✍️✍️✍️ Childhood Trauma Case Study

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Childhood Trauma Case Study

Namespaces Article Talk. Hippocampus and amygdala volumes Childhood Trauma Case Study patients with borderline personality disorder Childhood Trauma Case Study or without posttraumatic stress disorder. Part Childhood Trauma Case Study Physical and emotional thorntons butter tablet and neglect". These events Childhood Trauma Case Study profound psychologicalCertified Nurses Aides: A Case Studyand sociological impacts and can have Urie Bronfenbrenners Theory Of Development, lasting effects Childhood Trauma Case Study health and well-being such as unsocial behaviors, attention deficit hyperactivity disorder ADHDand sleep disturbances. Childhood Trauma Case Study Psychiatry. Childhood sexual abuse and suicidal behavior: How Does The Amount Of Baking Soda Mixed With Vinegar Affect The Volume Of Gas Produced? Childhood Trauma Case Study. Moreover, patients Childhood Trauma Case Study a history of emotional abuse Childhood Trauma Case Study higher severity scores on Childhood Trauma Case Study symptoms, including depression, hopelessness, suicidal ideation, anxiety, and impulsivity. In Childhood Trauma Case Study primates and in Childhood Trauma Case Study, several paradigms of stress early in life, including maternal Childhood Trauma Case Study or Childhood Trauma Case Study stress Childhood Trauma Case Study been associated with epigenetic alterations via DNA methylation Childhood Trauma Case Study 7879 ]. Dysregulation Childhood Trauma Case Study regional endogenous opioid function in borderline personality disorder.

Childhood Trauma: Managing PTSD Through Therapy - Julia Torres Barden - TEDxGraceStreetWomen

These findings suggest that the endogenous opioid system is involved in mediating separation-induced vocalizations and influences the HPA axis activation following a stress condition. In humans, regional endogenous opioid system activation has been associated with suppression of both sensory and affective qualities of stressors and with trait impulsivity [ 58 — 60 ] whereas its regional deactivation has been related to hyperalgesic responses and increases in negative affect during stress [ 61 ]. However, to date, there is only limited evidence of alterations of endogenous opioid levels in BPD patients.

To date, several functional and structural in vivo neuroimaging studies have been performed in BPD patients, detecting alterations mainly localized in the limbic circuit and in frontal cortex. These regions are related to the distinctive clinical features of the disorder i. The most replicated result, confirmed in recent meta-analyses [ 37 , 62 , 63 ], is represented by the reduction in the volumes of the hippocampus and the amygdala of BPD patients compared to controls [ 36 , 64 — 69 ].

The robustness of this finding seems to suggest that volumetric decreases in these two brain areas could be specific for BPD and thus useful as possible endophenotypes of illness. Moreover, hippocampal volumes were negatively correlated with the extent and the duration of self-reported early trauma, but only in the entire sample of BPD patients and controls. The role of PTSD and trauma as comorbidity with BPD on hippocampus and amygdala volumes has been object of investigation but the results are still controversial. Schmahl and colleagues [ 38 ] compared two groups of un-medicated BPD female patients with and without comorbid PTSD and 25 female controls.

Boen and collaborators [ 71 ] investigated the volumes of the Cornu Ammonis CA and the Dentate Gyrus DG , two hippocampal structures prone to morphological changes [ 72 ] in response to adverse environmental changes in a group of 18 women with BPD and 21 controls. However, they did not identify any significant association between subfield volumes and reported childhood trauma. In another interesting study, Kuhlmann and collaborators [ 73 ] investigated alterations in the grey matter of central stress-regulating structures, including hippocampus, amygdala, anterior cingulate cortex and hypothalamus, in female patients with BPD and controls.

The authors also explored whether grey matter volume of these four brain structures was associated with childhood trauma, reporting that patients with BPD showed lower hippocampal volumes than healthy controls, but higher volumes in the hypothalamus. Interestingly, hypothalamic volume correlated positively with a history of trauma in patients with BPD.

