Research Overview

The Mood and Personality Disorders Research Program currently focuses on personality and on the underlying psychological and neurobiological factors that contribute to personality traits and to disorders such as borderline personality disorder (BPD) and schizotypal personality disorder (SPD).

Our investigations utilize a number of research strategies, including neuropsychological testing, functional neuroimaging studies, genetic studies, and treatment trials using psychotherapy and psychopharmacology.

Through this research we arrive at answers that not only add to the current body of psychiatric knowledge and deepen our understanding of personality, but lead to better treatment for patients whose lives and relationships are impaired by personality disorders.

What is Personality

There are many different ways to understand the term "personality." In the field of personality disorders, we use "personality" to describe the set of characteristics that guide how an individual behaves, perceives him/herself, and interacts with others. When these characteristics interfere with an individual's ability to function in a work setting or in personal relationships, this may be a sign of a personality disorder. We believe that personality disorders result from underlying biological predispositions which interact with past and present life events to cause clinical symptoms. Our research group focuses on bettering our understanding of predisposition and causation in an effort to improve treatment.


Borderline Personality Disorder

Borderline Personality Disorder (BPD) is a diagnosis that has many different meanings depending on the tradition or discipline from which it is viewed. In this sense, the disorder is somewhat like the elephant in the parable of the blind man and the elephant. Psychoanalytically oriented practitioners focus on its intrapsychic structures and defense mechanisms such as "splitting," while interpersonally oriented clinicians understand the borderline in terms of disturbances in their interpersonal relatedness. Psychopharmacologists tend to understand borderline patients in terms of atypical affective disorders, or impulse related disorders and treat according to these target symptom areas.

The two hallmark psychobiologic vulnerabilities or temperamental predispositions are affective instability and impulse aggression. The individual with BPD is exquisitely affectively sensitive to environmental shifts, particularly in their interpersonal sphere, so that they react with feelings of, for example, rage and despair and separation, humiliation and fury at a setback at work, etc. It is likely that this highly sensitive affective thermostat is present from a very early age and may apparently have genetic as well as early environmental antecedents. This affective sensitivity during the course of early development may prove a challenge to the successful mastery of the developmental tasks of childhood and adolescence. For example, an infant who is very sensitive to separation or bodily pain may cry more frequently and be more difficult to soothe when mother or other caretaker leaves, the baby may cry loudly and persistently. For a depressed or affectively sensitive parent, such a child can present a particularly formidable challenge. As the child grows older, these crying spells may turn into temper tantrums. For even the most empathic parent, there may be a temptation to respond to these tantrums with either excessive indulgence or at other times inattention of neglect. For the child, these inconsistent responses may constitute a sort of "intermittent reinforcement" making their temper tantrums more likely. The temper tantrums may be the antecedents to affective storms that we may see in the borderline patient during adulthood when threatened with a potential loss of a relationship or feelings of abandonment.

There are some suggestions that there may be biologic underpinnings to this affective sensitivity or instability. Patients with BPD tend to show greater responses to pharmacologic agents that may induce affective changes. For example, work in our laboratory has suggested that borderline patients with affective instability respond to administration of physostigmine, a cholinesterase inhibitor that prevents the breakdown of acetylcholine, with marked feelings of negative mood or dysphoria. This response was not observed in patients with other personality disorders or a normal volunteer comparison group. This dysphoric response parallels that seen in depressed patients, both when acutely ill or intermittent, suggesting that the cholinergic system may play a role in mediating the dysphoric affects of borderline personality disorder patients. Interestingly, the degree of dysphoric responses are correlated with affective instability and related traits at baseline, but not with other criteria for borderline personality disorders that reflect impulsivity and aggression.

Impulsive aggression is also a core feature of BPD. The borderline patients engage in self damaging acts, including self mutilating behavior and suicide attempts, particularly when frustrated or disappointed. These may be considered as instances of self directed aggression. They also are prone to angry outbursts that interfere with the stability of their relationships. They are impulsive, reflected in behavior such as binge eating, gambling, substance abuse, promiscuity, or reckless driving.

The borderline personality disordered individual appears to have a lower threshold to environmental stimuli, particularly frustrating stimuli, resulting in disinhibited impulsive aggressive behaviors. In addition, their propensity towards self directed aggression is also greater. Their personality may in part be organized around these aggressive outbursts or traits and intimacy becomes difficult because of their chronic irritability and anger. Their motor disinhibition is associated with a difficulty in mastering aggression and effectively separating or individuating from others they depend on during the course of their development.

