The human fear-circuitry and fear-induced fainting in healthy individuals

The Paleolithic-Threat hypothesis reviewed here posits that habitual efferent fainting can be traced back to fear-induced allelic polymorphisms that were selected into some genomes of anatomically, mitochondrially, and neurally modern humans (Homo sapiens sapiens) in the Mid-Paleolithic because of the survival advantage they conferred during periods of inescapable threat. We posit that during Mid-Paleolithic warfare an encounter with "a stranger holding a sharp object" was consistently associated with threat to life. A heritable hardwired or firm-wired (prepotentiated) predisposition to abruptly increase vagal tone and collapse flaccidly rather than freeze or attempt to flee or fight in response to an approaching sharp object, a minor injury, or the sight of blood, may have evolved as an alternative stress-induced fear-circuitry response. Such a stable (balanced) polymorphism for the hemodynamically "paradoxical" flaccid-immobility in response to these stimuli may have increased some non-combatants' chances of survival. This is consistent with the unusual age and sex pattern of fear-induced fainting. The Paleolithic-Threat hypothesis also predicts a link to various hypo-androgenic states (e. g. low dehydroxy-epiandrosterone-sulfate. We offer five predictions testable via epidemiological, clinical, and ethological/ primatological methods. The Paleolithic-Threat hypothesis has implications for research in the aftermath of man-made disasters, such as terrorism against civilians, a traumatic event in which this hypothesis predicts epidemics of fear-induced fainting.     

Active vasodilation during fainting: A hypothesis revisited

The current concept is that the vasodilation which contributes to fainting (vasovagal syncope) is caused entirely by withdrawal of sympathetic vasoconstrictor tone (i.e. passive vasodilation).^1,2 This concept has supplanted the idea that an active, sympathetically mediated component to the vasodilation exists in humans.³ We have several lines of evidence suggesting that there can be sympathetically mediated active vasodilation in humans. We speculate that this active vasodilation may be linked to the release of the recently identified vasodilator nitric oxide. Along these lines, we have experimental evidence consistent with neurally mediated nitric oxide release during several types of sympathoexcitatory maneuvers in humans. We have also observed forearm vasodilation during a vasovagal response after -adrenergic blockade of the forearm under study. These observations indicate that the potential role of active vasodilation during fainting in humans should be revisited.     

Assessment of child neurology outpatients with headache, dizziness, and fainting

Neurologic symptoms such as headache, vertigo, dizziness, and fainting can create a diagnostic problem in pediatric neurology practice because they are also the most common presenting symptoms of psychiatric disorders. Children, especially adolescents, who are often admitted with such autonomic symptoms, are frequently misdiagnosed. In this study, we aimed to investigate the psychiatric morbidity and comorbidity rate in children and adolescents presenting with neurologic symptoms such as headache, vertigo, and syncope. We investigated 31 children who presented with these symptoms. All children were evaluated for their medical history and had a physical and neurologic examination. We attempted to rule out a possible organic etiology. All patients received a complete laboratory examination (blood count, electroencephalography), pediatric cardiology and otorhinolaryngology consultations, and a caloric test. All patients were assessed according to Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. The majority of the patients (93.5%) received a psychiatric diagnosis according to the DSM-IV criteria. Most of these patients were adolescents and female. Psychosocial stressors such as academic problems, familial dysfunction, parental psychopathology, and child sexual abuse were associated with somatic symptoms. The results of this study demonstrated the importance of differential diagnosis and psychiatric comorbidity in a pediatric neurologic outpatient population. Treatment should be directed at biopsychosocial integrity, and a multidisciplinary treatment approach should be applied.     

Low creatine kinase is associated with a high population incidence of fainting

Objective  Vasoconstrictor capacity, skeletal muscle tone, and renal sodium retention are involved in the pathogenesis of fainting. As muscle contractility and ion transport are highly energy-demanding processes, we hypothesized that a low activity of the energy-generating enzyme creatine kinase (CK) is associated with a higher risk of fainting. The aim of this observational study was to explore the association of vasovagal syncope with low CK. Methods  A random sample of 1,000 subjects aged 34–60 years was drawn from the general population, with 442 subjects eventually included in the study. Data on fainting history were collected with the investigators blinded to participants’ CK level. We prepared this report according to the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) statement. The main outcome was the lifetime cumulative incidence of vasovagal syncope in subjects with low versus high-normal serum CK after a 3 days rest. Results  The proportion of fainters within the high CK group was 29 out of 130 (22%) versus 121 out of 312 (39%) in the low CK group; a 73% greater occurrence of fainting with low CK (P = 0.0005). This finding was consistent across recurrent fainters, and in men and women. Interpretation  Low CK is associated with a 73% higher incidence of fainting in a random population sample. The association is biologically plausible, as CK enhances cardiovascular and skeletal muscle contractility and salt retention. The presented data suggest that low CK activity is a potential new risk factor for vasovagal syncope.     

