programming of a number of adult stress responses is influenced significantly by maternal interactions with the neonates (eg reviewed in Mirescu et al (2004); Sanchez et al (2001)). While the mechanisms for these changes are not yet fully described, differences in the quality of maternal care can have longlasting influences on rat pups that manifest themselves as altered HPA axis responses to psychological stressors in the adult (Levine, 2001;Champagne and Meaney, 2001).…”

Section: Introductionmentioning

confidence: 99%

Early-Life Immune Challenge: Defining a Critical Window for Effects on Adult Responses to Immune Challenge

Spencer

Martin

Mouihate

et al. 2006

Neuropsychopharmacol

100

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Many aspects of mammalian physiology are functionally immature at birth and continue to develop throughout at least the first few weeks of life. Animals are therefore vulnerable during this time to environmental influences such as stress and challenges to the immune system that may permanently affect adult function. The adult immune system is uniquely sensitive to immune challenges encountered during the neonatal period, but it is unknown where the critical window for this programming lies. We subjected male Sprague-Dawley rats at postnatal day (P)7, P14, P21, and P28 to either a saline or lipopolysaccharide (LPS) injection and examined them in adulthood for differences in responses to a further LPS injection. Adult febrile and cyclooxygenase-2 responses to LPS were attenuated in rats given LPS at P14 and P21, but not in those treated at P7 or P28, while P7-LPS rats displayed lower adult body weights than those treated at other times. P28-LPS rats also tended to display enhanced anxiety in the elevated plus maze. In further experiments, we examined maternal-pup interactions, looking at the mothers' preference in two pup-retrieval tasks, and found no differences in maternal attention to LPS-treated pups. We therefore demonstrate a 'critical window' for the effects of a neonatal immune challenge on adult febrile responses to inflammation and suggest that there are other critical time points during development for the programming of adult physiology. We also show that the neonatal LPS effects on the adult immune system are not likely due to overt differences in maternal attention.

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Early life experience alters response of adult neurogenesis to stress

Cited by 556 publications

References 42 publications

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Early-Life Immune Challenge: Defining a Critical Window for Effects on Adult Responses to Immune Challenge

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