Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder
Open accessAbstract
Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation.
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Written from the paper’s full text.
TL;DR
In a multi-site sample of 120 children and adolescents with ASD, greater lower GI tract symptoms were associated with a larger post-stress cortisol response, especially in those with regressive autism, but not with TNF-α or IL-6. Exploratory analyses linked cortisol and cytokines to intelligence, behavior, and anxiety.
Key findings
- Greater lower GI tract symptoms were significantly positively associated with cortisol response to stress, controlling for age, gender, and pre-stress cortisol: r = 0.27, p = 0.021, 95% CI = [0.04–0.47].
- Presence of regressive autism significantly modified the relationship between lower GI tract score and cortisol response: p = 0.007 for the interaction term; slope in the presence of regressive autism = 11.88, slope in the absence = 0.79.
- Lower GI tract symptoms were not associated with TNF-α or IL-6. TNF-α was significantly positively correlated with upper GI tract score, controlling for age and gender: p = 0.039, r = 0.20, 95% CI = [0.01–0.38].
- Exploratory analyses found cortisol response positively correlated with FSIQ (r = 0.27, p = 0.037) and negatively correlated with ABC Inappropriate Speech (r = −0.27, p = 0.023) and Hyperactivity (r = −0.28, p = 0.019); IL-6 was negatively related to FSIQ (p < 0.01, r = −0.29) and Vineland Socialization (p = 0.017, r = −0.27); TNF-α was related to ABC Irritability (p = 0.043, r = 0.20) and presence of an anxiety disorder (p = 0.037, Cohen’s d = 0.423).
Methods
- Multi-site study of 120 individuals with ASD (mean age = 11.8, SD = 3.8, range = 6–18; mean FSIQ = 84, SD = 22.6; 111 Caucasian, 108 males), recruited through the Autism Speaks–Autism Treatment Network and clinics at the University of Missouri Thompson Center and Vanderbilt Kennedy Center. ASD diagnosis was based on DSM-IV-TR criteria and verified by ADOS; exclusions included known mitochondrial disorder, genetic disorder such as Fragile X syndrome or tuberous sclerosis, or bleeding disorder.
- GI symptoms were assessed with the parent-report Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III (QPGS-RIII), yielding continuous upper and lower GI tract scores. Cytokines IL-6 and TNF-α were measured from fasting blood via ELISA; salivary cortisol was collected pre- and post-stress; the stress protocol used cold pressor and vibrotactile stimulation with ECG and skin conductance monitoring.
- Analyses used Pearson partial correlations controlling for age and gender, and for cortisol response also pre-stress cortisol; candidate effect modifiers were tested with likelihood ratio tests on interaction terms in multiple linear regression. A significance level of 0.05 was used without correction for multiple testing. Suitable samples were available for 107 IL-6, 105 TNF-α, and 81 pre-stress and 79 post-stress cortisol measurements.
Limitations
- Stated: the study omitted individuals with ASD and mitochondrial disorders or genetic disorders such as Fragile X syndrome and tuberous sclerosis, so findings are not generalizable to those individuals.
- Stated: the study targeted specific cytokines most related to stress, ASD, and GI symptomatology; larger future studies should explore a broader range of cytokines.
- Stated: conclusions were based on significance levels uncorrected for multiple comparisons in this exploratory study, so findings should be investigated further. Evident from the text: the correlational design cannot establish causal relationships, and the sample was predominantly male and Caucasian, which may limit generalizability.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 19 cited sources checked · 0 supported · 0 flagged
- Findingown data
A significant positive relationship was found between cortisol response to stress and a greater lower GI tract score from the QPGS-RIII, r = 0.27, p = 0.021, 95% CI = [0.04-0.47], controlling for age, gender and pre-stress cortisol concentration.
“A significant positive relationship was found between cortisol response to stress and a greater lower GI tract score from the QPGS-RIII, r = 0.27, p = 0.021, 95% CI = [0.04–0.47], controlling for age, gender and pre-stress cortisol concentration.”
Quote in the paperSubstantial claim - Findingown data
Cortisol response significantly modified the relationship between lower GI tract score and psychophysiological stress response as measured by change in pNN50 due to cold-pressor stimulation (p = 0.040 for the interaction term; slope at quartile 1 = −17.88, slope at quartile 3 = −36.87).
“Furthermore, cortisol response significantly modified the relationship between lower GI tract score and psychophysiological stress response as measured by change in pNN50 due to cold-pressor stimulation (p = 0.040 for the interaction term, slope between lower GI tract score and change in pNN50 at quartile 1 of cortisol response = −17.88, slope at quartile 3 = −36.87).”