Two recent meta-analyses [ 37 , 63 ] evaluated whether the magnitude of hippocampus and amygdala volume reductions may be associated with state-of-illness factors and psychiatric disorders i. They showed that both the left and the right sides of hippocampal volumes were reduced in BPD patients with PTSD when compared to controls. Taken together, all these studies show that the main brain regions involved in BPD are those associated to stress and highlight the importance of classifying subgroups of patients with BPD, especially taking into account the presence of comorbidity with PTSD or of a history of childhood trauma. Notwithstanding, the association between the volume reduction and the degree to which childhood trauma could be responsible for these changes remains unclear.

Despite a large amount of data referred to volumetric and morphological alterations in brain regions associated to specific clinical features of BPD, not many neuroimaging studies have been conducted to investigate the role of the endogenous opioid system in BPD. Among the most investigated epigenetic mechanisms there are: i DNA methylation, which occurs at CG dinucleotides CpG and can influence the spatial structure of the DNA and the binding or the repression of specific DNA-binding proteins to the DNA [ 75 ], ii histone modifications, which influence the condensation of the DNA around histone proteins and regulate the accessibility of functional regions to transcriptional factors [ 76 ] and iii post-transcriptional regulation by non-coding RNAs such as microRNAs miRNAs [ 77 ].

All these epigenetic processes and, in particular, changes in DNA methylation have been widely investigated in the context of long-term negative effects of early life stressful events. In non-human primates and in rodents, several paradigms of stress early in life, including maternal separation or prenatal stress have been associated with epigenetic alterations via DNA methylation [ 78 , 79 ]. The hypothesis is that the quality of maternal care, affected by stress or depression in pregnancy and post-partum [ 80 , 81 ] could impact, through epigenetic mechanisms, on gene expression and behavioral traits that are maintained throughout life [ 78 ].

Recently, McGowan and colleagues [ 79 ] examined DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing the NR3C1 gene in the hippocampus of adult rat offspring, whose mothers differed in the frequency of maternal care. The authors found that the adult offspring of high compared to low maternal care showed a pattern of regions spanning the NR3C1 gene which were differentially methylated and acetylated, highlighting the idea that epigenetic changes, in the context of early life stress, involve alterations in gene-networks rather than in a single or few genes. Similarly, studies in humans reported similar results as those found in rodents, including the increased methylation levels within the NR3C1 promoter region in subjects who reported a history of early life adverse events [ 82 — 84 ].

For example, in another interesting study, McGowan and collaborators [ 82 ] found that in humans the cytosine methylation levels of the NR3C1 promoter were significantly increased in the postmortem hippocampus obtained from suicide victims with a history of childhood abuse as compared with those from suicide victims with no childhood abuse or with control samples. Decreased levels of NR3C1 mRNA were also identified, suggesting an effect of childhood abuse on NR3C1 methylation status and gene expression, independently from suicide.

Several epigenetic studies have been also conducted in control subjects characterized for a history of childhood trauma compared to those with no childhood trauma. In this context, Suderman and colleagues [ 85 ] have demonstrated, by using a genome-wide promoter DNA methylation approach, an abuse-associated hypermethylation in 31 miRNAs in a sample of control adult males exposed to childhood abuse. The hypermethylated state for 6 of these miRNAs was consistent with an hypomethylation status of their target genes. Reduced methylation levels of FKBP5 gene within regions containing functional glucocorticoid responsive elements GRE were also found in the blood of control individuals exposed to childhood abuse when compared to subjects without a history of trauma [ 86 ].

This demethylation was linked to increased stress-dependent gene transcription followed by a long-term dysregulation of the stress hormone system and a global effect on the function of immune cells and brain areas associated with stress regulation. Methylation profiles were then compared with corresponding genome-wide gene expression profiles. Despite the contribution of DNA methylation has been extensively investigated in association with childhood trauma in the context of pathologies related to stress, studies on the possible involvement of epigenetic mechanisms in BPD vulnerability are only at their birth.

