The psychophysiology of blood-injection-injury phobia: Looking beyond the diphasic response paradigm

“…of anxiety by exposure is based on the idea that during exposure, the patient first exhibits a steady increase in physiological activation, anxiety, and arousal, which then should be resolved during later stages of exposure through processing of fearincompatible experience (Foa & Kozak, 1986).”

“To estimate cardiac vagal activity in a more conservative way, a number of adjustment procedures have been proposed that should become a standard part of the experimenter’s instrumentation (Grossman & Taylor, 2007; Ritz et al., 2001; 2006; Wilhelm et al., 2004).”

“From this perspective, the respiratory relief maneuver could be expected to lead to symptomatic worsening in panic patients, given the likelihood of CO2 build-up that has been suspected of triggering a suffocation alarm system in panic patients (Klein, 1993; Roth et al., 2005).”

“…applied relaxation demonstrated equal if not stronger effects in reductions on standard measures of the phobia, such as the Fear Survey Schedule (Wolpe and Lang, 1964) or the Mutilation Questionnaire (Klorman et al., 1974); e.g., the range of effect sizes (g) was 1.82–2.13 versus 2.73–3.73 for…”

“Lay instructions to “take a deep breath” to overcome anxiety may speak to that, as well as the demonstrated positive impact of paced breathing instructions (Clark & Hirschman, 1990; Harris et al., 1976) or instructions in “focused breathing” (Arch & Craske, 2006) on negative affect.”

“Indices such as HR or BP are ambiguous with respect to the underlying autonomic regulation (Berntson et al., 1991).”

“, 2009), and physiological changes and effects sizes of other outcome measures do not suggest a clear superiority of applied tension over other techniques: in particular, exposure alone and/or applied relaxation demonstrated equal if not stronger effects in reductions on standard measures of the phobia, such as the Fe…”

“Beyond their successful combination in exposure and cognitive therapy interventions for specific phobias (Choy et al., 2007), it would be impossible to administer in vivo exposure without at least minimal cognitive elements, such as provision of a treatment rationale and discussion of the patient’s…”

“Challenging laboratory stressors, particularly those requiring some type of active coping, clearly can be expected to increase HR and BP substantially (Obrist, 1976).”

“In this region, low-frequency cardiovascular fluctuations related to baroreflex regulation are located, which can be superimposed with fluctuations in RSA when respiration rate slows down to this frequency (resonance frequency; Lehrer et al., 2003).”

“It is well-known that breathing excursions systematically modulate HR and BP (Hirsch & Bischop, 1981; Grossman et al., 1991; Eckberg, 2003).”

“Interestingly, hyperventilation has been linked to experiential states of overwhelming distress, pain, passive coping, or failure to mount an adequate coping response (Boiten et al., 1994).”

“…been demonstrated in aborting or delaying fainting responses due to orthostatic challenges in patients with autonomic failure or unspecified vasovagal syncope (Krediet et al., 2002; Kim et al., 2005; ten Harkel et al., 1994; van Dijk et al., 2005; van Lieshout et al., 1992; Wieling et al., 1993).”

“Again, most evidence is available from orthostatic stress testing, with some studies finding decreases in noradrenaline and/or increases in adrenaline leading up to or following syncope (Van Lieshout et al., 1991; 1997).”

“Thomas Lewis (1932), who had introduced the term “vasovagal syncope,” described two phenomena: the bradycardia with massive HR slowing and a vasodilation with an excessive fall in BP.”

“Again, most evidence is available from orthostatic stress testing, with some studies finding decreases in noradrenaline and/or increases in adrenaline leading up to or following syncope (Van Lieshout et al., 1991; 1997).”

“Keywords Blood-injection-injury phobia; diphasic response; vasovagal syncope; respiration; hyperventilation; applied tension Blood-injection-injury phobia is a Specific Phobia that affects about 4% of the population in the United States (Stinson et al., 2007).”

