The Etiology of Panic Disorder
The Etiology of Panic Disorder
By John C Goodman, LCSW, MSOD-President of
Center for Internal Change, Inc.
Introduction
The etiology of panic disorder (PD) remains a mystery. This paper will explore, compare and contrast the historical and current thinking behind the possible etiologies of PD. There is much conflict, contradiction and overlap between existing theories. These theories tend to fall within one of the following three categories: biological/physiological, psychological, and psychobiological causation (which tends to be the current school of thought).
PD will first be examined for a historical perspective, where it was considered to be of biological origin. Then PD will be examined in terms of its influence on the psychic structure and its defense mechanisms. This will be explained from the psychoanalytical perspective. Then the biological and psychological implications of PD on human growth and development will be explored.
From it earliest reference the etiology of what has come to be know as PD was considered to be biologic, more specifically cardiovascular in nature (Raj & Sheehan, 1990). More recently PD has been considered to be caused by abnormalities in the sympathetic nervous system (SNS). DaCosta, in 1871 (Heninger, 1998) observed a condition among soldiers during the American Civil War, which he referred to as “irritable heart.” This condition consisted mainly of palpitations, chest pains and dizziness with no apparent trigger (Barlow, 1988) . DaCosta attributed it to a “hyperaesthesia of the cardiac nerve centers” (Heninger, 1998, p.522). In 1919, during World War I, Lewis described a very similar syndrome he called effort syndrome.” This condition had the same exact symptoms. Lewis observed that a large number of soldiers developed this syndrome during physical activity or combat. The symptoms appeared to manifest themselves in soldiers with either a nervous or physical weakness in their character or those that had been exposed to stress. Lewis hypothesized that blood acidosis generated by changes in carbon-dioxide (C02) or lactate acid levels was responsible for these attacks (Barlow, 1988). It is interesting to note that Lewis was making a psychological distinction between those who experience “effort syndrome’ and those who did not, e.g. nervous characteristics and exposure to stress. Though this condition was presented from a biological/physiological prospective it appears to indicate the presents of a psychological trigger and/or predisposition.
In 1941, Wood determined that “irritable heart” and “effort syndrome” was the same condition and named them neurocirculatory asthenia or cardiac neurosis, referring to an anxiety state with pronounced cardiovascular characteristics. Other names given to these same disorders over history were vasoregulatory asthenia, vasomotor neurosis, nervous tachycardia, and nervous exhaustion, all reflecting the same biological origin (Barlow, 1988).
In 1959 Roth discovered a separate condition referred to as phobic anxiety-depersonalization syndrome. “Roth proposed that “depersonalization and the underlying psychophysiology of the regulation of awareness associated with depersonalization might be important keys to the disorder” (Barlow, 1988, p. 90). Roth’s explanation was the first to distinguish between panic attacks and anxiety neurosis (Barlow, 1988).
Pitts and McClure were credited for defining PD as a disease. In 1967 they infused sodium lactate into subjects with a histories of spontaneous PAs to demonstrate that this would trigger a PA. Subjects with no history of PAs were unaffected by the infusion. Sims & Snaith believed this experiment substantiated that psychiatric symptoms could be induced through chemical means (1988).
In 1976 Wooley proposed that PD and mitral valve prolapse were the same illness. He found the symptoms of the two to be very similar (Raj & Sheehan, 1990). This appears to be an oversimplification. Wooley likely confused similarities, and cause and effect between symptoms of MVP and PD. Hamada, Koshino, Misawa, Isaki, and Gejyo, (1998) studied the relationship of MVP and autonomic PD. Studying 121 subjects with PD, they found the occurrence of MVP was higher in these subjects (32.2%) than in the control group(16.7%), yet they determined the difference to be insignificant. In a subgroup of PD subjects with depression, the MVP rate was 58.1%, significantly higher than the value of 25.7% observed in the PD patients without depression. These findings appear to indicate a strong relationship with the parasympathetic nervous system (Hamada, et al., 1998, p.143).
Research supports the theory that the brain chemistry of panickers may be out of balance or different then non-panickers, yet the reason remains unclear. The biological view of growth and development within the PD sufferer may be best understood by the word “predisposition.” A 1990 study by Rosenhaum revealed that:
children of parents with panic disorder and agoraphobia have particularly high rates of behavioral inhibitions to the unfamiliar compared with controls. . . . [He found] that about 15% of the normal population manifests early in life (as young as 21 months) a temperamental quality known as behavioral inhibition to the unfamiliar (Rosenbaum, 1990, p. 464).