There is good evidence that the tendency to impulsive aggression has psychobiologic substrates. The serotonin system is a behavioral suppressive system that is involved in modulation of appetite, mood, temperature regulation, and a variety of vegetative functions. Serotonergic neuronal activities increase during repetitive self directed behaviors and may decrease when an organism attends to novel events in their environment. Lesions of serotonergic neurons, result in disinhibited aggression, for example, in rats - the killing of mice placed in their vicinity. Furthermore, rats with lesions of the serotonergic system cannot learn to extinguish or dampen bar pressing behavior in paradigms where the bar pressing was previously rewarded and is currently punished. In other words, these animals appear to have a deficit in the suppression of punished behaviors.

In humans, reductions in serotonergic activity are associated with impulsive aggressive behavior. Neuroendocrine responses to the serotonin releasing agent fenfluramine are blunted, suggesting reduced serotonergic activity in patients with BPD. They are specifically associated with those criteria of BPD that reflect impulsive aggressive traits that reflect impulsive aggressive traits such as angry outbursts, impulsivity, and self-damaging acts. They are not associated with interpersonal or affective related traits, however. Indeed, the prolactin response to fenfluramine is highly inversely associated with self ratings of irritability and assaultiveness, with the greatest reductions in serotonergic activity being associated with the highest reported irritability and aggression. Thus, the association between reduced serotonergic activity and aggression does not seem specific to BPD, but rather to impulsivity and aggression which may be found in other personality disorders such as antisocial personality disorder as well. In fact, studies of antisocial personality disorder patients also reported blunted prolactin responses to fenfluramine.

Genetic studies of monozygotic and dizygotic twins suggest that there may be genetic factors for these dimensions of emotional reactivity and impulsive aggression, while there does not appear to be a heritability for BPD as a category. Family members of BPD patients are more likely to demonstrate affective instability or impulsivity, although not necessarily both. Impulsivity and aggression seem to be heritable in studies of normal twins as well. It is noteworthy that in the studies of prolactin responses to fenfluramine, blunted prolactin response to fenfluramine in a patient is a better predictor of impulsivity and aggression in their relatives than was impulsive aggression as a behavior in itself in the patient. These results would suggest that what is inherited is not the behavior, but an alteration in the serotonergic system that may at times be expressed in a propensity to impulsive aggression.

It is also clear that the environment plays an important role in the development of borderline personality disorder and may even influence the biology of impulse and affect regulation. One prominent environmental antecedent to BPD is a history of abuse or neglect. Many studies suggest a high proportion of borderline patients have experienced some form of abuse, particularly sexual abuse, during their development. While it is not clear that BPD over other personality disorders always have a demonstrated increased history of abuse, there is no doubt that the history of abuse is common in personality disorder patients, particularly in BPD patients.

New studies suggest that abuse may sensitize or alter the activity of the stress system such as the hypothalamopituitary-adrenal (HPA) axis and may have long term effects on the monoamine systems as well. Some studies even suggest that certain kinds of trauma or early abuse may actually cause structural changes in a central part of the brain involved in emotional memories, the hippocampus. Thus, we are just beginning to understand the biologic sequelae of early events of abuse.

While we are only beginning to understand the biologic aspects of BPD, it is clear that the development of BPD depends on an interaction of constitutional biologic vulnerabilities with often adverse environmental circumstances during development. However, we are only beginning to understand the mechanism by which these events happen. Hopefully, a more thorough understanding of the psychobiology of this disorder may promote improved treatment, both psychopharmacologically, and psychotherapeutically in an interpersonal content.

Courtesy of Larry J. Siever, M.D.
The Journal of the California for the Mentally Ill


