27 September 2017

Personality crisis: looking beyond the borderline

Clinical Mental Health Psychiatry

Emma cuts her arms and wrists and says that this makes her feel alive. She struggled to finish school, has trouble remembering things and says she often feels empty inside. Sometimes the 26-year-old looks dazed. At other times, she flies into a rage over small things. 

When she was five years old, Emma’s father left and she was raised by her single mother, and later sexually abused by her mother’s boyfriend over a six-year period. When Emma told her mum, she wasn’t believed. 

Now, seeking help, she visits a doctor. 

The patient is overweight, she’s attempted suicide 11 times and been admitted to psychiatric wards a handful of times.  Since leaving home at 16, Emma has had problems with methamphetamine and alcohol use. 

This recognisable, but fictional, story is described by Professor Jayashri Kulkarni, a leading psychiatrist and researcher on borderline personality disorder, to highlight an important feature of the condition that is often overlooked. 

Patients with borderline personality disorder, such as Emma, often get shunted around the healthcare system. It can be difficult with a patient when you feel like you’re walking on eggshells, never knowing when they’re going to explode, she says. The struggle of this push-pull dynamic with patients is made worse by the nihilism that surrounds their prognosis. 

Professor Kulkarni recognises this, but is on a mission to bring to light the growing body of research on the role trauma has in disrupting the body’s normal response to stress and the flaws in our understanding of the condition. 

Borderline personality disorder, which affects an estimated 2% to 6% of the Australian population, has high morbidity and mortality and, as a result, creates a substantial burden on the healthcare system. 

But unlike other medical conditions such as cancer, it remains underfunded and a very misunderstood condition, says Professor Kulkarni, who heads up a women’s mental health outpatient clinic in Melbourne. 

Patients are thought of as “bad, manipulative and attention-seeking”, she says, which is a misrepresentation of the hallmark symptoms of borderline personality disorder of rage, self-mutilation, difficulty with relationships, poor self-esteem and volatile mood swings. 

But what sets this apart from bipolar disorders is that the mood instability and exaggerated emotions are in reaction to stressors. 

It has also become clear that the majority of people diagnosed with borderline personality disorder have experienced trauma, particularly occurring in early life which is often severe or chronic. One study of 500 children sexually or physically abused or neglected and 400 matched controls found that the mistreated children were significantly more likely to meet a borderline personality disorder diagnosis in adulthood compared to the control group, and research now suggests that the severity and type of trauma may be reflected in the severity of symptoms in adulthood. 

Professor Kulkarni and her research team at the Monash Alfred Psychiatry Research Centre have been given an NHMRC grant to further investigate the impact of early life stress on the development of these personality disorders. 

“When we looked at what constitutes borderline personality disorder, in about 80% of cases there’s a history of trauma against the individual,” Professor Kulkarni says. 

Anxiety is very common in patients with the condition, as you would expect, Professor Kulkarni says. “We have a mental picture of children who live a life tightly wound up because they’re so on edge,” she says. They live on high alert because they fear bad things happening, but even if the bad things stop, “the anxiety carries on”.  

“When we looked at these symptoms, the constant anxiety pointed us towards the idea that what’s going on here is high levels of cortisol, the stress hormone, in that people who have high levels of stress in early life reset their HPA (hypothalamic-pituitary-adrenal) axis so that they have a dysregulation in cortisol levels.” 

Clinicians have also noticed that many of the symptoms overlap with post-traumatic stress disorder. In both conditions patients can be highly anxious, angry, emotionally numb, have a quick startle response, experience flashbacks and hear and smell things not currently present. 

Plenty of research has been done investigating the HPA axis in patients with either PTSD or depression, but it is only more recently that a picture is beginning to emerge that similar issues may be at play for borderline personality disorder. 

THE HPA AXIS 

The HPA axis is known for its role in the fight or flight response, where it signals to the body to prepare for a stressful situation. Downstream effects trigger the release of glucocorticoids such as cortisol, which is one of the key features of the HPA-axis and a hormone involved in everything from metabolism to cognition, behaviour, growth, inflammation and cardiovascular health. 

Normally the body then brings the system back to baseline once the stressor is gone. This negative feedback loop works when the receptors back in the anterior pituitary detect high levels of cortisol and shut down the stress response. But perhaps if the stress is too severe or too frequent it can disrupt the normal cycle, and lead to some of the features we see in personality disorders. 

