Etiology

There is evidence for both environmental and genetic effects on the development of personality disorders; however, the relative contribution of each is variable.[16][17][18][19][20][21][22]

One line of research has looked into brain changes in patients with personality disorders. The neurobiological findings may be genetically determined, a direct cause of early emotional trauma, or a consequence of the elevated activity of stress-associated neurobiological systems. Research has suggested a linkage between early trauma and later neurobiological dysfunctions.[23] There is evidence to support a combined genetic-environmental contribution to the development of specific aspects of personality disorders, such as emotional instability and suicidal behavior.[24][25]

A study of the genetic variants of the hypothalamus-pituitary-adrenal axis found a strong association between childhood trauma and genetic polymorphisms in men and women with borderline personality disorder (BPD).[26]​ Genetic factors and adverse childhood experiences may interact to affect brain development via altered hormones and neuropeptides, increasing the risk of BPD.[11][27][28][29][30]​​ It has been postulated that adverse childhood experiences may modulate gene expression and lead to stable personality traits.[28][29][30]​​ Although most clinicians believe that adverse childhood experiences such as physical, sexual, or emotional abuse and neglect are more common in people with BPD, not all people diagnosed with BPD have had such adverse childhood experiences.[31]

​​​There is a familial predisposition of BPD with this disorder being more common in people with a family history of BPD.[32]​ In one population-based Swedish study that included 1,851,755 participants, of whom 11,665 (0.6%) had a diagnosis of BPD according to the International Classification of Diseases (ICD-10), it was estimated that the heritability of BPD was 46%; the remaining 54% of variance was explained by nonshared environmental factors.[33]​ No single-nucleotide variants have been identified for BPD.[34]

Individuals with schizotypal personality disorder are more likely to have a first-degree relative with schizophrenia or a schizophrenia-spectrum disorder. Schizotypal personality disorder has a stronger genetic link with schizophrenia than schizoid personality disorder.[35][36]

In a longitudinal study of children followed over 4.5 years after birth, it was found that exposure to maternal stress in infancy sensitized the children’s pituitary-adrenal responses to subsequent stress exposure.[37] Similarly, an investigation of exposure to prenatal adversities (i.e., tobacco use, alcohol consumption, anxiety, and depression) found that exposure to increased stress in utero was associated with BPD in children 11 to 12 years later.[38]

Environmental factors that have been linked to development of personality disorders include: childhood maltreatment, particularly a history of childhood physical abuse; sexual abuse; and neglect.[39] Individuals who have experienced childhood abuse or neglect were found to be more than 4 times as likely as those without such a history to be diagnosed with personality disorders.[39] However, results varied based on whether the source of information was self-report or documented records from a time concurrent with the events.[39] A cross-sectional study that compared self-reports of adults diagnosed with avoidant personality disorder to those with social phobia found that avoidant personality disorder was highly correlated with neglect and most pronounced for physical neglect.[40] A prospective study found higher rates of BPD in children with histories of physical abuse or neglect (but not sexual abuse) compared with controls.[41] However, when factors such as parental alcohol/drug use and employment status were considered, the relationship between abuse and BPD was no longer significant, demonstrating the multifactorial nature of this disorder.

Pathophysiology

Most studies of the biological bases of personality disorders have focused on schizotypal and BPD.[42] Schizotypal personality disorder has been associated with movement abnormalities and minor physical abnormalities not found in patients with other personality disorders or controls.[42] Studies also indicate differences in neurobiological measures that distinguish patients with schizotypal personality disorder from both control subjects and patients with schizophrenia.[42]

BPD has been associated with disruption in the serotonin (5-HT) system, disruption in the endogenous opiate pathway (implicated in repeated nonsuicidal self-mutilation behavior), and altered functioning in areas of the brain responsible for impulsive aggression and affective regulation.[42] Genetic studies have found abnormalities of the 5-HT transporter, the tryptophan hydroxylase, as well as the 5-HT2A receptor gene.[43]

Connections between the prefrontal cortex and the amygdala are thought to play a key role in regulating emotional and behavioral responses. Emotional dysregulation and impulsivity, which are common manifestations of personality disorders, might be related to decreased prefrontal regulation and/or increased amygdala activation.[44]​ In a neurobiologic model of BPD, the most consistent finding was hyperactivity of the amygdala but the role of the amygdala in this context remains unclear.[45][46]​​​

Dopaminergic activity is thought to be important in emotion, information processing, impulse control, and cognition; hence a dopamine dysfunction theory has been proposed, which is derived from the reduction of some symptoms in BPD with treatment of dopamine receptor antagonists.[47] The theory of dopamine system involvement in BPD is also supported by the results of provocative challenges with amphetamine and methylphenidate in people with the disorder.[47]

The role of the adrenergic nervous system has also been shown by dysfunction or dysregulations of the hypothalamic-pituitary-adrenal axis.[26][43]

Oxytocin has been proposed as a factor in BPD psychopathology due to its effects on empathy and reward networks, affective regulation, and adaptive behavior.[48] The role of oxytocin in BPD is still under investigation. However, some studies suggest that low levels of endogenous oxytocin are a factor and dysregulations in the oxytocin system have been found in patients diagnosed with BPD.[49]

Classification

Diagnostic and statistical manual of mental disorders, 5th edition, text revision (DSM-5-TR) classification of personality disorders[1]

Three clusters: cluster A (odd/eccentric); cluster B (dramatic); cluster C (anxious/fearful).

  • Cluster A: schizoid, schizotypal, paranoid

  • Cluster B: borderline, histrionic, antisocial, narcissistic

  • Cluster C: avoidant, dependent, obsessive-compulsive

International statistical classification of diseases and related health problems, 11th revision (ICD-11)[2]

  • Mild personality disorders

  • Moderate personality disorders

  • Severe personality disorders

Personality difficulty refers to pronounced personality characteristics that may affect a patient’s interaction with health services, but are not severe enough to warrant a diagnosis of personality disorder. Characteristics of personality difficulty are only manifested at low intensity, or intermittently.[2]

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