H
uman beings have attempted to make sense of our mental and emo-tional life and mental illness for centuries. We are bound by our style of scientific inquiry, philosophy, spiritual frame of reference, cultural biases, and technology. These factors have determined how we have defined anxiety disorders through time. We have tried to explain anxiety dis-orders and other mental illness with various theories: demonic possession, physical anomalies, nerve problems, personal weakness, and brain dysfunction.Physicians, scientists, and philosophers have wrestled with ways to make sense of and cure or alleviate anxiety for centuries. There were hints of insight along the way. The Greeks figured it out the best without the technology to truly examine their theories. At a fundamental level, they understood the role of the brain and the nervous system. Unfortunately, these theories were lost for centuries, as the technology to provide the supporting evidence was not yet developed.
Great advances were made in the latter half of the twentieth century.
Research in the 1990s, in particular, propelled us forward, during what was designated the Decade of the Brain. Technological advances allowed great leaps in our understanding of brain anatomy, neurocircuitry, and neurochemi-cals, and they raised even more new questions. Technology changes rapidly,
and it is staggering to imagine the discoveries ahead of us. Advances in sci-ence hold great promise for our ability to make even greater strides.
CLASSIFICATION
As mentioned earlier, there is an ever-evolving attempt to improve the classification of mental disorders, including anxiety disorders. Current classifi-cation issues regarding anxiety disorders include the investigation of biological and genetic determinants and differences in treatment outcome that may aid in differentiating subtypes of disorders. The ultimate goal of improving classifi-cation is to enhance treatment efficacy.
Researchers are attempting to tease out differences in obsessive-compulsive disorder (OCD) symptoms and what are called OCD spectrum disorders. The symptom of hoarding has been classified under OCD since it clearly involves obsessions and compulsions. Hoarding occasionally occurs with other OCD symptoms, but is usually the predominant and often the solitary symptom. The manifestations range from collecting newspapers and magazines, food items, old bills, and bank statements to taking in large numbers of animals. The symptom of hoarding does not respond to treatment with medication and is very resistant to exposure-response prevention (ERP) strategies. Genetic stud-ies have indicated a distinct feature on chromosome 14 that is unique to hoarders. In addition, a positron emission tomography (PET) imaging study conducted at the Neuropsychiatric Institute of the University of California, Los Angeles (UCLA), has discovered that the brain activity of patients with hoarding compulsions differs from those with other OCD symptoms. This find-ing will hopefully lead to the development of different medications that could improve treatment success for patients who hoard.
The Decade of the Brain
In 1990, President George H.W. Bush designated the 1990s the Decade of the Brain, ‘‘to enhance public awareness of the benefits to be derived from brain research’’ through ‘‘appropriate programs, ceremonies, and activities.’’ The National Institute of Mental Health and the Library of Congress endeavored to advance the goals set forth in the president’s proclamation. Research, educational activities, and conferences were initiated and funded to expand exploration and to acquaint both the general public and lawmakers with cutting-edge research on the brain (http://
www.loc.gov/loc/brain/).
Hoarding appears to be differentiated from other OCD symptoms, and many of its sufferers tend to be more impaired than those with nonhoarding OCD.
Furthermore, the hoarding of animals has components that distinguish it from typical hoarding and OCD. People who suffer from this type of hoarding are predominantly female, over sixty years of age, and unmarried, and more than half of sufferers live alone. Animal control authorities often discover that there are numerous dead animals in the home and that the animals are neglected and living in filth. The patient generally insists that the animals are well maintained and is unable to acknowledge the dire conditions. Treatment is seldom effective, and the recidivism rate is very high. Research is indicating that general hoard-ing and animal hoardhoard-ing should be either subcategories of OCD or identified as distinct disorders. More research is called for to explore distinguishing character-istics and to propose improved treatment regimens.
