A Biological Comparison of Borderline Personality Disorder and Bipolar Disorders

ABSTRACT:

This paper covers the basic neurophysiological, morphological, and metabolic differences

between borderline personality disorder and bipolar disorder. It also addresses the

symptomatology and treatment differences. Evidence supports that borderline personality

disorder and bipolar disorder are separate disorders. Furthermore, this paper addresses the

potential of using biological techniques to aid in the diagnostic process.

INTRODUCTION:

Bipolar disorder (BP) and borderline personality disorder (BPD) are both serious mental

disorders that influence the regulation and processing of emotions. With many overlapping

symptoms, these disorders often appear similar during diagnosis (Ruggero, Zimmerman,

Chelminski & Young 2010), the possibility of comorbidity adding further complication. Mental

health professionals call into question the incidence rate of diagnosis as many people refuse

diagnosis and treatment for these disorders. BPD and BP have many negative stigmatisms related

to them, particularly BPD due to it being a personality disorder. The same continuum hypothesis,

suggested by Gunderson and Phillips in 1991, proposes that BDP is a subcategory of BP Despite

the morphological and physiological differences discovered, there is still division among the

psychiatric community as to the validity of this hypothesis. Furthermore, scientists have yet to

come to a consensus as to the effectiveness of modern biological techniques in aiding diagnosis.

I argue that bipolar disorder and borderline personality disorder are separate continuum disorders

and that modern biological techniques will have strong potential to aid in diagnosis in the future.

BIPOLAR DISORDER OVERVIEW:

Diagnosed in 1.5-3% of the general population (Hirschfeld, Petukhova, Ph, Kessler & Ph,

2008; Rossi et al., 2013), BP is a complicated disorder consisting of several subtypes: BP 1, BP

2, and Not Otherwise Specified (BP-NOS) (American Psychological Association, 2013). The

classic presentation of BP is a cyclical pattern of manic and depressive episodes. Mania is

typically thought to be presented as purely elevated mood , however this is not the case with

many patients. Mania can be presented as either euphoric mania or dysphoric mania. Euphoric

mania is the classic presentation of mania resulting in elevated mood, high energy, poor

judgement, irritability, hallucinations, and feelings of grandiose among other symptoms.

Dysphoric manic episodes are also more accurately referred to as mixed episodes, presented as

characteristics of depression and mania at the same time.

Influencing the clinical presentation of bipolar disorders, classifiers such as cyclothymia and

rapid cycling can be added to the subtypes above. Rapid cycling decreases the time between

cycles to over four times per year while cyclothymia expresses as decreased symptoms and is

often referred to a less severe form of BP. Being the leading cause of death in BP patients, lethal

suicide occurs 19% of the time while attempted suicide occurs about 50% of the time (Latalova,

Kamaradova & Prasko, 2014). Three celebrated men who have been thought to have suffered

from this disorder are Vincent Van Gough (an artist), Robert Fitzroy (a scientist), and Robert

Williams (an actor). These men expressed the symptoms of bipolar disorder by cycling between

periods of depression and mania.

BORDERLINE PERSONALITY DISORDER OVERVIEW:

Borderline personality disorder is serious and highly stigmatized (Kernberg &Yeomans,

2013), afflicting about 1.5% of the general population (Rossi et al., 2013). As its name suggests,

common themes of this disorder are emotional and thought instability and regulation, resulting in

many of the clinical symptoms of BPD (American Psychological Association, 2013). Patients

with borderline personality disorder have an unstable sense of self, which can result in sudden

changes of goals and values. They may also experience dissociations which can cause them to

become psychotic. Rather than being cyclical like bipolar disorder, symptoms in BPD seem to be

influenced by interpersonal relationships.

