The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

Heim, Christine; Nemeroff, Charles B.

doi:10.1016/s0006-3223(01)01157-x

Cited by 2,393 publications

(1,655 citation statements)

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“…Studies of interpersonal early life trauma (I‐ELT) have further revealed increases in reactivity to fear‐conditioning and startle paradigms (Jovanovic et al., 2009, 2011; Ornitz & Pynoos, 1989), decreases in stress regulation (Gunnar, Frenn, Wewerka, & Van Ryzin, 2009), and impaired emotion regulation abilities (McLaughlin, Hatzenbuehler, Mennin, & Nolen‐Hoeksema, 2011). Such behavioral alterations have been associated with increased risk of developing psychopathology in adulthood (Heim & Nemeroff, 2001), especially posttraumatic stress disorder (PTSD) (Lanius, Frewen, Vermetten, & Yehuda, 2010; McKeever & Huff, 2003; Pratchett & Yehuda, 2011). …”

Section: Introductionmentioning

confidence: 99%

Interpersonal early‐life trauma alters amygdala connectivity and sustained attention performance

et al. 2017

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IntroductionInterpersonal early life trauma (I‐ELT) is associated with a myriad of functional impairments in adulthood, increased risk of drug addiction, and neuropsychiatric disorders. While deficits in emotional regulation and amygdala functioning are well characterized, deficits in general cognitive functioning have also been documented. However, the neural underpinnings of cognitive dysfunction in adults with a history of I‐ELT and the potential relationship between amygdala‐based functional connectivity and behavioral performance are currently poorly understood. This study examined how I‐ELT affects the cognitive and neural mechanisms supporting sustained attention.MethodsA total of 66 Veterans (18 with and 48 without a history of I‐ELT) completed a nonemotional sustained attention task during functional MRI.ResultsThe individuals with I‐ELT showed significant impairments in sustained attention (i.e., higher error rates, greater response variability). This cohort exhibited increased amygdala functional connectivity with the prefrontal cortex and decreased functional connectivity with the parahippocampal gyrus when compared to those without I‐ELT. These connections were significantly correlated with individual differences in sustained attention performance. Notably, classification analyses revealed that the pattern of amygdala connectivity across the whole brain was able to classify I‐ELT status with 70% accuracy.ConclusionThese results provide evidence of a lasting negative impact for those with a history of I‐ELT on sustained attention ability. They also highlight a critical role for amygdala functioning in cognitive control and sustained attention for those with a history of I‐ELT, which may underlie the observed attention deficits in clinical assessments and cognitive tests involving both emotional and nonemotional stimuli.

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Section: Introductionmentioning

confidence: 99%

Interpersonal early‐life trauma alters amygdala connectivity and sustained attention performance

et al. 2017

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“…A neurobiological mechanism proposed by Heim and Nemeroff [20] emphasizes the role of stressful life events especially in early childhood and preschool age. Early life stress induces persistent hyperactivity of hypothalamic pituitary axis (HPA), resulting in increased endocrine, autonomic, and behavioral stress responsiveness.…”

Section: Introductionmentioning

confidence: 99%

Impact of life events on child mental health before school entry at age six

Fürniss

Beyer

Müller

2009

Eur Child Adolesc Psychiatry

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The study examined the association between life events and early child mental health prior to school entry. The impact of single life events and the cumulative effect of multiple life events on child mental health were examined. In a northern German city, the complete 1-year intake of preschool children at the primary school entry assessment was included. In 1,887 children, life events and psychiatric symptoms were recorded by means of standardized parent questionnaires. Included were all life events between child's birth and school entry. For more than 80 percent of all children, at least one life event was reported. The number of life events was independent of any demographic variable; the mean was 2.2. The number of life events had a highly significant effect on the prevalence of child mental health problems. Six family-change-factors, especially coherent in content, could be identified by factor analysis. The study provides important data on the epidemiology and clinical impact of life events and psychopathology in early childhood. For child mental health, the cumulative effect of multiple life events was found to be much more important than the effect of specific single life events.