“An exception is the role of disgust as a key response to BII-stimulus exposure, which has received a more in-depth treatment recently (for a review see Cisler et al., 2009).”

“The typical response pattern has been described in the literature as an event comprising two phases, the diphasic (alternatively, using the Latin prefix: biphasic) response (e.g., Engel, 1978; Kozak and Montgomery, 1981; Thyer and Curtis, 1985).”

“In healthy individuals, voluntary hyperventilation from a PCO2 of 40 down to 20 mmHg leads to reductions in CBF of approximately 50% (Claassen et al., 2007), which is markedly more than can be achieved through orthostatic stress by lower body negative pressure alone (Levine et al., 1994).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript susceptible individuals (Papp et al., 1993; Abelson et al., 2001; Wilhelm, Trabert, et al., 2001).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript 2000; Tolin et al., 1997), although studies are not consistent (see also Sawchuk et al., 2002).”

“This second phase makes BII phobia a unique phenomenon among the anxiety disorders and has provoked a plethora of functional interpretations and speculations about its adaptivity (e.g., Alboni et al., 2008; Bracha et al. 2007; Marks, 1988).”

“In the central nervous system, adenosine is known to inhibit excitatory neurotransmission and to induce sleep (Gallopin et al., 2005).”

“In earlier reports, respiratory abnormalities such as frequent yawning, sighing, or hypocapnia have been observed during or preceding the development of syncope induced by orthostatic stress (e.g., Weissler et al., 1957; Epstein et al., 1968; see also Lipsitz et al. 1998; van Lieshout et al., 1991).”

“Novak et al. (1998) observed no significant change in the overall average respiration rate during tilt-table testing, but reported qualitative observations of episodes of rhythmic breathing interrupted by deep breaths, faster respiration rate, irregular respiration, or apneas.”

“In contrast to classical breathing retraining or the respiratory control technique, which emphasize “deep” abdominal breathing (Schmidt et al., 2000; Craske et al., 1997), the shallowness aspect aimed to Ritz et al.”

“Similarly, novel stimuli elicit orienting responses that entail HR decelerations below initial levels (e.g., Turpin, 1986; Öhman et al., 2000).”

“There are also indications that BII-phobia patients have a heightened disgust sensitivity in specific domains, such as body envelope violations, contamination, or death (e.g., de Jong & Merckelbach, 1998; Sawchuk et al., Int J Psychophysiol.”

“…(Ohi et al., 1994) is responsible for drastic falls in HR or even cardiac arrest, as is seen in neonates with immaturity of respiratory control (Abu-Shaweesh & Martin, 2008), pallid breath-holding spells in childhood (Stephenson, 1978), or in cases of apnoeic asphyxia in adults (Daly et al.,…”

“Qualitative inspection of the data of Öst et al. 1984 also showed considerable falls in HR and BP values during late stages of surgery film viewing.”

“…(Ohi et al., 1994) is responsible for drastic falls in HR or even cardiac arrest, as is seen in neonates with immaturity of respiratory control (Abu-Shaweesh & Martin, 2008), pallid breath-holding spells in childhood (Stephenson, 1978), or in cases of apnoeic asphyxia in adults (Daly et al., 1979).”

“Following voluntary hyperventilation, rebreathing to increase PCO2 from 20 to 60mmHg leads to an almost three-fold increase in CBF, and more than 100% from a baseline of 40mmHg (Claassen et al., 2007).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript susceptible individuals (Papp et al., 1993; Abelson et al., 2001; Wilhelm, Trabert, et al., 2001).”

“In contrast to classical breathing retraining or the respiratory control technique, which emphasize “deep” abdominal breathing (Schmidt et al., 2000; Craske et al., 1997), the shallowness aspect aimed to Ritz et al.”

“Orthostatic stress can also be applied in doses that would almost certainly lead to fainting, even in individuals that are ordinarily not susceptible to syncope (Zhang et al., 1998).”

“The subsequent second phase is characterized by a sharp fall in HR (bradycardia) as well as BP (hypotension) leading to reduced cerebral blood flow and ultimately fainting (e.g., Graham et al., 1961).”

