As is the case with other mental disorders, the causes of<unk>  are complex and not fully agreed upon. Evidence suggests that<unk>  and post-traumatic stress disorder (PTSD) may be related in some way. Most researchers agree that a history of childhood trauma can be a contributing factor, but less attention has historically been paid to investigating the causal roles played by congenital brain abnormalities, genetics, neurobiological factors, and environmental factors other than trauma. Social factors include how people interact in their early development with their family, friends, and other children. Psychological factors include the individual's personality and temperament, shaped by their environment and learned coping skills that deal with stress. These different factors together suggest that there are multiple factors that may contribute to the disorder. Genetics The heritability of<unk>  is estimated to be between 37% to 69%. That is, 37% to 69% of the variability in liability underlying<unk>  in the population can be explained by genetic differences. Twin studies may overestimate the effect of genes on variability in personality disorders due to the complicating factor of a shared family environment. Even so, the researchers of one study concluded that personality disorders "seem to be more strongly influenced by genetic effects than almost any Axis I disorder e.g., depression, eating disorders, and more than most broad personality dimensions". Moreover, the study found that<unk>  was estimated to be the third most-heritable personality disorder out of the 10 personality disorders reviewed. Twin, sibling, and other family studies indicate partial heritability for impulsive aggression, but studies of serotonin-related genes have suggested only modest contributions to behavior. Families with twins in the Netherlands were participants of an ongoing study by Trull and colleagues, in which 711 pairs of siblings and 561 parents were examined to identify the location of genetic traits that influenced the development of<unk> . Research collaborators found that genetic material on chromosome 9 was linked to<unk>  features. The researchers concluded that "genetic factors play a major role in individual differences of<unk>  features". These same researchers had earlier concluded in a previous study that 42% of variation in<unk>  features was attributable to genetic influences and 58% was attributable to environmental influences. Genes under investigation include the 7-repeat polymorphism of the dopamine D4 receptor (DRD4) on chromosome 11, which has been linked to disorganized attachment, whilst the combined effect of the 7-repeat polymorphism and the 10/10 dopamine transporter (DAT) genotype has been linked to abnormalities in inhibitory control, both noted features of<unk> . There is a possible connection to chromosome 5. Brain abnormalities A number of neuroimaging studies in<unk>  have reported findings of reductions in regions of the brain involved in the regulation of stress responses and emotion, affecting the hippocampus, the orbitofrontal cortex, and the amygdala, amongst other areas. A smaller number of studies have used magnetic resonance spectroscopy to explore changes in the concentrations of neurometabolites in certain brain regions of<unk>  patients, looking specifically at neurometabolites such as N-acetylaspartate, creatine, glutamate-related compounds, and choline-containing compounds. Some studies have identified increased gray matter in areas such as the bilateral supplementary motor area, dentate gyrus, and bilateral precuneus, which extends to the bilateral posterior cingulate cortex (PCC). The hippocampus tends to be smaller in people with<unk> , as it is in people with post-traumatic stress disorder (PTSD). However, in<unk> , unlike PTSD, the amygdala also tends to be smaller. This unusually strong activity may explain the unusual strength and longevity of fear, sadness, anger, and shame experienced by people with<unk> , as well as their heightened sensitivity to displays of these emotions in others. Given its role in regulating emotional arousal, the relative inactivity of the prefrontal cortex might explain the difficulties people with<unk>  experience in regulating their emotions and responses to stress. Neurobiology<unk>  has previously been strongly associated with the occurrence of childhood trauma. While many psychiatric diagnoses are believed to be associated with traumatic experiences occurring during critical periods of childhood, specific neurobiological factors have been identified within patients diagnosed with<unk> . Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol levels have been intensively studied in individuals who have experienced childhood traumas and have been formally diagnosed with<unk> . The HPA axis functions to maintain homeostasis when the body is exposed to stressors but has been found to be dysregulated among individuals with a history of childhood abuse. When the body is exposed to stress, the hypothalamus, specifically the paraventricular nucleus (PVN) releases peptides arginine vasopressin (AVP) and corticotropin-releasing factor (CRF). When these peptides travel through the body, they stimulate corticotrophic cells, resulting in the release of adrenocorticotropic hormone (ACTH). ACTH binds to receptors in the adrenal cortex, which stimulates the release of cortisol. Intracellular glucocorticoid receptor subtypes of mineralocorticoid receptor (MR) and low-affinity type receptor (GR) have been found to mediate the effects of cortisol on different areas of the body. While MRs have high affinity for cortisol and are highly saturated in response to stress, GRs have low affinity for cortisol and bind cortisol at high concentrations when an individual is exposed to a stressor. There have also been associations identified with FKBP5 polymorphisms, rs4713902 and rs9470079 in individuals with<unk> . For those with<unk>  who have experienced childhood trauma, rs3798347-T and rs10947563-A have been associated, specifically in individuals with both<unk>  diagnosis and a history of childhood physical abuse and emotional neglect. Hypothalamic-pituitary-adrenal axis The hypothalamic-pituitary-adrenal axis (HPA axis) regulates cortisol production, which is released in response to stress. Cortisol production tends to be elevated in people with<unk> , indicating a hyperactive HPA axis in these individuals. This causes them to experience a greater biological stress response, which might explain their greater vulnerability to irritability. Since traumatic events can increase cortisol production and HPA axis activity, one possibility is that the prevalence of higher than average activity in the HPA axis of people with<unk>  may simply be a reflection of the higher than average prevalence of traumatic childhood and maturational events among people with<unk> . Estrogen Individual differences in women's estrogen cycles may be related to the expression of<unk>  symptoms in female patients. A 2003 study found that women's<unk>  symptoms were predicted by changes in estrogen levels throughout their menstrual cycles, an effect that remained significant when the results were controlled for a general increase in negative affect. Developmental factors Childhood trauma There is a strong correlation between child abuse, especially child sexual abuse, and development of<unk> . Many individuals with<unk>  report a history of abuse and neglect as young children, but causation is still debated. Patients with<unk>  have been found to be significantly more likely to report having been verbally, emotionally, physically, or sexually abused by caregivers of either sex. They also report a high incidence of incest and loss of caregivers in early childhood. Individuals with<unk>  were also likely to report having caregivers of both sexes deny the validity of their thoughts and feelings. Caregivers were also reported to have failed to provide needed protection and to have neglected their child's physical care. Parents of both sexes were typically reported to have withdrawn from the child emotionally and to have treated the child inconsistently. Additionally, women with<unk>  who reported a previous history of neglect by a female caregiver or abuse by a male caregiver were significantly more likely to have experienced sexual abuse by a non-caregiver. It has been suggested that children who experience chronic early maltreatment and attachment difficulties may go on to develop<unk> . Writing in the psychoanalytic tradition, Otto Kernberg argues that a child's failure to achieve the developmental task of psychic clarification of self and other and failure to overcome splitting might increase the risk of developing a<unk>  personality. Neurological patterns The intensity and reactivity of a person's negative affectivity, or tendency to feel negative emotions, predicts<unk>  symptoms more strongly than does childhood sexual abuse. This finding, differences in brain structure (see Brain abnormalities), and the fact that some patients with<unk>  do not report a traumatic history suggest that<unk>  is distinct from the post-traumatic stress disorder which frequently accompanies it. Thus, researchers examine developmental causes in addition to childhood trauma. Research published in January 2013 by Anthony Ruocco at the University of Toronto has highlighted two patterns of brain activity that may underlie the dysregulation of emotion indicated in this disorder: (1) increased activity in the brain circuits responsible for the experience of heightened emotional pain, coupled with (2) reduced activation of the brain circuits that normally regulate or suppress these generated painful emotions. These two neural networks are seen to be dysfunctionally operative in the limbic system, but the specific regions vary widely in individuals, which calls for the analysis of more neuroimaging studies. Also (contrary to the results of earlier studies) sufferers of<unk>  showed less activation in the amygdala in situations of increased negative emotionality than the control group. John Krystal, editor of the journal Biological Psychiatry, wrote that these results
Borderline personality disorder
Substance use disorder
Depressive personality disorder
Cluster B personality disorders
Organic personality disorder
Identity disorder
Dependent personality disorder
Post-traumatic stress disorder