Oscillating between idealization and devaluation of their companions, patients can switch

between intense depressions to uncontrollable rage in a matter of seconds (American

Psychological Association, 2013). Having an extreme fear of abandonment (real or imagined),

people with BPD have trouble tolerating being alone and are constantly accompanied by chronic

emptiness and loneliness. Engaging in impulsive and dangerous behaviors, often to keep

someone close to them, patients will often engage in manipulation and suicidal gestures. Self-

harm is the most common symptom of BPD and is not an attempt at suicide. The patients do not

see the cutting, burning or other self-harm acts as harmful, but instead as a way of regulating

their emotions and/or punishing themselves. While self-harm is not a death wish, suicidal

gestures and idealization are quite common, resulting in a 10% lethal suicide rate and is the

leading cause of death for borderline personality disorder patients (Kernberg et al, 2013). Some

women who have been thought to have BPD are Princess Dianna and Marilyn Monroe. These

women were said to have engaged in self-harm, had unstable relationships, and made suicidal

gestures.

NEUROPHARMOCOLOGY IN BP:

Knowledge of neurotransmitters being involved in the pathophysiology of many

psychiatric disorders has developed for over 50 years. However, there is very little progression of

research regarding how neurotransmitters may be involved in producing the behaviors observed

in borderline personality disorder and bipolar disorder. In recent years, researchers have started

to further investigate dopamine, norepinephrine, GABA, and serotonin; neurotransmitters that

are involved in mood and emotional regulation.

Some recreational drugs, such as cocaine, increase dopamine concentrations and have been

observed to cause a similar state to a manic episode displayed in BP patients (Anand et al.,

2011). Because of the similarity in behavior resulting from an increase in dopamine, researchers

thought that abnormalities may exist in dopamine transporters in the brains of BP patients.

Specifically, it was thought that when in a manic phase, less binding would occur and during a

depressive phase more binding would occur. If this were the case, these abnormalities in

dopamine transporters may cause dopamine to be present or absent inappropriately. When tested

however, BP patients did show less dopamine transporter availability than in healthy individuals,

but there was no disruption of dopamine binding across phases. These results strongly indicate

that there are other factors, including other neurotransmitters involved in the cyclical patternof

bipolar disorder. It also suggests that dopamine may not be the lead cause for the cyclical nature

of BP.

Studying abnormalities of neurotransmitter levels in the bipolar, schizophrenic, and majorly

depressed brains, researchers attempted to further study a decreased expression of specific

GABA subunits (Fatemi, Folsom, Rooney, Thuras, 2013). These researchers were interested in

the miRNA expression of the GABA subunits in question and observed an increase of GABA

miRNA presence, which was mirrored by an overall decrease in several types of GABA

subunits. This indicates that GABA is less active in people with these disorders, and also further

supports the idea that there may be abnormalities in the genome of people with BP. Some

research has also been performed regarding serotonin and norepinephrine (Wiste, Arango,

Ellis,Ji, 2008). Compared to normal suicide cases, individuals who have committed suicide while

in a depressive phase have shown fewer indicators of serotonin and norepinephrine. This shows

that serotonin and norepinephrine may be altered between bipolar phases.

NEUROPHARMOCOLOGY IN BPD:

While there is no direct research on norepinephrine, serotonin, or GABA in borderline

personality disorder patients, methylation of the dopamine receptor DRD2 has been studied in

some individuals with BPD (Groleau et al., 2014). Previous studies have found increased

methylation of the dopamine receptor D2 (DRD2) in individuals with Bulimia Nervosa (, a

history of child abuse, and BPD. There was increased methylation found in the tested BPD and

child abuse populations in comparison to the patients with Bulimia Nervosa. When methylation

of the DRD2 occurs, it causes less dopamine to be present. These results insinuate that there are

lower than normal levels of dopamine presentin the brains of BPD patients, especially in those

who have suffered through child abuse. While there is a shared decrease of dopamine across

borderline personality disorder and bipolar disorder, the causes of these deficiencies still haven’t

been determined. Furthermore, not enough distinct similarities or differences been identified to

support or contradict the same continuum hypothesis.

