How do childhood trauma affect adulthood?
Consequences of early traumatisation from a neurobiological point of view
The connection between early trauma in childhood and an increased risk of mental illness has long been well documented in the specialist literature. It is only in the last few years, due to technological advances, that we have begun to understand how early traumas are physically written down and how they can affect various aspects of our behavior and experience throughout our lives. This overview first briefly summarizes the current state of knowledge on the neurobiological effects of childhood trauma. Then genetic and epigenetic factors are considered as possible mechanisms of biological embedding.
Childhood trauma is one of the most well-established risk factors for the development of mental disorders. Due to the availability of new technologies, we are now beginning to understand how early trauma gets under the skin and exerts a sustained influence on various domains of psychological functioning and health. In the present review we will first briefly summarize what is currently known about the neurobiological effects of childhood trauma. We will then consider genetic and epigenetic factors as possible mechanisms mediating the biological embedding of childhood trauma.
Childhood trauma is now considered to be one of the most certain risk factors for the development of mental disorders later in life. In epidemiological studies worldwide, participants with trauma exposure in childhood show a significantly higher lifetime prevalence of almost every mental disorder compared to subjects without childhood trauma. According to the estimates of these studies, almost 30% of all mental disorders can be traced back to childhood trauma and other adverse childhood circumstances (Kessler et al. 2010). However, childhood trauma is also associated with an increased risk of physical illnesses such as B. cardiac and autoimmune diseases are associated (e.g. Goodwin and Stein 2004).
An explanatory model for the far-reaching and lifelong influence of early trauma states that childhood trauma induces changes in neurobiological systems, which in turn increase the vulnerability to diseases (biological embedding hypothesis). Most neurobiological systems are not yet mature at the time of birth. Persistent trauma during sensitive development phases presumably interferes with maturation processes and thereby changes the functioning of neurobiological systems in the long term (Heim and Binder 2012).
The diverse effects of childhood trauma have been described in a wealth of studies, which can be divided into different groups based on their focus of evaluation (Fig. 1). More recent studies focus increasingly on the immediate biological effects of trauma (level 1 in Fig. 1, proximal factors related to the biological mechanism, such as DNA methylation), while earlier studies often looked at distal impact factors (level 4 in Fig . 1, e.g. diseases).
In the following we briefly summarize the current state of knowledge on the neurobiological effects of trauma in childhood and then go into more detail on (epi) genetic processes as possible transmission mechanisms. The focus here is on genetic findings on the stress hormone system. Since it is not possible for reasons of space to go into all studies from this area (levels 0–2 in Fig. 1), the results of review articles and other selected studies are preferred. Reference is made to further review articles in Fig. 1.
Neurobiological correlates of childhood trauma
Almost all studies view childhood trauma as a form of environmental stress that triggers a biological stress response. The hypothalamic-pituitary-adrenal [HPA] axis is therefore the best-studied neurobiological system in connection with childhood trauma.
Description of the HPA axis:
When the HPA axis is activated (e.g. in threatening situations), the corticotropin-releasing hormone (CRH) and vasopressin (AVP) are released in the hypothalamus. CRH and AVP then bind to their specific receptors CRHR1 and V1b in the pituitary gland, which stimulates the production of adrenocorticotropic hormone (ACTH). ACTH in turn triggers the production and release of glucocorticoids (e.g. cortisol) in the adrenal cortex. Glucocorticoids have a broad spectrum of physiological effects; they lead, inter alia. to mobilize glucose from energy stores, increase cardiovascular activity, dampen the immune system and support the body's adaptation to stressful situations in the short term. Glucocorticoids act on the system through negative feedback loops. The synthesis and release of CRH in the hypothalamus and of ACTH in the adrenal cortex and thus the activation of the HPA axis are terminated by the binding of glucocorticoids to glucocorticoid receptors (GR) (Holsboer 2000). If glucocorticoids bind to the GR, it changes its shape and can then bind to so-called glucocorticoid-responsive elements (GRE) of the DNA, whereby the expression of nearby genes is modulated. The GR becomes a transcription factor through the binding of the ligand (de Kloet et al. 2005).
