Early Stressful Experiences Research Articles

Defining and distinguishing early life stress, trauma, adversity, toxic and chronic stress and allostatic load: a descriptive review.

Various concepts are used to study the impact of stress on childhood development. These concepts are often used inconsistently or interchangeably. Our main objectives were to determine how selected stress concepts (chronic stress, toxic stress, allostatic load, early life stress, childhood adversity, childhood trauma and adverse childhood experiences; ACEs) are defined, operationalized and described, and to provide a theoretical context to aid the choice for a preferred concept in public health research. For this descriptive review, we systematically searched for literature published before 4 August 2021, on PubMed, Embase and PsycInfo. Two independent reviewers included studies. Exclusion criteria were: no systematic review, not peer reviewed, not published in English, selected stress concepts were no predetermined variable or a substantial topic in the discussion, full text was unobtainable or study described non-human or non-childhood populations. Data extraction forms were used. Descriptives were gathered, publication fields were identified through Journal Citation Reports categories, and verbatim descriptions were ordered in text and Venn diagrams. Of 264 screened studies, 124 were included. ACEs, childhood adversity and childhood trauma were used most. ACEs were the main concept used most frequently (47.6%). A total of 11 of 14 public and environmental health journals used ACEs. All concepts refer to prolonged, repeated, interpersonal stress from 0 to 18 years, that can alter physiological systems. Four concepts were stressor oriented, two concepts focused on stress response and effect and one on the state of challenged homeostasis. ACEs seem most fitting for public health setting, due to their operationalizability, large set of core experiences and widespread use.

Nostalgia for the old country—A histological exploration of early childhood physiological stress experiences in colonial Otago, New Zealand

AbstractMany mid‐19th‐century immigrants to New Zealand are presumed to have been in pursuit of a “better life” than was achievable in their origin countries. Here, we utilize histological analyses of internal indicators of enamel growth disruption (accentuated lines [ALs]) in 19 European and Chinese immigrants and five colony‐born children from three 19th‐century Otago sites. Observations of regular enamel microstructure were used to estimate a chronology of periods of enamel growth disruption. Clear or potential ALs were present in 18/19 (95%) adults and 4/5 (80%) subadults. Mean occurrence of ALs was higher in Chinese individuals than in European individuals between birth and 1 year of age (Chinese mean = 11; European mean = 3.8) and between 3 and 5 years of age (Chinese mean = 12.7; European mean = 1.3). Potential prenatal ALs were observed in three colony‐born children. Although similar stressors such as malnutrition and infectious disease would have been present in both Europe and China, their expression in these individuals may reflect the embodiment of different push factors that stimulated emigration to New World colonies such as New Zealand. The presence of ALs in colony‐born children indicates some continuation of developmental stressors in New Zealand. The results presented here highlight the value of utilizing microscopic analyses on poorly preserved archeological samples that are frequently excluded from histological examination. This preliminary glimpse into enamel formation disruption challenges the ubiquitous 19th‐century narrative of New Zealand as free from the hardships of industrial revolution era Europe and sheds light on the stresses of childhoods spent in rural China and the potential attractions of the Pacific goldfields in comparison. Future work with larger sample sizes will contribute to a critical exploration of experiences of childhood physiological stress in those who lived and died in colonial New Zealand.

Early Adverse Family Experiences and Elevated Adrenocorticotropic Hormone Predict Non-Suicidal Self-Injury in Females with Non-Psychotic Mental Disorders and Suicidal Ideation.

Nonsuicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD and suicidal ideation. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD and suicidal ideation was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

Predictors of Improvement in Parental Stress After the First Three Months at Home with a Medically Fragile Infant.

