Etiological Models Research Articles

The relationship between executive functioning and addictive behavior: new insights from a longitudinal community study

RationaleAlthough there is evidence that impaired executive functioning plays a role in addictive behavior, the longitudinal relationship between the two remains relatively unknown.ObjectivesIn a prospective-longitudinal community study, we tested the hypothesis that lower executive functioning is associated with more addictive behavior at one point in time and over time.MethodsThree hundred and thirty-eight individuals (19–27 years, 59% female) from a random community sample were recruited into three groups: addictive disorders related to substances (n = 100) or to behaviors (n = 118), or healthy controls (n = 120). At baseline, participants completed nine executive function tasks from which a latent variable of general executive functioning (GEF) was derived. Addictive behavior (i.e., quantity and frequency of use, and number of DSM-5 criteria met) were assessed using standardized clinical interviews at baseline and three annual follow-ups. The trajectories of addictive behaviors were examined using latent growth curve modeling.ResultsAt baseline, we found weak to no evidence of an associations between GEF and addictive behavior. We found evidence for an association between a lower GEF at baseline and a higher increase in the quantity of use and a smaller decrease in frequency of use over time, but no evidence for an association with an increase in the number of DSM-5 criteria met.ConclusionsLower EFs appear to lead to a continuing loss of control over use, whereas addictive disorders may develop secondarily after a long period of risky use. Previous etiological models assuming lower EF as a direct vulnerability factor for addictive disorders need to be refined.

S1127 EUS-Guided Gastroenterostomy vs. Enteral Stenting for Palliation of Benign and Malignant Gastric Outlet Obstruction

Introduction: Gastric outlet obstruction (GOO) can occur due to benign or malignant etiologies. Enteral stenting (ES) using self-expanding metal stents has been around for decades and remains a widely used technique in the palliation of GOO. With the advancement of interventional endoscopic ultrasound (EUS) techniques and the advent of lumen-apposing metal stents, EUS-guided gastroenterostomy (EUS-GE) has been adopted as a novel technique for treating symptomatic GOO in benign and malignant etiologies. We conducted a retrospective study to evaluate the outcomes of technical and clinical success and safety in patients with GOO undergoing EUS-GE versus ES. Methods: Patients who underwent EUS-GE or ES for GOO between September 2015 and December 2021 were included in the study. Primary outcomes included technical success defined as successful deployment of the stent and clinical success defined as relief of symptoms and tolerance of oral intake. Secondary outcomes were timing of unplanned re-intervention based on etiology and serious adverse events. Results: A total of 107 procedures among 103 patients met inclusion criteria, 63 (58.9%) underwent ES, and 44 (41.2%) underwent EUS-GE (Table). A higher percentage of malignant etiologies were in the enteral stenting group versus the EUS-GE group (88.9% vs 59.1%, p = 0.0003). Technical success among EUS-GE and ES patients was 100%. Clinical success was achieved by 90.5% of EUS-GE patients compared to 97.7% of ES patients, which was similar in both groups (p = 0.24). There was no significant difference in serious adverse events between EUS-GE and ES patients (3.2% vs 6.8%, p = 0.4). Thirteen ES patients required unplanned re-intervention compared to four EUS-GE patients (20.6% vs 9.1%) but the cumulative incidence functions were not significantly different (p = 0.11). The median time for reintervention in EUS-GE patients was 154 (50,425) days and 94 (43,112) days for ES patients. EUS-GE was associated with a significantly reduced need for unplanned reintervention in an adjusted model for etiology (benign or malignant) (HR: 0.264; 95% CI: 0.086, 0.813; p = 0.02). Conclusion: Technical success, clinical success, and rate of serious adverse events did not significantly differ among EUS-GE and ES patients. However, the rate of unplanned reintervention was significantly lower in the EUS-GE group when adjusted for the etiology of GOO, thus EUS-GE can be considered as a first line therapy for these patients. Table 1. - Summary of Patient Characteristics and Clinical Outcomes Procedures N = 107 Patients N = 103 Enteral Stenting N = 63 EUS-GE N = 44 P-value Age 0.19 Mean (SD) 69.5 (13.2) 65.9 (14.8) Range 38, 95 34, 91 Sex, n (%) 0.64 Male 33 (52.4%) 21 (47.7%) Female 30 (47.6%) 23 (52.3%) Etiology, n (%) 0.0003 Benign 7 (11.1%) 18 (40.9%) Malignant 56 (88.9%) 26 (59.1%) Technical success, n (%) N/A Yes 63 (100.0%) 44 (100.0%) Clinical success, n (%) 0.24 Yes 57 (90.5%) 42 (97.7%) Missing/Unknown 0 1 Serious Adverse event, n (%) 0.4 Yes 2 (3.2%) 3 (6.8%) Unplanned reintervention, n (%) 0.11 Yes 13 (20.6%) 4 (9.1%)

The costs of anticipating and perseverating about racism: Mechanisms of the associations between racial discrimination, anxious arousal, and low positive affect.

