Adverse Childhood Experiences Are Associated With Migraine
Adverse Childhood Experiences Are Associated With Migraine
Original enrollment in the biomarker portion of this study was conducted between February 2006 and October 2008 after approval by the institutional review board.
Participants were recruited from advertisements in the ambulatory Headache Center, university campus website, institution-wide e-mail, radio, and the local newspaper. Within the Headache Center, participation was offered to consecutive eligible patients after evaluation by the principal investigator (PI) to determine eligibility. The enrollment plan was to include equal numbers of women with MA and migraine without aura (MO), in addition to non-migraine controls. Inclusion criteria for migraineurs were as follows: (1) women with MA or MO, as defined by criteria set forth in the ICHD-2 (codes 1.1, 1.2, 1.5); (2) age 18–50 years; (3) premenopausal status; and (4) headache-free for at least 7 days at the time of enrollment. Potential headache-free female control subjects who matched the ages of the cases (based on 5-year group intervals) were screened for enrollment according to a standardized questionnaire to determine eligibility. Exclusion criteria were as follows: (1) not physically well enough to give blood; (2) presence of diabetes mellitus, vasculitis, prior stroke/transient ischemic attack, pregnancy (self-reported), myocardial infarction, or systemic lupus erythematosus; (3) use of anticoagulants; (4) use of non-steroidal anti-inflammatory drugs or other antiplatelet agents in the week before testing; and (5) not literate in English.
At the study encounter, the participants completed a questionnaire regarding age, education, household income, height, weight, age of headache onset, headache-related disability, physician-diagnosed medical conditions (including hypertension, smoking, hyperlipidemia, history of deep venous thrombosis, pulmonary embolism). The PI supplied the following information when applicable: medications, ICHD-2 headache diagnoses, and average monthly days with headache during the prior 3 months. For those migraineurs with 15 or more headache days per month (chronic migraine [CM]), the PI also recorded whether there was a history of transformation from episodic to chronic frequency (transformed migraine [TM]) and whether the subject experienced continuous headache.
The methods have been previously described. All testing was done after the subjects had not taken non-steroidal anti-inflammatory drugs or other antiplatelet agents for at least 1 week and after an overnight fast. Those with migraine needed to be headache-free for 1 week. Urine and blood samples were collected between 8 AM and 9 AM. Blood was drawn without a tourniquet. Analysis was performed blinded to participants' health or laboratory information. Assays for von Willebrand factor (vWF) activity, high-sensitivity C-reactive protein (hsCRP), tissue plasminogen activator (tPA) antigen, and prothrombin activation fragment (F1.2) were performed by Esoterix, Inc. (Aurora, CO, USA). The vWF activity assay uses plasma vWF to agglutinate platelets in the presence of ristocetin. By comparing the rate of agglutination against a normal reference curve, the vWF activity as a percentage was quantified. tPA antigen and F1.2 assays were performed by enzyme-linked immunosorbent assay. The hsCRP assay was done with the nephelometry technique. Assays for tissue necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta 1, interleukin 6 (IL-6), and adiponectin were performed by AssayGate (Ijamsville, MD, USA) using a multiplex assay on a Luminex Bead-based sandwich immunoassay platform. Urinary total nitrate/nitrite assays were performed by Cayman Chemical Co, Ann Arbor, MI, USA. A calorimetric assay method was used to measure urine nitrate/nitrite concentration (NOx), and results are reported as total nitrate/nitrite levels.
After institutional review board approval, a 1-page 10-item (multicomponent), closed format questionnaire was mailed to study participants in November 2010 to assess adverse childhood experiences (ACEs). This questionnaire has been used previously for numerous studies that explored relationship of ACEs with health outcomes in adults. Questions (see Appendix) were related to experiences occurring when under the age of 18 years old, including abuse (emotional, physical, sexual), neglect (emotional, physical), and exposure to household dysfunction (violence against mother/stepmother, parental substance abuse, mental illness, criminal behavior, and parental separation or divorce). Respondents were defined as exposed to a category if they responded "yes" to 1 or more of the questions in that category. The total number of these exposures (range 0–10) was summed to create the ACE score. Several techniques were used to help maximize the survey response rate, including limiting the length of the questionnaire to 1 page, offering a 5-dollar monetary incentive, personalizing the letter that introduced the questionnaire, and using multiple contacts. Approximately 2 weeks after the initial mailing, a second wave was sent to those who had not responded. Two weeks after the second mailing, a final third wave mailing was sent to nonrespondents. Participants were identified by a code to ensure their confidentiality, and only those who had not responded were contacted for follow-up mailings. All of these procedures were intended to reduce nonrespondent bias and increase the external validity of the results. After receiving all surveys, the code sheet was destroyed to maintain confidentiality.
Data from the study were analyzed using SPSS 17.0 (SPSS, Inc., Chicago, IL, USA). Data analysis included descriptive statistics with a report of the appropriate frequencies, means, and standard deviations to describe the responses to the questionnaire items, as well as the demographic and background characteristics of the respondents. Chi-square tests and logistic regressions were computed to determine differences between groups of categorical variables. Similarly, t-tests were conducted to determine differences among multiple categorical independent and parametric dependent variables. Pearson's correlation analysis was run to assess the association between continuous variables.
