Background: Although the association of the measles, mumps, and rubella vaccine with autism spectrum disorder has been convincingly disproven, the onset of certain brain-related autoimmune and inflammatory disorders has been found to be temporally associated with the antecedent administration of various vaccines. This study examines whether antecedent vaccinations are associated with increased incidence of obsessive–compulsive disorder (OCD), anorexia nervosa (AN), anxiety disorder, chronic tic disorder, attention deficit hyperactivity disorder, major depressive disorder, and bipolar disorder in a national sample of privately insured children.
Methods: Using claims data, we compared the prior year’s occurrence of vaccinations in children and adolescents aged 6–15 years with the above neuropsychiatric disorders that were newly diagnosed between January 2002 and December 2007, as well as two control conditions, broken bones and open wounds. Subjects were matched with controls according to age, gender, geographical area, and seasonality. Conditional logistic regression models were used to determine the association of prior vaccinations with each condition.
Results: Subjects with newly diagnosed AN were more likely than controls to have had any vaccination in the previous 3 months [hazard ratio (HR) 1.80, 95% confidence interval 1.21–2.68]. Influenza vaccinations during the prior 3, 6, and 12 months were also associated with incident diagnoses of AN, OCD, and an anxiety disorder. Several other associations were also significant with HRs greater than 1.40 (hepatitis A with OCD and AN; hepatitis B with AN; and meningitis with AN and chronic tic disorder).
Conclusion: This pilot epidemiologic analysis implies that the onset of some neuropsychiatric disorders may be temporally related to prior vaccinations in a subset of individuals. These findings warrant further investigation, but do not prove a causal role of antecedent infections or vaccinations in the pathoetiology of these conditions. Given the modest magnitude of these findings in contrast to the clear public health benefits of the timely administration of vaccines in preventing mortality and morbidity in childhood infectious diseases, we encourage families to maintain vaccination schedules according to CDC guidelines.
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The principal findings of this study are as follows: (i) children with OCD, AN, anxiety disorder, and tic disorder were more likely to have received influenza vaccine during the preceding 1-year period (for OCD in the preceding 3-, 6-, and 12-month periods; for AN in the preceding 3- and 6-month periods; for anxiety disorder in the preceding 6- and 12-month periods; for tic disorder in the preceding 6- and 12-month periods) and (ii) HRs associated with receipt of any vaccine were highest for children with AN, ranging from 1.47 for the 12-month preceding period to 1.80 for the 3-month preceding period, followed by OCD, which ranged from 1.23 for both the 12- and 3-month preceding periods to 1.27 for the 6-month preceding period. However, if we apply a high standard [so that the upper limit of the of the 95% CI of the HR observed for the association between the administration of any vaccine and the subsequent occurrence of a broken bone (1.11) falls below the lower limit of the 95% CI observed for any of the HRs for any of the neuropsychiatric disorders], only the findings for AN pass this stringent threshold (Table 2). Applying a similar high standard for the individual vaccines, the only associations that pass this threshold concern the influenza vaccine given in the preceding 6- and 12-month periods for OCD and anxiety disorders.
Our findings showing that children with AN, OCD, or a tic disorder were more likely to have received the influenza vaccine in the preceding periods were noteworthy given the findings of increased incidence of narcolepsy in Finland, Sweden, Ireland, Norway, England, and France after vaccination with AS03-adjuvanted H1N1 vaccine (17, 18). Studies also show a threefold increase in the incidence of narcolepsy after following the 2009 H1N1 pandemic in China (30). Although the strong association between HLA class II and narcolepsy suggests that narcolepsy may be an autoimmune disorder, the exact mechanism leading to immune-related narcolepsy is not completely understood and other host factors are likely to play an important role (31, 32). Investigators have made use of in silico techniques to begin to identify potential causal pathways and the relevant host factors (19). More recently, Ahmed et al. (23) have shown that the H1N1 influenza vaccine containing the AS03 adjuvant triggers antibodies that bind to hypocretin receptor 2a. Additional work is needed to replicate and extend these findings.
It is also of note that the observed association between the antecedent administration of the influenza vaccine and the new onset of AN and OCD may suggest that aberrant immune functioning may be a common pathogenetic pathway for OCD and AN. The high comorbidity rates between OCD and AN, common cortico-striatal abnormalities in neuroimaging studies, and anti-putamen antibodies both in OCD and AN cases are some of the shared features of these two disorders worth considering (33–35). In addition, the increased risk for autoimmune disorders (such as type 1 diabetes mellitus, Crohn’s disease, and celiac disease) in eating disorders (36) and the documented comorbidity of OCD and autoimmune diseases (such as systemic lupus erythematosus, thyroid dysfunction, and multiple sclerosis) (35) indicate the possible shared host factors and the role of immune-mediated mechanisms in the development of AN and OCD. We also note the findings of Zastrow and colleagues that vaccination to prevent H1N1 influenza is recommendable even in extremely underweight AN patients (37).
http://journal.frontiersin.org/article/10.3389/fpsyt.2017.00003/full
open access
Methods: Using claims data, we compared the prior year’s occurrence of vaccinations in children and adolescents aged 6–15 years with the above neuropsychiatric disorders that were newly diagnosed between January 2002 and December 2007, as well as two control conditions, broken bones and open wounds. Subjects were matched with controls according to age, gender, geographical area, and seasonality. Conditional logistic regression models were used to determine the association of prior vaccinations with each condition.