This quality appears to heighten inhibition and arousal in times of uncertainty and challenge and may be a marker for PD later in life. There appears to be increased locus ceruleus firing and a possible lower limbic threshold to arousal and inhibition caused by unfamiliar situations (Rosenbaum, 1990). However this appears to ignore the influence of environment cues the child may be internalizing through learning or modeling, e.g. parental anxiety.
Several studies using twins also imply a genetic factor for PD (Barlow, 1988). One study (Andrews et al., 1990) on twins concludes that although there was no inheritance of specific disorders . . . there was a genetic contribution to the predisposing trait(p. 23).
Battaglia et al (1998) conducted a study to detect possible genetic or familial relationship to the onset and severity of PD. Their findings suggest:
a significant decrease in the time before the first episode of panic and onset of panic disorder from the older to the younger generation. No evidence of a generational effect on the index of severity of agoraphobia was found. Corrections for possible biases suggested that these results are not likely to be simple artifacts. (p.595)
Battaglia et al (1998) concluded that if their findings are correct then trinucleotide repeat sequences might account for the familial aggregation of PD.
Much research continues to point towards a dysfunction of the central nervous system (CNS) as the cause of PD. Though the specific dysfunctions are unknown, it appears that the midbrain structure and the noradrenegic and serotonergic neurotransmitter system may play a major role (Taylor & Arnow, 1988). The speculation that PD is caused by a neurobiological problem is supported by the consistency with which lactate, caffeine, isoproterenol, yohimbine, and epinephrine induce panic (Barlow, 1988), as well as evidence that C02 inhalation, hyperventilation, and behavior also trigger PAs (Taylor & Arnow, 1988). Reiman (1987) used a PET to identify several abnormalities in subjects with PD. Creating lactate-induced anxiety attacks in them he found they “had abnormal hemispheric asymmetries of parahippocampal blood flow, blood volume, and oxygen metabolism; abnormally high whole brain metabolism; and abnormal susceptibility to episodic hyperventilation”. (p.87) Reiman et al. (1989) again utilizing PET measurements and lactate-induced panic this time finding:
significant blood flow increases bilaterally in the temporal poles; bilaterally in insular cortex, claustrum, or lateral putamen; bilaterally in or near the superior colliculus; and in or near the left anterior cerebellar vermis. Lactate infusion was not associated with significant changes in regional blood flow incontrol subjects. Thus, the identified regions seemed to be involved in an anxiety attack. (p.493)
Another study found that PD patients sensitive to sodium lactate who were observed with a MRI scan had neuroanatomical abnormalities that usually involved the right temporal lobe. It was reported that “(s)ubjects with temporal abnormalities were significantly younger at the onset of PD and had more panic attacks compared with patients with normal MRI scans” (Ontivero et al., 1989, p. 404). Although it is clear that the neurological change can be trigger by injecting foreign substances, which unfortunately there remains no consensus as to why these agents cause panic.
It is interesting to note that many panickers trace the onset of their PD to the use of cocaine, amphetamine, or caffeine. These all increase central nervous system (CNS), noradrenergic activity, supporting the theory that noradrenergic dysfunction may be a key to the development of PD. If this theory is correct:
the main neuroanatomic structures involved with panic disorder would include the locus coeruleus and other noradrenergic midbrain sites and their ascending pathways. Yet, again, abnormalities in other neurotransmitter systems cannot be ruled out (Taylor & Arnow, 1988, p 150).
In recent clinical trials Bell & Nutt (1998) provide evidence that Serotonin has an instrumental role in PD and serotoergic dysfunction. Their study indicated the effectiveness of Serotonin reuptake inhibitors (SSRIs) in the management of PD. In conjunction with previous research showing the effectiveness of tricyclic and monoamine oxidase inhibitors in treating PD indicates a clear biological connection to PD. However they admit their findings do not fit a single theory. They concluded that it is likely different brain regions and 5-HT receptors are involved in specific ways (1998).
Recent research conducted by Wilkinson et al (1998) reveals a marked increase in the total body epinephrine-appearance rate and a smaller increase in the norepinephrine-appearance rate in subjects during spontaneous PAs.