The goal of this study was to test a new etiological model of how racial discrimination is associated with anxious arousal and low positive affect. The overarching model posits that racial discrimination will be associated with anxious arousal and low positive affect through prolonged activation of race-related stress processes (i.e., anticipatory race-related fear and race-related rumination), the effects of which are conditioned on attention bias to threat. A total of 326 Black participants (72.4% women) completed the study. For anxious arousal, the indirect effect of racial discrimination through anticipatory race-related fear depended on degree of attention bias, with the effect only reaching statistical significance at mean and relatively higher levels of attention bias to threat. For low positive affect, the indirect effect of racial discrimination through race-related rumination only reached a statistical significance at mean and relatively lower levels of attention bias to threat. Racial discrimination is indirectly associated with anxious arousal and low positive affect through the effects of anticipatory race-related fear and race-related rumination, respectively. Implications for etiology and treatment of anxious arousal and low positive affect are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Considering patient narrative-based and medico-scientific epistemologies in framing psychiatric care.

Personal narratives of lived experience with psychiatric illness and distress remain central in the epistemology of mental illness. We provide a commentary on this potential bridging of patient narrative-based epistemology, and medico-scientific epistemology used by psychiatrists used for diagnosis, formulation, prognosis and treatment. Discussion and planning of psychiatric care can be framed by understanding the narrative-based epistemology of a patient's illness as highlighted by five key questions to explore the patient's illness explanatory models. We propose five key questions for the psychiatrist's complementary consideration of medico-scientific epistemology that frame conceptual models of aetiology, pathophysiology, diagnosis, formulation, prognosis and treatment, which are embedded in the predominant socio-cultural environment. These questions assist in bridging patient narrative and medico-scientific explanatory models to facilitate more effective collaborative care planning.

Functional neurological disorder and placebo and nocebo effects: shared mechanisms

Functional neurological disorder (FND) is characterized by neurological symptoms that cannot be explained by a structural neurological cause. Among the different aetiological models that have been proposed for FND, of note is the Bayesian predictive coding model, which posits that perception relies on top-down cortical predictions (priors) to infer the source of incoming sensory information. This model can also apply to non-pathological experiences, such as placebo and nocebo effects, wherein sensory information is shaped by prior expectations and learning. To date, most studies of the relationship between placebo and nocebo effects and FND have focused on the use of placebos for diagnosis and treatment of FND. Here, we propose that this relationship might go beyond diagnosis and therapy. We develop a framework in which shared cognitive, personality and neuroanatomical factors justify the consideration of a deeper link between FND and placebo and nocebo effects. This new perspective might offer guidance for clarification of the pathogenesis of FND and for the identification of potential biomarkers and therapeutic targets.

Childhood behavioral inhibition and attachment: Links to generalized anxiety disorder in young adulthood.

Generalized anxiety disorder (GAD) is under-treated yet prevalent among young adults. Identifying early risk factors for GAD would contribute to its etiological model and identify potential targets for intervention. Insecure attachment patterns, specifically ambivalent and disorganized, have long been proposed as childhood risk factors for GAD. Similarly, childhood behavioral inhibition has been consistently associated with anxiety disorders in adulthood, including GAD. Intolerance of uncertainty (IU), the tendency to react negatively to uncertain situations, has also been shown to be a crucial component of GAD. Furthermore, maternal anxiety is an important feature of developmental models of anxiety including GAD. Yet, to date, no study has examined, within a comprehensive model, how attachment and behavioral inhibition in childhood, maternal anxiety in adolescence, and IU in emerging adulthood contribute to GAD in adulthood. The present study thus examines these links using a longitudinal design with 62 Canadian participants and their mothers. At age 6, participants' attachment and behavioral inhibition were assessed observationally. Maternal anxiety was measured when participants were 14 years of age. IU and GAD were assessed when participants were 21 and 23 years of age, respectively. Structural equation modeling showed that IU mediates the relationships between behavioral inhibition and GAD, while controlling for maternal anxiety. Ambivalent and disorganized-controlling attachment patterns are also indirectly associated with increased GAD symptoms via greater IU scores. Furthermore, a direct and positive effect of behaviorally disorganized attachment was found on GAD symptoms. This longitudinal study supports integrating attachment, behavioral inhibition, and IU in a model of GAD.