Disgust, anxiety and fainting symptoms associated with blood-injection-injury fears: a structural model

The present study examines the structural relations between disgust sensitivity, anxiety symptoms, blood-injection-injury (BII) fears, and fainting symptoms associated with BII fears in 259 nonclinical participants. Results revealed that both disgust and BII fear were independent predictors of fainting symptoms. However, structural equation modeling revealed that the relation between disgust sensitivity and fainting was reduced to negative and non-significance when the path from BII fear to fainting was also introduced. Subsequent analysis indicated that the relation between disgust sensitivity and fainting symptoms was fully mediated by BII fear. It was also found that animal reminder disgust was related to fainting symptoms whereas core disgust was not. However, the relation between animal reminder disgust and fainting was also fully mediated by BII fear. Furthermore, anxiety symptoms did not add directly to the structural model predicting fainting associated with BII fears. Implications of these findings for better understanding the interaction of the emotional mechanisms that mediate fainting responses in BII phobia are discussed.     

The relation between disgust-sensitivity, blood-injection-injury fears and vasovagal symptoms in blood donors: disgust sensitivity cannot explain fainting or blood donation-related symptoms

Background and objectivesPage’s (1994) prominent theory for the explanation of fainting in blood-injection-injury situations holds that disgust sensitivity contributes to syncopal reactions. We investigated if blood donation-related vasovagal symptoms (1) or fainting related to blood donations (2) are associated with disgust sensitivity.MethodsIn an online sample of 361 blood donors, we assessed blood-injection-injury fears, disgust sensitivity, history of blood donation related fainting and retrospective self-ratings of vasovagal symptoms. For the assessment of blood-injection-injury fears we used the BII-Q which has excellent psychometric properties and does not confound disgust and anxiety sensitivity. Vasovagal symptoms were measured by the Blood Donation Reactions Inventory (BDRI) which captures mild and strong vasovagal symptoms and has been used in previous studies with blood donors.ResultsDisgust sensitivity did not significantly contribute to the explanation of self-reported vasovagal symptoms in a regression model with gender, blood-injection-injury fear and disgust sensitivity as predictors. We did not find any significant group differences in disgust sensitivity for blood donors with or without a fainting history (statistical power = 0.95) and a Bayesian model selection procedure showed that it is more likely that both groups are equally disgust sensitive than it is that the fainters are more disgust sensitive.LimitationsFurther research is required to confirm the findings in prospective studies.ConclusionOur results indicate that disgust sensitivity is not relevant for the development of vasovagal syncopes.     

Behavioral avoidance and self-reported fainting symptoms in blood/injury fearful individuals: an experimental test of disgust domain specificity

This study examined the specificity of disgust in predicting avoidance in blood/injury (BI) phobia. Participants high (n=38) and low (n=46) in BI fear completed measures of disgust across multiple domains and severity of BI-related fear. They then completed three randomly presented behavioral avoidance tasks (BATs) that consisted of exposure to a 15' severed deer leg (BI task), a live spider (spider task), and a 'contaminated' cookie (cookie task). Fainting symptoms associated with each BAT were recorded as well. When controlling for gender and BI fear group membership, mutilation disgust contributed unique variance to avoidance on the BI task and animal disgust contributed unique variance to avoidance on the spider task. None of the disgust domains contributed unique variance to avoidance on the cookie task. For the high BI fear group, self-reported fainting symptoms were more pronounced during the BI and spider BAT than during the cookie BAT. Although mutilation disgust was significantly associated with self-reported fainting symptoms on the BI task among the high BI fear group, this relationship became nonsignificant when controlling for BI-related fear severity. Implications of the domain specificity of disgust and its relevance for understanding fainting responses in BI phobia are discussed.