Little is known about the early stress experiences of parents of infants with serious life-limiting/life-threatening conditions during the initial months after discharge from hospital. The aim of the study was to measure change, and predictors of change, in parenting stress at the time of transition from hospital to home (T1) with a medically fragile infant, and after a 3-month period (T2). Parents of infants identified as meeting ≥ 1 palliative care referral criterion were recruited in a Midwestern United States tertiary pediatric hospital (2012-2014) within 2 weeks of hospital discharge. A repeated measures design was used to assess change on a validated parenting stress inventory over the two timepoints (T1 and T2). Fifty-two parents (61 infants) participated at T1 and 44 (85%) at T2. On discharge (T1) stress was moderately high 3 months post discharge (T2) overall and domain-specific stress scores improved, except stress related to parent role functioning and participation in their child's medical care. Independent predictors of improvement in overall parenting stress scores (T2-T1) were being a younger parent and having experienced prior pregnancy-related loss. The time of discharge from hospital to home is often stressful for parents of medically fragile infants. Improvements were found during the first 3 months at home, but improvement was minimal for stress related to role function and providing medical care. Past experience with pregnancy-related loss and being younger were associated with improvement in stress across theoretical domains. Screening for stress should be included as part of routine pre- and post-neonatal intensive care unit discharge psychosocial assessments of parents caring for infants with serious illness to ensure their unique support needs continue to be met over time.

High levels of childhood trauma associated with changes in hippocampal functional activity and connectivity in young adults during novelty salience

Childhood trauma (CT) has been linked to increased risk for psychosis. Moreover, CT has been linked to psychosis phenotypes such as impaired cognitive and sensory functions involved in the detection of novel sensory stimuli. Our objective was to investigate if CT was associated with changes in hippocampal and superior temporal gyrus functional activation and connectivity during a novelty detection task. Fifty-eight young adults were assigned to High-CT (n = 28) and Low-CT (n = 24) groups based on their scores on the childhood trauma questionnaire (CTQ) and underwent functional Magnetic Resonance Imaging during an auditory oddball task (AOT). Relative to the Low CT group, High CT participants showed reduced functional activation in the left hippocampus during the unpredictable tone condition of the AOT. Furthermore, in the High CT group, psychophysiological interaction analysis revealed hypoconnectivity between the hippocampus and temporal and medial regions. The present study indicates both altered hippocampal activation and hippocampal-temporal-prefrontal connectivity during novelty detection in individuals that experienced CT, similarly to that reported in psychosis risk populations. Early stressful experiences and environments may alter hippocampal function during salient events, mediating the relationship between childhood trauma and psychosis risk.

Low levels of Methyl-CpG binding protein 2 are accompanied by an increased vulnerability to the negative outcomes of stress exposure during childhood in healthy women

Numerous mental illnesses arise following stressful events in vulnerable individuals, with females being generally more affected than males. Adverse childhood experiences are known to increase the risk of developing psychopathologies and DNA methylation was demonstrated to drive the long-lasting effects of early life stress and promote stress susceptibility. Methyl-CpG binding protein 2 (MECP2), an X-linked reader of the DNA methylome, is altered in many mental disorders of stress origin, suggesting MECP2 as a marker of stress susceptibility; previous works also suggest a link between MECP2 and early stress experiences. The present work explored whether a reduced expression of MECP2 is paralleled by an increased vulnerability to the negative outcomes of stress exposure during childhood. To this aim, blood MECP2 mRNA levels were analyzed in 63 people without history of mental disorders and traits pertaining to depressive and anxiety symptom clusters were assessed as proxies of the vulnerability to develop stress-related disorders; stress exposure during childhood was also evaluated. Using structural equation modeling, we demonstrate that reduced MECP2 expression is accompanied by symptoms of anxiety/depression in association with exposure to stress in early life, selectively in healthy women. These results suggest a gender-specific involvement of MECP2 in the maladaptive outcomes of childhood adversities, and shed new light on the complex biology underlying gender bias in stress susceptibility.

Prenatal stress induces a depressive-like phenotype in adolescent rats: The key role of TGF-β1 pathway.

