What & Where is the Mind?:

The question of what etiologies could cause human anxieties is complicated, for me, by more esoteric questions such as: ‘where does anxiety ‘live’’, ‘what is it made of really?’, and ‘where does it really come from?‘. Coming from a medical anthropological perspective, one can also ask, ’who made western medical theory and Judeo-Christian cosmology the be-all-and-end-all of explaining things? Can we really say it’s a ‘thing‘: a biochemical by-product or a constellation of somatic, affective and cognitive sequalae that are a reaction to fear? Is it simply somatic reactions to the brains’ interpretation of sensory inputs? Perhaps emotions such as ‘anxiety’ are labeled as such because most people can not perceive and process the real source of it, nor the mechanics of it‘s creation and dissolution? Perhaps this is why western medicine really can not cure or heal anxiety disorders permanently and completely; not with drugs and/or counseling, not even with EFT or EMDR, or other American ‘mind-body’ techniques.

Let’s examine the following suppositions: the human body has many complex, interdependent homeostatic systems that affect the mind, the intangible ‘place’ where anxiety comes from. We know that we live in a quantum universe, where Newtonian and Einsteinian ‘cause and effect’ science is redundant. We know that human physiology is not only biochemical and biophysical in nature, but also bioenergetic. That is, not only can chemical compounds and various vibrational energy frequencies and durations of light, sound and ‘gross’ radiation affect human anatomy and physiology, but also ‘subtle’ energy, (beyond ordinary human perception), An example of ’subtle energy’ is the ’prana’ , ’ki’ or ’qi’ or ’lifeforce’ described in Asian medical systems like Aryveda, Traditional Chinese Medicine and the Blessing Ways of modern American Indian medicine. Grace is a ‘subtle energy’ and is by which science has proven the power of prayer in healing. Science has already discovered the biophysical mechanism by which subtle vibrational energies can affect human cell membrane physiology.

Unfortunately, human consciousness is affected by all these things, but human senses can only ‘pick up’ very small ranges of light, sound and energy. Few humans have the rare gift of sensing and being able to use Grace, prana or qi, be it in martial arts, religious practice or in the healing arts. And therein lies the caveat of this question of the etiology of Anxiety Disorders. That is, we as ordinary humans, who were trained in the classical but unreal cause-and-effect universe, and are ill equipped to explore the ‘primary mind’ in any way. We can only explore it indirectly. The discussion here of etiologies, then, is necessarily archaic; limited to popular, mainstream western biology and psychology as we know it.

The Caveat:
Let’s assume the mind is the foci of the ‘lesion’ of anxiety. The mind is not physical or chemical. All primary etiologies, therefore, must be non-chemical and non-physical. Hmm, well that is a bit of a jump. Since we know not of the nature of the connection between brain and mind, body and mind, or emotions and mind, (since we do not know what or where the mind is), we must logically assume that all suspected physical or chemical causes of anxiety disorders are necessarily secondary and in nature. This includes biological as well as psychological factors. We must also assume all symptoms are therefore secondary and indirect consequences. This is
because, due to our limited senses, we can not elucidate the true, ‘primary etiologies’ of imbalances or injuries of the mind, or consciousness.

In many ancient wisdom traditions, here is a physical body, emotional, mental and spiritual/soul body. Any imbalance or injury to an organ or system in any of these ‘bodies‘, results in messages being sent to our brain signaling distress. Spiritual, or energetic faculties of a human, permeate through these body systems as well as emotions, mind and resultant behavior. This is rarely acknowledged in science-based disciplines but worth mentioning, since this is, in my opinion, the source of ‘primary etiologies’ as well as more appropriate interventions needed to better understand problems of the mind, (consciousness-unconsciousness), and to elicit a complete and permanent cure. That being said, the confines of this paper are being limited to commonly understood biological and psychological etiologies and treatment theories as found in mainstream western medical literature.

The currently accepted biological theories about Anxiety Disorders:

There are 10 sub-types of Anxiety Disorder. They are General Anxiety Disorder, (GAD), Panic Disorder, Stress-related Anxiety, Stress-induced Insomnia, Social Phobias, Iatrogenic etiology ( drug induced ), Anxiety Disorder secondary to a primary medical illness, and Anxiety Disorder secondary to another primary mental disorder, Obsessive-Compulsive Disorder, (OCD), and Post-Traumatic Stress Disorder, (PSTD), as subcategories of Anxiety Disorder, (DSM IV, American Psychiatric Association).