Associations between Schizotypal Facets and Symptoms of Disordered Eating in Women.

Research has suggested that schizotypy—a personality organisation representing latent vulnerability for schizophrenia-spectrum disorders—may be elevated in women with symptoms of disordered eating. However, studies have not fully considered associations between symptoms of disordered eating and multidimensional schizotypy. To overcome this limitation, we asked an online sample of 235 women from the United States to complete measures of symptoms of disordered eating (drive for thinness, body dissatisfaction, and bulimic symptoms) and multidimensional schizotypy. Correlational analyses indicated significant associations between drive for thinness and bulimic symptoms, respectively, and most schizotypal facets. Body dissatisfaction was significantly associated with only two schizotypal facets. Overall, the strength of correlations was weak-to-moderate. Regression results indicated that only the schizotypal feature of excessive social anxiety was significantly associated with all risk for disordered eating factors. These results are consistent with aetiological models of disordered eating that highlight socio-affective difficulties as risk factors for symptoms of disordered eating.

Gambling Associated Risk-taking Behaviors Correlate with Emotional Regulation and the Iowa Gambling Task but not Wisconsin Card Sorting.

It is not known why some novice gamblers eventually develop Gambling Disorder while most do not. This study tested predictions from two competing models of Gambling Disorder etiology: the Pathways Model of Problem and Pathological Gambling (Blaszczynski & Nower, 2002) and the Allostatic Model of addictions (Koob & Schulkin, 2019) applied to Gambling Disorder. Participants were drawn from introductory psychology courses and screened as non-gamblers (N = 91). They completed computerized versions of the Iowa Gambling Task (IGT-2), Wisconsin Sorting Task (WCST-64), and a Difficulties with Emotional Regulation Scale (DERS). Risk-taking tendencies were observed by having participants play a typical electronic slots game for up to 15min. Higher betting on the slots game was correlated with the frequency of Deck A selections on the IGT-2 and lower total DERS scores. There were no significant correlations involving slots betting and the WCST-64. Greater risk-taking on the slots game was correlated with more frequent wins, partial losses that were disguised as wins, bonus game features, and the largest nominal amount won on a single spin. However, there were no significant correlations between betting behaviors and the 'payback percentage', defined as total winnings as a proportion of total wagers made throughout the session. Post-game ratings were positively correlated with frequency of reinforcing outcomes. These findings suggest that novice gamblers' likelihood of further gambling participation may be elevated by high sensitivity to immediate rewards and low difficulty self-regulating negative emotions. These findings are consistent with the Allostatic Model; they are not consistent with Pathways Model.

Interoceptive accuracy and bias in somatic symptom disorder, illness anxiety disorder, and functional syndromes: A systematic review and meta-analysis.

Somatic symptom disorder, illness anxiety disorder, and functional syndromes are characterized by burdensome preoccupation with somatic symptoms. Etiological models propose either increased interoceptive accuracy through hypervigilance to the body, or decreased and biased interoception through top-down predictions about sensory events. This systematic review and meta-analysis summarizes findings of 68 studies examining interoceptive accuracy and 8 studies examining response biases in clinical or non-clinical groups. Analyses yielded a medium population effect size for decreased interoceptive accuracy in functional syndromes, but no observable effect in somatic symptom disorder and illness anxiety disorder. The overall effect size was highly heterogeneous. Regarding response bias, there was a small significant effect in somatic symptom disorder and illness anxiety disorder. Our findings strengthen the notion of top-down factors that result in biased rather than accurate perception of body signals in somatic symptom disorder and illness anxiety disorder.

