Research

The Mood and Personality Disorders Research Program (MPDP) explores the disturbances in personality which significantly interfere with the ability to handle stress, deal with people, think clearly, and function well in the social world or in the workplace. MPDP focuses on the common personality disorders such as Borderline Personality Disorder (BPD), Avoidant Personality Disorder (AvPD), and Schizotypal Personality Disorder (SPD), but also studies personality traits impaired across a range of different diagnoses or even disabling in people without a clear psychiatric diagnosis. We seek to better understand these conditions in order to develop more effective ways to diagnose, prevent, and treat them.

Among the important personality functions that we are currently studying are the abilities to regulate and control emotion effectively, to accurately read social cues and respond to people in social interactions, to hold and manipulate ideas in working memory, to control aggression, and to develop trust. We use a multimodal approach, combining neuroimaging (fMRI, PET scans), electrophysiological measures (blink-startle, skin conductance, heart rate, eye gaze), molecular and genetic analyses, computer games, questionnaires, and responses to psychological and medication treatments. 

Learn more about participating in our research studies.

National Institute of Mental Health (R01 MH109730): “Regulating Emotional Responses to Spoken Comments and Visual Images Across the Affective Instability Spectrum: An fMRI Study”
Principal Investigator: Harold W. Koenigsberg, MD
Emotionally distressing, aversive, or painful experiences are a part of everyday life experience. Crucial to emotional resilience is the capacity to voluntarily regulate one’s emotional reaction to such experiences. This permits maintaining emotional equilibrium and adaptively responding to emotional situations. However, some individuals are emotionally highly unstable, reacting rapidly and with exteme emotion, and suffer abrupt mood swings, difficulties in personal relationships and in the workplace, and even life-threatening symptoms. This study uses neuroimaging methods to determine whether emotional instablity is associated with an impairment in the ability to use effective emotion regulation mechanisms, and whether such impairments are related to disturbances in the activity of the brain systems which typically regulate emotion. Such knowledge could help to develop new treatments specifically targeted to reduce emotional instablity.

National Institute of Mental Health (R01 MH077813):  “An fMRI Study of the Enhancement of Emotion Regulation in Borderline Patients”
Principal Investigator: Harold W. Koenigsberg, MD
This project  builds upon our previous neuroimaging work, which has shown that when BPD patients try to control their emotions by employing a method that healthy people frequently use quite effectively–taking an emotional distance from what is upsetting–BPD patients are not able to quiet down the part of their brain that sends out emotional alarm signals. The objective of the present study is to determine whether giving BPD patients special training in using this healthy distancing stragegy can help them to improve their ability to regulate their emotions and return their brain activity to a more normal pattern. We will do this by using fMRI to record brain activity as BPD subjects try to use distancing to reduce their emotional reactions to upsetting pictures before any training, then to have them receive specific training in the distancing strategy. After this training, we will again obtain an fMRI scan to determine whether their pattern of brain activation has normalized and whether they have been able to better reduce their negative reactions to the pictures.

National Institute of Mental Health (R01 MH63875): “5HTT and 5-HT2a Receptors in Impulsive Aggression and Effects of Fluoxetine”
Principal Investigators: Larry Siever, MD & Harold Koenigsberg, MD
This project examines the role of two important components of serotonergic neurotransmission: the serotonin transporter protein, and the 2a serotonin receptor in impulsive aggression using positron emission tomographic (PET) imaging. It investigates the effect of treatment with the serotonergic antidepressant, fluoxetine, upon impulsive aggression and these particular components of the serotonin system. 

VA MERIT I01CX000609: “White matter abnormalities in the schizophrenia spectrum”
Principal Investigator: Erin A. Hazlett, PhD                                 
This study examines diffusion tensor imaging measures of white matter integrity and white matter genes in Veterans with schizotypal personality disorder and age- and sex-matched healthy controls.

VA Merit Award 1I01CX001206: “Neurobiology of affective instability in veterans at low and high risk for suicide”
Principal Investigator: Erin A. Hazlett, PhD
This study examines affective startle modulation and frontal-amygdala circuitry as biomarkers of high risk suicidal behavior in Veterans.

VA Rehabilitation Research and Development Service (RR&D), V1 I21 RX001911-01A1 (PI: Goodman)
Principle Investigator: Marianne Goodman
“Suicide Safety Planning Group Treatment - “Project Life Force”
This project pilots a new treatment intervention for suicidal Veterans incorporating emotion regulation skills training with suicide safety planning.

VA Rehabilitation Research & Development, VA Office of Research & Development, # 1 I01 RX002432-01,
“SAFER: A Brief Intervention Involving Family Members in Suicide Safety Planning”
Principal Investigators: D.A. Perlick & M.G. Goodman

KL2 TR001435_01 Faculty Scholar Award NIH/NCATS
UL1TR000067NIH Clinical and Translational Science Award (CTSA) to Mount Sinai: “Examining Endophenotypes of Genetic Risk and Resiliency in Bipolar Disorder through Multimodal Measures of Emotional Processing”
Principal Investigator: Mercedes Perez-Rodriguez, MD, PhD
Our aim is to apply the endophenotype strategy to assess the genetic status of emotion processing deficits in Bipolar Disorder by collecting multimodal emotion processing measures (imaging, startle, neurocognition) in Bipolar Disorder patients and unaffected siblings.

Brain and Behavior Research Foundation Young Investigator Award:
“Neuroimaging Endophenotypes In Patients With Bipolar Disorder And Unaffected Siblings”
Principal Investigator: Mercedes Perez-Rodriguez, MD, PhD
The major aims of this project are to: 1) examine fMRI abnormalities in BD and to determine whether these are present in unaffected siblings; 2) examine structural brain abnormalities using DTI in BD and to determine whether these are present in unaffected siblings; 3) examine the relationship between the brain abnormalities found using DTI and fMRI in BD and unaffected siblings and particular neurocognitive deficits.