These findings support the idea that the core abnormalities in panic disorderwill be found in those central neurobiological systems that regulate SNS function. These data suggest that the panic attack originates in the brain and only secondarily is there an excessive SNS discharge. There is an increasingly detailed and differentiated body of knowledge describing the brain regions, neuroanatomical pathways, and neurotransmitter systems relevant to fear and anxiety. [3] These are an essential aspect of the complex circuitry mediating the central pathology of panic disorder-the spontaneous panic attack-thought to be the result in appropriately triggered alarm systems. [4]
It has been shown that patients with panic disorder have a lower threshold for panic attacks to agents that stimulate several different neurobiological systems, including alterations of electrolyte balance (e.g., carbon dioxide and sodium lactate infusion [5,6]), increased adrenergic system function (e.g., yohimbine [7]), increased cholecystokinin, [8] and impaired gamma-aminobutyric acid (GABA) function (e.g., flumazenil [9]). (Wilkinson, 1998, p515)
Heninger believes the GABAA system is the most likely candidate for the central neurobiologic system regulating SNS function, where an abnormality could explain the etiology of PD (1998). Malizia et al. (1998) found supporting evidence an association with the benzodiazepine-GABA (A) receptor to PD and demonstrated that decreased flumazenil binding at this site might underlie PD.
Yet around the same time Crowe et al (1997) failed to support these findings. “Within the limitations of the candidate gene linkage method, panic disorder does not appear to be caused by mutation in any of the eight GABAA receptor genes tested”(Crowe et al., p.1098, 1997). In his admittedly limited and restricted study, no evidence was found connecting PD and eight of the 13 known human GABAA receptor subunit genes, thus DISCounting this as an indicator of familial panic disorder (Crowe et al, 1997). As he failed to investigate five of the 13 GABAA receptor subunit genes he many have only succeeded in narrowing down the scope of possible subunit genes.
Clearly external biochemical agents can trigger a PA in some individuals who may be biological or genetic predisposition to with PD. Substance abuse or use (e.g. cocaine, marijuana, and alcohol) appears in many to play an important role as a trigger, byproduct, or symptom of PD. Louie, Lannon, and Ketter (1989) found a significant relationship between cocaine use and PD. They speculated that repeated cocaine use might gradually deepen panic pathways in the brain over time having a cumulative affect, which could lead to PD.
There has also been research showing a relationship between marijuana abuse and the occurrence of PA’s and/or PD (e.g. Weil, 1970; Michelson, 1990; Strohle, Muller, & Rupprecht 1998). It has been reported that marijuana abuse may provoke panic attacks. A strong association between agoraphobia and the consumption of marijuana have been found, as well as an increased risk of anxiety reactions in patients with PD who smoke marijuana. Complicating the diagnosis of PD in marijuana users is that depersonalization (often a symptom of PD) is often the most noticeable feature of marijuana precipitated psychopathology.
In an antidotal case study an adolescent experienced onset of a PD with agoraphobia after a single PA during marijuana intoxication. Although there was no family history of PD both parents had been abstinent alcoholics for over 10 years. They suggest the possibility of a genetic link of an increased risk for PD and that there many be a greater chance of adverse subjective experiences during intoxication for those who experience depersonalization during marijuana intoxication (Strohle, Muller, & Rupprecht 1998).
A study conducted by George, Nutt, Dwyer, & Linnoila (1990) on alcoholic patients found a very high degree of PD in alcoholics. There was a positive correlation between the amount of alcohol they consumed and the degree of their anxiety. Also, they found an increased amount of alcoholism in first-stage relations of people with PD:
Common, or overlapping, neurochemical perturbations may play a role in the etiology of both disorders. This is supported by biochemicals measured in both disorders that show similar changes in the noradrenergic and GABA Systems in alcohol withdrawal and during panic attacks (George et al., 1990, p. 103).
George et al. also questions whether alcoholism may increase the chance of PD in predisposed people. Although this study implies that there might be the same type of genetic predisposition as found in alcoholism (1990), it really is not known whether psychological factors (e.g. weak ego structure, cognitive, modeled or learned factors) could also predispose one to similar neurochemical changes and PD.
Some panickers were found to have low exercise tolerance and higher than normal blood lactate levels preceding exercise (Taylor & Arnow, 1988). As mentioned earlier, Lewis first made a lactate/exercise connection in 1919. Lactate is produced naturally through physical exercise and this increase in lactate through exercise as well as when injected induces PAs in the panickers (Barlow, 1988).
In 1988, Gorman countered these theories by pointing out that some panicker’s panic while breathing normal room air, which would not alter the chemoregulatory centers in the way suggested (Taylor & Arnow, 1986). This would imply a cognitive expectation. Barlow conducted an experiment where he gave panickers CO2 mixed air to inhale and a nonfunctioning control dial to regulate the intake of the CO2 and air mixture. Although the dials did not work, the subjects rarely panicked (1988). This study will be discussed later.
Conflicting biological theories continue to abound in attempting to determine the etiology of PD. Rosenblat proposed that some PD might actually be an epileptiform phenomenon. This theory is based on the use of phobic stimulation to induce PA (1989), thus supporting a psychobiological causation. Bouwer and Stein’s research indicates there may be a direct relationship between PD and a history of traumatic suffocation, which primarily consists of respiratory symptoms and nocturnal PAs. They hypothesized such a history of may play a part instrumental in the etiology of PD (1997). These findings also suggest a psychobiological relationship of PD.
