Brain Chemistry Basics

You've probably heard the term "neurotransmitter" before, but what does this really mean? Neurotransmitters are chemical messengers in the brain that facilitate communication between nerve cells. Let's illustrate with serotonin. Figure 1 depicts the junction between two nerve cells. Packets of serotonin molecules are released from the end of the presynaptic cell (the axon) into the space between the two nerve cells (the synapse). These molecules may then be taken up by serotonin receptors of the postsynaptic nerve cell (the dendrite) and thus pass along their chemical message. Excess molecules are taken back up by the presynaptic cell and reprocessed.

Several things might potentially go wrong with this process and lead to a serotonin deficit. Just to enumerate a few possibilities:

• Not enough serotonin is produced,
• Not enough receptor sites to receive serotonin,
• Serotonin is being taken back up too quickly before it can reach receptor sites,
• Chemical precursors (molecules that serotonin is manufactured from) may be in short supply, or
• Molecules that facilitate the production of serotonin may be in short supply.

As you can see, if there is a breakdown anywhere along the path, neurotransmitter supplies may not be adequate for your needs. Inadequate supplies lead to the symptoms that we know as depression.

The Primary Players

There are three basic molecules, known chemically as monoamines, which are thought to play a role in mood regulation: norepinephrine, serotonin and dopamine.

In the 1960s Joseph J. Schildkraut of Harvard University cast his vote with norepinephrine as the causative factor for depression in the now classic "catecholamine" hypothesis of mood disorders. He proposed that depression stems from a deficiency of norepinephrine in certain brain circuits and that mania arises from an overabundance of this substance.1 There is indeed a large body of evidence2 that supports this hypothesis, however, changes in norepinephrine levels do not affect mood in everyone. The implication is that medications such as reboxetine, which specifically targets norepinephrine, will work for some persons but not others.3

Obviously there must be some other factor that interacts with norepinephrine to cause depression. Serotonin has been found to be this other factor. This molecule has taken center stage in the past two decades thanks to Prozac and other Selective Serotonin Reuptake Inhibitors (SSRI's), which selectively act on this molecule. Serious investigations into serotonin's role in mood disorders, however, have been going on for almost 30 years, ever since Arthur J. Prange, Jr., of the University of North Carolina at Chapel Hill, Alec Coppen of the Medical Research Council in England and their co-workers put forward the so-called "permissive hypothesis". This view held that synaptic depletion of serotonin was another cause of depression, one that worked by promoting, or "permitting," a fall in norepinephrine levels. So, although, norepinephrine still played a major role in depression, serotonin levels could be manipulated to indirectly raise norepinephrine. Newer antidepressants like Effexor are actually targeted at both serotonin and norepinephrine.4 Tricyclics (TCAs) also affect both norepinephrine and serotonin, however, they have the added effect of influencing histamine and acetylcholine, which produces the side-effects that TCAs are known for, such as dry mouth or eyes, peculiar taste in mouth, sensitivity to light of the eyes, blurry vision, constipation, uninary hesitancy, and others. SSRIs do not affect histamine and acetylcholine and thus do not have the same side-effects as the older medications.5

A third substance that may play a role in mood is dopamine. Dopamine is associated with the reward, or reinforcement, that we get which causes us to continue participating in an activity. It has been implicated in such conditions as Parkinson's Disease and schizophrenia. There is also some evidence that, at least for a subset of patients, dopamine plays a role in depression.6 Dopaminergic substances and stimulants have been used as antidepressants when other measures have failed.7 Some studies have investigated dopaminergic agents as a rapid method of relieving depression (in contrast to medications which may take up to six weeks to exhibit their full effect).8

Although agents that work selectively on dopamine have the benefit of fast action, they have also exhibited some properties which have kept them from being as widely used as other antidepressants. Dopamine is a neurotransmitter that is associated with addiction and it's production is stimulated by drugs such as cocaine, opiates and alcohol (which may explain why depressed persons choose to self-medicate with drugs and alcohol.9) Drug specifically targeted at dopamine, for example amineptine (Survector), present the potential for abuse.10 For this reason, amineptine is not approved for use in the US or Britain at this time.