Repeated evidence of dysregulation of the HPA axis in persons abused in childhood:
Numerous studies have observed a dysregulation of the HPA axis in abused children and adults who retrospectively report abuse in childhood. However, the results of these studies do not always point in the same direction, and childhood trauma has been associated with both hyper- and hypoactivity of the HPA axis (summarized in detail in De Bellis and Zisk 2014; Danese and McEwen 2012; Heim et al. 2008). According to Danese and McEwen (2012) v. a. Studies examining the mentally ill show a significant association between child abuse and characteristics of increased HPA activity, such as: B. increased cortisol values, increased CRH concentrations in the cerebrospinal fluid (CSF), stronger cortisol response to a psychosocial stress test and less suppression of the cortisol response after administration of a synthetic glucocorticoid (dexamethasone, DEX) in combination with CRH (DEX / CRH test). In contrast, there are studies that report lower basal cortisol levels and a weakened cortisol response in response to the DEX / CRH test or a psychosocial stress test in mostly healthy people with child abuse compared to non-abused controls (Danese and McEwen 2012). There are also individual studies on abused children that did not observe any HPA axis abnormalities (e.g. De Bellis et al. 1994; Kaufman et al. 1997). Many factors can explain the inconsistent results. Depending on the type and duration of the trauma, the age at the time of the trauma, the presence of mental disorders and additional trauma, there may be other relationships between childhood trauma and HPA axis activity (Nemeroff 2016). The time that has elapsed since the trauma and the associated physiological habitat processes are also an important factor. One of the few longitudinal studies in the field showed that the initially increased morning cortisol levels in sexually abused girls decrease with increasing age and the time lag behind the trauma and, in adulthood, fall below the values of a non-traumatized comparison group (Trickett et al. 2010).
Parental sensitivity and secure parent-child bond as a stress buffer:
A secure attachment to at least one parent (e.g. one parent abused but the other parent is securely attached) could cushion the damaging effects of childhood trauma and explain why childhood trauma has different effects on the stress hormone system. Studies in healthy, non-abused children show e.g. For example, high maternal sensitivity has a dampening effect on the child's HPA axis activity in stressful situations (e.g. Albers et al. 2008). It is assumed that in the first years of life the parent-child interaction takes on the role of an external regulator of the child's HPA axis (Gunnar and Donzella 2002). If this social regulator fails because z. For example, if the abuse originates from the parents, the child could experience an increase in glucocorticoids, which may lead to dysregulation during the development of stress-sensitive brain regions (e.g. hippocampus).
Isolated indications of altered oxytocin concentrations in abused people:
While some studies reported an inverse relationship between childhood trauma and the attachment hormone oxytocin (e.g. Heim et al. 2009b), other studies found increased oxytocin concentrations in persons abused in childhood (e.g. Pierrehumbert et al. 2010; Seltzer et al . 2014). Oxytocin usually reduces the stress response. The study by Seltzer et al. (2014) found the lowest cortisol levels in response to a psychosocial stress test in the group of abused girls with the highest levels of oxytocin. It is unclear why child abuse is associated with increased oxytocin concentrations in some cases and lower concentrations in others. It is believed that the way the person deals with the trauma plays a role. For example, Mohiyeddini et al. (2014) found that coping strategies characterized by the suppression of emotional expression (e.g., keeping feelings to oneself) and possibly related to the avoidance of social contact reinforce the association between childhood trauma and low oxytocin levels in adulthood.
In adults and adolescents, childhood trauma is associated with increased inflammatory parameters:
In various studies, adults and adolescents who were abused in childhood showed increased levels of C ‑ reactive protein (CRP), higher fibrinogen levels and proinflammatory cytokines (overview by Coelho et al. 2014). An epidemiological longitudinal study, which reports a prospective connection between abuse in childhood (up to the age of 11) and increased CRP or fibrinogen values as well as a higher number of white blood cells at the age of 32 years, is particularly meaningful (Danese et al . 2007). Interestingly, this relationship was particularly pronounced in subjects with depression (Danese et al. 2008). Elevated inflammation levels may play a role in mediating the effects of childhood trauma on later psychological and internal illnesses.