Examining the etiology of PD in terms of gender differences Yonkers et al. conducted a longitudinal study, which indicated no significant differences between gender in panic symptoms or degree of severity initially. Although women run a higher risk of have PD with agoraphobia and are more likely than men to have a recurrence of panic symptoms following remission of panic. Their study was not able to determine what types of biological and psychosocial substrates contribute to the more chronic course women often experience (1998).
In examining how men and women cope with PD, Chambless and Mason (1986) found women tend to manage panic through the defense of avoidance, while men usually used external coping mechanisms, i.e. alcohol. They also found that in testing for masculinity the less masculine a subject tested the greater the likelihood of using avoidance as a defense for coping with stress and anxiety, regardless of gender. George (1990) postulates that it is possible that separation anxiety, particularly in women, may be the early form of a defense, which will later manifest itself as PD or agoraphobia. [The relationship between separation anxiety and PD will be explored later in this paper.] Also, cultural and social factors may influence the type of avoidance chosen i.e. agoraphobia for women and alcoholism and drug abuse for men.
The psychological perspective of PD offers a diversity of explanations for its etiology. In examining the psychic structure of PD it is generally believed that PAs are not truly spontaneous. Psychoanalysts believe that these seemingly spontaneous attacks are related to the unconscious mind.
Freud, who approached psychology from a medical perspective, offers what may be more accurately described as a psychobiological interpreted what has now become known as PD. Freud believed unconscious thoughts, ideas, and fantasies, which were usually related to events during childhood, were the cause for anxiety. In Freud’s model sexual instinct also played a key role in the causation of anxiety. He also believed that PAs were triggered by both past and present events (Taylor & Arnow, 1988). Freud considered anxiety as the ego’s response to the threat of a traumatic situation. The dangers triggering anxiety entail fantasized situations with respect to separation from, or loss of, a loved object or a loss of its love (Taylor & Arnow, 1988). The particular fantasies that create anxiety are determined by a developmental progression that is influenced both by maturation and by learning (Taylor & Arnow, 1988, p. 19).
In 1917 Freud described an anxiety model distinguishing three types of anxiety: expected anxiety, phobic anxiety, and anxiety attacks. It is anxiety attacks that are now referred to as PA (Barlow, 1988). Even before that, in 1895 Freud first described what we now know as PD, referring to it as anxiety neurosis (Holland, 1989); but even for Freud, panic was not clear-cut. He found a connection between PA and agoraphobia.
In the case of agoraphobia . . . we often find the recollection of an anxiety attack and what the patient actually fears is the occurrence of such an attack under the special conditions from which he believes he cannot escape it. (Sims & Snaith, 1988, p.26).
In 1919 Freud hypothesized that “defenses against impulses toward … parental figures resulted in panic attacks (Taylor & Arnow, 1988, p. 18). These PAs may have been caused by suppressed rage. (Taylor & Arnow, 1988)
In 1920 Freud again wrote about the difficulty of defining panic:
Sometimes it is used to describe any collective fear, sometimes even fear in an individual when it exceeds all bounds, and often the name seems to be reserved for cases in which the outbreak of fear is not warranted by the occasion. Fear in an individual is provoked either by the greatness of a danger or by the cessation of emotional ties (libidinal cathexes); the latter is the case of neurotic fear or anxiety (Sims & Snaith, 1988, p. 26).
Fenichel wrote that postponement of affects or delayed emotional outbursts are often related to incidents of grief and rage as well as being used by the ego in dealing with issues of shame, disgust and danger. When the ego needs to protect itself from fear it can defer feelings to a later time. This postponement may later return as a PA (1945).
Most psychoanalysts view inhibition, symptoms, and anxiety as being inherently connected. Inhibitions restrict instinctual expression in order to avoid the anxiety occasioned by the associated unconscious dangers. The symptom is a sign of, and a substitute for, instinctual satisfaction or conflict (Taylor & Arnow, 1988, p. 17).
Psychoanalytical theories also focus on the significance of interpersonal relationships, current experiences, narcissistic disasters, i.e., fear of humiliation and loss of self-esteem and troubles with self-identity, as triggering anxiety and panic (Taylor & Arnow, 1988).