Many drugs and compounds are known to cause anxiety and other psychiatric symptoms. For example, overuse of beta-agonists such as asthma inhalers (albuterol), and decongestants (phenylephrine, pseudoephedrine) and antihistamines, (diphenhydramine, hydroxazine) and ulcer medications, (cimetidine, famotidine) can cause symptoms of delirium, confusion, psychosis with anxiety. Others include corticosteroids, (prednisone), stimulants such as caffeine, guarana, ginseng, gotu kola, kola nut, ma huang and amphetamines; appetite suppressants, and cocaine. Nicotine, marijuana and cigarette smoking, (cadmium), have been implicated in causing Panic Disorders in young people, (Wikipedia - Panic Disorder).

Some diseases that mimic or create co-morbid symptoms of anxiety are cardiac injury or disease, (angina), hormonal imbalances, (PMS, adrenal exhaustion), delirium secondary to excessively high fevers, acute acid-base and glucose dysfunction, (hyper/hypoglycemia), or toxic conditions, (alcohol poisoning). Infectious diseases such as AIDS (Acquired Bacterial meningitis immuno-deficiency syndrome), parasitic encephalitis, herpes encephalitis, neurosyphilis, fungal meningitis, and behcet's syndrome have co-morbidities of anxiety disorders, delirium and so on.

Other biological etiologies may include genetic disorders or pre-dispositions. There is evidence that those with hereditary risk for alcoholism or Bipolar Disorder are also at risk for developing Panic Disorder, (Wikipedia - Panic Disorder). Nutritional deficiencies such as hypomagnesaemia has been well documented in medical literature to correlate with anxiety disorders. Other nutritional deficiencies that mimic or increase the risk of psychiatric disorders and anxiety disorders include low levels of B1, B3, B9, B12 and Vitamin C. Excessive, prolonged physical stress, trauma and/ or injury, (torture), can also cause psychotic and anxiety disorders.

The currently accepted psychological theories.

Not only are there generally agreed upon ‘usual causes’ and risk factors for various anxiety disorders, but each personality theory has it’s own view on the causes of, and treatment approaches for, anxiety disorders. In my opinion, anxiety is perceived by an individual (or organism), when any organ or combination of organs and systems become imbalanced or displaced to such a point that the body believes it is experiencing a present-time threat to the source of its life-force, and responds in any number or ways in an effort to restore alignment and balance. The foci of the threat or ‘lesion’ could be in the physical, emotional, mental or spiritual ‘body’. The sequalae may manifest in any configuration of these bodies, as with the treatment and cure.

In higher order creatures such as mammals and primates, including humans, I believe anxiety is essentially an unconscious, egoic reaction in its effort to maintain the status quo against any perceived threats ( i.e., changes, redefining) to its existence as it is. Essentially, it is a biochemical, biophysical and bioenergetic reaction to a deep, primordial, egoic fear of death. This is very similar to S. Freuds’ theory (Inhibitions, Symptoms and Anxiety, 1926), where any first real sign of neurosis most commonly presents itself as anxiety. Freud believed that anxiety is a warning to the Ego it is in impending danger of being overwhelmed by the resurgence of repressed, unconscious wishes.

Behavior Theorists believe Anxiety Disorders such as simple phobias (Social Phobia), as well as more complex ones like Panic Disorder and Obsessive-Compulsive disorders are a result of a conditioned response to fear and avoidance to certain objects, environments and situations. Behavioral-Cognitive and Cognitive Theorists add the factor of a danger-related cognitive distortion or bias of certain objects, environments and situations, being a source of fear, panic, anxiety and negative appraisals of the world and self, (Corsini & Wedding, 2008).

The Cognitive Model of Anxiety Disorders also includes the malfunctioning or excessive functioning of normal survival mechanisms. Examples are compulsive hand-washing from irrational fear of contamination, or hypervigilance of threat of rape or combat in PSTD rape victims or military combat veterans, respectively. Essentially, cognitive content “revolves around themes of danger, and the individual tends to maximize the likelihood of harm and minimize his or her ability to cope.” (Corsini & Wedding, 2008).

Gestalt Theory of Anxiety Disorders are more concerned with the process of anxiety rather than the content. Fritz Perls defined anxiety as ‘excitement minus support‘, (F. Perls 1942/92, F. Perls et al., 1951/92). Perls believed that failing to remain centered in the present, ‘futurizing’, or predicting future failure, such as stage fright, as well as irrational beliefs and misinterpretations can all trigger anxiety. Perls also considered incorrect or unsupported breathing, especially when the body needed to ramp up oxygenation, to contribute to sensations of anxiety, increased heart--rate and hyperventilation symptoms, (Corsini & Weding, 2008) . Other psychological therapies found to produce good outcomes with Anxiety Disorders are Alderian, Existential, Person-centered, Rational-Emotive, Reality Therapies and Transactional Analysis, (Psychotherapy, Psychweb.com) .