The OCD spectrum disorders include obsessive-compulsive personality disor-der (the presence of OCD traits without intense anxiety and impairment); tic dis-orders, such as Tourette’s disorder (the presence of vocal and motor tics);
hypochondria (preoccupation with having a serious disease); trichotillomania (hair pulling and skin picking); body dysmorphic disorder (having the fixed belief that an aspect of one’s appearance is grossly flawed and trying compulsively to hide or alter that aspect); and, some would suggest, eating disorders. Patients who suffer from these spectrum disorders often also meet the criteria for OCD, but these disorders are not classified as anxiety disorders. Researchers are exploring their relationship to OCD and reexamining their classification.
The various circumstances under which someone develops posttraumatic stress disorder (PTSD) are also being examined for possible subtyping and characterization. Prolonged, ongoing trauma, as in the case of long-term refu-gee status and ongoing child abuse or sexual molestation, creates a different stress pattern than a one-time event. Patients suffering from complex PTSD experience unique symptoms. The survivor may feel responsible for the abuse, can be preoccupied with the perpetrator and his or her alleged power, and may seek revenge. In addition, those who suffer from chronic traumatic experi-ences sometimes have severe problems with affect regulation, where emotional responses are uncontrollable and unpredictable, and often resort to self-harm or self-mutilation as a way to cope with distressing affect. Frequently, survivors of chronic abuse are diagnosed with a personality disorder such as borderline, dependent, or histrionic personality, and there is a tendency to blame the vic-tim. From the borderline personality disorder (BPD) frame of reference, it has been observed that many patients with BPD have a trauma history. Again, fur-ther knowledge about this phenomenon will aid in the development of effec-tive treatment.
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ETIOLOGY AND BIOLOGY
Of all the anxiety disorders, PTSD had been the least researched disorder until recent years. Fortunately, the wealth of research currently being con-ducted has revealed much about this complex disorder and its contributing eti-ological factors. For example, women are twice as likely to develop PTSD as men, and it has been observed that African Americans and Hispanic Ameri-cans are more likely to develop PTSD than European AmeriAmeri-cans. This was identified even after taking into account or controlling for the fact that, in the United States, these former groups are exposed to more traumatic events. No clear answers exist as to why women and members of the above racial and eth-nic groups are more vulnerable to the development of PTSD. Many questions need to be answered regarding PTSD and resilience, constitutional factors, and the role of environment and family. The goal of research is to improve prediction and enhance the ability to develop hardiness or resistance to PTSD, especially for members of the military.
Genetics
The study of genetics holds much promise for the ability to predict, treat, and hopefully alter the development of anxiety disorders. Recognizing that people who have a genetic predisposition to anxiety disorders are more easily triggered by stress to experience impairing anxiety, Finnish researcher Iiris Hovatta and colleagues focus their work on trying to understand the molecular and cellular processes that link genes to the regulation of anxiety behavior. In a study published in 2008, Hovatta’s team found that specific genes correlated with specific anxiety disorders, including generalized anxiety disorder (GAD), social phobia, and panic disorder. Further work is necessary to replicate these findings and support this research, but the outlook is promising. Already, col-laborators in Spain and the United States are attempting to replicate these findings to see whether the genes identified by Hovatta’s group also predispose other populations to anxiety disorders.
As mentioned earlier, there are interesting findings around the catechol-O-methyltransferase gene (see Chapter 5). Again, replication is important, as is further research on the exact action of the enzyme produced and its impact on the neurotransmitters in the prefrontal cortex.
Neurobiology
Some of our knowledge about neurotransmitters has come from studies focused on the function of the drugs used to treat anxiety disorders. This area
still holds promise as research continues. An interesting example of this is a result of the 1977 discovery of benzodiazepine receptors in the brain, which led to the conclusion that the naturally occurring substance in the brain that binds to these receptors may be anxiolytic. These substances have yet to be discovered. The discovery that selective serotonin reuptake inhibitors (SSRIs) seem to stimulate the growth of serotonin-specific neurons leads to further research on the exact mechanism of how the brain creates and utilizes sero-tonin in response to SSRI treatment.