Quote in the paperSubstantial claim - Findingown data
For TNF-α concentration, a significant negative relationship was found with the ABC Irritability score, p = 0.043, r = 0.20, 95% CI = [0.01-0.38].
“For TNF-α concentration, a significant negative relationship was found with the ABC Irritability score, p = 0.043, r = 0.20, 95% CI = [0.01–0.38].”
Quote in the paperNot a substantial claim - Findingown data
For IL-6 concentration, a significant negative relationship was found with the Vineland Socialization domain scale score, p = 0.017, r = −0.27, 95% CI = [−0.47 to 0.05].
“and a significant negative relationship was found with the Vineland Socialization domain scale score, p = 0.017, r = −0.27, 95% CI = [−0.47 to 0.05].”
Quote in the paperNot a substantial claim - Findingown data
For IL-6, no significant relationship was found with upper or lower GI tract scores from the QPGS-RIII.
“For IL-6, no significant relationship was found with upper or lower GI tract scores from the QPGS-RIII.”
Quote in the paperNot a substantial claim
- Findingown data
A significant relationship was found between TNF-α concentration and presence of an anxiety disorder, p = 0.037, Cohen's d = 0.423.
“For key co-occurring conditions, a significant relationship was found between TNF-α concentration and presence of an anxiety disorder (p = 0.037, Cohen’s d = 0.423).”
Quote in the paperSubstantial claim - Findingown data
A significant negative correlation was found between cortisol response to stress and the ABC Hyperactivity subscale, r = −0.28, p = 0.019, 95% CI = [−0.48 to −0.05].
“and the Hyperactivity subscale, r = −0.28, p = 0.019, 95% CI = [−0.48 to −0.05].”
Quote in the paperNot a substantial claim - Findingown data
No relationships were observed between TNF-α concentration and depression or seizures.
“No such relationships were observed with depression or seizures.”
Quote in the paperNot a substantial claim - Findingown data
Change in pNN50 due to cold-pressor stimulation is uncorrelated with cortisol concentrations in this sample.
“Change in pNN50 due to cold-pressor stimulation is uncorrelated with cortisol concentrations in this sample”
Quote in the paperNot a substantial claim - Findingown data
A significant negative correlation was found between cortisol response to stress and the ABC Inappropriate Speech subscale, r = −0.27, p = 0.023, 95% CI = [−0.47 to −0.04].
“significant negative correlations were found between the cortisol response to stress and both the ABC Inappropriate Speech subscale, r = −0.27, p = 0.023, 95% CI = [−0.47 to −0.04]”
Quote in the paperNot a substantial claim - Findingown data
A significant positive correlation was identified between cortisol response to stress and FSIQ, r = 0.27, p = 0.037, 95% CI = [0.02-0.49].
“A significant positive correlation was identified between cortisol response to stress and FSIQ, r = 0.27, p = 0.037, 95% CI = [0.02–0.49].”
Quote in the paperNot a substantial claim - Findingown data
For IL-6 concentration, a significant negative relationship was found with FSIQ, p < 0.01, r = −0.29, 95% CI = [−0.46 to −0.08].
“For IL-6 concentration, a significant negative relationship was found with FSIQ, p < 0.01, r = −0.29, 95% CI = [−0.46 to −0.08]”
Quote in the paperNot a substantial claim - Findingown data
In both cases, subjects with the condition had higher TNF-α concentrations on average.
“In both cases, subjects with the condition had higher TNF-α concentrations on average.”
Quote in the paperNot a substantial claim - Findingown data
Presence of regressive autism was a significant effect modifier for the relationship between lower GI tract score and cortisol response (p = 0.007 for the interaction term; slope in the presence of regressive autism = 11.88, slope in the absence of regressive autism = 0.79).
“Presence of regressive autism was found to be a significant effect modifier for the relationship between lower GI tract score and cortisol response (p = 0.007 for the interaction term, slope in the presence of regressive autism = 11.88, slope in the absence of regressive autism = 0.79)”
Quote in the paperSubstantial claim - Findingown data
A weak relationship was observed between TNF-α concentration and reporting regressive autism, p = 0.096, Cohen's d = 0.351.
“A weak relationship was observed between TNF-α concentration and reporting regressive autism (p = 0.096, Cohen’s d = 0.351).”