Modes of action of the medications used to treat these disorders.

BENZODIAZEPINES:
Benzodiazepines (BZDs), bind to GABA receptors in the brain. This potentiates the effects of GABA in inhibiting the hyperactivity of the brain in producing anxiety. As a therapeutic class, BZDs are Federal Drug Administration (FDA) approved for the management of Anxiety Disorders such as acute stress-induced anxiety. Some are approved for Panic Disorder. The use of diazepam, (Valium), for Panic Disorder is not FDA approved and is considered legally off-label or investigational for that indication.

Clonazepam, (Klonopin), lorazepam, (Ativan) and alprazolam, (Xanax) are FDA approved for Panic Disorder, with or without agoraphobia. Clonazepams’ off-label and investigational use includes Bipolar Disorder and as an adjunct treatment for managing Schizoprenia. Alprazolams’ off-label and investigational use includes the management of anxiety in children.

BZDs bind to steriospecific benzodiazepine receptors on the post-synaptic GABA neuron. This occurs at several sites in the central nervous system, including the limbic system, and the reticular formation. Binding to benzodiazepine receptors result in an increase in membrane permeability of the these cells. This creates a greater influx of chloride ions through the cell membrane. This shift in chloride ions results in hyperpolarization of the cell to a less excitable state, thereby increasing stabilization.

This results in the enhancement of the inhibitory effect of GABA on neuronal excitability. With the inhibition of neuronal excitation in these specific brain locations, the net physiological effect is that of a sedative and tranquilizer. In fact, benzodiazepines are often referred to as ’Sedatives’, ’Hypnotics’ or ’Tranquilizers’ . This drug class is used primarily for stress-induced initial insomnia or stress-induced anxiety
ANTIDEPRESSANTS:
A. SSRIs: Serotonin is a neurotransmitter that inhibits anger, aggression, mood, sexuality, appetite and sleep, and is found in a large part of the entire brain, from spinal cord to the cerebella cortex, (Wikipedia). SSRIs are antidepressants with selective inhibitory affects on pre-synaptic serotonin (5-HT) reuptake and only very weak effects on nor epinephrine and dopamine neuronal uptake. It has the effect of increasing the pre-synaptic availability by blocking serotonin resorption. In vitro studies show no significant activity for adrenergic, (alpha, beta receptors), cholinergic, (muscarinic receptors), GABA, dopaminergic, histaminergic, serotinergic or benzodiazepine receptors. Selective Serotonin Reuptake Inhibitors, (SSRIs) such as sertraline, (Zoloft), are FDA indicated for OCD, Panic Disorder, Social Anxiety Disorder and PTSD. Sertraline is not FDA approved for GAD. SSRIs may be useful as adjunctive therapy for anxiety disorders which are secondary to depression, (Drug Information Handbook).

B. TCAs: Tricyclic Antidepressants are FDA approved for OCD only. Off label and investigational uses include depression, panic attacks and chronic pain. Clomipramine (Anafranil), is drug of choice for OCD. It’s mechanism of action appears to affect serotonin uptake while its active metabolite, desmethylclomipramine, affects norepinephrine uptake. Norepinephrine is made from dopamine in the adrenal medulla and in the presynaptic area of neuronal cells. Norepinephrine, epinephrine and dopamine are integral to the ‘fight-flight’ stress response, increasing blood pressure, heart rate, blood glucose, alertness and attention. Prolonged elevated levels of these adrenergic neurotransmitters result in ‘adrenal burnout’ and low levels in the brain, resulting in low Cortisol levels and increasing the risk of developing ADHD, depression, anxiety disorders and cardiovascular effects, (Norepinephrine, Wikipedia). TCAs are not popular due to their non-selective receptor activity, causing many side-effects that adversely affects patient compliance. They are also dosed 3-4 times a day while newer agents are ‘cleaner’ and are usually taken only once daily.

