The document discusses the biology of borderline personality disorder (BPD). It covers the history of BPD and notes that early life stress and trauma are risk factors. Genetics and changes in brain structure/functioning also contribute to BPD risk. People with BPD may have reduced activity in prefrontal regions involved in emotional regulation and increased reactivity in limbic regions like the amygdala. Oxytocin levels are also involved, and treatment focuses on regulating these biological systems through medications and therapies. In conclusion, BPD arises from an interaction of environmental, anatomical, functional, genetic, and epigenetic factors.

2. Biology of Borderline Personality
Disorder
Prof. Hani Hamed Dessoki, M.D.PsychiatryProf. Hani Hamed Dessoki, M.D.Psychiatry
Prof. PsychiatryProf. Psychiatry
Acting Dean, Faculty of NursingActing Dean, Faculty of Nursing
Beni Suef UniversityBeni Suef University
Supervisor of Psychiatry DepartmentSupervisor of Psychiatry Department
El-Fayoum UniversityEl-Fayoum University
Treasure of Egyptian Psychiatric AssociationTreasure of Egyptian Psychiatric Association

4. Agenda
 History
 Overview
 Risk Factors
 Biological consideration
 Oxytocine
 Conclusion
 Message

5. History
 Borderline personality disorder (BPD) is complex and
its phenomenology is hard to define, contributing to
the view that it is not a “real” disorder.
 Yet increasingly powerful research suggests that it is
both “real” and disabling, with high morbidity and
even mortality.

6. History
 The concept of borderline syndrome is the
subject of current debate because of its
ambiguity and lack of homogeneity.
 Furthermore, the concept is rejected by many
authors as a common category for atypical
and non-specific disorders that cannot be
classified elsewhere.

7. History
 There is discrepancy on whether this term
determines a level of severity, an organization
of personality or a defined syndromic entity. In
1938, Stern was the first author to use the
term borderline, and it was not introduced in
the DSM III until 1980.

8. Overview
 Borderline personality disorder is a mental
illness marked by an ongoing pattern of
varying moods, self-image, and behavior.
 These symptoms often result in impulsive
actions and problems in relationships.
 People with borderline personality disorder
may experience intense episodes of anger,
depression, and anxiety that can last from a
few hours to days.

9. What Does “Borderline Personality
Disorder” Mean?
 Historically, the term “borderline” has been
the subject of much debate. BPD used to be
considered on the “borderline” between
psychosis and neurosis.
 The name stuck, even though it doesn’t
describe the condition very well and, in fact,
may be more harmful than helpful. The term
“borderline” also has a history of misuse and
prejudice—BPD is a clinical diagnosis, not a
judgment.

10. What Does “Borderline Personality
Disorder” Mean?
Current ideas about the condition focus
on ongoing patterns of difficulty with
self-regulation (the ability to soothe
oneself in times of stress) and trouble
with emotions, thinking, behaviors,
relationships and self-image.
Some people refer to BPD as “Emotion
Disregulation.”

11. Many symptoms of Borderline Personality disorder are
similar to other disorders, such as anxiety disorder,
schizophrenia, and other personality disorders
 histrionic personality self-dramatizing, self-indulgent,
demanding, excitable, vain
 narcissistic personality intolerant of criticism, self-
important, lacking in empathy, envious, constantly
demanding special favors
 antisocial personality callous, reckless, impulsive,
irritable, deceitful, and emotionally shallow.

12. Incidence
 BPD affects 5.9% of adults (about 14 million
Americans) at some time in their life.
 BPD affects 50% more people than
Alzheimer’s disease and nearly as many as
schizophrenia and bipolar combined (2.25%).
 BPD affects 20% of patients admitted to
psychiatric hospitals.
 BPD affects 10% of people in outpatient
mental health treatment.

15. Risk Factors
The cause of borderline personality
disorder is not yet clear, but
research suggests that genetics,
brain structure and function, and
environmental, cultural, and social
factors play a role, or may increase
the risk for developing borderline
personality disorder.

16. Family History
People who have a close family
member, such as a parent or sibling
with the disorder may be at higher
risk of developing borderline
personality disorder.

17. Brain Factors
Studies show that people with borderline
personality disorder can have structural
and functional changes in the brain
especially in the areas that control
impulses and emotional regulation.
But is it not clear whether these changes
are risk factors for the disorder, or caused
by the disorder.

18. Environmental, Cultural, and
Social Factors
Many people with borderline
personality disorder report
experiencing traumatic life events,
such as abuse, abandonment, or
adversity during childhood. Others
may have been exposed to
unstable, invalidating relationships,
and hostile conflicts.