Stressful experiences early in life, especially in the prenatal period, can increase the risk to develop depression during adolescence. However, there may be important qualitative and quantitative differences in outcome of prenatal stress (PNS), where some individuals exposed to PNS are vulnerable and develop a depressive-like phenotype, while others appear to be resilient. PNS exposure, a well-established rat model of early life stress, is known to increase vulnerability to depression and a recent study demonstrated a strong interaction between transforming growth factor-β1 (TGF-β1) gene and PNS in the pathogenesis of depression. Moreover, it is well-known that the exposure to early life stress experiences induces brain oxidative damage by increasing nitric oxide levels and decreasing antioxidant factors. In the present work, we examined the role of TGF-β1 pathway in an animal model of adolescent depression induced by PNS obtained by exposing pregnant females to a stressful condition during the last week of gestation. We performed behavioral tests to identify vulnerable or resilient subjects in the obtained litters (postnatal day, PND > 35) and we carried out molecular analyses on hippocampus, a brain area with a key role in the pathogenesis of depression. We found that female, but not male, PNS adolescent rats exhibited a depressive-like behavior in forced swim test (FST), whereas both male and female PNS rats showed a deficit of recognition memory as assessed by novel object recognition test (NOR). Interestingly, we found an increased expression of type 2 TGF-β1 receptor (TGFβ-R2) in the hippocampus of both male and female resilient PNS rats, with higher plasma TGF-β1 levels in male, but not in female, PNS rats. Furthermore, PNS induced the activation of oxidative stress pathways by increasing inducible nitric oxide synthase (iNOS), NADPH oxidase 1 (NOX1) and NOX2 levels in the hippocampus of both male and female PNS adolescent rats. Our data suggest that high levels of TGF-β1 and its receptor TGFβ-R2 can significantly increase the resiliency of adolescent rats to PNS, suggesting that TGF-β1 pathway might represent a novel pharmacological target to prevent adolescent depression in rats.

Corticotropin releasing factor neurons in the visual cortex mediate long-term changes in visual function induced by early adversity

Early adversity can cause malfunction of the visual system in adulthood. Adult female but not male mice undergoing early chronic mild stress (ECMS) maintain ocular dominance (OD) plasticity after the critical period. How early stressful experiences have a long-term impact on it is largely unknown. Here, we observed a wide distribution of corticotropin-releasing factor (CRF)-positive neurons, which mainly colocalized with a subpopulation of GABAergic interneurons in the mouse primary visual cortex (V1). Optogenetic activation of CRF-positive neurons transfected with AAV-ChR2 evoked inhibitory currents in nearby pyramidal cells. ECMS induced a reduction in the expression of CRF mRNA in adult mouse V1. Chemogenetic activation of V1 CRF neurons impaired OD plasticity in adult ECMS females. We further showed that local administration of the corticotropin releasing factor receptor 1 (CRFR1) antagonist via an osmotic minipump into the visual cortex mimicked OD plasticity in adult ECMS females. Whole-cell recording in layer 2/3 pyramidal neurons revealed that the CRFR1 antagonist reduced the short-term depression (STD) of evoked inhibitory postsynaptic current (IPSC) in females but not in males. Likewise, CRF agonists have the opposite effect. In summary, our findings indicate that the local CRF-CRFR1 system within V1 may mediate the long-term and sex-dependent effect of early stress experiences on visual plasticity and provide a target for the prevention of visual deficits in adults with a history of early-life adversity.

Early life stressful experiences escalate aggressive behavior in adulthood via changes in transthyretin expression and function

Escalated and inappropriate levels of aggressive behavior referred to as pathological in psychiatry can lead to violent outcomes with detrimental impact on health and society. Early life stressful experiences might increase the risk of developing pathological aggressive behavior in adulthood, though molecular mechanisms remain elusive. Here, we provide prefrontal cortex and hypothalamus specific transcriptome profiles of peripubertal stress (PPS) exposed Balb/c adult male mice exhibiting escalated aggression and adult female mice resilient to such aberrant behavioral responses. We identify transthyretin (TTR), a well known thyroid hormone transporter, as a key regulator of PPS induced escalated aggressive behavior in males. Brain-region-specific long-term changes in Ttr gene expression and thyroid hormone (TH) availability were evident in PPS induced escalated aggressive male mice, circulating TH being unaltered. Ttr promoter methylation marks were also altered being hypermethylated in hypothalamus and hypomethylated in prefrontal cortex corroborating with its expression pattern. Further, Ttr knockdown in hypothalamus resulted in escalated aggressive behavior in males without PPS and also reduced TH levels and expression of TH-responsive genes (Nrgn, Trh, and Hr). Escalated aggressive behavior along with reduced Ttr gene expression and TH levels in hypothalamus was also evident in next generation F1 male progenies. Our findings reveal that stressful experiences during puberty might trigger lasting escalated aggression by modulating TTR expression in brain. TTR can serve as a potential target in reversal of escalated aggression and related psychopathologies.

