Personality disorders affect an estimated 9.1% of the general population, including 25 to 50% of psychiatric outpatients and up to 80% of inpatients. They constitute heterogeneous clinical presentations characterized by interpersonal deficits owing to disturbances in self and interpersonal functioning. Personality disorders frequently co-occur with other psychiatric conditions and tend to be refractory to traditional pharmacologic treatments, and patients with these disorders have a reduced quality of life and carry significant risk of death by suicide. Research over the last 25 years has advanced our understanding of the neurobiology, neurochemistry, physiology, genetics, and epigenetics that contribute to these complex presentations. A review of the neurobiological basis of personality disorders demonstrates that, in most cases, personality pathology represents a confluence of traits that are on a spectrum with normal personality functioning and other mental disorders. Schizotypal personality disorder, borderline personality disorder, antisocial personality disorder, avoidant personality disorder, and obsessive-compulsive personality disorder are among the disorders with sufficient evidence to support their conceptualization as discrete nosologic entities. Functional neuroimaging and connectivity studies, as well as genetic and epigenetic research, have highlighted structural, neurochemical, environmental, and behavioral targets that hold promise for treatment. This review contains 6 figures, 6 tables, and 116 references. Key words: antisocial, avoidant, borderline, connectivity, functional magnetic resonance imaging, heritability, obsessive-compulsive, personality, personality disorder, schizotypal
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