Structural Brain Abnormalities In Those With BPD

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

We found a significant reduction of hippocampal and amydgala volumes in borderline personality disorder.  There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate gyrus.

Biol Psychiatry 2003 Jul 15;54(2):163-71



A study of 21 women with BPD showed that those with BPD had a 16% reduction in size of a crucial limbic system component - the hippocampus.  This may partly explain the memory problems those with BPD usually experience since the hippocampus is a critical location for memory.  The reduction in hippocampus size was directly correlated with the severity of childhood trauma.

The amygdala may have a reduced size as well, but this has not been scientifically proven at this time.  The amygdala is another limbic system structure strongly correlated with an emotional response to the environment, particularly anger and rage.

Archives of General Psychiatry, December 2000.



Int J Psychophysiol 2004 Jun;53(1):57-70
"Effects of BPD features and a family history of alcohol or drug dependence on P300 in adolescents."
The "P300 amplitude" (a measurement found on a brain wave test - EEG) is associated with BPD symptoms during adolescence.

Psychiatry Res 2004 Jul 30;131(2):125-33
"Anatomical MRI study of BPD patients"
This study also found diminished hippocampal volumes. Putamen enlargement seems to be due to substance use disorders.

Prog Neuropsychopharmacol Biol Psychiatry 2004 Mar;28(2):329-41
"Neurocognitive function in BPD."
Neuropsychological testing implied a dysfunction in the right hemisphere frontotemporal region in BPD individuals.

Psychiatry Res 2004 Jan 1;121(3):239-52
"Neurobiological correlates of diagnosis and underlying traits in patients with BPD compared with normal controls."
Psychological and neurotransmitter testing suggest that serotonin system abnormalities are associated with impulsive traits.

Biol Psychiatry 2004 Apr 1;55(7):759-65 (from Germany)
"A positron emission tomography study of memories of childhood abuse in BPD"
"Dysfunction of dorsolateral and medial prefrontal cortex, including anterior cingulate, seems to be correlated with the recall of traumatic memories in women with BPD. These brain areas might mediate trauma-related symptoms, such as dissociation or affective instability, in patients with BPD."

Curr Psychiatry Rep. 2005; 7(1):65-72
"Neuroimaging and personality disorders"
"Functional and structural studies provide support for dysfunction in fronto-limbic circuits in BPD and APD, whereas temporal lobe and basal striatal-thalamic compromise is evident in schizotypal personality disorder.

Neuroreport 2005; 16(3):289-93
"Distinct pattern of P3a event-related potential in BPD"
"...distinctive disturbances in P3a in (unmedicated) BPD patients were found: abnormally enhanced amplitude, failure to habituate and a loss of temporal locking with P3b."

Dev Psychopathol. 2005; 17(4):1197-206
"Defining the neurocircuitry of BPD: functional neuroimaging approaches"
"Functional neuroimaging...is beginning to identify abnormal frontolimbic circuitry..."

Clin Neurophysiol. 2005; 116(6):1424=32
"BPD features in adolescent girls: P300 evidence of altered brain maturation."
"The present findings suggest abnormal brain maturation among adolescent girls exhibiting features of BPD."

J Psychiatr Res. 2005; 39(5);489-98
"Increased delta power and discrepancies in objective and subjective sleep measurements in BPD"
"BPD patients showed a tendency for shortened REM latency and significantly decreased NonREM sleep (stage 2)...There was a marked discrepancy between objective and subjective sleep measurements, which indicates an altered perception of sleep in BPD."

Am J Psychiatry 2005; 162(12):2360-73
"BPD, impulsivity, and the orbitofrontal cortex"
"The patients with orbitofrontal cortex lesions and the patients with BPD performed similarly on several measures.  Both groups were more impulsive and reported more inappropriate behaviors."
(Note: the orbitofrontal cortex is considered part of the limbic system)



J Neuropsychiatry Clin Neurosci 2007 Fall;19(4):383-90
"Frontal white matter integrity in BPD with self-injurious behavior"
"Women with BPD self-injurious behavior exhibit decreased white matter microstructural integrity in inferior frontal brain regions that may include components of orbito-frontal circuitry."
(Another study showing BPD neurological abnormalities.  The orbito-frontal cortex is part of the limbic system.)

Psychiatry Res 2007 Nov 15;156(2):139-49 (from Germany)
"Size abnormalities of the superior parietal cortices are related to dissociation in BPD"
"Recent evidence suggests that BPD is related to reduced size of the parietal lobe.  Dissociative symptoms occur in the majority of individuals with BPD. ...Compared with control subjects, BPD subjects had significantly smaller right-sided precuneus (-9%) volumes.  The left postcentral gyrus of BPD subjects with the comorbid diagnosis of dissociative amnesia or dissociative identity disorder (DID) was significantly increased compared with controls (+13%) and compared with BPD subjects without these disorders (+11%).  In BPD subjects, stronger depersonalization was significantly related to larger right precuneus size.  Possibly, larger precuneus size in BPD is related to symptoms of depersonalization.  Increased postcentral gyrus size in BPD may be related to the development of dissociative amnesia or dissociative identity disorder (DID) in the presence of severe childhood abuse."
(Note: most borderlines do not have dissociative symptoms or dissociative amnesia, and DID is extremely rare, although everyone I’ve treated for DID also had the BPD.  None-the-less this is an important study furthering the biological basis of the BPD.  The "precuneus" is a portion of the brain’s parietal lobe, believed by many to be part of the limbic system.)