“2 Hyperventilation, fainting, and the “propensity factor X”—How does hyperventilation translate into fainting in syncopal patients if it does not lead to fainting in other anxiety disorders (e.g., Alpers et al., 2005; Wilhelm, Gerlach, et al., 2001; Meuret et al., 2008)? In healthy individuals, voluntary hyperventilat…”

“…(Ohi et al., 1994) is responsible for drastic falls in HR or even cardiac arrest, as is seen in neonates with immaturity of respiratory control (Abu-Shaweesh & Martin, 2008), pallid breath-holding spells in childhood (Stephenson, 1978), or in cases of apnoeic asphyxia in adults (Daly et al., 1979).”

“Constant tension, which was similar to that described by Öst and Sterner (1987), involved tensing for 15 s and then releasing the tension for 15 s. Rhythmic tension, which was based on Foulds et al. (1990), required tension for 5 seconds and release for 5 seconds, with both conditions continuing…”

“Studies attempting to decrease orthostatic hypotension due to autonomic failure (e.g., ten Harkel et al., 1994; van Lieshout et al., 1992) noted that a small increase in BP produced considerable improvements in orthostatic tolerance.”

“There is also a solid literature on panic induction by CO2 challenge tests (e.g., Fyer et al., 1987; Papp et al., 1993; Perna et al., 1994), which may be part of the reason the augmented respiratory relief intervention has received little further scrutiny.”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript 2000; Tolin et al., 1997), although studies are not consistent (see also Sawchuk et al., 2002).”

“Wieling et al. (1993) suggested that small changes in BP through increased venous return of blood flow from the legs may be sufficient to prevent syncope by increasing CBF minimally above the threshold necessary.”

“…was not related to success of treatment of BII-phobia patients with applied tension (Hellström et al., 1996) and/or other treatment techniques (e.g. Öst et al., 1991) and (ii) that patients at follow-up reported not using the technique but were nevertheless further improved, implies that some…”

“Hyperventilation is known to lead to airway narrowing (van den Elshout et al., 1991).”

“PCO2 showed phasic decreases below 30mmHg, which is sometimes taken as the level that is indicative of full-blown hyperventilation (Bass & Gardner, 1985).”

“Studies attempting to decrease orthostatic hypotension due to autonomic failure (e.g., ten Harkel et al., 1994; van Lieshout et al., 1992) noted that a small increase in BP produced considerable improvements in orthostatic tolerance.”

“Thus, in most cases, hypocapnia may be “an important factor accentuating cardiovascular embarrassment” in syncope (Weissler et al., 1957, p.881), but most probably, additional predisposing factors must be invoked to explain actual fainting.”

“It has been known for some time that increases in respiration rate can reduce RSA while increases in tidal volume can increase it, independent of changes in vagal outflow (Hirsch & Bischop, 1981; Grossman, Karemaker & Wieling, 1991; Ritz & Dahme, 2006).”

“Most importantly, there are no differences in effectiveness of the technique between patients who faint (defined by an initial exposure test; Hellström et al., 1996) and those who do not, although the rationale holds that its key effects should unfold when presyncopal symptoms or BP drops set in.”

“There is also a solid literature on panic induction by CO2 challenge tests (e.g., Fyer et al., 1987; Papp et al., 1993; Perna et al., 1994), which may be part of the reason the augmented respiratory relief intervention has received little further scrutiny.”

“How does hyperventilation translate into fainting in syncopal patients if it does not lead to fainting in other anxiety disorders (e.g., Alpers et al., 2005; Wilhelm, Gerlach, et al., 2001; Meuret et al., 2008)?”

“5.2.3 Hypoventilation techniques—Based on prior work targeting hyperventilation in panic disorder patients (Meuret et al., 2008; 2004; 2001), we recently pilot-tested a hypoventilation technique that attempted to target the respiratory dysregulation observed in BII patients (Ayala, Ritz, et al.…”

“Respiratory inductance plethysmography and capnography currently provide more precise techniques for capturing these aspects of ventilation noninvasively (Ritz et al., 2002; Meuret et al., 2004).”