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“…Recently, Koike et al 1 identified a 25-bp deletion in a coding exon of the Disrupted-In-Schizophrenia (DISC1) gene in the 129S6/SvEv strain, which was also confirmed at the genomic level for all extant 129 mouse inbred substrains. 2 This mutation could interfere with the production of the full-length DISC1 protein.…”

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confidence: 85%

“…Early life stress including physical/sexual abuse as well as neglect has been associated with a number of adverse health outcomes including increased anxiety and depression. 1 We recently reported that adolescent rhesus monkeys (Macaca mulatta) exposed to physical abuse and high levels of maternal rejection as infants exhibit increased distress and anxiety, delayed social development and reduced exploration, compared to non-abused animals. 2,3 This early exposure to poor maternal care was also associated with reduced brain serotonergic function as reflected by decreased CSF concentrations of serotonin (5-HT) and the serotonin metabolite, 5-HIAA, that were in turn correlated with increased anxiety-like behavior during adolescence.…”

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confidence: 99%

“…When the 129S6/SvEv-derived DISC1 gene was transferred to C57BL/6J genetic background, the resultant mice displayed a subtle behavioral abnormality in working memory, without any other major deficits in behavior and brain anatomy. 1 Several lines of evidence from animal models with RNA interference to DISC1, as well as studies in patient-derived lymphoblasts, suggest that loss of DISC1 function may be involved in the abnormalities underlying the pathophysiology of major mental conditions. 3 The minor behavioral abnormality resulting from the 25-bp deletion is in contrast to the results of three independent groups who have generated partial lossof-function models by expressing dominant-negative DISC1 constructs and obtained substantial changes in behavior, including deficits in prepulse inhibition, latent inhibition and working memory.…”

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Activated p38 MAPK is associated with decreased CSF 5-HIAA and increased maternal rejection during infancy in rhesus monkeys

et al. 2007

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These data accord with earlier studies demonstrating regulation of RGS4 expression by dopamine 4 and specifically by COMT genotype. 8 Lipska and colleagues showed significantly decreased RGS4 mRNA expression in the DLPFC of Val/Val subjects, relative to Met-carriers. These changes suggest that variation in cortical dopamine may alter RGS4-dependent signaling by regulating its transcription. Alternatively or in addition, genetic variation in RGS4 may become more manifest in COMT Val/Val subjects, whose cortical synaptic dopamine levels are lower. Our findings support earlier statistical genetic and neuropathological evidence for epistasis between COMT and RGS4 by demonstrating an interaction between these two putative risk genes on an in vivo measure of prefrontal function. These results bolster the notion that COMT val158met genetic background mediates the impact of other schizophrenia susceptibility genes. Recent data indicate that activation of the p38 mitogen-activated protein kinase (MAPK) signaling cascade by cytokines including interleukin (IL)-1 and tumor necrosis factor (TNF)-a increases the expression and activity of the serotonin transporter (SERT). Herein, we report that increased p38 activity, as manifested by an increased percentage of peripheral blood monocytes staining positive for intracellular phosphorylated p38 (p-p38), was associated with decreased cerebrospinal fluid (CSF) concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and increased maternal rejection in 17 rhesus monkeys, 8 of whom were exposed to poor maternal care as infants. These data provide the first evidence of an in vivo relationship between p38 MAPK activation and brain serotonin metabolism in an animal model of early life stress and indicate that activation of p38 MAPK signaling pathways may participate in the contribution of early life stress to psychiatric morbidity. Early life stress including physical/sexual abuse as well as neglect has been associated with a number of adverse health outcomes including increased anxiety and depression. 1 We recently reported that adolescent rhesus monkeys (Macaca mulatta) exposed to physical abuse and high levels of maternal rejection as infants exhibit increased distress and anxiety, delayed social development and reduced exploration, compared to non-abused animals. 2,3 This early exposure to poor maternal care was also associated with reduced brain serotonergic function as reflected by decreased CSF concentrations of serotonin (5-HT) and the serotonin metabolite, 5-HIAA, that were in turn correlated with increased anxiety-like behavior during adolescence. 4 Data indicate that stress, including early life stress, also can be associated with activation of innate immune responses including release of proinflammatory cytokines and activation of proinflammatory cytokine signaling cascades. 5,6 Relevant to the impact of early life stress on serotonin metabolism, the cytokine signaling pathway, p38 MAPK, has been found to increase expression and activity of the SERT...

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The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

Cited by 2,393 publications

References 139 publications

Interpersonal early‐life trauma alters amygdala connectivity and sustained attention performance

Interpersonal early‐life trauma alters amygdala connectivity and sustained attention performance

Impact of life events on child mental health before school entry at age six

Activated p38 MAPK is associated with decreased CSF 5-HIAA and increased maternal rejection during infancy in rhesus monkeys

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