Schizotypal Personality Disorder

Although schizotypal personality disorder shares an extensive array of similarities with schizophrenia in terms of genetics, phenomenology, neurochemistry, structural anatomy, and functional anatomy, patients with schizotypal personality disorder are spared overt psychotic symptoms and have less severe cognitive disturbances than patients with schizophrenia. Several possibilities may be hypothesized regarding the relationship between schizotypal personality disorder and schizophrenia. One is that schizophrenia and schizotypal personality disorders are truly distinct and only have superficial similarities. This hypothesis is unlikely given the common genetic factors shared between the two disorders, but could still apply to many schizotypal personality disorder subjects drawn from clinical or volunteer populations. While difficult to disprove definitively, this hypothesis would imply that an in-depth examination of genetic susceptibility factors, structural and functional neuroanatomy, and cognitive impairment would yield distinct differences and few similarities in the patterns of abnormalities of subjects with the schizotypal and schizophrenia disorders. A second hypothesis is that the two disorders are identical and differ only in severity, predicting that specific abnormalities in these domains would be identical in character and differ only in the extent of the abnormality. Finally, a third hypothesis posits that the disorders are partially overlapping in etiology and genetics with both similarities, i.e., common risk or susceptibility factors that they share as part of the schizophrenia spectrum and differences, that account for the sparing of schizotypal patients from frank psychosis and cognitive deterioration.

If this third hypothesis proves true, a better understanding of these differences would enable us to approach schizotypal personality disorder as an experiment of nature, and an opportunity to better understand the basis of psychosis and the cognitive impairments of schizophrenia can be afforded. It may also help us to disentangle the contributions of genetic and environmental factors in the development of schizophrenia. Recent findings of neurobiological differences between schizotypal personality disorder and schizophrenia are beginning to suggest specific factors that may be protective against overt psychotic symptoms in the schizophrenia spectrum and that explain the more circumscribed cognitive impairments in schizotypal personality disorder... These differences provide important clues to risk for "core" cognitive and social deficits and protective factors against psychosis and severe functional deterioration in the schizophrenia spectrum.

From: Larry J. Siever, Harold W. Koenigsberg, Philip Harvey, Vivian Mitropoulou, Marc Laruelle, Anissa Abi-Dargham, Marianne Goodman and Monte Buchsbaum, Cognitive and brain function in schizotypal personality disorder, Schizophrenia Research, Volume 54, Issues 1-2, 1 March 2002, Pages 157-167.



We have found that, in many instances, our program can help clarify the underlying roots of the problems experienced by patients with personality disorders. The program offers a comprehensive individualized feedback session with a research psychiatrist or psychologist, which can be helpful to future treatment planning, given at the end of the evaluation.

Participation in this program is free, since it is funded by the National Institute of Mental Health and the Veterans Administration. If you are interested, for more information please call (212) 241-9775. You may participate in the studies at either of our facilities: The Mount Sinai Health System or the James J. Peters VA Medical Center. Reimbursement is available for travel time and/or expenses.

Sample case histories of the types of patients seen in our program and results of their evaluations along with the scientific rationale for our research are outlined in New View of Self: How Genes and Neurotansmitters Shape Your Mind, Your Personality, and Your Mental Health, a book written by Larry J. Siever, M.D. who is the Director of the program and a Professor of Psychiatry at Icahn School of Medicine. The book outlines the scientific revolution that has occurred in the past twenty years in our understanding of the factors responsible for the formation of personality.

Initial assessments offered to all participants, depending on eligibility, may include the following:

· A complete medical examination along with laboratory tests to rule out any underlying medical condition

·An interview with a clinical psychologist on lifetime symptoms and treatment.

· A testing session to assess memory, attention, and perception processing. Vulnerabilities in these areas may be associated with certain personality traits or disorders.

·Self-report questionnaires that assess personality traits such as hostility, depression, impulsivity, anxiety and hostility.

Optional Assessments (recommended when appropriate) include:

·Brain Imaging (through MRI, fMRI and/or PET scans) under baseline and pharmacologic conditions.

·Evaluation of the function of brain chemical systems that are involved in the mental disorders (serotonin, dopamine, norepinephrine).

·Tests for stress sensitivity and trauma exposure.

·Treatment trials, when appropriate, including psychotherapy and/or medicine trials.

Depending on an individual’s interests, availability and eligibility, a subject in our research program may participate in one or just a few of our program’s components, or else in many different components. Each component may take anywhere from a half-hour to several hours of the participant’s time. (You will be notified in advance how long you will be expected to be at our research facility for any component in which you agree to participate.)

Understanding BPD [PDF]

Treatment [PDF]

Imaging and Genetics [PDF]

The Pathophysiology of Schizophrenia Disorders: Perspectives from the Spectrum [PDF]



Contact Us

Lauren Zaluda 
Tel: 212-241-0442
Fax: 212-241-7930
Send e-mail

Mood and Personality Disorders Research Program
Department of Psychiatry
Box 1230
One Gustave L. Levy Place
New York, NY 10029