References

1. Nemeroff, Charles B. The Neurobiology of Depression. Scientific American, June 1998 [journal online]; Internet; cited May 15, 2000.
2. Goldberg, Ivan T. The Cholinergic Hypothesis of Affective Disorders: A MEDLINE Search. [Web site]; cited May 15, 2000.
3. Nemeroff.
4. Ibid.
5. Gelwan, Eliot. Tricyclic Antidepressants. Posted 9/30/92. [article online]; Internet, cited May 15, 2000.

1. No longer available)
2. California State University, Chico, Department of Psychology. Dopamine. [Web site]; cited May 15, 2000.
3. Nierenberg, AA, Dougherty D, Rosenbaum JF. Dopaminergic agents and stimulants as antidepressant augementation strategies. J Clin Psychiatry, 1998, 59 Suppl 5:60-3, discussion 64. [Web site]; Internet; cited May 15, 2000.
4. Willner P. The mesolimbic dopamine system as a target for rapid antidepressant action. Int Clin Psychopharmacol, 1997 Jul, 12 Suppl. 3:S7-14. [Web site]; Internet; cited May 15, 2000.
5. Flaherty, Michael T. What is the Relationship between Depression and Alcohol Use? [article online]; cited May 15, 2000.
6. Perera, I, Lim L. Amineptine and Midazolam Dependence. Singapore Medical Journal, date unknown. [online journal]; Internet; cited May 15, 2000

Post Traumatic Stress Disorder Research Fact Sheet

From: The National Institute of Mental Health (NIMH)

• Introduction
• Research on Possible Risk Factors for PTSD
• Research on Treating PTSD
• The Next Steps for PTSD Research
• Where Can I Get More Information?
• References

Introduction

Post-traumatic stress disorder (PTSD) is an anxiety disorder that some people develop after seeing or living through an event that caused or threatened serious harm or death. Symptoms include flashbacks or bad dreams, emotional numbness, intense guilt or worry, angry outbursts, feeling “on edge,” or avoiding thoughts and situations that remind them of the trauma. In PTSD, these symptoms last at least one month.

To aid those who suffer with PTSD, the National Institute of Mental Health (NIMH) is supporting PTSD-focused research, and related studies on anxiety and fear, to find better ways of helping people cope with trauma, as well as better ways to treat and ultimately prevent the disorder. This research fact sheet will highlight several important areas that NIMH researchers have recently learned about:

• possible risk factors,
• treating the disorder, and
• next steps for PTSD research.

For more information about PTSD, please see the NIMH Post-Traumatic Stress Disorder booklet. You can also find a list of places to find more information about PTSD and NIMH at the end of this fact sheet.

Research on Possible Risk Factors for PTSD

Currently, many scientists are focusing on genes that play a role in creating fear memories. Understanding how fear memories are created may help to refine or find new interventions for reducing the symptoms of PTSD. For example, PTSD researchers have pinpointed genes that make:

• Stathmin, a protein needed to form fear memories. In one study, mice that did not make stathmin were less likely than normal mice to “freeze,” a natural, protective response to danger, after being exposed to a fearful experience. They also showed less innate fear by exploring open spaces more willingly than normal mice.¹
• GRP (gastrin-releasing peptide), a signaling chemical in the brain released during emotional events. In mice, GRP seems to help control the fear response, and lack of GRP may lead to the creation of greater and more lasting memories of fear.²

Researchers have also found a version of the 5-HTTLPR gene, which controls levels of serotonin — a brain chemical related to mood-that appears to fuel the fear response.³ Like other mental disorders, it is likely that many genes with small effects are at work in PTSD.

Studying parts of the brain involved in dealing with fear and stress also helps researchers to better understand possible causes of PTSD. One such brain structure is the amygdala, known for its role in emotion, learning, and memory. The amygdala appears to be active in fear acquisition, or learning to fear an event (such as touching a hot stove), as well as in the early stages of fear extinction, or learning not to fear.⁴

Storing extinction memories and dampening the original fear response appears to involve the prefrontal cortex (PFC) area of the brain,⁴ involved in tasks such as decision-making, problem-solving, and judgment. Certain areas of the PFC play slightly different roles. For example, when it deems a source of stress controllable, the medial PFC suppresses the amygdala an alarm center deep in the brainstem and controls the stress response.⁵ The ventromedial PFC helps sustain long-term extinction of fearful memories, and the size of this brain area may affect its ability to do so.⁶

Individual differences in these genes or brain areas may only set the stage for PTSD without actually causing symptoms. Environmental factors, such as childhood trauma, head injury, or a history of mental illness, may further increase a person's risk by affecting the early growth of the brain.⁷ Also, personality and cognitive factors, such as optimism and the tendency to view challenges in a positive or negative way, as well as social factors, such as the availability and use of social support, appear to influence how people adjust to trauma.⁸ More research may show what combinations of these or perhaps other factors could be used someday to predict who will develop PTSD following a traumatic event.