TREATMENT DIFFERENCES:

The most common and effective treatments for borderline personality disorder are therapies

that focus on interpersonal relationships in combination with FDA approved prescribed

antidepressants (Bellino, Bozzatello, Bogetto, 2015). While the antidepressants work to lessen

the depressive symptoms present in BPD patients, the therapy helps to teach these individuals

better ways of handling and maintaining interpersonal relationships. The most common

antidepressants used are monoamine oxidase inhibiters (MAOIs), tricyclics (TCAs), or most

recently, reuptake inhibiters (SSRIs). SSRIs and TCAs alter the levels of various

neurotransmitters available using the reuptake process. MAOIs alter the levels of

neurotransmitters by inhibiting the enzyme monoamine oxidase, which breaks down common

neurotransmitters that influence mood. Some antipsychotics and anticonvulsants are also used to

treat BPD off-label.

Effective treatments for BP vary significantly from BPD. Most antidepressants are very

rarely used to treat depressive phases in bipolar patients. Instead of removing them from the

cycles of bipolar, often times they are forced into a manic phase; though this may be different

depending on the type of cycling experienced (Tundo, Calabrese, Proietti, 2015). Common

pharmaceuticals prescribed to treat BP are antipsychotics and anticonvulsants, which are both

commonly referred to as ‘mood stabilizers’. While many antipsychotics inhibit the binding of

dopamine and serotonin to receptors, anticonvulsants tend to increase activity of the

(GABA)ergic systems. Unlike BPD, therapy is often not used to treat BP. However, recent

studies have shown that, while it may not be the most effective on its own, when combined with

pharmacotherapies it may be beneficial, especially in cases of comorbidity (Peters, Sylvia,

Magalhaes, 2014).

While research on neurotransmitters provides little evidence regarding the same continuum

hypothesis, the differences in effective treatments indicate fundamental differences in the

pathophysiologies of borderline personality disorder and bipolar disorder. Furthermore, it has

been suggested that bipolar disorder may be related, or similar to, epilepsy (Mazzaet al., 2014).

The researchers have shown evidence that BP and epilepsy are highly comorbid, have similar

pathophysiologies and are often treated with similar medications. To our knowledge, there is no

evidence of epilepsy overlapping with BPD, separating BP from BPD even further.

MORPHOLOGY:

The morphology of the brain has been shown to mimic behavioral patterns, specifically in

mental disorders. When investigating the neural morphologies of the two disorders, the most

common tools used by researchers to measure the mass of cortical and subcortical features are

neuroimaging, voxel-based-morphology (VBM), and spectroscopy (MRS). The brain is made up

of gray matter (GM) and white matter (WM), which are commonly measured in neural

morphological studies. WM refers to mostly glial cells in the central nervous system, specifically

oligodendroglia, which form myelin sheaths around the axons of neurons. GM refers to

unmyelinated cells in the central nervous system. Knowing that there are lower volumes of GM

and WM in the brains of patients with borderline personality disorder and bipolar disorder

compared to healthy controls, researchers studying neural anatomy suggested that if the same

continuum hypothesis were likely, data gathered from BPD and BP patients would not be

statistically significant (Rossiet al., 2013).

In comparing the volumes of GM and WM in BP and BPD patients, Rossi et. al (2013)

observed twice as much atrophy in the GM of BP patients in comparison to BPD patients. The

loss of WM between the two groups was not noticeably different, though both disorders showed

more WM loss than that of healthy controls. While this alone is not substantial evidence in

support of or against the same continuum hypothesis, in studying the potential for GM

differences between BP І and BP ІІ, Ha, Ha, Kim, and Choi (2009) discovered that there are

almost no noticeable differences between the two subtypes. When examining the possibility of

morphological differences of BP І and ІІ to that of rapid cycling BP І and ІІ, research shows that

there is more GM loss in rapid cycling BP cases (Naritaet al., 2010). As Rossi et al. (2013)

demonstrated, there is less GM loss in BPD cases than in BP patients, not more, as was found in

rapid cycling bipolar disorder (Naritaet al., 2010). This suggests that it is likely that BPD is not a

form of rapid cycling bipolar disorder.