“It is well-known that breathing excursions systematically modulate HR and BP (Hirsch & Bischop, 1981; Grossman et al., 1991; Eckberg, 2003).”

“Julu et al. (2003) administered tilt-table tests and lower body negative pressure and terminated testing when SBP fell to 80 mmHg and pre-syncopal symptoms occurred.”

“For example, it is common for individuals with panic disorder to report feelings of faintness (Meuret et al., 2006), even though actual fainting rarely happens.”

“…a condition that simulates syncope by overt signs of loss of postural tone or motionlessness and closed eyes, but with no measurable drops in BP and HR or EEG delta activity that are typical for syncope with loss of consciousness (Moya et al., 2009; Benbadis & Chichkova, 2006; Thijs et al., 2004).”

“…been demonstrated in aborting or delaying fainting responses due to orthostatic challenges in patients with autonomic failure or unspecified vasovagal syncope (Krediet et al., 2002; Kim et al., 2005; ten Harkel et al., 1994; van Dijk et al., 2005; van Lieshout et al., 1992; Wieling et al., 1993).”

“Qualitative inspection of the data of Öst et al. 1984 also showed considerable falls in HR and BP values during late stages of surgery film viewing.”

“For example, Ditto et al. (2003) observed a reduction in blood donationrelated symptoms (including faintness, weakness, nausea) and a reduced need for chair reclining in women when instructing them in repeated 5-s tension of arm and leg muscles during and after a blood draw.”

“In at least one study, the sample included patients with a history of vasovagal syncope due to pain or unusually strong emotions (Krediet et al., 2005).”

“This second phase makes BII phobia a unique phenomenon among the anxiety disorders and has provoked a plethora of functional interpretations and speculations about its adaptivity (e.g., Alboni et al., 2008; Bracha et al. 2007; Marks, 1988).”

“Among the most interesting ones, high baseline levels of adenosine and further increases during syncope have been observed patients with neurocardiogenic syncope (Shen et al., 1996; Saadjian et al., 2002).”

“Among the most interesting ones, high baseline levels of adenosine and further increases during syncope have been observed patients with neurocardiogenic syncope (Shen et al., 1996; Saadjian et al., 2002).”

“In a rare comparison of these subtypes, Accurso et al. (2001) showed a strong susceptibility of BII-phobia patients to faint under tilt-table testing.”

“Findings of Hermann et al. (2007) that suggest a reduction in inhibitory control by the medial prefrontal cortex in BII-phobia patients compared to controls exposed to blood and wound pictures may be additionally instructive in this context.”

“Changes in perceived control could explain the fact that some patients treated with the applied tension technique reported no longer needing the technique at follow-up (Öst et al., 1989, 1991).”

“Indeed, during tilt-table testing-induced vasovagal syncope, muscle sympathetic nerve activity is reduced in late phases (Jardine et al., 2002; see also Sarlo et al., 2008).”

“While basic research and treatment literatures are divided over the specificity of hyperventilation for panic disorder (e.g., Meuret et al., 2005; Roth, Wilhelm & Pettit, 2005; Wilhelm, Gerlach, et al., 2001; Van den Hout et al., 1992), such concerns are secondary in the context of BII…”

“Carey et al. (2001) found on average small reductions (−3.8 mmHg) in end-tidal PCO2 in 7 patients with neurally mediated syncope and healthy controls before syncope, whereas Norcliff-Kaufmann et al. (2008) observed marked falls in end-tidal PCO2 to levels around 21–22 mmHg at presyncope in a sample…”

“…the latter study was limited because of a lack of respiratory control of RSA and both studies may have been limited in that the venipuncture situation did not entail the supposedly phobia-relevant factor of contaminationproneness (Page, 2003) and the guided imagery did not contain images of blood.”

