NMDA neurotransmission as a critical mediator of borderline personality disorder

NMDA neurotransmission as a critical mediator of borderline personality disorder


J Psychiatry Neurosci 2007;32(2):103-15

Bernadette Grosjean, MD; Guochuan E. Tsai, MD

Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, California, and Los Angeles Biomedical Research Institute.


Studies of the neurobehavioural components of borderline personality disorder (BPD) have shown that symptoms and behaviours of BPD are partly associated with disruptions in basic neurocognitive processes, in particular, in the executive neurocognition and memory systems. A growing body of data indicates that the glutamatergic system, in particular, the N-methyl-D-aspartate (NMDA) subtype receptor, plays a major role in neuronal plasticity, cognition and memory and may underlie the pathophysiology of multiple psychiatric disorders. In this paper, we review the literature regarding BPD and its cognitive deficits and the current data on glutamatergic and NMDA neurotransmission. We propose that multiple cognitive dysfunctions and symptoms presented by BPD patients, like dissociation, psychosis and impaired nociception, may result from the dysregulation of the NMDA neurotransmission. This impairment may be the result of a combination of biological vulnerability and environmental influences mediated by the NMDA neurotransmission.


Des études portant sur les éléments neurocomportementaux du trouble de la personnalité limite (TPL) ont montré qu’il y a un lien partiel entre les symptômes et les comportements du TPL et des perturbations des processus neurocognitifs fondamentaux, et en particulier des systèmes de la neurocognition exécutive et de la mémoire. De plus en plus de données indiquent que le système glutamatergique, et en particulier le récepteur du sous-type N-méthyl-D-aspartate (NMDA), joue un rôle majeur dans la plasticité des neurones, la cognition et la mémoire et peut sous-tendre la pathophysiologie de multiples troubles psychiatriques. Dans cette communication, nous passons en revue les publications sur le TPL et ses déficits cognitifs, ainsi que les données de l’heure sur la neurotransmission glutamatergique et par NMDA. Nous posons en hypothèse que de multiples symptômes et dysfonctionnements de la cognition que présentent des patients atteints de TPL, comme la dissociation, la psychose et le déficit de la nociception, peuvent découler de la dysrégulation de la neurotransmission par NMDA. Ce déficit peut résulter d’une vulnérabilité biologique conjuguée à des influences environnementales médiées par la neurotransmission par NMDA.

Medical subject headings: borderline personality disorder; cognitive dysfunction; NMDA neurotransmission.

Competing interests: None declared.

Acknowledgements: The authors thank Drs. Anthony Bateman, Kyle Boone, Ira Lesser and Michael Makhinson for their critical review of the manuscript. Dr. Tsai is supported in part by Los Angeles Biomedical Institute, Torrance, California and an Independent Investigator Award from NARSAD. In memory of Jambur Ananth M.D. for his unconditional support.

Contributors: Drs. Grosjean and Tsai designed the study. Dr. Grosjean acquired and analyzed the data. Drs. Grosjean and Tsai wrote the article and critically reviewed it. Both authors gave approval for the final version of the article to be published.

Submitted June 27, 2006; Revised Sept. 12, 2006; Accepted Sept. 13, 2006

Correspondence to: Dr. Bernadette Grosjean, Department of Psychiatry, Harbor-UCLA Medical Center, 1000 West Carson Street, Box 497, Torrance 90509, CA, USA; bernaharbor@yahoo.com