Furthermore, damaged areas of non-overlap outnumbered the damaged areas of overlap

(Rossi et al., 2013), particularly in WM. In both disorders, the frontal lobe and corpus callosum

were both greatly damaged, though more so in the brains of bipolar disorder patients. In patients

with borderline personality disorder, mainly key structures of the limbic system involved with

emotional regulation and processing along with impulse control were found to be reduced. While

damage in the brains of BP patients included some of these areas, there was also widespread

damage elsewhere. In addition, BPD patients showed decreased volume of the amygdale, a

strong correlate to BPD’s clinical phenomenology. Rossi et al. (2013) found there to be little to

no damage in the amygdale of BP patients, results that had also been observed by Almeidaet al.

(2007). This, along with many other subcortical differences, indicates little overlap in the

morphological manifestations of the two disorders.

ACTIVITY:

Several researchers including Daviset al. (2014) and Jacob et al. (2013), have attempted to

measure electrical and metabolic activity in BPD patients. Following the clinical phenomenology

of BPD, researchers would expect to see increased activity in the amygdale and decreased

activity in the frontal lobe when exposed to emotionally charged stimuli compared to healthy

individuals. Both fMRI data and self-reports support the hypothesized pattern when participants

were exposed to angry and sad stimuli. Furthermore, there was little difference between the

activity in the amygdale and frontal lobes in BPD patients compared to that of healthy

individuals when exposed to happy or neutral stimuli.

Since self-harm is such an integral part of borderline personality disorder and an important

element of bipolar disorder, Davis et al. (2014) attempted to measure brain activity and ability to

regulate emotions in individuals who have previously engaged in deliberate self-harm and

compare them to individuals with diagnosed unipolar depression. While self-reports and fMRI

data indicate that both groups experience the sad stimulus in the same way and at the same

intensity, the deliberate self-harm group was less able to regulate their emotions in response to

the stimulus when compared to the unipolar depression group.

While the results appear may be similar to BP, attempts have recently been made to measure

the electrical and metabolic activity in BP І and BP ІІ patients in response to negative stimuli

(Caseras, Murphy, Lawrence et al. 2015). If BPD and BP were same continuum disorders, it

would be likely to see increased amygdale activity and decreased frontal lobe activity in BP

brains; similar to the results of BPD patients. Instead of finding similar results between the BP І

and ІІ patients, BP І participants responded more slowly, and with increased activity in the

frontal lobe and amygdale when compared to that of healthy controls and BP ІІ participants.

Caseras et al. (2015) believes this indicates decreased ability to regulate emotions in BP І

patients compared to healthy individuals and BP ІІ participants.

There were also large amounts of connectivity deficits in the WM between the cortical and

subcortical features in the BP І participants compared to the healthy individuals and BP ІІ

participants (Caseras et al., 2015). While the BP ІІ patients showed similar results in activities to

the BP І patients, they showed none of the WM connectivity deficiencies, nor a decrease in

reaction time. This led the researchers to believe that decreased emotional regulation is more

unique to BP І then BP ІІ. While the fMRI results of the BP І participants in Caseras’ et al.

(2015) study may seem similar to previous BPD fMRI findings (Jacob et al., 2013), this likeness

reflects the similarity in behavioral symptoms as the deficits in WM connectivity sets the two

disorders apart morphologically.

MORPHOLOGICAL DIGNOSIS:

Testing for morphological differences may prove beneficial in the pursuit of diagnosis. In

the Rossi et al. (2013) study, the researchers showed that the atrophy was located in mostly

differing parts of the brain between the two disorders. While these researchers agree that this

insinuates that borderline personality disorder and bipolar disorder are separate disorders, this

also may indicate that BP and BPD can be differentiated using neuroimaging techniques.

Researchers have tested the accuracy of using volumetric data in distinguishing BPD patients

from healthy controls (Satoet al. 2012). About 80% of the participants were correctly classified.