C. MOAIs: MOAIs are thought to act by increasing endogenous concentrations of norepinephrine, dopamine and serotonin by inhibiting the enzyme monoamine oxidase. This enzyme is responsible for the metabolic breakdown of these neurotransmitters. Monoamine Oxidase Inhibitors such as phenelzine (Nardil) are rarely used for Anxiety Disorder as they are not FDA approved for such use. Tranylcypromine, (Parnate) is recognized in professional pharmacy and medical reference texts for off-label and investigational use for PTSD. Some clinical studies have suggested utility of MOAIs in Panic Disorder and Social Phobias, (Drug Information Handbook)

D. Atypicals: The Atypicals are one-of-a-kind agents that have no others in their chemical drug class. Buspirone, (Buspar) is FDA indicated and is the drug of choice for GAD. The mechanism of action is unknown. Buspirone has a high affinity for serotonin receptors (5-HT1a, 5-HT 2). It has moderate affinity for dopamine D2 receptors. Venlafaxine, (Effexor) is another currently popular drug for GAD and social phobia. It is off-label and investigational use only, for OCD. It also has a unique mechanism of action. Venlafaxine and its active metabolite, o-desmethylvenlafaxine are potent inhibitors of neuronal seratonin and norepinephrine reuptake. They are weak inhibitors of dopamine reuptake. Recent studies postulate that this may have something to do with increasing the transmission of neuronal dopamine, (Dopamine, Wikipedia).

Mirtazapine, (Remeron), is a newer FDA approved antidepressant. It is not approved for use in children. In recent years it has been seeing increased off-label trials as second or third line adjunct in various anxiety disorders. Mirtazepine is a unique drug with a complex mechanism of action. It has central pre-synaptic alpha-2 antagonist effects, which result in increased release of nor epinephrine and serotonin. It is also a potent central serotonin and histamine receptor blocker, as well as a moderate peripheral alpha-1 and muscarinic receptor blocker, . (Drug Information Handbook). All these non-selective receptor affinities, both peripherally and centrally, result in many higher risks of side-effects. Along with the fact that this drug is available brand only, not on many insurance drug-formularies , and is still prohibitively expensive, precludes this drug from being a first line agent for a few more years yet.

BETA BLOCKERS:
Beta Blockers, primarily propranolol, (Inderal) are used off-label and investigationally for ‘Acute Panic‘, such as in panic attacks and social phobias such as stage fright. Propranolol is a non-selective beta-adrenergic receptor blocker that competitively blocks response to B1 and B2 -adrenergic stimulation. This results in decreases in heart rate, blood pressure and myocardial demand which are some of the signs of acute panic attacks, (Drug Information Handbook).

The process you would go through when seeing a patient with one of these disorders:

Staging and Triage:
There are many possible etiologies for Anxiety Disorder. As hypothesizes above, all of them would necessarily be indirect or secondary in nature. A partial listing of organic/biological, environmental, pharmacological, situational and psychological risks for the development of Anxiety Disorders are discussed above. Generally, my immediate concerns would to identify, triage and stabilize the most acute and potentially dangerous signs and symptoms being presented first, if any. Sometimes the attending spouse, caregiver or other relative is also distressed in some way and may need immediate attention also.

For example, there would be a large difference in approach and treatment intensity with a destabilized GAD patient who sustained a motor vehicle accident presenting in ER, accompanied by her chain-smoking, COPD’er mother who was in the middle of a Panic Attack, versus a stage-fright issue with a young gymnast on the fast-track to the Olympics. Generally, after intake information and a signed consent form session was done, detailed history, observation, patient inquiry and lab tests would be used to rule out other possibilities and begin to differentiate the probable etiology, contributing factors, and diagnosis.

Differential Diagnosis and Treatment:
Any iatrogenic causes or co-morbidities would be either ruled out or reassessed and managed with changes in the drug regimen, diet, life-style or other interventions. This would include any contributing mental or medical illnesses, environmental toxicities, nutritional deficiencies, drug side-effects or drug interactions and so on.

If there were no evidence of acute panic attacks or chronic anxiety symptoms, it would probably be a case of an acute stress-induced anxiety event, easily treated with short term use of benzodiazepines. If discreet incidences of panic attacks seem to be the probable problem, a two phased approach would be in order. ‘Phase 1’ is for reducing the frequency and intensity of panic attacks. High potency BZDs such as lorazepam, (Ativan), and an antidepressant such as the SSRI, fluoxetine, (Prozac) would be started and discontinued six months after the patient reached symptomatic relief. Due to the many side-effects and food-drug interactions found with MOAI’s, I would avoid them. ‘Phase 2’ is concurrent counseling to address anticipatory phobias, anxiety and avoidance with gradual re-exposure techniques, as well as skill building in breathing techniques, meditation and bioenergetic self-management.