Psychoanalytical theory describes how the psychic structure attempts to use defense mechanisms to ward off PA in people with PD. Typically defense mechanisms reduce anxiety by regulating or inhibiting the desires related to the perceived danger (Taylor & Arnow, 1988). Panic occurs when the ego becomes overwhelmed by anxiety causing a failure in its ability to regulate and control. Instead of using its defense mechanisms to avoid a traumatic state it may actually create one. PAs occurs when these defenses become overwhelmed and are unable to defend against disturbing memories, images, or feelings, although the actual content often remains unconscious (Taylor & Arnow, 1988).
In individuals with PAs affect becomes overpowering, causing [seemingly] spontaneous and random anxiety (Fenichel, 1945). Normally the ego uses its defenses to cope with anxiety. Fenichel explains:
Defenses against instinctual drives are used by the ego:
to avoid the pain of traumatic panic or of loss of self-esteem. Thus… any defense is a defense against affect…. They are used so as not to feel pain. But because the anxiety, which motivates instinctual drive defenses, can be so painful itself there are defenses used directly toward the avoidance of the very feeling of anxiety (Fenichel, 1945, p. 161).
Powerful quantities of counter cathexes are often invested in the defense against anxiety. Many defensive attitudes are not directed against the situation in which the anxiety may arise but only against the appearance of the anxiety itself (Fenichel, l945, p. 479). This concept of anticipatory anxiety is a key focus for treatment in cognitive and behavioral therapies.
“The egos signal fails when the person is, as a result of previous repression, in a dammed-up state, the slight anxiety added by the judgment of danger acts like a lighted match in a powder keg (Fenichel, 1945, p. 133).
Other psychological theories define the etiology of PD and how it relates to growth and development within their paradigms. Learning theory, dating back to 1917 points to anxiety as a conditioned response to a fearful situation. As recently as 1998 a study conducted by Larson, Asmundson, and Stein substantiated previous studies showing that the resting heart rate of patients with PD is higher than a group with social phobia and a control group deemed healthy. Their findings imply that the subject with PD appeared to suffer from anticipatory anxiety (Larson et al. 1998).
The use of modeling may explain why those with panic often have at least one parent with an anxiety or depressive disorder. As children they may have picked up cues and attributes from their over-protective, abusive or neurotic parents (Taylor & Arnow, 1988). Although this argument can also be used to imply a genetic predisposition, a conditioned behavior, or ineffective parents who lacked the ability to meet the needs of their child.
Learning and behavior therapists believe that PAs are not spontaneous. Rather, a PA is a conditioned response to stimulus conditioned to elicit a panic, which is unknown to the panicker. The fact that PA is experienced as spontaneous makes it devastating to the sufferer and often leads to avoidance behavior.
Cognitive therapy differs from the learning or behavioral models in that it suggests panickers have fear of fear, they learn to anticipate danger in the presence of certain cues. It is these terrifying thoughts that produce PD (Taylor & Arnow, 1988). This cognitive explanation appears to be consistent with psychoanalytical theorists such as Freud and Fenichel as to the concept of PAs being a fear of fear, anxiety over anxiety, or panic over panic. In other words PA appears to be a response to anticipatory fear or anxiety of a consciously unknown nature. Taylor & Arnow, refer to Clark’s research in 1986, which indicated that lactate-induced panic in PD sufferers might be due to their interpretation of somatic sensations catastrophically. This would support the notion that lactate-induced panic might be psychologically caused. The physiologic symptoms caused by lactate infusion may cause subjects to interpret these as signaling the onset of a panic attack (1988). The difference is the psychoanalytic theorists believe the response to be due to ineffective ego strength and defense regulation, whereas the cognitive therapist believe it to based on learned responses or cognitive distortions.
Mechanic, in 1972, found that stressors may alter how separate events are evaluated, e.g., illness, death of a relative or witnessing an accident can increase awareness of the same events occurring in those with panic. Illness, for example, may direct attention toward somatic sensations, and if they are perceived as threatening they may trigger anxiety (Hallam, 1985). Preoccupation of these somatic sensations may intensify them, reinforcing the fears of illness and/or death. The somatic sensations occurring during times of panic and anxiety are similar to those of many illnesses, i.e., weakness, rapid heart beat, breathing problems and dizziness. This may create an over identification with others on both an affective and somatic level. This could be explained psychoanalytically as over identification; behaviorally as modeling, cognitively as catastrophic thinking, cause and effect, or other cognitive distortions; through learning theory as a learned response or relationship; or biologically as a predisposed hypersensitive autonomic nervous system.