Research on Treating PTSD

Currently, people with PTSD may be treated with psychotherapy (“talk” therapy), medications, or a combination of the two.

Psychotherapy

Cognitive behavioral therapy (CBT) teaches different ways of thinking and reacting to the frightening events that trigger PTSD symptoms and can help bring those symptoms under control. There are several types of CBT, including

• exposure therapy — uses mental imagery, writing, or visiting the scene of a trauma to help survivors face and gain control of overwhelming fear and distress
• cognitive restructuring — encourages survivors to talk about upsetting (often incorrect) thoughts about the trauma, question those thoughts, and replace them with more balanced and correct ones.
• stress inoculation training — teaches anxiety reduction techniques and coping skills to reduce PTSD symptosm, and helps correct inaccurate thoughts related to the trauma.

NIMH is currently studying how the brain responds to CBT compared to sertraline (Zoloft), one of the two medications recommended and approved by the U.S. Food and Drug Administration (FDA) for treating PTSD. This research may help clarify why some people respond well to medication and others to psychotherapy

Medications

In a small study, NIMH researchers recently found that for people already taking a bedtime dose of the medication prazosin (Minipress), adding a daytime dose helped to reduce overall PTSD symptom severity, as well as stressful responses to trauma reminders.⁹

Another medication of interest is D-cycloserine (Seromycin), which boosts the activity of a brain chemical called NMDA, which is needed for fear extinction. In a study of 28 people with a fear of heights, scientists found that those treated with D-cycloserine before exposure therapy showed reduced fear during the therapy sessions compared to those who did not receive the drug.¹⁰ Researchers are currently studying the effects of using D-cycloserine with therapy to treat PTSD.

Propranolol (Inderal), a type of medicine called a beta-blocker, is also being studied to see if it may help reduce stress following a traumatic event and interrupt the creation of fearful memories. Early studies have successfully reduced or seemingly prevented PTSD in small numbers of trauma victims.¹¹

Treatment After Mass Trauma

NIMH researchers are testing creative approaches to making CBT widely available, such as with Internet-based self-help therapy and telephone-assisted therapy. Less formal treatments for those experiencing acute stress reactions are also being explored to reduce chances of developing full blown PTSD

For example, in one preliminary study, researchers created a self-help website using concepts of stress inoculation training. People with PTSD first met face-to-face with a therapist. After this meeting, participants could log onto the website to find more information about PTSD and ways to cope, and their therapists could also log on to give advice or coaching as needed. Overall, the scientists found delivering therapy this way to be a promising method for reaching a large number of people suffering with PTSD symptoms.¹²

Researchers are also working to improve methods of screening, providing early treatment, and tracking mass trauma survivors; and approaches for guiding survivors through self-evaluation/screening and prompting referral to mental health care providers based on need.

The Next Steps for PTSD Research

In the last decade, rapid progress in research on the mental and biological foundations of PTSD has lead scientists to focus on prevention as a realistic and important goal.

For example, NIMH-funded researchers are exploring new and orphan medications thought to target underlying causes of PTSD in an effort to prevent the disorder. Other research is attempting to enhance cognitive, personality, and social protective factors and to minimize risk factors to ward off full-blown PTSD after trauma. Still other research is attempting to identify what factors determine whether someone with PTSD will respond well to one type of intervention or another, aiming to develop more personalized, effective and efficient treatments.

The examples described here are only a small sampling of the ongoing work at NIMH. To find more information about ongoing PTSD clinical studies, see NIMH's PTSD clinical trials Web page. As gene research and brain imaging technologies continue to improve, scientists are more likely to be able to pinpoint when and where in the brain PTSD begins. This understanding may then lead to better targeted treatments to suit each person's own needs or even prevent the disorder before it causes harm.

Where Can I Get More Information?