“Such objections have originally been raised against breathing retraining interventions in panic disorder treatment (e.g. Craske et al., 1997; Garssen et al., 1992; Schmidt et al., 2000; for a review see Meuret et al., 2003).”

“Lay instructions to “take a deep breath” to overcome anxiety may speak to that, as well as the demonstrated positive impact of paced breathing instructions (Clark & Hirschman, 1990; Harris et al., 1976) or instructions in “focused breathing” (Arch & Craske, 2006) on negative affect.”

“Such objections have originally been raised against breathing retraining interventions in panic disorder treatment (e.g. Craske et al., 1997; Garssen et al., 1992; Schmidt et al., 2000; for a review see Meuret et al., 2003).”

“Hyperventilation certainly cannot serve as a diagnostic marker for BII phobia, given that it is also common to other anxiety disorders or states (Roth, 2005).”

“Lumley and Melamed (1992) observed only increases in HR during a surgery film.”

“loss of muscle tone triggered by strong emotions (often laughter) that can lead to postural collapse but is accompanied by full consciousness (Thijs et al., 2004).”

“Sarlo et al. (2002; 2008) measured T-wave amplitude or pre-ejection period, respectively, during film presentation and observed initial decreases followed by subsequent increases in these indices, suggesting elevated and reduced sympathetic activity, respectively.”

“…function of the tidal volume-driven increase in ventilation, beyond those considered earlier (see 4.1.2), could be a “respiratory pump” effect, which may be an attempt to increase venous return by producing a larger negative intrathoracic pressure (Lagi et al., 2001; Lipsitz et al., 1998).”

“On a cautionary note, as most of the cited studies have employed end-tidal measures of PCO2 levels, the extent to which these dissociate from arterial PCO2 in syncope by orthostatic stress testing requires further exploration (Serrador et al., 2006).”

“[PubMed: 18765268] Vingerhoets AJ, 1984 Biochemical changes in two subjects succumbing to syncope.”

“There are also observations that a pronounced situational stress activation can be followed by rebound, a phenomenon in which the system deactivates below baseline levels (Gellhorn, 1970).”

“A promising avenue is the exploration of mediators and moderators of treatment (Meuret et al., 2009), which have demonstrated that in panic disorder treatment, capnometry-assisted reductions in hyperventilation are prospectively associated with an increasing sense of control and decline in panic symptom severity, but…”

“However, earlier insights into antecedents of vasovagal syncope were gained by retrospective reports (Sledge, 1978).”

“…function of the tidal volume-driven increase in ventilation, beyond those considered earlier (see 4.1.2), could be a “respiratory pump” effect, which may be an attempt to increase venous return by producing a larger negative intrathoracic pressure (Lagi et al., 2001; Lipsitz et al., 1998).”

“To estimate cardiac vagal activity in a more conservative way, a number of adjustment procedures have been proposed that should become a standard part of the experimenter’s instrumentation (Grossman & Taylor, 2007; Ritz et al., 2001; 2006; Wilhelm et al., 2004).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript demonstrate HR falls below neutral levels (Sarlo et al., 2002; Steptoe and Wardle, 1988; Vögele et al., 2003).”

“From this perspective, the respiratory relief maneuver could be expected to lead to symptomatic worsening in panic patients, given the likelihood of CO2 build-up that has been suspected of triggering a suffocation alarm system in panic patients (Klein, 1993; Roth et al., 2005).”

“Again, most evidence is available from orthostatic stress testing, with some studies finding decreases in noradrenaline and/or increases in adrenaline leading up to or following syncope (Van Lieshout et al., 1991; 1997).”

“Gerlach et al. (2006) observed no falls below initial levels of HR and BP in a group of BII phobia patients undergoing venipuncture, but two participants that fainted showed such falls.”

“Lay instructions to “take a deep breath” to overcome anxiety may speak to that, as well as the demonstrated positive impact of paced breathing instructions (Clark & Hirschman, 1990; Harris et al., 1976) or instructions in “focused breathing” (Arch & Craske, 2006) on negative affect.”