20. Environmental, Cultural, and
Social Factors
Although these factors may increase
a person’s risk, it does not mean
that the person will develop
borderline personality disorder.
Likewise, there may be people
without these risk factors who will
develop borderline personality
disorder in their lifetime.

21. The Biology of Borderline Personality
Disorder
 One observation that appears to be consistent across
the illness continuum of BPD is the presence of
childhood trauma.
 Trauma or neglect is observed in up to 87% of
patients with BPD, and of these patients, 40%-71%
have been sexually abused.
 Moreover, 30.2% of patients with BPD may also be
diagnosed with post-traumatic stress disorder
(PTSD).

22. The Biology of Borderline Personality
Disorder
 In other words, patients with a history of trauma are
more likely to develop BPD and PTSD, but in 24.2%
of patients where both disorders
coexist, diagnostic accuracy can be a challenge if
DSM criteria are solely used.
 Focusing on trauma and its history, quality, and
phenomenology can provide an idea of where to
begin in terms of diagnosis.

23. The Biology of Borderline Personality
Disorder
 It is important to understand to what extent
early life stress relates to "chronic emptiness"
and the "inability to form stable interpersonal
relationships"; an inverse relationship between
early stress and oxytocin levels, which is a
neuropeptide related to attachment and
bonding in mammals, has been observed.
 In particular, BPD has been associated with
excessive socioaffective vigilance and
enhanced reactivity to emotional and social
stimuli.

24. The Biology of Borderline Personality
Disorder
 Hypervigilance to emotionally charged social
situations has been associated with enhanced
amygdala reactivity to minimally
unpleasant and even neutral stimuli.
 Examination of hypothalamic and
extrahypothalamic stress response reveals
at least partial mediation of the association
between oxytocin levels and BPD
psychopathology.
 In other words, the stress response affects
how oxytocin levels and BPD symptoms relate.

25. The Biology of Borderline Personality
Disorder
 Research is beginning to demonstrate a
consistent relationship among secure
and insecure attachment; oxytocin
levels; and differences in activation of
the medial prefrontal cortex (mPFC),
where thinking and emotion interact, and
the ventral striatum (ie, nucleus
accumbens or pleasure center of the
brain).

26. Neuroanatomy and imaging
 Most of the findings pertain to brain
regions involved in emotional
processing, such as the amygdala,
insula, posterior cingulate cortex,
hippocampus, anterior cingulate
cortex, and prefrontal regulatory
regions

28. Volume
 A meta-analysis of brain volume—which
comprised 281 persons with BPD and 293
healthy controls—and 19 imaging studies
noted left amygdala and right hippocampus
gray volume decreases in persons with
BPD.

29. Function
 A meta-analysis of functional MRI (fMRI)
findings in persons with BPD revealed
heightened activation during processing of
negative emotional stimuli in the left
amygdala, left hippocampus, and posterior
cingulate cortex as well as diminished
activation in prefrontal regions (including the
dorsal lateral prefrontal cortex).

30.  Conflicting amygdala results are believed to result
from the medication status of research participants
because psychoactive drugs attenuate limbic activity.
 Pharmacologic probes have also shown decreased
metabolic activity in the anterior cingulate cortex and
orbital frontal cortex in response to serotonergic
challenge in impulsive-aggressive and affectively
unstable BPD populations.

31.  Dialectical behavioral therapy (DBT) was found
to attenuate amygdala hyperactivity at baseline,
which correlated with changes in a measure of
emotion regulation and increased use of
emotion regulation strategies.
 Taken together, these findings highlight that
dysfunctional circuits involving hyperactive
limbic regions and hypoactive prefrontal
modulation—most pronounced in the dorsal
lateral prefrontal cortex—represent the
anatomical corollaries to BPD.

32. Connectivity
 Connectivity studies developed over the past 2 years
introduced novel research strategies that heavily rely on
fMRI.
 Connectivity can be described in terms of anatomical and
functional connectivity.
 While such work in BPD is in its infancy, initial data suggest
that deficits in frontolimbic connections relate to the
severity of symptoms such as affective instability, avoidance
of abandonment, and anger.

33.  The default mode: a network activated when
the brain is at rest in the absence of goal-
directed activity; it is influenced by the medial
prefrontal cortex and posterior cingulate cortex
and is responsible for self-referential thinking.
 The salience network, including the orbital
frontal insula and the dorsal anterior cingulate
cortex.
 The medial temporal lobe network, which is
responsible for processing negative emotions.

34. In BPD, there are alterations in the
connections between these 3 networks
with particularly problematic connectivity
between salience detection and self-
referential encoding.
This results in misidentification with
neutral stimuli as well as a failure to
integrate salience information with
internal representations.