NARSAD Young Investigator Award, Brain & Behavior Research Foundation
Principle Investigator: Margaret M. McClure, PhD
This project is designed to evaluate the impact of a cognitive remediation therapy and guanfacine, a noradrenergic agonist, on neuropsychological performance

Hazlett EA(2016). Invited commentary: Neural substrates of emotion processing abnormalities in borderline personality disorder. Biol Psychiatry 79:74-75. PMID: 26674587.

Goodman M, Banthin D, Blair NJ, Mascitelli KA, Wilsnack J, Chen J, Messenger JW, Perez-Rodriguez MM, Triebwasser J, Koenigsberg HW, Goetz RR, Hazlett EA, & New AS (2016). A randomized trial of dialectical behavior therapy in high-risk suicidal veterans. J Clinical Psychiatry. PMID: 27780335.

Denny BT, Fan J, Liu X, Guerreri S, Mayson SJ, Rimsky L, McMaster A, Alexander H, New AS, Goodman M, Perez-Rodriguez M, Siever LJ, Koenigsberg HW: Brain Structural Anomalies in Borderline and Avoidant Personality Disorder Patients and Their Associations With Disorder-Specific Symptoms. J Affective Dis, 200:266-274, 2016 

Hazlett EA,Blair NJ, Fernandez N, Mascitelli K, Perez-Rodriguez MM, New AS, Goetz RR, & Goodman M (2016). Startle amplitude during unpleasant pictures is greater in veterans with multiple-suicide attempts and predicts a future suicide attempt. Psychophysiology 53:1524-1534. PMID: 27378071.

Denny BT, Fan J, Xun L, Ochsner KN, Guerreri S, Mayson SJ, Rimsky L, McMaster A, New AS, Goodman M, Siever LJ, Koenigsberg HW: Elevated Amygdala Activity During Reappraisal Anticipation Predicts Anxiety in Avoidant Personality Disorder. J Affective Dis 2014 Sep 28;172C:1-7. doi: 10.1016/j.jad.2014.09.017. [Epub ahead of print]

Koenigsberg HW, Denny BT, Fan J, Liu X, Guerreri S, Mayson SJ, Rimsky L, New AS, Goodman M, Siever LJ: The neural correlates of anomalous habituation to negative emotional pictures in borderline and avoidant personality disorder patients. American Journal of Psychiatry, 171(1), 82-90, 2014.

Sher, L., Fisher, A. M., Kelliher, C. H., Penner, J. D., Goodman, M., Koenigsberg, H. W., ... & Hazlett, E. A. (2016). Clinical features and psychiatric comorbidities of borderline personality disorder patients with versus without a history of suicide attempt. Psychiatry Research, 246, 261-266.

Goldstein KE, Berlin HA, Hamilton HK, Mitsis EM, McClure MM, Savage KR, Blair NJ, Feder MR, Siever LJ, New AS, & Hazlett EA (2016). Neurocognition and temperament in borderline and schizotypal personality disorders. Psychology, 7:292-299.

Pier K, Marin L, Costello T, Wilsnack J., Goodman M. The Neurobiology of Personality Disorders, Scientific American, in press.

McClure, M. M. & Parmenter, M.  (in press)  Childhood trauma, trait anxiety, and anxious attachment as predictors of intimate partner violence in college students. Journal of Interpersonal Violence.

Graff, F. S., McClure, M. M., & Siever, L. J.  (2014).  Remediation and cognitive enhancers in schizotypal personality disorder. Current Treatment Options in Psychiatry, 1, 369-375.

Rosell DR, Siever LJ. The neurobiology of aggression and violence. CNS Spectr. 2015 Jun;20(3):254-79. doi: 10.1017/S109285291500019X. Review. PubMed PMID: 25936249.  

van de Giessen E, Rosell DR, Thompson JL, Xu X, Girgis RR, Ehrlich Y, Slifstein M, Abi-Dargham A, Siever LJ. Serotonin transporter availability in impulsive aggressive personality disordered patients: a PET study with [11C]DASB. J Psychiatr Res. 2014 Nov;58:147-54. doi: 10.1016/j.jpsychires.2014.07.025. PubMed PMID: 25145808.  

Rosell DR, Zaluda LC, McClure MM, Perez-Rodriguez MM, Strike KS, Barch DM, Harvey PD, Girgis RR, Hazlett EA, Mailman RB, Abi-Dargham A, Lieberman JA, Siever LJ. Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder. Neuropsychopharmacology. 2015 Jan;40(2):446-53. doi: 10.1038/npp.2014.192. PubMed PMID: 25074637; PubMed Central PMCID: PMC4443959.  

Rosell DR, Futterman SE, McMaster A, Siever LJ. Schizotypal personality disorder: a current review. Curr Psychiatry Rep. 2014 Jul;16(7):452. doi: 10.1007/s11920-014-0452-1. Review. PubMed PMID: 24828284; PubMed Central PMCID: PMC4182925.  

Thompson JL, Rosell DR, Slifstein M, Girgis RR, Xu X, Ehrlich Y, Kegeles LS, Hazlett EA, Abi-Dargham A, Siever LJ. Prefrontal dopamine D1 receptors and working memory in schizotypal personality disorder: a PET study with [¹¹C]NNC112. Psychopharmacology (Berl). 2014 Oct;231(21):4231-40. doi: 10.1007/s00213-014-3566-6. PubMed PMID: 24781514; PubMed Central PMCID: PMC4194223.

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