In a 2009 literature review on the personality disorder and the HPA axis, US psychiatrists Dr Daniel Zimmerman and Dr Lois Choi-Kain explained that the core symptoms of impulsivity, mood reactivity, self-injury, suicidality and dissociation “reflect both the vulnerability of individuals with BPD to stress and the maladaptive responses of such individuals to stress”. 

Previous animal research has found that prenatal stress and disruptions in early attachment are linked to dysfunction in the HPA axis. In addition, that the interaction between the HPA axis and the sympathetic nervous system is crucial to a healthy stress response, they wrote in the Harvard Review of Psychiatry.

When it comes to humans, the findings have been complicated. 

For example, people with both PTSD and borderline personality disorder have been shown to have lower 24-hour urinary cortisol levels compared with those with PTSD alone. Other research shows patients with borderline personality disorder have higher free cortisol levels in their urine overnight compared to a healthy control group, but when comparing patients with a high or low number of PTSD symptoms, it was only those with low PTSD symptoms that had very high cortisol levels. 

Still more research shows that patients with borderline personality disorder who had experienced childhood abuse had an exaggerated cortisol and ACTH response. 

Investigations into gene variations show patients with borderline personality disorder have certain polymorphisms in genes involved in the HPA axis, as did people who had experienced physical abuse or emotional neglect in childhood. 

Overall, they appear to show borderline personality disorder patients have an exaggerated response to HPA activation and higher baseline cortisol levels than healthy individuals. 

“Taken together, these observations allow us to conclude that functioning of the HPA axis in BPD [borderline personality disorder] is abnormal, with features of dysregulated feedback inhibition, which is at times suppressed, especially with comorbid depression,” Dr Zimmerman wrote. 

“Much of the evidence presented in this review suggests that comorbid MDD [major depressive disorder], PTSD, and childhood abuse are significant factors that determine the level of dysfunction detected in the HPA axis,” he added.

The link between mood symptoms and high cortisol levels as well as the chronic nature of mood problems among these patients suggest they might be experiencing chronic elevated cortisol, Dr Zimmerman wrote. 

Writing in the BMC Psychiatry journal a few months ago, Italian researchers also argued that people with borderline personality disorder have evidence of abnormal HPA function and sensitivity.

Changes to cortisol circadian rhythm and levels indicated “dysregulation of the HPA axis responsiveness, due to childhood trauma experiences”, they wrote.  Other imaging the brains of people with borderline personality disorder found changes to the volume of the hippocampus and amygdala, both integral to stress response, cognition, memory and emotional regulation.

As well as changes to the HPA axis, childhood trauma may also affect neurotransmission, the endogenous opioid system and neuroplasticity, research suggests.

Another element that is suggestive of the neuroendocrine disruption is the way that women commonly deteriorate premenstrually, perimenopausally, or when there is low dose oestrogen combined with certain types of progesterone in the oral contraceptive pill, Professor Kulkarni explains.

Of course, it may be that these findings are simply associations and explained by another causal factor, or that the borderline personality disorder itself causes these changes. More research is still needed. But the more we know about the complex biological differences among people with borderline personality disorder, the more sympathetically these patients may be treated.  

BORDERLINE WHAT? 

As well as investigating and understanding the biological mechanisms behind borderline personality disorder, Professor Kulkarni says there is also a political or social movement to change the label to recognise the legacy of trauma. 

When it comes to the label of “borderline personality disorder”, Professor Kulkarni shifts from a sympathetic and caring clinician to a frustrated one. It is a “completely stupid term”, she says. “This is one of the most ridiculous terms that the field of psychiatry could come up with. And we have come up with a lot of useless stuff in the past.” 

When the most recent DSM was in development, Professor Kulkarni was invited to the working party on the condition, but says her proposal to include trauma in the definition was vetoed by a US veterans lobby group who didn’t want PTSD or another trauma disorder muddied by this patient population. The next iteration of the ICD is a little more promising, where the condition is expected to sit partially among the personality disorders, but also largely alongside PTSD in a category called “complex PTSD”. 

From Professor Kulkarni’s perspective, ignoring trauma gives the medical field and practitioners permission to ignore the background history when a patient comes in, sometimes with a minor overdose or self-harming behaviours. 

“There’s a sense of ‘why can’t she just pull her socks up and stop slashing her wrists or overdosing’, because that’s all under her control,” according to Professor Kulkarni. “But what’s often missed is that it’s a rage response that should be directed at the abuse perpetrator.”

Unlike patients with PTSD though, who have an obvious trauma such as a war or robbery that is easy for clinicians to identify, the trauma behind borderline personality disorder may be harder to identify. For these patients, the source of their rage and trauma is often either long gone, or buried. 