“Some studies suggest that drops in HR or BP may lag considerably behind the onset of hyperventilation (see 4.1.1 and 4.2.1) or CBF reductions (Dan et al., 2002).”

“…and treatment literatures are divided over the specificity of hyperventilation for panic disorder (e.g., Meuret et al., 2005; Roth, Wilhelm & Pettit, 2005; Wilhelm, Gerlach, et al., 2001; Van den Hout et al., 1992), such concerns are secondary in the context of BII phobia-specific responding.”

“The typical response pattern has been described in the literature as an event comprising two phases, the diphasic (alternatively, using the Latin prefix: biphasic) response (e.g., Engel, 1978; Kozak and Montgomery, 1981; Thyer and Curtis, 1985).”

“Indeed, during tilt-table testing-induced vasovagal syncope, muscle sympathetic nerve activity is reduced in late phases (Jardine et al., 2002; see also Sarlo et al., 2008).”

“The usefulness of physical maneuvers such as squatting, leg muscle pumping (tiptoeing), and/or tensing (leg crossing) has been demonstrated in aborting or delaying fainting responses due to orthostatic challenges in patients with autonomic failure or unspecified vasovagal syncope (Krediet et al., 2002; Kim et al., 200…”

“In a study by Thijs et al. (2008), psychology students viewing a syncopal episode on video were able to correctly remember less that half of its symptomatic features.”

“Overall, these findings closely match our recent observations with BII-phobia patients during exposure to surgery films (Ayala et al., 2010; Ritz et al., 2005; 2009).”

“Overall, these findings closely match our recent observations with BII-phobia patients during exposure to surgery films (Ayala et al., 2010; Ritz et al., 2005; 2009).”

“Intermittent deep breaths have been shown to be functional in reducing airway resistance, probably by relengthening the contracted smooth muscles of the airways (Lavoie et al., 2009).”

“Depression of ventilation is normally observed after a period of hyperventilation, which can also result in complete cessation of breathing excursions (Meah & Gardner, 1994).”

“Studies also suggest that patients may show reduced CBF before syncope despite a lack of notable reductions in HR and BP (Sung et al., 2000).”

“Indeed, reductions in baroreflex sensitivity have been demonstrated in presyncopal states by some studies, although the literature is not consistent, probably also due to methodological differences (e.g., Iacoviello et al., 2008; Samniah et al., 2004).”

“Similarly, van Overveld et al. (2009) found no association between RSA or salivary flow rate and blood-injury sensitivity in students when exposed to injury-related guided imagery.”

“…was similar to that described by Öst and Sterner (1987), involved tensing for 15 s and then releasing the tension for 15 s. Rhythmic tension, which was based on Foulds et al. (1990), required tension for 5 seconds and release for 5 seconds, with both conditions continuing the pattern for 2 minutes.”

“…reported evidence for structural variations in midbrain and medulla regions involved in BP and baroreflex regulation in patients with neurocardiogenic syncope (Beacher et al., 2009), which could serve as dispositional factors contributing to vasomotor abnormalities and thus fainting risk.”

“demonstrate HR falls below neutral levels (Sarlo et al., 2002; Steptoe and Wardle, 1988; Vögele et al., 2003).”

“The typical response pattern has been described in the literature as an event comprising two phases, the diphasic (alternatively, using the Latin prefix: biphasic) response (e.g., Engel, 1978; Kozak and Montgomery, 1981; Thyer and Curtis, 1985).”

“In a small study, Hohoff et al. (2009) recently found significant enhancement of respiratory and cardiac responses to venipuncture in BII-phobia patients explained by polymorphism of the adenosine A2A receptor gene.”

“Overall, these findings closely match our recent observations with BII-phobia patients during exposure to surgery films (Ayala et al., 2010; Ritz et al., 2005; 2009).”

“In addition, a considerable number of patients may actually show strongest symptoms after termination of exposure (Graham et al., 1961; Kleinknecht et al., 1990).”