MedlinePlus, a service of the U.S. National Library of Medicine and the National Institutes of Health, provides updated information and resource lists for many health topics, including post-traumatic stress disorder (PTSD) (En Español)

Information from NIMH is available online, in PDF, or as paper brochures sent through the mail. If you would like to have NIMH publications, you can order them at http://www.nimh.nih.gov or contact NIMH at the numbers listed below.

National Institute of Mental Health
Office of Science Policy, Planning, and Communications
6001 Executive Boulevard
Room 8184, MSC 9663
Bethesda, MD 20892-9663
Phone: 301-443- 4513, 1-866-615-NIMH (6464) toll-free
TTY: 1-866-415-8051 toll free
Fax: 301-443-4279
E-mail: nimhinfo@nih.gov

References

1. Shumyatsky GP, Malleret G, Shin RM, et al. stathmin, a Gene Enriched in the Amygdala, Controls Both Learned and Innate Fear. Cell. Nov 18 2005;123(4):697-709.

2. Shumyatsky GP, Tsvetkov E, Malleret G, et al. Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear. Cell. Dec 13 2002;111(6):905-918.

3. Hariri AR, Mattay VS, Tessitore A, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science. Jul 19 2002;297(5580):400-403.

4. Milad MR, Quirk GJ. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature. Nov 7 2002;420(6911):70-74.

5. Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci. Mar 2005;8(3):365-371.

6. Milad MR, Quinn BT, Pitman RK, Orr SP, Fischl B, Rauch SL. Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory. Proc Natl Acad Sci U S A. Jul 26 2005;102(30):10706-10711.

7. Gurvits TV, Gilbertson MW, Lasko NB, et al. Neurologic soft signs in chronic posttraumatic stress disorder. Arch Gen Psychiatry. Feb 2000;57(2):181-186.

8. Brewin CR. Risk factor effect sizes in PTSD: what this means for intervention. J Trauma Dissociation. 2005;6(2):123-130.

9. Taylor FB, Lowe K, Thompson C, et al. Daytime Prazosin Reduces Psychological Distress to Trauma Specific Cues in Civilian Trauma Posttraumatic Stress Disorder. Biol Psychiatry. Feb 3 2006.

10. Ressler KJ, Rothbaum BO, Tannenbaum L, et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry. Nov 2004;61(11):1136-1144.

11. Pitman RK, Sanders KM, Zusman RM, et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. Jan 15 2002;51(2):189-192.

12. Litz BT WL, Wang J, Bryant R, Engel CC. A therapist-assisted Internet self-help program for traumatic stress. Prof Psychol Res Pr. December 2004;35(6):628-634.

NIMH publications are in the public domain and may be reproduced or copied without the permission from the National Institute of Mental Health (NIMH). NIMH encourages you to reproduce them and use them in your efforts to improve public health. Citation of the National Institute of Mental Health as a source is appreciated. However, using government materials inappropriately can raise legal or ethical concerns, so we ask you to use these guidelines:

• NIMH does not endorse or recommend any commercial products, processes, or services, and publications may not be used for advertising or endorsement purposes.
• NIMH does not provide specific medical advice or treatment recommendations or referrals; these materials may not be used in a manner that has the appearance of such information.
• NIMH requests that non-Federal organizations not alter publications in a way that will jeopardize the integrity and "brand" when using publications.
• Addition of Non-Federal Government logos and website links may not have the appearance of NIMH endorsement of any specific commercial products or services or medical treatments or services.

If you have questions regarding these guidelines and use of NIMH publications, please contact the NIMH Information Center at 1-866-615-6464 or at nimhinfo@nih.gov.

Borderline: Walking the Line

From: Psychology Today

Can you live with, and move beyond, a relationship with a borderline parent?
By Matthew Hutson, Psychology Today

Your childhood was full of tantrums—impulsivity, mood swings, neediness, fear of abandonment, and extreme sensitivity to rejection. And this isn't you we're talking about; it's your mom.

If you grew up the constant target of finicky and derisive comments, or the emotional caretaker for one of your parents, you know all too well the pain of having a father or (usually) mother with Borderline Personality Disorder. BPD doesn't just affect the one who receives the diagnosis; it often leaves a wake of turmoil through entire families as the emotional and relational disturbances ripple outward.

When a role model treats you as an extension of herself—there to meet her needs—the trauma can be long lasting. It takes a very strong person to overcome the effects, let alone maintain a constructive relationship with the parent. But there's hope. Here are several guidelines for dealing with a borderline parent, and for moving on with your own life.