Many psychological theories recognized control, loss, and separation issues to be primary issues within the psychic structure of those with PA and PD (e.g. Hallam, 1995; Barlow, 1988; Taylor & Arnow,1988) This can be observed by how unfamiliar perceptual experiences can cause panic, i.e., drug experiences, anesthesia, and depersonalization. What these seem to have in common is a fear of a perceived loss of control (Hallam, 1985). Mellman and Uhde found that for people with sleep panic (which occurs in 1 in 3 panickers), PA often occurs when entering the stage of deep sleep. They believe that the degree of relaxation experienced at this level can cause PA and that the panic sufferer’s mechanisms due to hypersensitivity (1990). In addition it has been shown that panic can also be induced through relaxation exercises and meditation. This too could be associated to the feeling of loss of control. The significance of these findings is that panic can be triggered without any neurobiological alteration, such as pharmacological or respiratory influences (Barlow, 1988), implying involvement of the psychological or cognitive influence.
Barlow found that panickers were hypervigilant about their body functions and had an overall feeling of helplessness and a sense of being out of control. In an experiment panickers were given CO2 mixed air to inhale and a control dial to regulate the amount of CO2 in the mixture. Although the dials did not work, the subjects rarely panicked because they had the illusion of control (1988). This appears to suggest that the psychi, based on its subjective interpretation can override a biological predisposition for panic.
Kelly (1971) found that by just being reassuring, doctors could keep some PD patients from having attacks (Taylor & Arnow, 1988). Their reassurance may interrupt the autonomic and/or cognitive chain reaction through distraction or by providing a more desirable outcome. These studies appear to indicate a mind-body or psychobiological connection between the strength and impact of one’s subjective beliefs and how they can trigger or prevent a PA. Again this can be accounted for in multiple ways depending on the paradigm one uses.
The impact on PD caused by issues of loss can be seen in terms of loss of control; loss of a significant other; loss of a job; or loss of self-esteem, self worth, or identity. “Problems with attachment and separation are linked, genetically, developmentally, and causally withpanic disorder in adults. (Taylor & Arnow, 1988, p. 24) Developmentally PD in adults appears to be related to separation anxiety in childhood. Neurotic anxiety or separation anxiety results from insecure bonding to the attachment figure, brought about by real life experiences of unavailable or unresponsive caregivers (Taylor & Arnow, 1988, p. 22). Taylor & Arnow pose an interesting question: Do the parents have trouble separating from their children, thereby teaching them to be phobic, and, if so, are both the problems of the parents and the children partly genetic? (1988, p. 23) Children experiencing panic and trauma upon separation from their love object may 1ater find it later manifesting itself as panic and/or agoraphobia, which is thought to be an adult expression of those childhood stresses. This hypothesis is supported by the “similarity of drug treatment effects for separation anxiety and adult agoraphobia; family concordance for separation anxiety and agoraphobia; and history of childhood separation anxiety in agoraphobia adults (Barlow, 1988, p. 212). Taylor & Arnow (1988) found that in adults most PDs begin as a spontaneous PA within six months after a major stressful event. Of these events, the number one stressful situation was separation, followed by job changes and pregnancy. Yet all of these examples can be explained in multiple ways: psychologically as an early development deficit, as a learned/modeled behavior, or a conditioned response, as well as a genetic predisposition.
Rosenbaum (1990) found that children of panickers were substantially more inhibited in novel situations than their peers. They also tended to be more fearful about normal stressful events such as going to the doctor, speaking in class or riding in elevators (p. 464).
Rosenbaum, (1990) admits it is unknown whether people are genetically predisposition to PD or if it is learned from nervous parents, yet he agreement that something must happen to trigger Pas. In addition to the feelings associated with separation anxiety in childhood and the disrupted attachment bonds from adults, child abuse, negative developmental experiences, physiological triggers such as substance abuse and major life events (i.e., college, moving to a new home, job changes and marital stress) appear to cause PD.
In conclusion, the original thinking on the etiology of PD was divided between a biological (neurological or cardiovascular) causation and a psychological (psychic defense overload or learned behavior) causation. Current thought takes the perspective of a multi-dimensional etiology. There appears to be a variety of pharmacological agents, which have been shown to induce panic, which are associated with several different neurobiological processes. Some of these processes appear mutually exclusive. Exploring the psychic structure of the panicker we see during PD the ego becomes overwhelmed by anxiety. It turns to its defense mechanisms for relief. These defenses become overwhelmed and somatic symptoms appear, thus producing a PA. The overwhelmed ego is expending all of its psychic energy on coping, leaving little energy to use for growth and development. It appears that loss is a psychological key to anxiety. e.g. love loss, love object loss, and loss of control. As development, growth and life proceed, various developmental, environmental or psychobiological events may cue any genetic or learned predisposition one may have and influence when and how one experience and copes with such situations. “These feelings of loss of control may be associated (learned) with specific patterns of somatic symptoms” (e.g. Lindemann & Finesinger, 1938) and may also be present in healthy individuals at less severe levels. More likely the answer will be found in a complex psychobiological interaction (Barlow, 1988). Although there is no definitive etiology to PD it is important to realize how common PD and PA is, what are there likely triggers, and to be aware of there prevalence with other psychiatric disorders.