In addition, these researchers also determined that the left middle temporal, left medial

orbitofrontal, right rostral anterior cingulate, and right parahippocampal regions provided the

most significant predictive power of the cortices in potential diagnosis. The researchers believe

that with the increasing number of advances being made in computational science and

neuroscience, the future prediction rate is likely to become more accurate. Ultimately, the

researchers determined the use of VBM and MRS to be helpful, unbiased aids in the diagnosis of

BPD.

NEUROPHARMACOLOGY AND GENETIC TESTING:

The current research on neuropharmacology is not advanced enough to distinguish

meaningful differences between BP and BPD. Also, considering that the similarities of the

neurochemistry of these disorders are similar to other disorders such as epilepsy, schizophrenia

and depression, it may only work to further confuse the diagnosis process at this time (Fatemi et

al. 2013).

Groleau’s et al. (2014) study may indicate that BPD has an environmental factor as well as

genetic one considering the link with past child abuse. While BP has been shown to have

environmental factors, twin studies have shown almost an 80% chance of heritability (Uher,

2014). Considering this genetic factor, it may be possible to test for a genetic disposition, but

because of the environmental factors it could only be used as a predicting factor.

FURTHER RESEARCH:

While neuroimaging techniques may be fairly unbiased, the undiscussed limitations leave

me skeptical as to the validity of this tool as a practical diagnostic aid. Firstly, initial tests only

included females which does not accurately represent the prevalence ratio of BPD in males and

females. VBM and MRS may be a valid tool in distinguishing a borderline personality patient

from a healthy control; however, studies have not explored the validity of this as a tool in

distinguishing borderline personality disorder from other psychiatric disorders. Furthermore, the

issue of potential comorbidities has not been addressed, which many other scientists believe to

be an integral and unique part of having BPD - considering that the frequencies of comorbidity in

patients with BPD are so high (Rossi et al., 2013). In addition, some researchers also noted

inconsistencies in some of the BP patient’s results which may indicate that the disease worsens

with age (Rossi et al., 2013). It has also been noted that in a study comparing the morphology of

bipolar І and ІІ there were unique abnormalities between the two (Ha et. al, 2009). This could

cause further confusion during morphological diagnosis. Nonetheless, if these limitations can be

accounted for in the future, then perhaps these techniques can be used as a diagnostic aid in a

limited fashion.

Rossi et al. (2013) and his team noted inconsistencies in some of the BP patient’s results

which may indicate that the disease worsens with age. This may indicate that people are not born

with this disorder and it is developed over time. Alternatively it could also suggest that damage

is occurring very early on and the damage is not detected until participants are old enough to

participate in research. Both of these possibilities should be pursued because early prevention has

been shown to decrease the severity of the disorder (Tundo et al. 2015). Similar research should

be conducted to see if BPD also worsens with age. Furthermore, while genetics may only be

used as a potential predictive tool, epigenetics is a rather new field of biology. If more research is

conducted, perhaps it can be used to measure what environmental and genetic factors are needed

in order to trigger the disorders and thereby reduce prevalence. Further research on the genetics

of borderline personality disorder and bipolar disorder may also lead to the potential of a gene

therapy treatment.

The connection between morphology, brain activity and neuropharmacology should be

explored further. The body has many different biological clocks that cause changes in the

biochemistry of the brain (Alloy, Nusslock & Boland, 2015). While neurotransmitters have yet to

reveal a pattern influencing an episode switch in bipolar disorder (Anandet al., 2011), research

has just begun on how these rhythms may alter the neuropathology of the disorder. Because of

how the circadian rhythm influences the cyclical nature of some mood disorders such as seasonal

affective disorder (American Psychological Association, 2013), it may be possible that the

episodic nature of BP has a similar trigger. Another cause of the episode switches in BP could be

seizures. Because of how epilepsy and BP are linked, it is also possible that the WM and GM

damage found (Rossi et al,, 2013) is caused by seizures.

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