Indeed, only few studies are available. In particular, Martin-Blanco and colleagues, investigated the association between NR3C1 methylation status, history of childhood trauma and clinical severity in blood samples of BPD subjects, showing an association between NR3C1 methylation and childhood trauma, in the form of physical abuse, and a trend towards significance for emotional neglect [ 88 ]. Regarding NR3C1 methylation and clinical severity, the authors also found a significant association with self injurious behavior and previous hospitalizations. All these findings support the hypothesis that alterations in NR3C1 methylation can occur early in life as consequence of stress exposure and can persist up to adulthood where subjects with higher NR3C1 methylation levels are also those with enhanced vulnerability to develop BPD.

Above to DNA methylation changes within NR3C1, hypo- or hyper-methylation within other genes have been found to play a key role in mediating the impact of early life stress on the development of stress-related disorders, including BPD [ 89 — 92 ]. Recently, Perroud and colleagues [ 91 ] investigated the role of childhood trauma on the methylation status of the Serotonin 3A Receptor 5-HT 3A R , including several CpGs located within or upstream this gene. The results showed that differential 5-HT 3A R methylation status was dependent on the history of childhood maltreatment and the clinical severity of the psychiatric disorder; this association was not specifically restricted to one specific psychiatric disorders investigated by the authors, but was found in patients who reported the higher severity indexes of childhood maltreatment, mainly represented by BPD patients.

In particular, childhood physical abuse was associated with higher 5-HT 3A R methylation levels, whereas childhood emotional neglect was inversely correlated with CpG1 I methylation levels. As suggested by the authors, these results highlight the need to search for history of childhood maltreatment in patients suffering from psychiatric disorders as these events could be associated with the worse negative outcomes. Since C allele has been also associated with a lower expression levels of 5HT 3A R, the authors suggested that increased methylation, due to exposure to childhood maltreatment, could lead to a further decrease in the expression of 5HT 3A R mRNA.

Aiming to identify novel genes that may exhibit aberrant DNA methylation frequencies in BPD patients, Teschler and collaborators [ 93 ] performed a genome-wide methylation analysis in the blood of BPD female patients and female controls. Similarly, using a whole-genome methylation approach, Prados and colleagues [ 94 ] analyzed the global DNA methylation status in the peripheral blood leukocytes of BPD patients with a history of childhood adversity and also in patients with MDD characterized by a low rate of childhood maltreatment. Contrary to Teschler [ 93 ], who used control subjects as reference group, in this study the authors used MDD subjects, most of them suicide attempters, thus controlling not only for MDD but also for a history of suicide.

The authors also assessed possible correlations between methylation signatures and the severity of childhood maltreatment. Taken together, all these studies reveal a complex interplay between BPD, early-life stressful adversities and epigenetic signatures. Neuroplasticity refers to brain-related mechanisms associated with the ability of the brain to perceive, adapt and respond to a variety of internal and external stimuli [ 96 , 97 ], including stress. The exposure to acute stressful challenges can induce several beneficial and protective effects for the body, which responds to almost any sudden, unexpected events by releasing chemical mediators — i.

However, a chronic exposure to stress and thus a chronic exposure to glucocorticoids can have negative and persistent effects on the body, including altered metabolism, altered immunity, enhanced inflammation, cognitive deficits, and also an enhanced vulnerability for psychiatric disorders and for medical conditions such as cardiovascular disease, metabolic disorders and cancer [ , ].

Neurotrophic factors, and in particular the neurotrophin Brain-Derived Neurotrophic Factor BDNF , have been identified as key mediators of stress on neuronal connectivity, dendritic arborization, synaptic plasticity and neurogenesis [ — ]. Since its crucial role in brain development and brain plasticity, BDNF has been widely investigated also in several psychiatric diseases, including BPD [ ]. Importantly, several findings have also documented epigenetic modifications on BDNF gene in patients with BPD , suggesting that childhood maltreatment in BPD patients can cause long term epigenetic alterations of genes crucially involved in brain functions and neurodevelopment, including BDNF, and that these alterations may contribute to enhanced vulnerability to develop BPD pathology.