Quote in the paperNot a substantial claim - Findingown data
For TNF-α, there was a significant positive correlation between TNF-α concentration and the QPGS-RIII upper GI tract score while controlling for age and gender, p = 0.039, r = 0.20, 95% CI = [0.01-0.38].
“For TNF-α, there was a significant positive correlation between TNF-α concentration and the QPGS-RIII upper GI tract score while controlling for age and gender, p = 0.039, r = 0.20, 95% CI = [0.01–0.38].”
Quote in the paperSubstantial claim - Premisecitation
In the general population, GI symptoms themselves have been reported to be associated with alterations in TNF-α and IL-6.
“In the general population, GI symptoms themselves have been reported to also be associated with alterations in TNF-α and IL-6, suggesting a potential interaction between stress and immune functioning in those with GI dysfunction (Lyte et al., 2011; von Känel et al., 2006).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Levels of the proinflammatory cytokines IL-6 and TNF-α, which lead to activation of the HPA axis, have been shown to be increased in those with ASD.
“Levels of the proinflammatory cytokines IL-6 and tumor necrosis factor-alpha (TNF-α), which lead to activation of the HPA axis (Dunn, 2006), have been shown to be increased in those with ASD (Ashwood et al., 2011; Emanuele et al., 2010; von Känel et al., 2005).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
A generalized increase in the stress response is characteristic of those with ASD relative to typically-developing individuals.
“Furthermore, a generalized increase in the stress response is also characteristic of those with ASD relative to typically-developing individuals (Ming et al., 2005; Mazurek et al., 2013; Spratt et al., 2012).”
Quote in the paperSubstantial claim0 of 3 sources checked - Study design and conductnone given
No differences were observed in any of the measures between the study sites.
“No differences were observed in any of the measures between the study sites.”
Quote in the paperSubstantial claim - Premisecitation
Individuals with ASD have an atypical immune response, including alterations in IL-12, IFN-γ, IL-2, IL-6, IL-10, and TNF-α.
“Several studies have shown that individuals with ASD have an atypical immune response, including alterations in IL-12, IFN-γ, IL-2, IL-6, IL-10, and TNF-α (Lyte et al., 2011; Goines and Ashwood, 2013).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Many studies suggest an increased prevalence of gastrointestinal (GI) problems in individuals with ASD relative to typically-developing individuals, especially for constipation.
“Many studies suggest an increased prevalence of gastrointestinal (GI) problems in individuals with ASD relative to typically-developing individuals (McElhanon et al., 2014; Chaidez et al., 2014), especially for constipation”
Quote in the paperNot a substantial claim0 of 2 sources checked - Study design and conductcitation
Cold pressor stimulation has been shown to elicit a cortisol response in ASD.
“All participants at each site engaged in a stress response protocol involving momentary, unpleasant physical stimuli, which has been shown to illicit a cortisol response in ASD (Taylor and Corbett, 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Taylor and Corbett, 2014
Not checked in the free run.
- Interpretationown data
The low incidence of seizures and low degree of depressive symptomatology in our study sample may explain the lack of relationships between TNF-α and depression or seizures.
“which may be related to the low incidence of seizures and the low degree of depressive symptomatology in our study sample.”
Quote in the paperSubstantial claim - Interpretationreasoning
The current findings are not generalizable to individuals with ASD and mitochondrial disorders or genetic disorders such as Fragile X syndrome and tuberous sclerosis.
“A potential limitation of the current study is the omission of individuals with ASD and mitochondrial disorders or genetic disorders such as Fragile X syndrome and tuberous sclerosis. As such, the current findings are not generalizable to these individuals.”
Quote in the paperNot a substantial claim - Interpretationown data
The increases in cortisol response do not appear to translate into effects on the stress-related cytokines, TNF-α and IL-6.
“The increases in cortisol response, however, do not appear to translate into effects on the stress-related cytokines, TNF-α and IL-6.”
Quote in the paperSubstantial claim - Interpretationown data
The negative correlation between psychophysiological stress response and lower GI tract score increases as the endocrine stress response increases.
“The negative correlation between psychophysiological stress response and lower GI tract score increases as the endocrine stress response increases.”
Quote in the paperSubstantial claim - Interpretationcitation
The modest relationship between upper GI tract symptoms and TNF-α is consistent with previous findings of increased TNF-α associated with GI symptoms in general.
“The modest relationship between upper GI tract symptoms and TNF-α is consistent with previous findings of increased TNF-α associated with GI symptoms in general (Ashwood et al., 2011), but this is limited by the paucity of upper GI tract symptoms in our sample.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ashwood et al., 2011 source
Not checked in the free run.
