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Vol 7 n° 2 - New Psychiatric Classification based on Endophenotypes

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posed a challenge to epidemiologists, clinicians, geneticists,

and psychologists. Because of the varied academic per-

spectives on these disorders that range from behaviorist to

schemata that have evolved to categorize the personality

disorders have been highly variable and controversial.The

defined, for example, in the Diagnostic and Statistical

polythetic criteria that in some cases reflect an epidemio-

logical and/or behavioral tradition, such as antisocial per-

sonality disorder, or in other cases, a psychoanalytically ori-

ented tradition, such as in narcissistic personality disorder.

An alternative approach to understanding and classifying

psychiatric disorders, which has not been extensively inves-

tigated in the personality disorders, is reframing the diag-

nostic nomenclature in terms of specific and measurable

biologically and/or genetically based endophenotypes,

which open up the possibility of identifying genetic pre-

disposing factors, as well as providing a possibly more

rational classification schema. This approach, while not

necessarily incompatible with other diagnostic approaches

that are formulated from alternative perspectives such as

behavioral or psychodynamic approaches, raises the pos-

sibility of generating an underlying “vocabulary” of per-

sonality disorders grounded in specific biologic substrates.

Combinations of these endophenotypically based dimen-

sions of personality disorders, such as affective instability

or impulsivity/aggression, might then become the basis of

more complex multifactorial personality disorders recog-

nized by the clinician, such as borderline personality dis-

order (BPD) or schizotypal personality disorder (SPD).

Furthermore, such an endophenotypic approach may help

Keywords: endophenotype; borderline personality disorder; schizotypal perso-

Author affiliations: Professor of Psychiatry, Mount Sinai School of Medicine,

New York, NY; Director, The Mood & Personality Disorders Research Program,

Mount Sinai School of Medicine, New York, NY; Executive Director, Mental

Illness Research, Education and Clinical Center (MIRECC), Bronx VA Medical

Address for correspondence: Larry J. Siever, MD, Mental Illness Research,

Education and Clinical Center (MIRECC), Bronx VA Medical Center, 130 West

The identification of endophenotypes in the personality

disorders may provide a basis for the identification of

dimensions of the personality disorders, as well as sus-

ceptibility to major psychiatric illnesses. Clinical dimen-

sions of personality disorders that lend themselves to the

tive instability, impulsivity, aggression, emotional infor-

deficits, and psychosis. For example, the propensity to

aggression can be evaluated by psychometric measures,

interview, laboratory paradigms, neurochemical imaging,

and pharmacological studies. These suggest that aggres-

sion is a measurable trait that may be related to reduced

serotonergic activity. Hyperresponsiveness of amygdala

and other limbic structures may be related to affective

instability, while structural and functional brain alter-

ations underlie the cognitive disorganization in psychotic-

like symptoms of schizotypal personality disorder. Thus,

an endophenotypic approach not only provides clues to

underlying candidate genes contributing to these behav-

ioral dimensions, but may also point the way to a better