Advances in problematic usage of the internet research – A narrative review by experts from the European network for problematic usage of the internet

Global concern about problematic usage of the internet (PUI), and its public health and societal costs, continues to grow, sharpened in focus under the privations of the COVID-19 pandemic. This narrative review reports the expert opinions of members of the largest international network of researchers on PUI in the framework of the European Cooperation in Science and Technology (COST) Action (CA 16207), on the scientific progress made and the critical knowledge gaps remaining to be filled as the term of the Action reaches its conclusion.A key advance has been achieving consensus on the clinical definition of various forms of PUI. Based on the overarching public health principles of protecting individuals and the public from harm and promoting the highest attainable standard of health, the World Health Organisation has introduced several new structured diagnoses into the ICD-11, including gambling disorder, gaming disorder, compulsive sexual behaviour disorder, and other unspecified or specified disorders due to addictive behaviours, alongside naming online activity as a diagnostic specifier. These definitions provide for the first time a sound platform for developing systematic networked research into various forms of PUI at global scale. Progress has also been made in areas such as refining and simplifying some of the available assessment instruments, clarifying the underpinning brain-based and social determinants, and building more empirically based etiological models, as a basis for therapeutic intervention, alongside public engagement initiatives.However, important gaps in our knowledge remain to be tackled. Principal among these include a better understanding of the course and evolution of the PUI-related problems, across different age groups, genders and other specific vulnerable groups, reliable methods for early identification of individuals at risk (before PUI becomes disordered), efficacious preventative and therapeutic interventions and ethical health and social policy changes that adequately safeguard human digital rights. The paper concludes with recommendations for achievable research goals, based on longitudinal analysis of a large multinational cohort co-designed with public stakeholders.

Maize Anthracnose Stalk Rot in the Genomic Era.

Anthracnose stalk rot (ASR) of maize results in millions of dollars in losses annually in the United States. ASR, together with anthracnose leaf blight and anthracnose top dieback, is caused by the fungus Colletotrichum graminicola. Current ASR management recommendations emphasize host resistance and reduction of plant stressors (e.g., drought, heat, low fertility, or soil acidity). Stress reduction may be more difficult to achieve in the future due to more high-intensity production protocols and climate change. Moreover, cultural and chemical management practices may conflict with other important goals, including environmental sustainability and maximization of yield potential. Thus, future ASR management may rely more heavily on host resistance, for which there are relatively few highly effective sources. The last comprehensive review of C. graminicola and maize anthracnose was written over two decades ago. The genomic age has brought important new insights into mechanisms governing the host-pathogen interaction from the application of molecular and cytological technologies. This review provides a summary of our current model of maize anthracnose etiology, including how increased knowledge of molecular and cellular events could contribute to better ASR management. Improved understanding of C. graminicola taxonomy has confirmed that the fungus is specific to Zea mays, and that it colonizes living maize tissues via a critical biotrophic phase. Successful biotrophic establishment relies on an array of secreted protein effectors and secondary metabolites produced at different stages of infection and dispersed to multiple locations. These molecules could provide therapeutic targets for the next generation of transgenic or gene-edited ASR-resistant hybrids.

A Longitudinal Process Model Evaluating the Effects of Cooperative Learning on Victimization, Stress, Mental Health, and Academic Engagement in Middle School.

Mental health is a significant concern among young people, particularly during the COVID-19 pandemic. Notably, mental health problems can significantly reduce student performance in school, including both engagement and achievement. Both mental health problems and reduced student performance often arise due to peer victimization, which can include teasing, racial- or gender-based discrimination, and/or physical assault. Stress has been proposed as one mechanism through which victimization influences mental health, and stress can also interfere with academic performance at school, including engagement and achievement. To date, however, no research has evaluated longitudinal associations between victimization and stress, and how these longitudinal patterns may impact adolescent behavior and mental health. In this study, we used data from a 2-year cluster randomized trial of cooperative learning to evaluate an etiological process model that includes (1) longitudinal reciprocal effects between victimization and stress, and (2) the effects of both victimization and stress on student mental health and academic engagement. We hypothesized that victimization and stress would have significant reciprocal effects, and that both would predict greater mental health problems and lower academic engagement. We further hypothesized that cooperative learning would have significant effects on all constructs. We found partial support for this model, whereby stress predicted greater victimization, but victimization did not predict increased stress. While both factors were linked to student outcomes, stress was a more powerful predictor. We also found significant salutary effects of cooperative learning on all constructs. The implications of these results for student behavioral and mental health are discussed.

Integrating fear of fatness into sociocultural models of body image and eating concerns

To date, sociocultural models of body dissatisfaction and disordered eating have predominantly focused on the pursuit of thinness and have somewhat neglected sociocultural discourse and pressures that increase fear of fatness. Therefore, we tested a model to determine whether sociocultural pressures from media and interpersonal sources were associated with drive for thinness and fear of fatness. We also examined whether beliefs about the controllability of shape and weight were in turn associated with body dissatisfaction and disordered eating. A sample of N = 226 female undergraduate students in the U.S. completed an online survey assessing the variables of interest. After minor modification to the model pathways, the model provided a good fit to the data. Sociocultural influences to pursue thinness and fear fat related to body dissatisfaction and disordered eating through internalization of the thin-ideal and fear of fat. Together, these findings suggest that the pursuit of thinness and fear of fatness are distinct elements in etiologic models of body dissatisfaction and disordered eating. Additional work, including longitudinal research and studies among more diverse groups of individuals, is warranted to further clarify these relationships.