The authors reported significantly higher methylation status in both CpG regions in patients than in controls, with the number of childhood trauma exposures associated with the high levels of BDNF methylation. They reported that bulimia nervosa was associated per se with an hypermethylation within BDNF promoter region sites. This was particularly evident when co-occurring with childhood abuse or BPD. Overall, these studies support the hypothesis that childhood trauma could be associated with changes in BDNF epigenetic signature, that in turn could contribute to alter cognitive functions in BPD patients.

Indeed, higher levels of gene methylation are commonly accompanied by a reduced gene expression. Up to now, neither a specific gene variant or biological mechanism has been exclusively associated with BPD, but the onset of this disorder has been suggested to depend on the combination of a vulnerable genetic background with adverse environmental factors during childhood. Among the biological systems found involved in BPD pathogenesis and particularly affected by childhood trauma events, there are: the HPA axis, the neurotransmission mechanisms, the endogenous opioid system and the neuroplasticity. Among the environmental factors, early life stressful events, in particular childhood trauma, have been proposed to negatively impact brain development through epigenetic mechanisms.

Although a complex interplay between BPD, early-life stressful adversities and epigenetic signatures has been suggested, further investigations are needed in order to better understand the role of genetic background and traumatic events during childhood in the onset of BPD. A better comprehension of these interactions could allow to identify at risk subjects, who could be treated with preventive therapies, such as psychotherapy, and to prevent or minimize the development of the disease later in life. This work was supported by an Eranet-Neuron Grant to A. All authors gave their scientific contribution and have approved the final manuscript. All the authors certify that the submission is an original work and it is not under review at any other journal.

Nadia Cattane, Email: ue. Roberta Rossi, Email: ue. Mariangela Lanfredi, Email: ue. National Center for Biotechnology Information , U. BMC Psychiatry. Published online Jun Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received Feb 7; Accepted Jun 6. This article has been cited by other articles in PMC. Associated Data Data Availability Statement The data supporting the conclusions of this article are included within the article. Abstract Background According to several studies, the onset of the Borderline Personality Disorder BPD depends on the combination between genetic and environmental factors GxE , in particular between biological vulnerabilities and the exposure to traumatic experiences during childhood.

Discussion We prove the role of alterations in Hypothalamic-Pituitary-Adrenal HPA axis, in neurotrasmission, in the endogenous opioid system and in neuroplasticity in the childhood trauma-associated vulnerability to develop BPD; we also confirm the presence of morphological changes in several BPD brain areas and in particular in those involved in stress response. Summary Not so many studies are available on epigenetic changes in BPD patients, although these mechanisms are widely investigated in relation to stress-related disorders.

Background Borderline Personality Disorder BPD is a pervasive pattern of emotional dysregulation, impulsiveness, unstable sense of identity and difficult interpersonal relationships [ 1 ]. Table 1 Summary of the papers cited in the review and showing alterations in different biological systems in BPD. Wingenfeld et al. Rinne et al. Carvalho Fernando et al. Martin-Blanco et al. Neurotransmission Wagner et al. Wagner et al. Tadic et al. Prossin et al. Neuroimaging studies Driessen et al. Schmahl et al. Kreisel et al. Boen et al.

Kuhlmann et al. Rodrigues et al. Ruocco et al. Epigenetics Martin-Blanco et al. Dammann et al. Perroud et al. Teschler et al. Prados et al. Neuroplasticity Koenigsberg et al. Thaler et al. Open in a separate window. BPD and neurotransmission In addition to the presence of HPA axis dysfunction, several studies have also proposed that childhood trauma can affect glutamatergic, serotonergic, dopaminergic and noradrenergic transmission, suggesting that BPD is the result of alterations in several interacting neurotransmitter systems [ 31 , 32 ].