Results: Subjects with newly diagnosed AN were more likely than controls to have had any vaccination in the previous 3 months [hazard ratio (HR) 1.80, 95% confidence interval 1.21–2.68]. Influenza vaccinations during the prior 3, 6, and 12 months were also associated with incident diagnoses of AN, OCD, and an anxiety disorder. Several other associations were also significant with HRs greater than 1.40 (hepatitis A with OCD and AN; hepatitis B with AN; and meningitis with AN and chronic tic disorder).
Conclusion: This pilot epidemiologic analysis implies that the onset of some neuropsychiatric disorders may be temporally related to prior vaccinations in a subset of individuals. These findings warrant further investigation, but do not prove a causal role of antecedent infections or vaccinations in the pathoetiology of these conditions. Given the modest magnitude of these findings in contrast to the clear public health benefits of the timely administration of vaccines in preventing mortality and morbidity in childhood infectious diseases, we encourage families to maintain vaccination schedules according to CDC guidelines.
========
...
The principal findings of this study are as follows: (i) children with OCD, AN, anxiety disorder, and tic disorder were more likely to have received influenza vaccine during the preceding 1-year period (for OCD in the preceding 3-, 6-, and 12-month periods; for AN in the preceding 3- and 6-month periods; for anxiety disorder in the preceding 6- and 12-month periods; for tic disorder in the preceding 6- and 12-month periods) and (ii) HRs associated with receipt of any vaccine were highest for children with AN, ranging from 1.47 for the 12-month preceding period to 1.80 for the 3-month preceding period, followed by OCD, which ranged from 1.23 for both the 12- and 3-month preceding periods to 1.27 for the 6-month preceding period. However, if we apply a high standard [so that the upper limit of the of the 95% CI of the HR observed for the association between the administration of any vaccine and the subsequent occurrence of a broken bone (1.11) falls below the lower limit of the 95% CI observed for any of the HRs for any of the neuropsychiatric disorders], only the findings for AN pass this stringent threshold (Table 2). Applying a similar high standard for the individual vaccines, the only associations that pass this threshold concern the influenza vaccine given in the preceding 6- and 12-month periods for OCD and anxiety disorders.
Our findings showing that children with AN, OCD, or a tic disorder were more likely to have received the influenza vaccine in the preceding periods were noteworthy given the findings of increased incidence of narcolepsy in Finland, Sweden, Ireland, Norway, England, and France after vaccination with AS03-adjuvanted H1N1 vaccine (17, 18). Studies also show a threefold increase in the incidence of narcolepsy after following the 2009 H1N1 pandemic in China (30). Although the strong association between HLA class II and narcolepsy suggests that narcolepsy may be an autoimmune disorder, the exact mechanism leading to immune-related narcolepsy is not completely understood and other host factors are likely to play an important role (31, 32). Investigators have made use of in silico techniques to begin to identify potential causal pathways and the relevant host factors (19). More recently, Ahmed et al. (23) have shown that the H1N1 influenza vaccine containing the AS03 adjuvant triggers antibodies that bind to hypocretin receptor 2a. Additional work is needed to replicate and extend these findings.
It is also of note that the observed association between the antecedent administration of the influenza vaccine and the new onset of AN and OCD may suggest that aberrant immune functioning may be a common pathogenetic pathway for OCD and AN. The high comorbidity rates between OCD and AN, common cortico-striatal abnormalities in neuroimaging studies, and anti-putamen antibodies both in OCD and AN cases are some of the shared features of these two disorders worth considering (33–35). In addition, the increased risk for autoimmune disorders (such as type 1 diabetes mellitus, Crohn’s disease, and celiac disease) in eating disorders (36) and the documented comorbidity of OCD and autoimmune diseases (such as systemic lupus erythematosus, thyroid dysfunction, and multiple sclerosis) (35) indicate the possible shared host factors and the role of immune-mediated mechanisms in the development of AN and OCD. We also note the findings of Zastrow and colleagues that vaccination to prevent H1N1 influenza is recommendable even in extremely underweight AN patients (37).
http://journal.frontiersin.org/article/10.3389/fpsyt.2017.00003/full
open access