Benchmarking of univariate pleiotropy detection methods applied to epilepsy.

Pleiotropy is a widespread phenomenon that may increase insight into the etiology of biological and disease traits. Since genome-wide association studies frequently provide information on a single trait only, only univariate pleiotropy detection methods are applicable, with yet unknown comparative performance. Here, we compared five such methods with respect to their ability to detect pleiotropy, including meta-analysis, ASSET, conditional false discovery rate (cFDR), cross-phenotype Bayes (CPBayes), and pleiotropic analysis under the composite null hypothesis (PLACO), by performing extended computer simulations that varied the underlying etiological model for pleiotropy for a pair of traits, including the number of causal variants, degree of traits' overlap, effect sizes as well as trait prevalence, and varying sample sizes. Our results indicate that ASSET provides the best trade-off between power and protection against false positives. We then applied ASSET to a previously published International League Against Epilepsy (ILAE) consortium data set on complex epilepsies, comprising genetic generalized epilepsy and focal epilepsy cases and corresponding controls. We identified a novel candidate locus at 17q21.32 and confirmed locus 2q24.3, previously identified to act pleiotropically on both epilepsy subtypes by a mega-analysis. Functional annotation, tissue-specific expression, and regulatory function analysis as well as Bayesian colocalization analysis corroborated this result, rendering 17q21.32 a worthwhile candidate for follow-up studies on pleiotropy in epilepsies.

Research progress on the comorbidity of anxiety and depression in children and adolescents

Anxiety and depression, as two emotional disorders with high incidence in children and adolescents, have become major public health issues for health and life safety. Anxiety and depression often exist in the form of comorbidities due to the common clinical manifestations, behavioral characteristics, genetic and environmental etiological mechanisms, which have short-term and long-term adverse health effects. This article summarizes the prevalence and characteristics of the comorbidity of anxiety and depression in children and adolescents, reviews the etiological models and influencing factors of the comorbidity of anxiety and depression, and reveals the underlying etiological mechanism, in order to provide a reference for the prevention and control of the comorbidity of anxiety and depression in children and adolescents.

Young women who develop anorexia nervosa exhibit a persistently low premorbid body weight on average: A longitudinal investigation of an important etiologic clue.

test whether (1) young women who subsequently show onset of anorexia nervosa (AN) exhibit persistently lower average premorbid BMI than those who subsequently show onset of bulimia nervosa (BN), binge eating disorder (BED), purging disorder (PD), or no eating disorder; (2) a proximal spike in other risk factors occurs immediately before AN emergence; and (3) psychological and behavioral factors differentiate youth who show persistently low BMI from those who do not. Data from a sample (N = 1952) of young women at high-risk for eating disorders followed for 3 years and a socioethno-racially representative sample (N = 496) of adolescent girls followed for 8 years were used to address these aims. Participants who developed AN exhibited significantly lower average measured premorbid BMI over repeated assessments than those who showed onset of other or no eating disorders. Dietary restraint, negative affect, and eating affect regulation expectancies significantly increased immediately before AN onset. Youth who showed persistently low BMI reported lower pressure for thinness, body dissatisfaction, and dieting at baseline, implying that elevations in these factors did not drive the low BMI. The evidence that young women who subsequently show AN onset exhibit a low premorbid BMI on average is novel and suggests that etiologic models should incorporate this finding and selective prevention programs should target low-BMI adolescent girls. The finding that dieting, negative affect, affect-regulation eating expectances spiked immediately before emergence of AN is also novel and suggests that it might be useful for selective prevention programs to target these factors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Relationship Between Self-Reported Misophonia Symptoms and Auditory Aversive Generalization Leaning: A Preliminary Report.