Biologically, PD sufferers may have a genetic time bomb waiting to go off, yet it appears there must be some trigger to ignite the fuse. Whether the trigger is genetically set or environmentally, psychologically, experientially, cognitively, or behaviorally triggered. With the knowledge and theories, which have evolved over time it is now possible to defuse, dismantle, or even dispose of this bomb through effective biological, cognitive, behavioral, and other interventions.
ADDIN ENBbu Andrews, G., Stewart, G., Allen, R., & Henderson, A. S. (1990). The genetics of six neurotic disorders: A twin study. Journal of Affective Disorders, 19(1), 23-29.
Balom, R., Jordan, M., Pohl, R., & Yeragini, V. (1989). Family history of anxiety disorder in control subjects with lactate induced panic attacks. American Journal of Psychiatry, 146(10), 1304-1311.
Barlow, D. H. (1988). Anxiety and its disorders. New York: Geilford Press.
Battaglia, M. MD, Bertella, S., MD, Bajo, S., MD, Binaghi, F. Ph.D., & Bellodi, L.,MD (1998). Anticipation of Age at Onset in Panic Disorder. The American Journal of Psychiatry, 155(5), 590-595.
Bell, C. J., & Nutt, D. J. (1998). Serotonin and panic. British Journal of Psychiatry, 172(June), 465-71.
Bellodi, L. M., MD, Giampaolo, P., Ph.D., Caldirola, D. MD, Arancio, C., MD, Bertani, A. MD, & Di Bella, D. MD (1998). CO2-Induced Panic Attacks: A Twin Study. The American Journal of Psychiatry, 155(g)(September), 1184-1188.
Bibb, J. L. Chambless, D.L. (1986). Alcohol use and abuse among diagnosed agoraphobics. Behavior Research and Therapy, 24(1), 49-58.
Bouwer, C. M.,& Stein, Dan J.(1997). Association of Panic Disorder With a History of Traumatic Suffocation. American Journal of Psychiatry, 154(11), 1566-1570.
Chambless, D. L., & Mason,J. (1986). Sex, sex-role stereotyping and agoraphobia. Behaviour Research and Therapy, 24(2), 231-235.
Crowe, R. R. MD, Wang, Z., MD, Noyes, R., Jr., MD, Albrecht, B. E., Ph.D., Darlison, M. G. Ph.D., Bailey, M. E., Ph.D., Johnson, K. J., Ph.D., Zoega, T., MD (1997). Candidate Gene Study of Eight GABA sub A Receptor Subunits in Panic Disorder.
Fenichel, O. (1945). The psychoanalytic theory of neurosis. New York: W. W. Norton.
George, D. T., Nutt, D. J., Dwyer, B. A., Linnoila, M. (1990). Alcoholism and panic disorder: Is the comorbibity more the coincidence? Acta Psychicatric Scandinavia, 81(2), 97-107.
Hallam, R. S. (1985). Anxiety: Psychological perspectives on panc and agoraphobia. New York: Academic Press.
Hamada, T., Koshino, Y., Misawa, T., Isaki, K., & Gejyo, F. (1998). Mitral valve prolapse and autonomic function in panic disorder. Acta Psychiatrica Scandinavica, 97(2), 139-143.
Heninger, G. R. (1998). Catecholamines and Pathogenesis in Panic Disorder (Commentary). Archives of General Psychiatry, 55(6), 522-523.
Holland, H. E. (1989). A hypnotherapeutic approach to panic disorder. In M. D. Yapko (Ed.), Brief therapy approcaches to treating anxiety and depression. (pp. 226-244). New York: Brunner/Mazel.
Larson, D. K., Asmundson, G. J., & Stein, M. B. (1998). Effect of a novel environment on resting heart rate in panic disorder. Depression Anxiety, 8(1), 24-8.
Louie A. K., Lannon R. A., & Ketter T. A. (1989). Treatment of cocaine-induced panic disorder. American Journal of Psychiatry, 146(1), 40-44.
Malizia, A. L. MBBS, MRCPsych, Cunningham, V. J. Ph.D., Bell, Caroline J. MBBChir, MRCPsych, Liddle, P. F. Ph.D., MBBS, FRCPsych, Jones, T. Ph.D., DSc(Hon), & Nutt, D. J. MBBS, DM, MRCP, FRCPsych (1998). Decreased Brain GABAA -Benzodiazepine Receptor Binding in Panic Disorder: Preliminary Results From a Quantitative PET Study. Archives of General Psychiatry, 55(8), 715-720.