Know the Type
Mothers with BPD outnumber fathers, and Christine Lawson, author of Understanding the Borderline Mother, has a taxonomy of the troubled parent: "The Queen is controlling, the Witch is sadistic, the Hermit is fearful, and the Waif is helpless," she says. And each requires a different approach. Don't let the Queen get the upper hand; be wary even of accepting gifts because it engenders expectations. Don't internalize the Hermit's fears or become limited by them. Don't allow yourself to be alone with the Witch; maintain distance for your own emotional and physical safety. And with the Waif, don't get pulled into her crises and sense of victimization; "pay attention to your own tendencies to want to rescue her, which just feeds the dynamic," Lawson says.

Build Fences
Borderline parents often can't separate their own needs from the needs of others. And sometimes they can't meet their own emotional needs, so they look to their children to fill it. When the child doesn't do the job, the parent can get angry, making resistance difficult. "Adult children need to define for themselves their limits and boundaries," says Kimberlee Roth, author of Surviving a Borderline Parent. "Let's say a parent regularly calls late at night to vent. Whatever your needs, communicate them in a calm, non-accusatory way: 'Mom, I'd like to listen but I can't do it late at night. How about if we talk in the morning instead?'" As a last resort, use Caller ID or voicemail.

Be Firm But Sensitive
Personal validation, which is important in any situation, is essential with a borderline parent. Express your awareness of her emotions even as you set boundaries. "You might feel like a broken record," Roth says, "but it's important to keep repeating your acknowledgement of the parent's needs without diminishing your own."

Trust Yourself
In writing her book, Roth encountered many children of borderline parents who said they felt crazy growing up. "They experienced a lot of inconsistencies—an action or statement that earned praise one day would touch off a three-day, stony silent treatment the next—as well as sudden outbursts and overreactions." So they never learn to trust their own judgment or feelings. The most important element to recovery, she says, is to accept that you're not crazy and that "it wasn't me."

Trust Others
People who've survived a borderline parent most frequently suffer from "feelings of worthlessness, fear of abandonment, and fear of people in general," according to Randi Kreger, co-author of the bestselling Stop Walking on Eggshells: Taking Your Life Back When Someone You Care About Has Borderline Personality Disorder. Because these adult children received "such mixed messages—you're a great person one day and you're horrible the next—there's a certain mistrust of people because you're always afraid they're going to hurt you." Kreger advises that they find friends and partners unlike the parent: consistent people who can provide unconditional love. And stop looking for sleights; hair-trigger defense systems that developed in the presence of abusive parents often lead people to see ill intentions where they don't exist and end up preemptively sabotaging relationships.

Defend Your Boundaries
Children of borderline parents are often forced to act as the parent themselves—"it's like a child raising a child," Kreger says—and this role can play itself out in other relationships. They grow up very quickly in many ways and act as caretaker for everyone, sometimes at the expense of taking care of themselves. "Having that undue sense of responsibility can leave them feeling very alone in the world," Lawson says. And they allow others to tread their boundaries just as the parent did. So once you learn to set limits for your parent, set them for other people and learn to put yourself first.

None of these steps will come easy. An abusive or inconsistent parent can leave a deep wound. "Trying to manage it can be a lifelong process," Kreger says. But she insists that with a good therapist, and support from a community of other people who have gone through the same thing, "there is real possibility to get better, and I know many people who have."

Suicides increased after antidepressant warning: Manitoba researcher

From: CBC News

Youth suicides increased after Health Canada warned about the use of antidepressants, a University of Manitoba researcher has found.

Health Canada issued a notice in 2004 that antidepressant drugs were linked to increased rates of suicidal thoughts in children and teens.

It advised patients under the age of 18 who were being treated with selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenalin reuptake inhibitors (SNRIs) to consult their physicians. A similar warning was issued around the same time in the U.S.

Dr. Laurence Katz, an associate professor of psychiatry at the University of Manitoba, studied provincial data from 2005 and 2006, and found some children and teens with mental illness stopped taking their medication and stopped regularly seeing their doctors following the warning.

Katz, of the university's child psychiatry department and mood and anxiety disorders research group, found youth suicides in Manitoba rose dramatically during that time.

Katz had been worried about the advisory and what it would mean for children's health.