Interactions between trauma-related changes in different hormonal systems:
A trauma-related dysregulation of the HPA axis most likely also affects various other neurobiological systems (e.g. immune system, serotonergic and dopaminergic systems), and conversely, dysregulations in these systems in turn influence the HPA axis. Struber et al. (2014) proposed a model that uses hormonal interactions to explain why childhood trauma can lead to both hypo- and hyperactivity of the HPA axis. The decisive factor is whether there is a secure bond with a parent, which causes an increased release of oxytocin. The interaction of the binding hormone oxytocin with glucocorticoids and serotonin results in a different biochemical development path for securely attached traumatized children, which in the long term ends in a hyperactive HPA axis, than for traumatized children without secure attachment (HPA axis hypoactivity; Struber et al. 2014). Hormonal interactions are poorly understood, but could explain inconsistent neurobiological findings related to childhood trauma.
People who were abused in childhood have structural and functional differences in the brain compared to non-abused people:
Based on the hypothesis that high cortisol concentrations can damage the brain during sensitive development phases, v. a. In regions with a high GR density (e.g. hippocampus, amygdala, prefrontal cortex; Lupien et al. 2009), several imaging studies examined differences in brain structures and the neural response to given stimuli between persons with and without child abuse. In a recent review of these studies, Teicher and Samson (2016) come to the conclusion that child abuse is associated with structural changes in the corpus callosum, in the anterior cingulate, dorsolateral prefrontal and orbitofrontal cortex, and in the hippocampus. While a smaller volume of the prefrontal cortex is seen in both abused children and adults, the finding of a smaller hippocampal volume is limited to adults (Danese and McEwen 2012). This could mean that structural changes in the hippocampus only occur with a certain latency or as a result of a post-traumatic stress disorder (PTSD; Smith 2005). The results of functional imaging studies showed that people who were abused in childhood reacted with a strong activation of the amygdala to negative stimuli (e.g. fearful, angry faces) and a weak activation of reward circuits (striatum) to positive stimuli such as reward anticipation (Teicher and Samson 2016).
Neurobiological abnormalities associated with childhood trauma as a sensible adaptation to the environment:
In the past, it was assumed that the frequently observed changes in neurobiological systems in people traumatized in childhood were unspecific consequences of high stress hormone levels (Lupien et al. 2009), today it is assumed that these are experience-dependent adaptation processes to the respective social environment (Danese and McEwen 2012; Teicher and Samson 2016). The stronger response to threat stimuli than to reward stimuli B. Recognizing dangers more quickly and represents a sensible reaction in a potentially dangerous environment. On the other hand, increased awareness of dangers and negative stimuli promotes the development of depression, anxiety and substance use disorders (Teicher and Samson 2016).
Summary of neurobiological correlates of childhood trauma:
Research on neurobiological effects focused on three closely interrelated biological systems: endocrine, immune and central nervous systems. Many studies now show that victims of early trauma show abnormalities in the functioning of all three systems (Danese and McEwen 2012; McCrory et al. 2011). How these trauma-related biological changes occur, i.e. the exact biological mechanisms on which these relationships of a correlative nature are based, are less well understood. Genetic factors and epigenetic modifications triggered by the environment could play a central role here (Blaze et al. 2015).
Genes as moderators of the effects of childhood trauma
Trauma does not always have negative effects on the organism. Whether someone develops a mental disorder after experiencing a childhood trauma appears to include genetic predisposition, d. H. to be dependent on variations of individual base pairs in the DNA strand. Caspi et al. (2002, 2003) were the first to use molecular genetic methods to demonstrate that gene variants moderate the much-observed relationship between childhood trauma and mental disorders. In their first pioneering gene-environment interaction study on male participants in the prospective epidemiological Dunedin study, a connection between child abuse and later antisocial behavior could only be demonstrated if those affected were carriers of the low-active variant of the monoamine oxidase A gene (MAOA-L) were (Tab. 1). Abused boys with the risk genotype (MAOA-L) developed significantly more behavioral disorders, a higher propensity for violence, more characteristics of an antisocial personality disorder and were convicted of violent crime more often than non-abused boys with the same genotype (Caspi et al. 2002). The latest meta-analysis on the subject, which summarizes the effects of 27 non-clinical studies with just over 18,400 study participants, also found that the development of antisocial behavior as a result of child abuse in men dated MAOAGenotype (Byrd and Manuck 2014).