35. Symptoms of BPD are typically
categorized into 4 phenotypes—the
“borderline sectors”—that coexist in
varying degrees within individuals
with BPD and, often, in their family
members.

36. 1) The affective sector includes
emotions that are characteristically
challenging for patients with BPD.
These include loneliness, emptiness,
inappropriate and intense anger, and
quick fluctuations in mood.

37. 2)The interpersonal sector of BPD
refers to these patients’ penchant for
intense and volatile relationships and
their tendency to be at once
manipulative, entitled, and devaluing
as well as dependent, idealizing, and
fearful of abandonment.

38. 3) The cognitive sector encompasses
distressing perceptual disturbances,
including dissociation and paranoia
during times of stress.

39. 4) The behavioral sector of BPD
describes risky, impulsive behaviors as
well as self-injury and threats of self-
harm common in this population.

40. The emotional regulation
The emotional regulation system may
be different in people with BPD,
suggesting that there is a neurological
basis for some of the symptoms.
Specifically, the portions of the brain
that control emotions and decision-
making/judgment may not
communicate optimally with one

41. It is thought that the phenotypic
expression of each of these sectors
represents a confluence of genetic
and environmental influences.

42. Genetics
 While no specific gene or gene profile
has been shown to directly cause BPD,
studies involving twins suggest this
illness has strong hereditary links.
BPD is about five times more common
among people who have a first-degree
relative with the disorder.

43.  The prevalence of BPD among relatives of
probands with BPD was 14.1% compared with
4.9% in the family members of controls.
 Aggregation of BPD in families occurred in
this study more than aggregation of any of
the sectors.

44. Molecular genetic studies have
focused on the rate-limiting enzyme
in serotonin (5-hydroxytryptamine
[5-HT]) synthesis, as well as 5-HT
receptor and transporter genes. 5-
HT derives from tryptophan through
a process mediated by tryptophan
hydroxylase

45. Of the serotonin receptor genes,
polymorphisms
in 5HTR2A and 5HTR2C have been
most closely correlated with BPD.
Variants of the 5HT2A receptor are
known to correlate with suicide,
affective lability, and impulse
control. 5HTR2A polymorphisms
correlate with borderline traits.

46. The Biology of Borderline Personality
Disorder
 Some insights on the molecular biology
of BPD have come from research on a
polymorphism of the promoter site for
serotonin transporter (SERT).
 As a result of such a predisposition, the
brain can be more susceptible to
symptoms, such as impulsive
aggression, repeated self-injury, and
chronic suicidal tendencies.

47. Epigenetic
 Just as genetics may predispose an individual
to the development of BPD, epigenetic
changes are also likely to play a role.
 Epigenetic modifications influence gene
expression without altering DNA sequences
and are dynamically shaped through
environmental factors (eg, trauma).

48. The Biology of Borderline Personality
Disorder
 Epigenetics refers to functionally relevant
modifications to the genome that do not
involve a change in the nucleotide sequence.
 Examples of such modifications are DNA
methylation and histone modification, both of
which serve to regulate gene expression
without altering the underlying DNA sequence.

49. Oxytocin as treatment
 Oxytocin is believed to regulate social
cognition through the frontolimbic system,
in which structural and functional
differences have been identified in persons
with BPD.

50. Facial recognition
 Oxytocin’s role in the salience network influences
interpersonal hypersensitivity in BPD.
 Oxytocin is also involved in regulating the
hypothalamic-pituitary-adrenal axis, helping to
habituate the fear circuitry and extinguish the startle
response in the face of previously emotionally
charged stimuli.
 Oxytocin’s modulation of attachment and affiliative
systems may influence the anger, impulsivity, and
emotional lability exhibited by persons with BPD in
response to perceived insult.

51. Conclusion
 Research clearly demonstrates that BPD
evolves from a complex interaction between
environmental, anatomical, functional,
genetic, and epigenetic factors.
 There are many risk factors, and each one
serves to strengthen the others.

52. the 5 recommendations put forth by the American Board
of Internal Medicine Foundation's Choosing
Wisely® campaign
1. Don't prescribe antipsychotic medications to patients for
any indication without appropriate initial evaluation and
appropriate ongoing monitoring.
2. Don't routinely prescribe 2 or more antipsychotic
medications concurrently.
3. Don't use antipsychotics as the first choice to treat
behavioral and psychological symptoms of dementia.
4. Don't routinely prescribe antipsychotic medications as a
first-line intervention for insomnia in adults.
5. Don't routinely prescribe antipsychotic medications as a
first-line intervention for children and adolescents for
any diagnosis other than psychotic disorders.