- May combine two claims. 9
- Classified as probably not a substantial claim. 11
May combine two claims.
Findingown dataThe most frequently occurring GI disorders in the sample were functional constipation (42.5%), irritable bowel syndrome (11.7%), lower abdominal pain associated with bowel symptoms (9.2%), and upper abdominal pain associated with bowel symptoms (7.5%).
“According to parental- and self-report on the QPGS-RIII, the most frequently occurring GI disorders present in the sample were: functional constipation (42.5%), irritable bowel syndrome (11.7%), and lower abdominal pain associated with bowel symptoms (9.2%), and upper abdominal pain associated with bowel symptoms (7.5%).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPre-stress cortisol concentration was uncorrelated with lower GI tract score and post-stress cortisol in this sample.
“The latter was uncorrelated with lower GI tract score and post-stress cortisol in this sample.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBoth pNN50 stress response and cortisol response are significant independent predictors of lower GI tract symptoms.
“both pNN50 stress response and cortisol response are significant independent predictors of lower GI tract symptoms.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationThe QPGS-RIII has been used to assess GI dysfunction in ASD with clinician-parent agreement at 92.1% for presence of any QPGS-RIII disorder, and fair agreement for functional constipation.
“The QPGS-RIII has been used to assess GI dysfunction in ASD with clinician-parent agreement at 92.1% for presence of any QPGS-RIII disorder, and fair agreement for functional constipation (Gorrindo et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gorrindo et al., 2012 source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenNo correction was made for multiple testing.
“No correction was made for multiple testing, and as such, conclusions may be interpreted as potential directions for future research.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataIntra-assay coefficient of variation for IL-6 and TNF-α was 2.6% and 4.7%, respectively.
“Intra-assay coefficient of variation (CV) for IL-6 and TNF-α was 2.6% and 4.7%, respectively.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationBoth acute and chronic stress are associated with the onset of GI disease as well as exacerbation of GI symptoms in individuals without ASD.
“Both acute and chronic stress are associated with the onset of GI disease as well as exacerbation of GI symptoms (Dinan et al., 2006).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Dinan et al., 2006 source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductown dataAnalyses controlled for age, gender, and pre-stress cortisol in the analysis of cortisol response.
“The relationships between the cytokine and cortisol response endpoints and GI functioning, as well as secondary variables such as FSIQ, ABC and Vineland, were assessed as Pearson partial correlations controlling for age and gender, and, in the analysis of cortisol response, pre-stress cortisol.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationActivation of the HPA axis in individuals with irritable bowel syndrome (IBS) without ASD is associated with an augmented adrenocorticotropic hormone (ACTH) and cortisol response, as well as increased sympathetic activity and low vagal tone.
“Activation of the HPA axis in individuals with irritable bowel syndrome (IBS) without ASD is associated with an augmented adrenocorticotropic hormone (ACTH) and cortisol response, as well as increased sympathetic activity and low vagal tone (Aggarwal et al., 1994; Mayer, 2000).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenIntra- and inter-assay CVs for the cortisol kit were 4.6% and 6%, respectively.
“Intra- and inter-assay CVs for the kit were 4.6% and 6%, respectively.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataInter-assay CV for IL-6 and TNF-α was 4.5% and 5.8%, respectively.
“Inter-assay CV for IL-6 and TNF-α was 4.5% and 5.8%, respectively.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationThe negative relationships between TNF-α and irritability and between IL-6 and sociability are consistent with previous observations of decreased immune markers with behavioral symptoms in ASD.
“The negative relationships between TNF-α and irritability and between IL-6 and sociability are consistent with previous observations of decreased immune markers with behavioral symptoms in ASD (Heuer et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Heuer et al., 2008 source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductreasoningCausal relationships are not able to be made from these correlational analyses.
“Causal relationships are not able to be made from these correlational analyses”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6.
“These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable).
Interpretationown dataThe relationship between lower GI tract symptoms and stress-related endocrine response raises the possibility that amelioration of the stress response might be an important aspect of treatment in some cases.
“The relationship between lower GI tract symptoms and stress-related endocrine response raises the possibility that amelioration of the stress response might be an important aspect of treatment in some cases.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe relationship between anxiety and TNF-α is not surprising given that the cytokines measured in this study are associated with the stress response in those without ASD.