In their much-noticed follow-up study, Caspi et al. (2003) found a significant gene-environment interaction (GxE) between the length polymorphism (5-HTTLPR) in the serotonin transporter (5-HTT) gene (SLC6A4) and child abuse as well as critical life events with regard to the prediction of depressive illnesses. In the presence of child abuse, homozygous carriers of the shorter allele had the highest risk of depression, followed by heterozygous carriers with only one copy of the short allele. Unlike MAOA, are the results of various meta-analyzes for 5-HTTLPR-GxE inconsistent. This could be due to the fact that different types of environmental factors were not always differentiated. Two more recent meta-analyzes showed a significant one 5-HTTLPR-Interaction effect e.g. B. only for child abuse and medical factors (e.g.serious illness), but not for critical life events (Karg et al. 2011; Sharpley et al. 2014). The results of a large-scale collaborative meta-analysis that differentiates between various stressors and includes unpublished data are still pending (Culverhouse et al. 2013).
Based on the studies by Caspi et al. (2002, 2003) were followed by numerous GxE studies, which extended the initial findings on the moderator role of genetic polymorphisms to other phenotypes and genes. For reasons of space, we cannot go into the entirety of this study. We focused on that in our own work FK506 binding protein 5 gene (FKBP5), an HPA axis gene that regulates the sensitivity of GR.
FKBP5 codes for a cochaperone (helper protein) of the heat shock protein 90 (hsp90), which inhibits the ability of the GR to bind to cortisol in the cell nucleus. The expression of FKBP5 is in turn induced by the binding of the GR to the GRE of the DNA, which is equivalent to an ultra-short negative feedback loop: GR induces FKBP5, which then reduces the GR activity. How strongly FKBP5 is expressed when the GR is activated depends in turn on polymorphisms in the FKBP5-Gene off. Carriers of the risk allele (T at SNP rs1360780) show stronger FKBP5 expression. High levels of FKBP5 can severely disrupt the negative feedback loop of the HPA axis: glucocorticoids are less able to bind to the GR, the stress response is not terminated by activation of the GR receptor, and a sustained stress reaction or cortisol secretion occurs Binder 2009; Halldorsdottir and Binder 2017).
We could inter alia show that both the severity of current PTSD symptoms (Binder et al. 2008) and an increased prospective risk of depression are due to a significant interaction between FKBP5 and predicting childhood trauma (Zimmermann et al. 2011). Other working groups were able to use our initial findings FKBP5-Confirm GxE and add other so-called intermediate phenotypes (Zannas et al. 2016; Zannas and Binder 2014). The latter is assumed to be between trauma exposure and the outbreak of the disease and thus closer to the suspected causal mechanism than manifest diseases (e.g. structural and functional abnormalities in the brain, stress reaction, etc.). In the meantime, GxE from FKBP5 with early trauma can be confirmed in studies of over 20,000 participants. Tab. 1 briefly summarizes some of the most important GxE findings with regard to childhood trauma and particularly goes into the genes for which the first epigenetic studies are now available.
Summary of GxE studies:
Despite the justified criticism of GxE studies (e.g. the risk of a high proportion of false-positive results due to underpowered analyzes, preferred publication of positive significant results, improper use of covariates; e.g. Duncan and Keller 2011; Keller 2014) , it would be wrong to assume that GxE does not exist per se. GxE still represent a plausible explanatory model for the individual effects of childhood trauma (Rutter et al. 2006). The insights gained from GxE studies include:
As a rule, GxE have a broad spectrum of activity. The same risk alleles have been associated with various mental illnesses in childhood trauma.