Behavioral effects of environmental enrichment on male and female wistar rats with early life stress experiences.

Exposure to adverse childhood experiences or early life stress experiences (ELSs) increase the risk of non-adaptive behaviors and psychopathology in adulthood. Environmental enrichment (EE) has been proposed to minimize these effects. The vast number of methodological variations in animal studies underscores the lack of systematicity in the studies and the need for a detailed understanding of how enrichment interacts with other variables. Here we evaluate the effects of environmental enrichment in male and female Wistar rats exposed to adverse early life experiences (prenatal, postnatal, and combined) on emotional (elevated plus maze), social (social interaction chamber), memory (Morris water maze) and flexibility tasks. Our results—collected from PND 51 to 64—confirmed: 1) the positive effect of environmental enrichment (PND 28–49) on anxiety-like behaviors in animals submitted to ELSs. These effects depended on type of experience and type of enrichment: foraging enrichment reduced anxiety-like behaviors in animals with prenatal and postnatal stress but increased them in animals without ELSs. This effect was sex-dependent: females showed lower anxiety compared to males. Our data also indicated that females exposed to prenatal and postnatal stress had lower anxious responses than males in the same conditions; 2) no differences were found for social interactions; 3) concerning memory, there was a significant interaction between the three factors: A significant interaction for males with prenatal stress was observed for foraging enrichment, while physical enrichment was positive for males with postnatal stress; d) regarding cognitive flexibility, a positive effect of EE was found in animals exposed to adverse ELSs: animals with combined stress and exposed to physical enrichment showed a higher index of cognitive flexibility than those not exposed to enrichment. Yet, within animals with no EE, those exposed to combined stress showed lower flexibility than those exposed to both prenatal stress and no stress. On the other hand, animals with prenatal stress and exposed to foraging-type enrichment showed lower cognitive flexibility than those with no EE. The prenatal stress-inducing conditions used here 5) did not induced fetal or maternal problems and 6) did not induced changes in the volume of the dentate gyrus of the hippocampus.

Early stressful experiences are associated with reduced neural responses to naturalistic emotional and social content in children

How do children’s experiences relate to their naturalistic emotional and social processing? Because children can struggle with tasks in the scanner, we collected fMRI data while 4-to-11-year-olds watched a short film with positive and negative emotional events, and rich parent-child interactions (n = 70). We captured broad, normative stressful experiences by examining socioeconomic status (SES) and stressful life events, as well as children’s more proximal experiences with their parents. For a sub-sample (n = 30), parenting behaviors were measured during a parent-child interaction, consisting of a picture book, a challenging puzzle, and free play with novel toys. We characterized positive parenting behaviors (e.g., warmth, praise) and negative parenting behaviors (e.g., harsh tone, physical control). We found that higher SES was related to greater activity in medial orbitofrontal cortex during parent-child interaction movie events. Negative parenting behaviors were associated with less activation of the ventral tegmental area and cerebellum during positive emotional events. In a region-of-interest analysis, we found that stressful life events and negative parenting behaviors were associated with less activation of the amygdala during positive emotional events. These exploratory results demonstrate the promise of using movie fMRI to study how early experiences may shape emotional, social, and motivational processes.

Promises and Pitfalls of NMDA Receptor Antagonists in Treating Violent Aggression