J Psychiatr Res 2007 Sep 7 (e-published, published in July 2008)
"Frontolimbic structural changes in BPD"
"Frontolimbic dysfunction is observed in BPD, with responses to emotional stimuli that are exaggerated in the amygdala and impaired in the anterior cingulate cortex (ACC)." CONCLUSIONS: "This sample of BPD patients exhibits gross structural changes in gray matter in cortical and subcortical limbic regions that parallel the regional distribution of altered functional activation to emotional stimuli among these same subjects."

Actas Esp Psiquiatr 2007 Aug 13 (from Spain)
"Association between the serotonin transporter gene and personality traits in BPD patients evaluated with Zuckerman-Kuhlman Personality Questionnaire (ZKPQ)"
"The results suggest a significant association between the 5-HTT (serotonin transporter) gene and some personality traits in BPD."

J Psychiatry Neurosci 2007 Jul;32(4):234-40 (from Germany)
"[I-123] ADAM and SPECT in patients with BPD and healthy control subjects"
"The study provides evidence of a serotonergic dysfunction in patients with BPD and suggests a serotonergic component in the pathophysiology of the disorder SERT (serotonin transporter) binding reflected the level of impulsiveness as a common feature in BPD."
(Note: low spinal fluid serotonin metabolite levels are strongly associated with suicidal and impulsive homicidal behavior with or without the BPD, and borderlines without strong suicidal ideation have normal levels)

Psychiatry Res 2007 Aug 15;155(3);231-43
"Fronto-limbic dysfunction in response to facial emotion in BPD: an event-related fMRI study"
"We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of anterior cingulate cortex activity.

Actas Esp Psiquiatr 2007 Nov-Dec;35(6):387-92 (from Spain)
"Serotonin transporter polymorphism and fluoxetine effect on impulsiveness and aggression in BPD"
"L-allele carriers responded better to fluoxetine than S carriers, in a way as in depression."
(Note: this study compared the "short allele {S}" to the {L} allele for the serotonin transporter gene.  In my experience Prozac (fluoxetine) is extraordinarily important for BPD treatment, although sometimes high doses are needed.  Some individuals with BPD need Tegretol (carbamazepine) in combination with Prozac (fluoxetine), and a genetic study of this combination with the S allele should be interesting.  A similar study with high doses of Effexor (venlafaxine) warrants investigation).

Biol Psychiatry 2007 Sep 15;62(6):580-7
"5HT2A receptor binding is increased in BPD"
"Postmortem studies in suicide victims demonstrate an increase in the number of post synaptic 5-HT(2A) receptor binding sites in ventral lateral and orbital frontal cortex.  Diminished metabolic responses to serotonergic activation are noted in these areas in impulsive subjects with BPD, a group at high risk for suicidal behavior." Conclusions: "5HT(2A) receptor binding is increased in the hippocampus of BPD subjects independent of depressed mood, impulsivity, aggression, suicidality or childhood abuse."

Psychiatr Genet 2007 Jun 17(3):153-7 (from Canada)
"Monoamine oxidase a gene is associated with BPD"
"We found that the BPD patients had a high frequency of the high activity VNTR alleles and a low frequency of the low activity haplotype."

Br J Psychiatry 2007 Apr; 190:357-8 (from Spain)
"Hypothalamic-pituitary-adrenal axis response in BPD without post-traumatic features."
"Baseline cortisol levels in the patients were ... lower than in the controls.  The 0.25mg dexamethasone suppression test reveals increased feedback inhibition of the HPA in BPD."

Neurosci Lett 2007 Apr 24;417(1):36-41 (from Germany)
"Evidence of disturbed amygdalar energy metabolism in patients with BPD"
"Confirming earlier reports we found a significant 11-17% reduction of amygdalar volumes in patients with BPD.  In addition there was a significant 17% increase in left amygdalar creatine concentrations in BPD patients."

Psychiatry Res 2007 Feb 28;154(157-70) (from Germany)
"Hippocampal volume reduction and history of aggressive behavior in patients with BPD"
"Hippocampal grey matter volume was significantly decreased in BPD patient: the reduction was more pronounced in patients with multiple hospitalizations."

Neuroimage 2007 Apr 1;35(2):738-47 (from Germany)
"Inferior frontal white matter microstructure and patterns of psychopathology in women with BPD and comorbid ADHD"
"Inferior frontal white matter microstructural abnormalities may be linked to key aspects of psychopathology in women with BPD and comorbid ADHD and add to alternations in orbitofrontal and limbic areas.  The relationship between neuropsychological functioning and white matter structure remains unclear. "

Biol Psychiatry 2007 Aug 1:62(3):250-5
"Exaggerated affect-modulated startle during unpleasant stimuli in BPD"
"The BPD patients exhibited larger startle eyeblink during unpleasant but not neutral words, indicating exaggerated physiological affect.  This finding remained significant when we controlled for comorbid diagnoses, including generalized anxiety disorder and PTSD (post traumatic stress disorder).  Greater symptom severity was associated with greater affective-startle difference scores.  CONCLUSIONS: Consistent with the symptom of affective dysregulation, these results suggest an abnormality in the processing of unpleasant emotional stimuli by BPD patients."

Psychol Med 2007 Jul;37:971-81 (from Germany)
"Enhanced emotion-induced amnesia in BPD"
"BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects.

Neuropsychopharmacology 2007 Jul, 32 (7):1629-40
"Amygdala-prefrontal disconnection in BPD"
"We demonstrated a tight coupling of metabolic activity between right orbitofrontal cortex and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in impulsive aggressive BPD.  We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls."

Psychiatry Res 2007 Jan 15;149(1-3):139-45
"Early visual information processing deficit in depression with and without BPD"
"Poor early information processing appears to be a feature of BPD, and may play a role in the impulsive behavior that is characteristic of the disorder"

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