Most GxE studies do not find any major genetic effects. This implies that the effect of certain genes only unfolds when confronted with a certain environmental factor. If the individual is not exposed to the environmental risk (e.g. childhood trauma), the adverse effects of a particular genotype do not appear.
The connection between a so-called risk allele and unfavorable health consequences is not always clear. In the groups without childhood trauma, carriers of the “risk allele” often had lower psychopathology values than carriers of the “protective allele” (“crossover” interactions; e.g. Binder et al. 2008). This suggests that the effects of an allele can be reversed under favorable environmental conditions. Belsky and Pluess (2013) therefore argue that the so-called risk alleles are plasticity alleles that are generally associated with an increased susceptibility to environmental effects, both positive and negative.
Not one SNP or gene alone, but numerous gene variants seem to moderate the effects of childhood trauma. Genome-wide GxE studies, which are still lacking in the area of childhood trauma, could help uncover previously unknown genetic factors.
To what extent a high genetic disposition for a certain illness increases the influence of childhood trauma on the development of the same illness (Peyrot et al. 2014) or whether severe child abuse is such a strong risk factor that triggers depression regardless of the genetic risk (Mullins et al. 2016) , must be clarified in further polygenic GxE studies.
The validation of a GxE finding across different levels of analysis (Fig. 1) including molecular and cellular processes is a promising approach to separate methodological artifacts from true GxE (Halldorsdottir and Binder 2017).
It is believed that changes in the epigenome (including DNA methylation, hydroxymethylation, histone modification, non-coding RNA, ATP-dependent chromatin changes) represent a central mechanism through which GxE and long-term effects of childhood trauma (Fig. 1) are biologically mediated ( Blaze et al. 2015). Epigenetic modifications lead to changes in gene expression / activity, i. That is, they determine whether and to what extent a gene is expressed (switched on), read (transcription) and translated into proteins (translation). A certain gene variant can only develop its effect if the gene is expressed.
One difficulty with epigenetic research in humans is that epigenetic markers are tissue-specific; that is, the methylation pattern of the same gene differs from each other in brain cells and peripheral cells. There are now initial indications that easily harvested peripheral cells are suitable for investigating the epigenetic consequences of environmental influences. Provençal et al. (2012) could e.g. B. show that rhesus monkeys that grew up separately from their mother showed changes in DNA methylation not only in the prefrontal cortex, but also in peripheral T cells.
Methylation of individual genes as a function of childhood trauma
Glucocorticoid Receptor Genes (NR3C1):
A study by Weaver et al. Marks the beginning of the investigation of epigenetic reactions to early environmental experiences. (2004) on rats. The authors were able to show for the first time that early social experiences lead to epigenetic changes that affect the stress reactivity of animals into adulthood. For example, rats that received a lot of maternal care (in the form of licking and grooming) in the first week after birth showed lower DNA methylation in the promoter of the GR gene compared to rats that were not cared for much (Nr3c1) and an increased expression of GR in the hippocampus (Weaver et al. 2004). In earlier experiments, the well-cared for rats showed, in addition to higher hippocampal GR expression, a more moderate cortisol and ACTH response to stress (Liu et al. 1997). McGowan et al. (2009) were able to transfer these findings almost one-to-one to humans and thus provided the first evidence of a connection between child abuse and epigenetic markers in humans. In their post-mortem study of 12 suicide victims with and without severe abuse in childhood and 12 controls who suffered sudden death, only suicide victims who were abused in childhood had higher DNA methylation in the promoter of NR3C1 and decreased expression of GR in the hippocampus. The clear majority of the subsequent human studies were able to confirm the finding of increased DNA methylation as a result of child abuse and other childhood trauma, although the majority examined the methylation status of GR in peripheral blood cells and not, as in the original study, in brain samples (Turecki and Meaney 2016). In the meantime, further studies have also shown that an increased NR3C1-Methylation is related to various psychopathological symptoms (e.g. Radtke et al. 2015).