During the two-year period studied, there was a 25 per cent increase in youth suicide and a 14 per cent drop in the use of antidepressants among children and teens.

There was also a 10 per cent drop in the number of doctor visits by depressed kids, suggesting the public didn't really understand the warning, Katz said.

"If people had followed those guidelines and adhered to the concern in the warning, we would have expected to see physician office visits increase. But, in fact, they went down."

More research needed

The results, released Monday in Winnipeg, don't surprise Bill Ashdown of the Mood Disorders Association of Manitoba.

"Having the advisory come out would certainly negatively impact the number of doctors who would simply say, 'No, I'm not going to bother prescribing because it will get me into a hassle.'"

Ashdown is convinced some patients would have simply stopped taking their medication without consulting their doctors. He said the warning should have been issued only to physicians through medical journals.

Katz said he didn't have a problem with the way the warning was worded — the problem was with how it was perceived. More research is needed, he added, into what role the warning played in the study's findings.

Borderline Personality Disorder

From: The National Institute of Mental Health

Raising questions, finding answers

Borderline personality disorder (BPD) is a serious mental illness characterized by pervasive instability in moods, interpersonal relationships, self-image, and behavior. This instability often disrupts family and work life, long-term planning, and the individual's sense of self-identity. Originally thought to be at the "borderline" of psychosis, people with BPD suffer from a disorder of emotion regulation. While less well known than schizophrenia or bipolar disorder (manic-depressive illness), BPD is more common, affecting 2 percent of adults, mostly young women.¹ There is a high rate of self-injury without suicide intent, as well as a significant rate of suicide attempts and completed suicide in severe cases.^2,3 Patients often need extensive mental health services, and account for 20 percent of psychiatric hospitalizations.⁴ Yet, with help, many improve over time and are eventually able to lead productive lives.

Symptoms

While a person with depression or bipolar disorder typically endures the same mood for weeks, a person with BPD may experience intense bouts of anger, depression, and anxiety that may last only hours, or at most a day.⁵ These may be associated with episodes of impulsive aggression, self-injury, and drug or alcohol abuse. Distortions in cognition and sense of self can lead to frequent changes in long-term goals, career plans, jobs, friendships, gender identity, and values. Sometimes people with BPD view themselves as fundamentally bad, or unworthy. They may feel unfairly misunderstood or mistreated, bored, empty, and have little idea who they are. Such symptoms are most acute when people with BPD feel isolated and lacking in social support, and may result in frantic efforts to avoid being alone.

People with BPD often have highly unstable patterns of social relationships. While they can develop intense but stormy attachments, their attitudes towards family, friends, and loved ones may suddenly shift from idealization (great admiration and love) to devaluation (intense anger and dislike). Thus, they may form an immediate attachment and idealize the other person, but when a slight separation or conflict occurs, they switch unexpectedly to the other extreme and angrily accuse the other person of not caring for them at all. Even with family members, individuals with BPD are highly sensitive to rejection, reacting with anger and distress to such mild separations as a vacation, a business trip, or a sudden change in plans. These fears of abandonment seem to be related to difficulties feeling emotionally connected to important persons when they are physically absent, leaving the individual with BPD feeling lost and perhaps worthless. Suicide threats and attempts may occur along with anger at perceived abandonment and disappointments.

People with BPD exhibit other impulsive behaviors, such as excessive spending, binge eating and risky sex. BPD often occurs together with other psychiatric problems, particularly bipolar disorder, depression, anxiety disorders, substance abuse, and other personality disorders.

Treatment

Treatments for BPD have improved in recent years. Group and individual psychotherapy are at least partially effective for many patients. Within the past 15 years, a new psychosocial treatment termed dialectical behavior therapy (DBT) was developed specifically to treat BPD, and this technique has looked promising in treatment studies.⁶ Pharmacological treatments are often prescribed based on specific target symptoms shown by the individual patient. Antidepressant drugs and mood stabilizers may be helpful for depressed and/or labile mood. Antipsychotic drugs may also be used when there are distortions in thinking.⁷

Recent Research Findings

Although the cause of BPD is unknown, both environmental and genetic factors are thought to play a role in predisposing patients to BPD symptoms and traits. Studies show that many, but not all individuals with BPD report a history of abuse, neglect, or separation as young children.⁸ Forty to 71 percent of BPD patients report having been sexually abused, usually by a non-caregiver.⁹ Researchers believe that BPD results from a combination of individual vulnerability to environmental stress, neglect or abuse as young children, and a series of events that trigger the onset of the disorder as young adults. Adults with BPD are also considerably more likely to be the victim of violence, including rape and other crimes. This may result from both harmful environments as well as impulsivity and poor judgement in choosing partners and lifestyles.