While the obvious sources for borderline personality disorder are sexual or physical abuse, emotional abuse can be harder to identify, but not necessarily less harmful.

“It can be chronic because, if a family member is the abuser, [usually] the abuser constantly abused them over years,” Professor Kulkarni says. “Also, a denigratory family life with harsh criticism and not a nice, warm, nurturing environment, for some people, can be experienced as quite severe trauma.”

It could even be that the grandparent, the primary caregiver, dies. Or maybe the family migrates away from a loved one at a young age, she says.

“So what is traumatic for one person may not be traumatic for another.”

HPA axis dysregulation is also found in PTSD patients, but because PTSD patients are mostly adults when the trauma happens, and the trauma is often acute, it’s a truncated version of what borderline personality patients undergo, she says. PTSD patients are also able to make sense of the event in a rational way that children may struggle with, and have better coping mechanisms to help them through. Without the capacity to understand the trauma logically, the anger and sadness can turn inwards on themselves and manifest in self-harm, Professor Kulkarni says. 

So why change the name? 

“Because it takes the stigma off the patient by saying it’s not a personality disorder, it’s not a disorder of the essence of her, she’s the victim and something bad has happened,” she says. “Also, when you think of trauma disorder you open up the treatment field to think about post-trauma treatment therapies.” 

Professor Gordon Parker, scientia professor of psychiatry at the University of NSW, echoes her discomfort with the label. In his own practice, he says it’s “almost unheard of to see a person who hasn’t had a traumatic childhood”, and yet telling them they have a “personality disorder” is akin to an ad hominem insult. 

Professor Parker advises his students not to diagnose patients with personality disorders because “it’s psychiatric shorthand for saying you don’t like that person”. Instead, he tells patients they have a certain number of traits that align with one or another diagnosis.  

Similarly, Professor Kulkarni describes a “personality disorder” diagnosis “the kiss of death”, saying in many cases it shuts clinicians off from treatment and they just think the patient is behaving badly. 

The way patients can perceive the borderline diagnosis is that the doctor is either telling them there is something existentially wrong with them as a person, or on the other hand as a not-quite-there diagnosis – that they are on the “borderline” of having a personality disorder. 

But the condition is also “a great mimicker”, making the diagnosis difficult, she says. 

Women she sees in the clinic can sometimes be on five different medications because of the way they have sought help at various iterations of the condition. High rates of anxiety and depression attract mood stabilisers, and sometimes the patient’s disclosure of hearing the voice of their abuser or other voices is misdiagnosed as psychosis, Professor Kulkarni explains. 

To add to this, changes to the HPA axis and other systems may be potentially affecting their oestrogen, fertility and immune system. 

Women with early trauma are also at a high risk of polycystic ovarian syndrome and premenstrual dysphoric disorder, according to Professor Kulkarni. There is also a hypersensitivity to drugs, she says. 

“This is the person who tells you they take half the antidepressant dose and get all of the side effects,” says Professor Kulkarni, which can be a frustrating thing for the treating clinician to hear.  

“But when we measure pharmacogenomic markers, we’ve found increased sensitivities, with changes in particular enzymes, in particular, those enzymes that metabolise antidepressants and other psychiatric medications.” 

It’s also a group of patients who have the worst flu when there is a flu going around, and commonly have severe glandular fever and other infections, she says.

Her team’s approach to these patients is to explain complex trauma and avoid the borderline label. Professor Kulkarni says they get incredible buy in from patients when their conditions are presented that way.

“The relief and the sense of hope that many of the patients get when you remove that borderline diagnosis is quite profound.” 

Some avenues they are exploring are how drugs that work on the NMDA regulation systems affect the glutamate system. The glutamate system is a key driver of brain plasticity and learning activities, as well as the key brain chemical involved in higher thinking tasks. She’s chosen to use the NMDA antagonist, memantine. They’ve opted against ketamine because of its dissociative effects. 

“It’s small numbers but memantine treatment is showing some improvement,” she says. It’s never going to be a pill to fix all the problems that a person with this diagnosis experiences, but if they can at least contain some of the life-threatening behaviours and engage the patient in psychological therapies, or help them maintain  healthy and supportive relationships or a job, “then hopefully we’ve done some good”. 

“At the very least, we want to kick-start a change in thinking – and get people to focus on the trauma that the patient has and maybe still is experiencing. Borderline personality disorder is not a personality flaw or disorder, but a devastating illness that can be treated, provided a sympathetic, holistic trauma-based approach is taken.”

 

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