In our own work, we have succeeded in elucidating the molecular genetic mechanism of GxE for the first time. Using data from the Grady Trauma Project, which includes the majority of poverty-stricken and multiply traumatized African Americans, we were able to demonstrate that the FKBP5-GxE regarding PTSD via an allele-specific DNA methylation in a functional GRE of FKBP5 mediated (Klengel and Binder 2015; Klengel et al. 2013). Subjects who were sexually and physically abused in their childhood showed lower methylation of the DNA in a GRE in intron 7 of the test subjects compared to non-abused subjects FKBP5Gene, but only if they were carriers of the T allele at SNP rs1360780. A number of cell experiments have shown that the demethylation of this locus is relevant for the transcription and expression of FKBP5 (Klengel et al. 2013). For trauma in adulthood, no demethylation of the FKBP5-Gens prove. The epigenetic changes could be limited to sensitive periods in childhood. Consistent with this are the results of a study carried out directly on children that showed significant demethylation of DNA at the same site FKBP5 Gens was observed in 3 to 5 year olds with abuse documented by child care workers (Tyrka et al. 2015). We suspect that childhood trauma and the associated high stress hormone concentrations in individuals with a genetic predisposition (T allele on SNP rs1360780) cause demethylation in the FKBP5-Gen triggers, whereby the already genetically determined high activity of FKBP5 is additionally increased. In turn, high levels of FKBP5 impair the negative feedback mechanism mediated by the GR, and the HPA axis is continuously activated (Klengel and Binder 2015; Klengel et al. 2013).
Serotonin Transporter Gene (SLC6A4):
Beach et al. (2010, 2011) were the first to find - based on data from the Iowa Adoption Study - increased methylation in the promoter of SLC6A4 reported in adults who were physically and sexually abused in childhood, and particularly in sexually abused women. Further analysis showed that the associated sexual abuse was stronger SLC6A4-Methylation correlated with symptoms of an antisocial personality disorder, particularly in carriers of the S allele (Beach et al. 2013, 2011). The only longitudinal study in this area found that identical twins exposed to massive bullying by their peers not only experienced increased methylation by the age of 10 SLC6A4 had a muffled cortisol reaction to a psychosocial stress test at the age of 12 years than the twins without bullying experience (Ouellet-Morin et al. 2013). However, the exact mechanism on which these findings are based has not yet been clarified. In the adoption sample from Iowa, an overall connection between the methylation of certain sites of the serotonin transporter gene and gene expression could be demonstrated, but not specifically for the region whose methylation status could be predicted from childhood trauma and genotype (Vijayendran et al. 2012).
A rapidly growing number of studies are investigating whether childhood trauma has a wider impact than just individual candidate genes. In the first epigenome-wide study, Labonte et al. (2012) 362 differently methylated promoters in the hippocampus of male suicide victims who were severely abused in their childhood, compared to controls consisting of suicide victims and those who died suddenly without experience of abuse. The greatest methylation differences were found for genes involved in neuronal plasticity. Subsequent studies with peripheral epigenetic markers determined a z. Sometimes even higher numbers of differently methylated genes in people who were exposed to childhood trauma or other adverse childhood circumstances. The differences primarily concerned genes that play a role in the transmission of excitation between nerve cells or the transcription of DNA into mRNA (e.g. Mehta et al. 2013; Suderman et al. 2014).
Previous human studies on the epigenetic effects of early trauma have focused on differences in the DNA methylation of a few candidate genes (esp. NR3C1, SLC6A4) in peripheral cells. Other genes and epigenetic mechanisms associated with childhood trauma are largely unexplored in humans. Almost every of the examined candidate genes was found to be associated with altered methylation in persons traumatized in childhood, even if, as in the case of SLC6A4, Direction of results (hypo- vs. hypermethylation) and methylation site did not always match. As far as the exact mechanism is concerned, we assume that early trauma changes transcription processes in the cell: The attachment of a methyl group to a CpG dinucleotide changes the chromatin structure (3-dimensional structure) of the DNA and thus the accessibility of these DNA sites for Transcription regulators. In addition, certain risk allelles appear to favor epigenetic modifications. The risk allele of the FKBP5-SNP rs1360780 (T allele) goes e.g. B. associated with a different chromate information, which favors a direct contact of the GRE in intron 2 with the transcription start side (TSS) and thus leads to an increased FKBP5 expression (Zannas et al. 2016). Genome-wide studies also suggest that childhood trauma leaves traces in the DNA of numerous genes.