Positron emission tomography (PET) allows the measurement of benzodiazepine-gamma-aminobutyric acidA (GABA(A)) receptor kinetics. We employed flumazenil radiolabeled with carbon 11, a radioligand that labels the benzodiazepine site on the GABA(A) receptor, and fully quantitative, high-sensitivity PET to test the hypothesis that central benzodiazepine site binding is decreased in medication-free patients with panic disorder. METHODS: We compared 7 patients with panic disorder who had been off medication for at least 6 months and who had never abused alcohol with 8 healthy controls. The resulting parametric voxel-by-voxel maps were analyzed by voxel-based and region of interest- based methods using both parametric and nonparametric statistics. RESULTS: The major finding was that there is a global reduction in benzodiazepine site binding throughout the brain in patients with panic disorder compared with controls. There were sex differences in the 2 samples, but a separate analysis excluding women led to the same conclusions. In addition, the loci with the largest regional decrease in binding (right orbitofrontal cortex and right insula) were areas thought to be essential in the central mediation of anxiety. CONCLUSION: These results must be considered preliminary but are congruous with previous clinical psychopharmacologic evidence of involvement of the benzodiazepine-GABA(A) receptor and demonstrate that decreased flumazenil binding at this site may underlie panic disorder.
Mellman, T. A., Uhde, T.W. (1990). Patients with frequent sleep panic: clinical findings and response to medication treatment. Journal of Clinical Psychiatry.
Michelson, L., Marchione, K., Greenwald, M., Glanz, L., Testa, S., & Marchione, N. (1990). Panic disorder: Cognitive-behavioral treatment. Behavior Research and Therapy, 28(2), 141-151.
Ontiveros, A., Fontaine, R., Breton, G., & Elie, K. (1989). Correlation of severity of panic disorder and neuroanatomixal changes on magnetic resonance imaging. Journal of Neuropsychiatry and Clinical Neuroscience., 1(4), 404-408.
Raj, A.,& Sheehan, D. V. (1990). Mitral valve prolapse and panic disorder. Bulletin of the Menninger Clinic, 54(2), 199-208.
Reiman, E. M. (1987). The study of panic disorder using positron emission tomography. Psychiatry Developments, 5(1), 63-78.
Reiman E. M., Raichle M. E., Robins E, Mintun M. A., Fusselman M.J., Fox P. T., Price J.L., and Hackman K.A. (1989). Neuroanatomical correlates of a lactate-induced anxiety attack. Archives of General Psychiatry, 46(6), pp.493-500.
Rosenbaum, J. F. (1990). A psychopharmacologist’s perspective on panic disorder. Bulletin of the Menninger Clinic, 54(2), 184-198.
Rosenblat, H. (1989). [Letter to the editor]. American Journal of Psychiatry, 146(6), 801-802.
Sims, A. Snaith, P. (1988). Anxiety in clinical practice. New York: John Wiley & Sons.
Strohle, A., Muller, M., & Rupprecht, R. (1998). Marijuana precipitation of panic disorder with agoraphobia. Acta Psychiatrica Scandinavica, 98(3), 254-255.
Taylor, C. B., & Arnow, B. (1988). The nature and treatment of anxiety disorder. New York: Free Press.
Weil, A. T. (1970). Adverse reactions to marijuana. Classification and suggested treatment. New England Journal of Medicine, 282(18):997-1000.
Wilkinson D. J., Thompson J. M., Lambert G. W., Jennings G. L., Schwarz R. G., Jefferys D., Turner A. G., & Esler M. D. (1998). Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Archives of Gem Psychiatry, 55, 511-520.
Yonkers, K. A. MD, Zlotnick, C., Ph.D.; Allsworth, J., Warshaw, M.,MSS, MA; Shea, T. Ph.D.; Keller, M. B., MD (1998). Is the Course of Panic Disorder the Same in Women and Men? The American Journal of Psychiatry, 155(5), 596-602.
John C Goodman, MSOD, LCSW, LCSW, is the President and Director of Center for Internal Change, Inc. and Center for Professional Change. He is a Personal & Business Coach, Psychotherapist, Change Facilitator, and Performance Enhancement Coach empowering individuals, couples, groups, and organizations. John specializes in NLP, EMDR, hypnosis, and cognitive technologies. He has a private practice in Glenview, IL 60025, Chicago and Oak Lawn. He consults, and offers workshop and seminars. John can be contacted a (847) 259-0005 or email us.