NIMH-funded neuroscience research is revealing brain mechanisms underlying the impulsivity, mood instability, aggression, anger, and negative emotion seen in BPD. Studies suggest that people predisposed to impulsive aggression have impaired regulation of the neural circuits that modulate emotion.¹⁰ The amygdala, a small almond-shaped structure deep inside the brain, is an important component of the circuit that regulates negative emotion. In response to signals from other brain centers indicating a perceived threat, it marshals fear and arousal. This might be more pronounced under the influence of drugs like alcohol, or stress. Areas in the front of the brain (pre-frontal area) act to dampen the activity of this circuit. Recent brain imaging studies show that individual differences in the ability to activate regions of the prefrontal cerebral cortex thought to be involved in inhibitory activity predict the ability to suppress negative emotion.¹¹

Serotonin, norepinephrine and acetylcholine are among the chemical messengers in these circuits that play a role in the regulation of emotions, including sadness, anger, anxiety, and irritability. Drugs that enhance brain serotonin function may improve emotional symptoms in BPD. Likewise, mood-stabilizing drugs that are known to enhance the activity of GABA, the brain's major inhibitory neurotransmitter, may help people who experience BPD-like mood swings. Such brain-based vulnerabilities can be managed with help from behavioral interventions and medications, much like people manage susceptibility to diabetes or high blood pressure.⁷

Future Progress

Studies that translate basic findings about the neural basis of temperament, mood regulation, and cognition into clinically relevant insights which bear directly on BPD represent a growing area of NIMH-supported research. Research is also underway to test the efficacy of combining medications with behavioral treatments like DBT, and gauging the effect of childhood abuse and other stress in BPD on brain hormones. Data from the first prospective, longitudinal study of BPD, which began in the early 1990s, is expected to reveal how treatment affects the course of the illness. It will also pinpoint specific environmental factors and personality traits that predict a more favorable outcome. The Institute is also collaborating with a private foundation to help attract new researchers to develop a better understanding and better treatment for BPD.

References

¹Swartz M, Blazer D, George L, Winfield I. Estimating the prevalence of borderline personality disorder in the community. Journal of Personality Disorders, 1990; 4(3): 257-72.

²Soloff PH, Lis JA, Kelly T, Cornelius J, Ulrich R. Self-mutilation and suicidal behavior in borderline personality disorder. Journal of Personality Disorders, 1994; 8(4): 257-67.

³Gardner DL, Cowdry RW. Suicidal and parasuicidal behavior in borderline personality disorder. Psychiatric Clinics of North America, 1985; 8(2): 389-403.

⁴Zanarini MC, Frankenburg FR. Treatment histories of borderline inpatients. Comprehensive Psychiatry, in press.

⁵Zanarini MC, Frankenburg FR, DeLuca CJ, Hennen J, Khera GS, Gunderson JG. The pain of being borderline: dysphoric states specific to borderline personality disorder. Harvard Review of Psychiatry, 1998; 6(4): 201-7.

⁶Koerner K, Linehan MM. Research on dialectical behavior therapy for patients with borderline personality disorder. Psychiatric Clinics of North America, 2000; 23(1): 151-67.

⁷Siever LJ, Koenigsberg HW. The frustrating no-mans-land of borderline personality disorder. Cerebrum, The Dana Forum on Brain Science, 2000; 2(4).

⁸Zanarini MC, Frankenburg. Pathways to the development of borderline personality disorder. Journal of Personality Disorders, 1997; 11(1): 93-104.

⁹Zanarini MC. Childhood experiences associated with the development of borderline personality disorder. Psychiatric Clinics of North America, 2000; 23(1): 89-101.

¹⁰Davidson RJ, Jackson DC, Kalin NH. Emotion, plasticity, context and regulation: perspectives from affective neuroscience. Psychological Bulletin, 2000; 126(6): 873-89.

¹¹Davidson RJ, Putnam KM, Larson CL. Dysfunction in the neural circuitry of emotion regulation - a possible prelude to violence. Science, 2000; 289(5479): 591-4.