“Indeed, reductions in baroreflex sensitivity have been demonstrated in presyncopal states by some studies, although the literature is not consistent, probably also due to methodological differences (e.g., Iacoviello et al., 2008; Samniah et al., 2004).”

“Typically, apnea is accompanied by a marked increase in sympathetic vasoconstrictor tone in the skeletal muscles (Jänig, 2006; Khayat et al., 2004) and cerebral vasodilation through its accompanying hypercapnia (Przybylowski et al., 2003).”

“Romano & Engel (1945) already mentioned the possibility of hyperventilation-induced apnea as a cause for a reflex-like cardiac standstill.”

“It could be further speculated whether oxygen desaturation during depressed ventilation or apneas (Ohi et al., 1994) is responsible for drastic falls in HR or even cardiac arrest, as is seen in neonates with immaturity of respiratory control (Abu-Shaweesh & Martin, 2008), pallid breath-holding spells in childhood (Ste…”

“This second phase makes BII phobia a unique phenomenon among the anxiety disorders and has provoked a plethora of functional interpretations and speculations about its adaptivity (e.g., Alboni et al., 2008; Bracha et al. 2007; Marks, 1988).”

“However, studies have generally focused on respiration rate, such as through the measurement with a single strain gauge (e.g., Kozak & Miller, 1985; Steptoe & Wardle, 1988; Vögele et al., 2003) or visual observation of breathing (e.g., Cohn et al., 1976), rather than implementing a full assessment…”

“Such measures could also address hypotheses about the role of cardiac filling in BII-phobia syncope (Henry, 1984), which have not receive unequivocal support in other research (Mitro & Hijová, 2006; van Lieshout et a., 1997).”

“Subsequently, Orwin (1973) experimented with adding CO2 in concentrations of 30 to 70% at re-initiation of breathing after breath-holding.”

“Beyond that, genuine cognitive techniques that address irrational expectations and beliefs need to be considered (Thompson, 1999).”

“Mostly qualitative observations and case studies have been published that reported hyperventilation or deep breathing in BII-phobia patients (e.g., Elmore et al., 1980; Foulds, 1993; Steptoe & Wardle, 1988).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript accompanying increase in metabolic activity (Foulds, 1993).”

“Such measures could also address hypotheses about the role of cardiac filling in BII-phobia syncope (Henry, 1984), which have not receive unequivocal support in other research (Mitro & Hijová, 2006; van Lieshout et a., 1997).”

“Of two patients with BII phobia, one treated with this “augmented respiratory relief” technique and the other one with regular respiratory relief, both were reported to be symptom free after treatment; however, the former had relapsed at 3–6 months follow-up (Orwin et al., 1975).”

“However, reports of syncope induced by hypocapnia alone a rare (e.g., David et al., 2003) or limited to special maneuvers that combine voluntary hyperventilation with straining and postural stress (the “fainting lark,” van Lieshout et al., 2003).”

“An exception is the study of Bodycoat et al. (2000) that compared the effect of two patterns of muscle tension, constant tension versus rhythmic tension of arm, chest and leg muscles, on BP in a nonphobic sample of 45 adults.”

“…episodes, the emphasis may then shift gradually towards additional cognitive factors, such as irrational beliefs about bodily harm or catastrophic cognitions and automatic negative thoughts related to BII stimuli, fainting, and associated fear (e.g., White & Sellwood, 1995; Thompson, 1999).”

“In our own research (Ritz et al., 2010-this issue), we found significantly lower PCO2 levels in a smaller sample of 15 asthma patients (33.8 mmHg) during neutral film viewing compared to blood-injection-injury phobics (n=12; 39.9 mmHg), with healthy controls (n=14) taking an intermediate position…”

“, 2009a, b; 2012), and signals potentially life-threatening open wounds (Ritz et al., 2010).”

“The aim of this survey was to report the prevalence of BII phobia, its heritability, and clinical characteristics among the males and females in the Indian subcontinent.”