Treatment options for chronically aggressive individuals remain limited despite recent medical advances. Traditional pharmacological agents used to treat aggression, such as atypical antipsychotics, have limited efficacy and are often replete with dangerous side effects. The non-competitive NMDAR antagonists ketamine and memantine are promising alternatives, but their effects appear to be highly dependent on dosage, context, and personal experience. Importantly, these drugs can increase aggression when combined with substances of abuse or during periods of heightened stress. This is likely due to mechanistic differences operating at specific synapses under different contexts. Previous findings from our lab and others have shown that early life stress, substance abuse, and attack experience promote aggression through NMDAR-dependent synaptic plasticity within aggression-related brain circuits. Ketamine and memantine affect these types of aggression in opposite ways. This has led us to propose that ketamine and memantine oppositely affect aggression brought on by early life stress, substance abuse, or attack experience through opposite effects on NMDAR-dependent synaptic plasticity. This would account for the persistent effects of these drugs on aggression and suggest they could be leveraged as a more long-lasting treatment option. However, a more thorough examination of the effects of ketamine and memantine on cellular and synaptic function will be necessary for responsible administration. Additionally, because the effects of ketamine and memantine are highly dependent on prior drug use, traumatic stress, or a history of aggressive behavior, we propose a more thorough medical evaluation and psychiatric assessment will be necessary to avoid possible adverse interactions with these drugs.

P137. Differential Effects of Early Life Stress During Sensitive Periods of Development on Anxiety-Like Behavior and Gene Expression Response in Adult Mice

Preclinical ELS models (e.g., maternal separation) have been extensively used to investigate biomolecular changes underlying the behavioral outcomes in response to stress exposure during early postnatal period. However, it still unclear how the reprograming effects of these early stress experiences could interact with the exposure to a second stressor during later periods of development, such as adolescence. To address that, this study investigated how maternal separation would interact with chronic adolescence stress exposure on anxiety-like response, gene and protein expression of GR and FKBP5 in the hippocampus.

Adherence to preventive behaviors among college students during COVID-19 pandemic in China: The role of health beliefs and COVID-19 stressors.

Before herd immunity is reached, preventive practices still play an important role in controlling the COVID-19 pandemic. Adherence to preventive behaviors could be determined by individuals’ health beliefs, which would be influenced by antecedent factors such as previous exposure to pandemic stressors. Applying the health belief model (HBM), this study aims to examine the mediation association among COVID-19 stressors, HBM constructs, and preventive behaviors. Longitudinal data were collected from 1225 Chinese college students using web-based surveys at wave 1 (w1; between January 31 and February 11, 2020) and wave 2 (w2; between March 20 and April 3, 2020). Participants reported their COVID-19 stressors (w1), five HBM constructs (w2), and preventive behaviors (w1 and w2). Paired t-tests suggested that social distancing and self-quarantine behaviors decreased while precautionary behaviors increased from w1 to w2. Path analysis indicated that two HBM constructs (perceived barriers and self-efficacy) mediated the association between COVID-19 stressors and precautionary behaviors. These findings suggested that tailored prevention intervention for college students should attend to perceived barriers and self-efficacy. Individuals who exposed to multiple pandemic stressors merit particular attention and intervention should account for their early pandemic stress experiences.

How Early Stressful Life Experiences Combine With Adolescents' Conjoint Health Risk Trajectories to Influence Cardiometabolic Disease Risk in Young Adulthood.

Research has primarily focused on additive (unique) associations between early stressful life experiences (specifically, socioeconomic adversity and maltreatment) and young adults' cardiometabolic disease risk without considering multiplicative (synergistic) influences. Furthermore, research has not fully considered the varying patterns of health risk trajectories (e.g., substance use, obesogenic-related behaviors, depressive symptoms) across adolescence and the transition to young adulthood that may link earlier stressful experiences and later cardiometabolic disease risk. This study examined heterogeneity in conjoint health risk trajectories from adolescence to the transition to young adulthood and their additive and multiplicative (synergistic) influences with early stressful life experiences on cardiometabolic disease risk in young adulthood using data from the National Longitudinal Study of Adolescent to Adult Health (n = 9,421; 55.6% female) over a period of 13 years. Four distinct conjoint health risk trajectories were identified considering trajectories of substance use behaviors, obesogenic-related behaviors, and depressive symptoms: (a) overall high-risk, (b) behavioral risks, (c) psycho-obesogenic risks, and (d) overall low-risk. Socioeconomic adversity and maltreatment were additively and multiplicatively associated with cardiometabolic disease risk in young adulthood. Individuals with overall high-risk conjoint trajectories averaged higher cardiometabolic disease risk in young adulthood when they were exposed to early socioeconomic adversity. Implications for personalized interventions for individuals who have experienced multiple forms of health risks are discussed.