Methods
Original enrollment in the biomarker portion of this study was conducted between February 2006 and October 2008 after approval by the institutional review board.
Study Participants
Participants were recruited from advertisements in the ambulatory Headache Center, university campus website, institution-wide e-mail, radio, and the local newspaper. Within the Headache Center, participation was offered to consecutive eligible patients after evaluation by the principal investigator (PI) to determine eligibility. The enrollment plan was to include equal numbers of women with MA and migraine without aura (MO), in addition to non-migraine controls. Inclusion criteria for migraineurs were as follows: (1) women with MA or MO, as defined by criteria set forth in the ICHD-2 (codes 1.1, 1.2, 1.5); (2) age 18–50 years; (3) premenopausal status; and (4) headache-free for at least 7 days at the time of enrollment. Potential headache-free female control subjects who matched the ages of the cases (based on 5-year group intervals) were screened for enrollment according to a standardized questionnaire to determine eligibility. Exclusion criteria were as follows: (1) not physically well enough to give blood; (2) presence of diabetes mellitus, vasculitis, prior stroke/transient ischemic attack, pregnancy (self-reported), myocardial infarction, or systemic lupus erythematosus; (3) use of anticoagulants; (4) use of non-steroidal anti-inflammatory drugs or other antiplatelet agents in the week before testing; and (5) not literate in English.
At the study encounter, the participants completed a questionnaire regarding age, education, household income, height, weight, age of headache onset, headache-related disability, physician-diagnosed medical conditions (including hypertension, smoking, hyperlipidemia, history of deep venous thrombosis, pulmonary embolism). The PI supplied the following information when applicable: medications, ICHD-2 headache diagnoses, and average monthly days with headache during the prior 3 months. For those migraineurs with 15 or more headache days per month (chronic migraine [CM]), the PI also recorded whether there was a history of transformation from episodic to chronic frequency (transformed migraine [TM]) and whether the subject experienced continuous headache.
Laboratory Methods
The methods have been previously described. All testing was done after the subjects had not taken non-steroidal anti-inflammatory drugs or other antiplatelet agents for at least 1 week and after an overnight fast. Those with migraine needed to be headache-free for 1 week. Urine and blood samples were collected between 8 AM and 9 AM. Blood was drawn without a tourniquet. Analysis was performed blinded to participants' health or laboratory information. Assays for von Willebrand factor (vWF) activity, high-sensitivity C-reactive protein (hsCRP), tissue plasminogen activator (tPA) antigen, and prothrombin activation fragment (F1.2) were performed by Esoterix, Inc. (Aurora, CO, USA). The vWF activity assay uses plasma vWF to agglutinate platelets in the presence of ristocetin. By comparing the rate of agglutination against a normal reference curve, the vWF activity as a percentage was quantified. tPA antigen and F1.2 assays were performed by enzyme-linked immunosorbent assay. The hsCRP assay was done with the nephelometry technique. Assays for tissue necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta 1, interleukin 6 (IL-6), and adiponectin were performed by AssayGate (Ijamsville, MD, USA) using a multiplex assay on a Luminex Bead-based sandwich immunoassay platform. Urinary total nitrate/nitrite assays were performed by Cayman Chemical Co, Ann Arbor, MI, USA. A calorimetric assay method was used to measure urine nitrate/nitrite concentration (NOx), and results are reported as total nitrate/nitrite levels.
Adverse Childhood Experiences Survey Instrument and Procedure
After institutional review board approval, a 1-page 10-item (multicomponent), closed format questionnaire was mailed to study participants in November 2010 to assess adverse childhood experiences (ACEs). This questionnaire has been used previously for numerous studies that explored relationship of ACEs with health outcomes in adults. Questions (see Appendix) were related to experiences occurring when under the age of 18 years old, including abuse (emotional, physical, sexual), neglect (emotional, physical), and exposure to household dysfunction (violence against mother/stepmother, parental substance abuse, mental illness, criminal behavior, and parental separation or divorce). Respondents were defined as exposed to a category if they responded "yes" to 1 or more of the questions in that category. The total number of these exposures (range 0–10) was summed to create the ACE score. Several techniques were used to help maximize the survey response rate, including limiting the length of the questionnaire to 1 page, offering a 5-dollar monetary incentive, personalizing the letter that introduced the questionnaire, and using multiple contacts. Approximately 2 weeks after the initial mailing, a second wave was sent to those who had not responded. Two weeks after the second mailing, a final third wave mailing was sent to nonrespondents. Participants were identified by a code to ensure their confidentiality, and only those who had not responded were contacted for follow-up mailings. All of these procedures were intended to reduce nonrespondent bias and increase the external validity of the results. After receiving all surveys, the code sheet was destroyed to maintain confidentiality.
Data Analysis
Data from the study were analyzed using SPSS 17.0 (SPSS, Inc., Chicago, IL, USA). Data analysis included descriptive statistics with a report of the appropriate frequencies, means, and standard deviations to describe the responses to the questionnaire items, as well as the demographic and background characteristics of the respondents. Chi-square tests and logistic regressions were computed to determine differences between groups of categorical variables. Similarly, t-tests were conducted to determine differences among multiple categorical independent and parametric dependent variables. Pearson's correlation analysis was run to assess the association between continuous variables.
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