Promising results from studies that have examined the neurobiological cor-relates of therapeutic improvement have emerged. Early studies have shown improved autonomic nervous system functioning, specifically improved para-sympathetic tone, following cognitive-behavioral therapy (CBT). Jeffrey Schwartz has reported brain activity changes observed via neuroimaging fol-lowing CBT treatment of OCD. Neuroimaging has allowed for the identifica-tion of the brain structures that are implicated in the experience of anxiety disorders. A PET scan, in which a radioactive isotope is attached to glucose, is used to identify active parts of the brain when the patient is introduced to par-ticular stimuli. A useful example of this is the identification of brain structures involved in OCD. In 1994, it was observed that there is a loop of electrical ac-tivity from the frontal lobe to the basal ganglia and back to the frontal lobe, seemingly creating a ‘‘stuckness’’ that is characteristic of OCD. This was dis-covered to be altered by the administration of Prozac. The use of PET scans and other neuroimaging techniques will lead to further discoveries about the functioning of the brain in anxiety disorders.
TREATMENT Psychopharmacology
A better understanding of the genetics and the biological processes of anxiety disorders will likely improve and expand their treatment options. No specific pharmaceutical solutions are currently available for anxiety, since benzodiaze-pines are not an answer and the antidepressants that are prescribed for the treat-ment of anxiety disorders are not effective for all patients. Researchers have noticed significant differences among SSRI nonresponders. For example, for some patients, SSRIs do not boost the availability of serotonin, while other patients may experience an increase in available serotonin but it is not utilized by the receptor sites. Scientists are investigating the causes of these failures and possible solutions. Deeper understanding of neurobiology will aid in the develop-ment of better drugs specifically targeting anxiety disorders.
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In 2006, pregabalin (Lyrica), a medication that had been approved for the management of neuropathic (nerve) pain and seizures, was approved in Europe for the treatment of GAD. Lyrica was approved following five randomized dou-ble-blind clinical trials involving more than two thousand patients, with sig-nificant findings of efficacy in managing emotional and physical symptoms of anxiety. A paper presented at the annual conference of the American Psychi-atric Association in 2009 reported promising results, especially with refractory anxiety disorders. Lyrica is believed to calm extra electrical signals in the nerves, thus reducing nerve pain, and also calming the increased neural excit-ability of anxiety. Further research is needed for U.S. Food and Drug Adminis-tration (FDA) approval of Lyrica in the United States. In addition, studying the mechanism of action of Lyrica may lead to increased understanding of the neural workings of anxiety disorders.
In the case of PTSD, there has been minimal support for pharmacological interventions. As mentioned, Zoloft has some support and received FDA ap-proval for PTSD management. In addition, Prozac has shown some efficacy in the treatment of women with PTSD. Psychopharmacological treatment of PTSD is still in its early stages, and attention needs to be focused on the vari-ous presentations of the disorder. Studies continue to develop new pharma-ceuticals and to examine combined treatments for PTSD.
Specific phobias seldom respond to pharmacological treatment, and if they do, the medication tends to interfere with CBT treatment. However, there may be certain types of specific phobias with similarities to panic with agora-phobia, such as the fears of driving and flying, and claustroagora-phobia, which may benefit from the use of an SSRI. Further research is needed to explore the via-bility of such treatment.
Other Biological Treatments
Eye movement desensitization and reprocessing (EMDR) is being used in the treatment of PTSD, and evidence has shown that it is possibly as effective as exposure and cognitive strategies, but not better. It is usually coupled with other treatment approaches, which makes the outcome of EMDR difficult to separate from the other components of treatment. Since there are no psycho-logical or cognitive neuroscience theories behind EMDR, basic research must be done to determine the neurological changes that allegedly take place and to determine whether it is a treatment component with any real value.
The psychosurgical intervention of bilateral cingulotomy for the treatment of OCD was discussed earlier, but there are also some early favorable results for other neurosurgical treatments. Deep brain stimulation (DBS), which was
developed in Europe in the late 1980s and first used in the United States at the Mayo Clinic, stimulates the brain with mild electrical signals, causing the brain’s electrical impulses to be reorganized. This has been used to treat essen-tial tremor and Parkinson’s disease since 1997. A battery-operated pulse gener-ator is implanted near the collarbone and is attached via a subcutaneous (under the skin) wire to an insulated wire lead with four electrodes at the tip, which is surgically implanted into the targeted area of the brain. The genera-tor is left on during waking hours and sends electrical impulses to the brain.