BPD and neuroimaging studies Volumetric alterations in brain areas involved in stress response To date, several functional and structural in vivo neuroimaging studies have been performed in BPD patients, detecting alterations mainly localized in the limbic circuit and in frontal cortex. Endogenous opiod system alterations in brain regions involved in stress response Despite a large amount of data referred to volumetric and morphological alterations in brain regions associated to specific clinical features of BPD, not many neuroimaging studies have been conducted to investigate the role of the endogenous opioid system in BPD.

BPD and neuroplasticity the role of BDNF Neuroplasticity refers to brain-related mechanisms associated with the ability of the brain to perceive, adapt and respond to a variety of internal and external stimuli [ 96 , 97 ], including stress. Conclusions Up to now, neither a specific gene variant or biological mechanism has been exclusively associated with BPD, but the onset of this disorder has been suggested to depend on the combination of a vulnerable genetic background with adverse environmental factors during childhood. Acknowledgements Not applicable. Availability of data and materials The data supporting the conclusions of this article are included within the article. Competing interests All the authors declare that they have no conflicts of interest.

Consent for publication Not applicable- as the submitted manuscript is a review. Ethics approval and consent to participate Not applicable- as the submitted manuscript is a review. Contributor Information Nadia Cattane, Email: ue. References 1. The DSM classification and criteria changes. World psychiatry : official journal of the World Psychiatric Association. Borderline personality disorder. Linehan MM. Dialectical behavior therapy for treatment of borderline personality disorder: implications for the treatment of substance abuse. A developmental neuroscience of borderline pathology: emotion dysregulation and social baseline theory.

J Abnorm Child Psychol. Affect dysregulation in borderline personality disorder and somatoform disorder: differentiating under- and over-regulation. J Personal Disord. Childhood maltreatment associated with adult personality disorders: findings from the collaborative longitudinal personality disorders study. Traumatic exposure and posttraumatic stress disorder in borderline, schizotypal, avoidant, and obsessive-compulsive personality disorders: findings from the collaborative longitudinal personality disorders study.

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A prospective investigation of borderline personality disorder in abused and neglected children followed up into adulthood. Comorbidity of borderline personality disorder and posttraumatic stress disorder in the U. J Psychiatr Res. Herman JL. J Trauma Stress ;5 3 — Luxenberg T, Spinazzola, J. Understanding interpersonal trauma in children: why we need a developmentally appropriate trauma diagnosis.

The American journal of orthopsychiatry. Eur J Psychotraumatol ;5. MacIntosh HG, N. Borderline personality disorder: disorder of trauma or personality, a review of the empirical literature. Can Psychol ;— The hypothalamic-pituitary-adrenal axis and serotonin abnormalities: a selective overview for the implications of suicide prevention. Eur Arch Psychiatry Clin Neurosci. The effects of stress and stress hormones on human cognition: implications for the field of brain and cognition. Brain Cogn. General and comparative endocrinology. De Kloet ER. Why dexamethasone poorly penetrates in brain. Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment.

Biol Psychiatry. Early-life stress, HPA Axis adaptation, and mechanisms contributing to later health outcomes. Front Endocrinol. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. Twenty-four-hour urine cortisol in combat veterans with PTSD and comorbid borderline personality disorder. Overnight urinary cortisol release in women with borderline personality disorder depends on comorbid PTSD and depressive psychopathology. European psychiatry : the journal of the Association of European Psychiatrists. Acute glucocorticoid effects on response inhibition in borderline personality disorder. The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder.

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Moreover, women with childhood trauma more frequently had perinatal depression than those without it, after the researchers adjusted for sociodemographic characteristics and personal history of major depressive episode and consideration of the timing of onset. Tebeka and colleagues noted a dose effect between the number of childhood trauma types and the risk for perinatal depression. By Joe Gramigna, MA. Disclosures: The authors report no relevant financial disclosures. Read next. September 20, Receive an email when new articles are posted on. Please provide your email address to receive an email when new articles are posted on. You've successfully added to your alerts. You will receive an email when new content is published.

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