Childhood Physical Neglect is Associated With Epigenetic Aging Acceleration Among Women With Cocaine Use Disorder

Evidence suggests accelerated aging mechanisms in drug addiction and this effect may be potentiated by stressful experiences, particularly those that occurred early in life. Most studies have been investigating cellular senescence and premature aging by the increase rate of the telomere shortening in psychiatric patients. Recent reports suggest that DNA methylation (DNAm) in blood also accounts as an epigenetic clock with recognized value as a biological aging marker. However, it is unknown whether accelerated DNAm aging is also evident in the blood of patients with cocaine use disorder (CUD), in particular in association with early life stressful experiences.

The burden of early life stress on the nociceptive system development and pain responses.

For a long time, the capacity of the newborn infant to feel pain was denied. Today it is clear that the nociceptive system, even if still immature, is functional enough in the newborn infant to elicit pain responses. Unfortunately, pain is often present in the neonatal period, in particular in the case of premature infants which are subjected to a high number of painful procedures during care. These are accompanied by a variety of environmental stressors, which could impact the maturation of the nociceptive system. Therefore, the question of the long-term consequences of early life stress is a critical question. Early stressful experience, both painful and non-painful, can imprint the nociceptive system and induce long-term alteration in brain function and nociceptive behavior, often leading to an increase sensitivity and higher susceptibility to chronic pain. Different animal models have been developed to understand the mechanisms underlying the long-term effects of different early life stressful procedures, including pain and maternal separation. This review will focus on the clinical and preclinical data about early life stress and its consequence on the nociceptive system.

Prenatal Stress and Early Childhood Body Mass Index: A Path Analysis Approach.

Stress experienced by mothers during the prenatal period can have negative impacts on offspring development. Elevated BMI in childhood in response to early stress experience is a particularly critical outcome of interest since high BMI in childhood is associated with diabetes, heart disease and stroke in later life. The primary objective of this study was to analyze pathways between prenatal stress and early childhood BMI at 54-months of age and to begin to explore ethnic variations in these pathways. This study used the Growing Up in New Zealand (GUiNZ) dataset, which is a longitudinal, representative birth cohort study that began with recruiting pregnant women in 2009 and 2010 in Auckland, New Zealand. Path analysis modeling was used to explore risk and protective pathways between prenatal maternal stress and early childhood body mass index (BMI) at 54-months of age and differences by ethnicity (n = 5510). Prenatal stress was positively associated with early childhood BMI at 54-months and maternal nutrition behaviors and length of exclusive breastfeeding mediated this direct relationship (χ2 (1) = 0.83, p = 0.36; AIC = 50,496). Mediation and moderation paths varied by ethnicity. These findings contribute to the understanding of the intergenerational transmission of stress with respect to early childhood obesity. Reducing early stress exposure and/or addressing mediating and moderating factors linking stress experience with obesity development may prove to be more effective than attempting to alter health behaviors and trajectories in adulthood.

Selective enhancement of fear learning and resistance to extinction in a mouse model of acute early life trauma.

Early life stress (ELS) experiences can cause changes in cognitive and affective functioning. This study examined the persistent effects of a single traumatic event in infancy on several adult behavioral outcomes in male and female C57BL/6J mice. Mice received 15 footshocks in infancy and were tested for stress-enhanced fear learning, extinction learning, discrimination and reversal learning, and novel object recognition. Infant trauma potentiated fear learning in adulthood and produced resistance to extinction but did not influence other behaviors, suggesting restricted effects of infant trauma on behaviors reliant on cortico-amygdala circuitry.

Long-term consequences of aversive childhood experiences: effects on cerebral structures

Long-term consequences of aversive childhood experiences: effects on cerebral structures Abstract. Early childhood stress experiences due to neglect, and physical, psychological or sexual abuse can lead to permanent changes in central nervous structures. The central nervous system generally shows a very high plasticity in early childhood. Objectively, these influences are reflected in functional and structural-morphological changes in certain brain areas. Subjectively, they are manifested through changes in cognitive, emotional, perceptive and social experiencing. This review aims to summarize the current status of the limited number of studies with human subjects on the consequences of early childhood stress experiences with focus on the central nervous system.