Telomeres are the long repetitive sequences of the nucleotides TTAGGG at the ends of chromosomes, which protect the DNA from decay during replication (Price et al. 2013). Telomeres shorten with every cell division, and the length of the telomeres is considered an indicator of biological aging. Just like epigenetic markers, the telomere length is tissue-specific and differs between different cell types (Blaze et al. 2015). First studies with z. A small sample size suggests that certain aversive childhood experiences such as neglect, physical abuse and indicators of insufficient parental sensitivity are associated with shorter telomere length (summarized in Blaze et al. 2015; Price et al. 2013). One of these studies deserves special mention because, based on the prospective measurement of both telomere length and experience of violence, it demonstrated an erosion of telomere length in 5- to 10-year-old children as a result of multiple exposure to violence in the home environment (Shalev et al. 2013). Taken together, these preliminary findings indicate an accelerated aging process as a result of adverse childhood circumstances.
Effects of trauma-associated neurobiological changes on mental functions and diseases
In some studies, the methylation differences associated with childhood trauma could be directly linked to abnormalities in stress regulation or symptoms of mental illness (e.g. Beach et al. 2011; Klengel et al. 2013; Yehuda et al. 2016). Apart from this, only a few studies have so far succeeded in integrating the results on the effects of childhood trauma across several levels of analysis (Fig. 1). Although it is known that childhood trauma is associated with various neurobiological abnormalities, it is still unclear to what extent these are directly responsible for changes in behavior, emotional experience and the risk of disease. This is also an important question for forensic practice. So was z. B. the MAOA- Findings by Caspi et al. (2002) first used in a European court in 2009 to reduce the sentence of a convicted murderer by one year (the Bayout case, Feresin 2009). The complex interplay between trauma-induced dysregulation in neurobiological and psychological functions over long periods of time makes it difficult to decipher causal processes. Represents a subdued cortisol response to acute stress that has been repeatedly observed in traumatized children, e.g. Is it a risk factor for behavior problems and the development of externalizing disorders, as some studies suggest (e.g. Jaffee et al. 2015; Ouellet-Morin et al. 2011)? Or are the problems in social behavior observed in abused children more of a predictor for low basal cortisol levels (Alink et al. 2012). The further the observed effects are temporally and systemically from immediate neurobiological consequences (level 1 in Fig. 1), the more factors come into question as additional moderating influences. The hypothetical case study below is intended to illustrate how we can understand the complex effects of early trauma as a function of genetic factors (using the example of FKBP5) to introduce.
Hypothetical case study:
Ben is 6 years old and has been physically abused by his parents since he was 3 years old. Due to the constant experience of abuse and the daily threat, his stress hormone levels are increased.Due to a genetic predisposition (T allele am FKBP5-SNP rs1360780), Ben's feedback mechanism for downregulating the stress hormone axis is impaired. It reacts to any form of stress with a prolonged release of cortisol. The repeated abuse in connection with the genetic predisposition lead to an excess of cortisol, which affects the entire organism. At the cell level, it triggers demethylation in the FKBP5-Gen off. The consequences of this epigenetic modification are an even stronger induction of FKBP5 and thus an even stronger activation of the stress hormone axis in the event of renewed stress. The abuse he has experienced also affects how Ben treats his peers. He feels attacked more quickly, reacts more strongly to threat / rejection signals (increased amygdala reactivity) and is aggressive towards his classmates. The associated social problems (stronger rejection from classmates) create additional stress, which in turn activates the HPA axis. Ben has trouble concentrating in school. He increasingly develops symptoms of a behavior disorder.
Passing trauma on to the next generation
Meanwhile, not only from the animal model there are indications that prenatal traumatization of the parents can leave epigenetic modifications in the offspring without the offspring themselves being traumatized (Blaze et al. 2015; Provençal and Binder 2015). This could be especially for the mother's stresses while
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