If the patient has signs and symptoms of chronic episodes of anxiety in social situations, as with social phobia, cognitive-behavioral psychotherapy is indicated, along with an SSRI or sustained release venlafaxine (Effexor), plus or minus low dose propranolol for adrenergic symptomatic relief. The drug regimens would be titrated up and adjusted to efficacy and tolerance to any side-effect complications. If the signs and symptoms indicate chronic, continuous anxiety behaviors, it may be wither GAD or OCD. If OCD behavior is evident, the treatment of choice is Behavior Therapy with an SSRI or a TCA (Tricyclic Antidepressant) like clomipramine, (Anafranil). The drug of choice for GAD is buspirone, (Buspar) and anSSRI, psychotherapy, and possibly venlafaxine, (Effexor) as an adjunct.

Again, treatment and follow-up management is also dependant on many factors: everything from insurance coverage, possible community, cultural & religious support systems versus caveats; the time-frame available for treatments and other interventions, the complexity of the etiology, the acuity of the presentation, related co-morbidities and influencing factors. As the psychotherapist, I would be included in the patients’ multi-disciplinary care team and would rely on a comprehensive, holistic approach to both differential diagnosis, as well as use Lazaruses’ BASIC ID holistic treatment approach for the care of anxiety disorder patients.

References:

1. Preston, J., Johnson, J., ‘Clinical Psychopharmacology made ridiculously simple’, Medmaster, 2008, Miami, Fl.

2. ‘Drug Information Handbook’, 13th Edition, Lexi-Comp, 2005, Hudson, OH

3.‘Diagnostic and Statistical Manual of Mental Disorders’, DSM-IV™, American Psychiatric Association, 1994

4. Corey G. ‘Theory and Practice of Counseling and Psychotherapy’, 1991

5. Carlson N. ‘Foundations of Physiological Psychology’, 1995

6. Boehler, C, Ph.D., ‘Human Services 101 - Lesson 8’, Coastal Community College, online reference:12/07http://dl.ccc.cccd.edu/classes/internet/humanservices101/lesson8.htm#multimodal

7. ‘Serotonin’, Wikipedia Online Encyclopedia, no author or date given, online reference: http://en.wikipedia.org/wiki/Serotonin

8. ‘The Brain from Top to Bottom’ , The Brain, No author or date given, online reference: http://thebrain.mcgill.ca/flash/i/i_04/i_04_m/i_04_m_peu/i_04_m_peu.html

9. Yoshimoto Sekine, M.D., Ph.D., ‘Association of Dopamine Transporter Loss in the Orbitofrontal and Dorsolateral Prefrontal Cortices With Methamphetamine-Related Psychiatric Symptoms’ Am J Psychiatry 160:1699-1701, September 2003, online reference: American Psychiatric Association

10 ‘Anxiety Disorder’, Wikipedia, no author given, 2/9/08, online reference: http://en.wikipedia.org/wiki/Anxiety_disorder

11. ‘Panic Disorder’, Wikipedia, no author given, 2/9/08, online reference: http://en.wikipedia.org/wiki/Panic_disorder

12. ‘Norepinephrine’, Wikipedia, no author given, 2/9/08, online reference: http://en.wikipedia.org/wiki/Norepinephrine

13. ‘Facts about Panic Disorder’. National Institute of Mental Health. Johnson, J. G., Cohen, P., Pine, D. S., Klein, D. F., Kasen, S., & Brook, J. S., 2000. Online reference: http://www.nimh.nih.gov/publicat/panicfacts.cfm

14. Breslau, N., & Klein, D. F. ‘Cigarette smoking and panic attacks among young adults in the community: The role of parental smoking and anxiety disorders.’ Biological psychiatry, 58(9), 686-693.1999

15. Johnson, J. G., Cohen, P., Pine, D. S., Klein, D. F., Kasen, S., & Brook, J. S. ‘Smoking and panic attacks: An epidemiologic investigation.’ Archives of General Psychiatry, 56(12), 1141-1147. 2000

16. Gorman, J. M., Kent, J., Martinez, J., Browne, S., Coplan, J., & Papp, L. A. ‘Differential carbon dioxide sensitivity in childhood anxiety disorders and non-ill comparison group.’ Archives of General Psychiatry, 57(10), 960-967. 2001. Online reference: http://ajp.psychiatryonline.org/cgi/content/full/160/9/1699
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