The most common side effects, which are mild and reversible, are a temporary tingling in the limbs, slight paralysis, slurred speech, and loss of balance.
Although the surgery is risky, patients tolerate the treatment well and have a significantly improved quality of life.
Scientists have observed that DBS also reduces depressive and obsessive-compulsive symptoms, and as a result, studies have focused on the use of DBS to treat these mental disorders. A modified device has been designed to target OCD, since the areas of the brain that are affected are different from those for movement symptoms. A study by Helen Mayberg of Emory University in 2005 identified the particular area to be targeted in the subgenual cingulate region of the brain. The device was approved for the treatment of severe, refractory OCD in early 2009. Unfortunately, the surgical procedure carries some risks, but the results have been dramatic. Subjects for this study, led by Benjamin Greenberger at Brown University, were severely impaired by their OCD, and most have been restored to a reasonable level of functioning in their lives, including returning to work. Research continues, and this technique could eventually replace cingulotomy as a treatment for refractory OCD.
Naturopathic Treatment of Anxiety Disorders
Alternative medicine attempts to address medical illnesses with a combina-tion of natural therapies in order to restore balance and normal bodily func-tioning. This approach has a very strong mind-body emphasis. Since the daily functioning of people affects their well-being, naturopathic physicians assess nutrition, sleep hygiene, and exercise level, and make adjustments as needed.
They also assess the presence of any underlying physical illnesses and treat them accordingly. Numerous strategies exist within the naturopathic realm.
Acupuncture falls into this category and has demonstrated some effectiveness in treating anxiety disorders. In addition, natural and synthetic supplements are widely utilized. Vitamins, such as B12 and B-complex, and minerals, such as magnesium, seem to have some effect on anxiety symptoms. Herbal prepara-tions, such as valerian and kava kava, have also been used to treat anxiety Future Directions 119
disorders. Since these substances are not regulated, their preparations are not standardized. There is very little rigorous study of these applications; however, recognition of their potential usefulness has begun to prompt scientific research. It is also important to assess side effects and any potential for toxic-ity. The use of kava kava has raised such questions, and it needs to be tested to determine its safety. Naturopathic treatment holds great promise but needs standardization and rigorous study to determine its usefulness and how it might be combined with other approaches to treat anxiety disorders.
Psychotherapeutic Treatment
The development of CBT was a major leap forward in the treatment of anxiety disorders. Scientists have developed new theories and techniques within this framework and have combined CBT with other psychotherapeutic approaches, including more psychodynamically oriented techniques. Com-bined methods of psychotherapeutic treatment are especially being studied for the treatment of PTSD. As an adjunctive therapy, interpersonal therapy, which has its roots in psychoanalysis and emphasizes the ways in which a per-son’s relationships and social context maintain symptoms, seems to have effi-cacy with some people who suffer from PTSD. Much treatment-outcome research focuses on finding what works best for whom by examining treatment methods designed for particular subpopulations of patients. A variety of factors may affect outcome, such as culture, intelligence, gender, comorbidity, and age. The military itself has taken a huge step forward by establishing programs for returning service people. For example, the U.S. Navy launched weekend workshops for returning personnel in July 2009.
Research is also focusing on early intervention and prevention of anxiety disorders. Learning about protective factors and parenting styles assists in designing these types of programs for children. For example, identifying chil-dren with behavioral inhibition or anxiety sensitivity can prompt a referral for early intervention. Research has shown a significant long-term reduction in anxiety in children with anxiety traits (anxious, but not yet meeting criteria for a specific diagnosis), separation anxiety, and social phobia who were treated in a school-based program. Programs are also being developed that can be family-based and include parent training. Some schools already have pro-grams to help children deal with bullying, which is a risk for shy, inhibited children. It would be interesting to do longitudinal studies of children who have received early intervention treatment to examine the course of the ill-ness over time and utilization rates of later therapy. Studies also have looked at the best years for early intervention. Some findings indicate that the best