“Although this is an appealing description of the blood donation context, given that risk for vasovagal reactions peak shortly after donors leave the donation chair,(28) empirical support for a diphasic response pattern is surprisingly inconsistent.(29) An intriguing new psychophysiologic model suggests that vasovagal…”

“Both panic disorders and specific phobias were related to asthma [31,32], and hyperventilation may provide an interesting link with asthma, based on sustained levels of hypocapnia [33,34].”

“It has been reported that blood phobia patients hyperventilate during exposure to a relevant stimulus, mainly because of deeper rather than fasting breathing [7, 56].”

“The physiological symptoms experienced when confronting their phobic stimuli is often a significant source of distress for adults with BII phobias and can perpetuate their avoidance of BII-related stimuli (Öst et al. 1984b; Page 1994; Ritz et al. 2010).”

“Findings on heart rate changes in BII phobia during confrontation are heterogeneous (for a review, see Ritz et al., 2010).”

“There is limited research on this topic (Ritz et al., 2010), though V€ogele, Coles, Wardle, and Steptoe (2003) found that people with a fainting history, compared to those without, experienced higher anxiety and lower blood pressure following a film of a surgery.”

“Future studies should consider additional cognitive aspects, such as sense of control or perceived control, which may mediate fear of BII-related stimuli (7).”

“[9] recently suggested that emotional fainting is due less to a diphasic cardiovascular response than altered breathing patterns that lead to hypocapnia.”

“Hyperventilation is a powerful cerebral vasoconstrictor, which could facilitate vasovagal episodes in individuals prone to fainting (Ritz et al., 2010).”

“…that went beyond that achieved by other non-phobic negative stimuli, whereas the second phasewould be accompanied by a deactivation below normal levels achieved by extended exposure to a benign neutral stimulus (for a detailed discussion of these methodological issues, see, Ritz et al., 2010).”

“In contrast to other phobia subtypes, BII-related phobia is associated with strong diphasic physiological reactions [21] which may result in fainting.”

“respiration rate and PETCO2, given the relationship between hypocapnia and respiration patterns, it is likely that additional assessment of breathing patterns may have yielded some indication of hyperventilation, specifically, increases in tidal volume or minute ventilation (Ritz et al., 2002; Ritz et al., 2010).”

“focused on the role of cardiovascular responses (8).”

“Similarly, people with chronically high levels of anxiety (Freire and Nardi 2012; Garcia de Miguel et al. 2012; Gold 2011; Nardi et al. 2009; Ritz et al. 2010) or anger (Rivera-Arzola and RamosGrenier 1997) tend to show generalized elevations in respiratory activity, as well as increased levels of both general physiol…”

“BII has been linked theoretically to autonomic system dysregulation although empirical evidence is mixed (Ritz et al., 2010).”

“…(characterized by an exaggerated decrease in blood pressure upon standing up from seated or lying down positions, resulting in vasovagal symptoms and syncope), as well as among nonclinical populations such as blood donors (Krediet et al., 2007; Ritz et al., 2010; Thijsen & Masser, 2019).”

“Older studies have shown fainting rates of up to 80% (42, 43), and even reported seizures, asystolia, and death (26, 32, 39, 44).”

“This constellation of symptoms may be due to autonomic response, which can ultimately lead to vasovagal syncope [21].”

“Blood injection injury phobia has been reported to cause vasovagal reflex, which usually occurs in two phases, referred to as a diphasic response [18].”

“Early investigations on orthostatically induced stress have reported respiratory abnormalities such as frequent yawning, sighing, or hypocapnia during or preceding the development of syncope.(27) Hypocapnic breathing has also been demonstrated to precede syncopes under experimental conditions (eg, by head-up tilt tabl…”

“Unlike most other speci fi c phobias, BII phobia is associated with a characteristic diphasic vasovagal response consisting of an initial sympathetic activation followed by parasympathetic overcompensation, which may result in hypotension, dizziness, or syncope (7, 9, 10).”