Misophonia is characterized by excessive aversive reactions to specific “trigger” sounds. Although this disorder is increasingly recognized in the literature, its etiological mechanisms and maintaining factors are currently unclear. Several etiological models propose a role of Pavlovian conditioning, an associative learning process heavily researched in similar fear and anxiety-related disorders. In addition, generalization of learned associations has been noted as a potential causal or contributory factor. Building upon this framework, we hypothesized that Misophonia symptoms arise as a consequence of overgeneralized associative learning, in which aversive responses to a noxious event also occur in response to similar events. Alternatively, heightened discrimination between conditioned threat and safety cues may be present in participants high in Misophonia symptoms, as predicted by associative learning models of Misophonia. This preliminary report (n = 34) examines auditory generalization learning using self-reported behavioral (i.e., valence and arousal ratings) and EEG alpha power reduction. Participants listened to three sine tones differing in pitch, with one pitch (i.e., CS+) paired with an aversive loud white noise blast, prompting aversive Pavlovian generalization learning. We assessed the extent to which overgeneralization versus heightened discrimination learning is associated with self-reported Misophonia symptoms, by comparing aversive responses to the CS+ and other tones similar in pitch. Behaviorally, all participants learned the contingencies between CS+ and noxious noise, with individuals endorsing elevated Misophonia showing heightened aversive sensitivity to all stimuli, regardless of conditioning and independent of hyperacusis status. Across participants, parieto-occipital EEG alpha-band power reduction was most pronounced in response to the CS+ tone, and this difference was greater in those with self-reported Misophonia symptoms. The current preliminary findings do not support the notion that overgeneralization is a feature of self-reported emotional experience in Misophonia, but that heightened sensitivity and discrimination learning may be present at the neural level.

Central Symptoms of Insomnia in Relation to Depression and COVID-19 Anxiety in General Population: A Network Analysis.

Background: Insomnia is prevalent among the general population, and studies have shown an increase in insomnia symptoms during the novel coronavirus (COVID-19) pandemic. Despite numerous studies of insomnia, few studies have investigated insomnia symptoms in detail. In this study, we used network analysis to investigate interactions between insomnia symptoms in the general population. Furthermore, given the effect of COVID-19 on mental health, we also investigated how anxiety response to COVID-19 and depression related to insomnia symptoms. Methods: Data from 785 non-infected participants were used. The Insomnia Severity Index (ISI), Stress and Anxiety to Viral Epidemics—6 Scale (SAVE-6), and Patient Health Questionnaire—9 (PHQ-9) were used to measure insomnia symptoms, anxiety response to COVID-19, and depression, respectively. Network analysis was performed using R Studio. Centrality indices and edge weights were obtained, and each index was evaluated using bootstrapping methods. Results: The network revealed ISI7 (worry about current sleep pattern) to be the most central insomnia symptom. ISI7 was strongly connected to SAVE-6 total score, and ISI2 (difficulty staying asleep) was strongly connected to PHQ-9 total score. Conclusion: High centrality of ISI7 supports the role of dysfunctional cognitions in etiological models of insomnia and thus the cognitive behavioral therapy for insomnia. The relationship between ISI7 and SAVE-6 is explained by transposition of worry and fear of contracting COVID-19 to worry about sleep patterns. The link between ISI2 and PHQ-9 necessitate further investigations of whether specific symptoms of insomnia are more associated with depression.

Persistence of gastrointestinal symptoms in irritable bowel syndrome and ulcerative colitis: study protocol for a three-arm randomised controlled trial (SOMA.GUT-RCT)

IntroductionUlcerative colitis (UC) and irritable bowel syndrome (IBS) are distressing chronic diseases associated with abdominal pain and altered bowel habits of unknown aetiology. Results from previous studies indicate that, across...

WITHDRAWN: Elevated histamine etiology model for most major vaccine associated adverse events including SARS-CoV-2 spike vaccines

Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients. Most of these vaccine adverse events are self-limiting and resolve within days. Many of these adverse events symptoms overlap symptoms associated with elevated histamine levels. Based on these observations, the hypothesis that the majority of vaccine associated reactogenicity adverse events are caused by temporal histamine intolerance in vaccinees is proposed. This hypothesis is based on a model of innate immune responses releasing a surge of inflammatory molecules including histamine; this surge is hypothesized to exceed the normal histamine tolerance level for vaccinees with reactogenicity adverse events. Further, these symptoms resolve as histamine levels fall below the vaccinee's tolerance threshold. This model can be evaluated by the detection of elevated histamine levels in vaccinees corresponding to timing of symptoms onset. If confirmed, a direct consequence of this model predicts that some antihistamine treatments, mast cell stabilizers, and possibly diamine oxidase enzyme may reduce the incidence or severity of adverse events experienced by vaccinees post vaccinations for most or all high reactogenicity vaccines including coronavirus disease 2019 (COVID-19) Spike vaccines.