“The relationship between anxiety and TNF-α is not surprising given that the cytokines measured in this study are associated with the stress response in those without ASD.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The etiology of gastrointestinal symptoms in autism spectrum disorder is currently unknown.
“Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown.”
The paper relies on this without support.
The relationship between the stress response and gastrointestinal symptoms in autism spectrum disorder is poorly understood.
“However, the relationship between the stress response and GI symptoms in ASD is poorly understood.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
It is proposed that FS in ASD patients may occur because some of them present food rejection, gastroesophageal reflux, chronic constipation, delayed gastro emptying, and functional dyspepsia.
“On the other hand, it is proposed that FS in ASD patients may occur because some of them present food rejection, gastroesophageal reflux, chronic constipation, delayed gastro emptying, and functional dyspepsia [78].”
From Food Selectivity and Its Implications Associated with Gastrointestinal Disorders in Children with Autism Spectrum Disorders (2022) · cites this paper as [78]
Heightened stress and anxiety, rigid-compulsive behavior, and sleep problems have been shown to be associated with GI symptoms in ASD, especially constipation.
“Heightened stress and anxiety, rigid-compulsive behavior, and sleep problems, have been shown to be associated with GI symptoms in ASD, especially constipation (6, 11, 12, 16–19).”
From The Relationship Among Gastrointestinal Symptoms, Problem Behaviors, and Internalizing Symptoms in Children and Adolescents with Autism Spectrum Disorder (2019) · cites this paper as [12]
Many individuals with ASD suffer from constipation.
“However, it appears that many individuals with ASD suffer from constipation (2, 3, 11, 12).”
From The Relationship Among Gastrointestinal Symptoms, Problem Behaviors, and Internalizing Symptoms in Children and Adolescents with Autism Spectrum Disorder (2019) · cites this paper as [12]
Children with ASD have greater GI symptoms correlated to higher post-stress cortisol levels.
“Children with ASD were also shown to have greater GI symptoms correlated to higher post-stress cortisol levels 36.”
From Gastrointestinal Issues and Autism Spectrum Disorder (2020) · cites this paper as [36]
ASD patients with GI problems have greater stress reactivity than non-ASD controls.
“ASD patients with GI problems have greater stress reactivity than non-ASD controls.”
From Gastrointestinal Issues and Autism Spectrum Disorder (2020) · cites this paper as [36]
Children with ASD and anxiety are at greater risk for lower GI problems.
“Children with ASD and anxiety have been shown to be at greater risk for lower GI problems”
From Gastrointestinal Issues and Autism Spectrum Disorder (2020) · cites this paper as [36]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
IL-6-socialization confidence interval conflicts with reported significance
MinorThe reported 95% confidence interval includes zero, which conflicts with the claim of a significant relationship at p = 0.017.
“a significant negative relationship was found with the Vineland Socialization domain scale score, p = 0.017”
“95% CI = [−0.47 to 0.05]”
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Gastrointestinal Disturbances in Autism Spectrum Disorder
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Self-citationAutism Spectrum Disorder, Fear Response, and Environmental Exposures
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- Authors
- Ferguson, B. J., Marler, S., Altstein, L. L., Lee, E. B., Mazurek, M. O., McLaughlin, A., Macklin, E. A., McDonnell, E., Davis, D. J., Belenchia, A. M., Gillespie, C. H., Peterson, C. A., Bauman, M. L., Margolis, K. G., Veenstra-VanderWeele, J., & Beversdorf, D. Q.
- Affiliations
- University of Missouri (US)
- Vanderbilt University Medical Center (US)
- Massachusetts General Hospital (US)
- Vanderbilt University (US)
- Harvard University (US)
- Boston University (US)
- Columbia University Irving Medical Center (US)
- NewYork–Presbyterian Hospital (US)
- Corresponding author
- Beversdorf, David Q.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 58
- Pages
- 57-62
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC5526212
- OpenAlex
- W2365518836
- Cited by
- 89
- References
- 50
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 6 · 2023: 11 · 2022: 14 · 2021: 9 · 2020: 8 · 2019: 20 · 2018: 7 · 2017: 3 · 2016: 1
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MOspace Institutional Repository (University of Missouri) (submittedVersion)
- Funders
- HRSA (UA3MC11054)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, gastrointestinal symptoms, stress response, cortisol, TNF-α, interleukin-6, cytokines, regressive autism, irritability, intelligence, socialization, inappropriate speech
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Child, Endocrine System, Female, Gastrointestinal Diseases, Humans, Hydrocortisone, Male, Stress, Psychological, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
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