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1.  Post-Traumatic Stress Disorder and Migraine: Epidemiology, Sex Differences, and Potential Mechanisms 
Headache  2011;51(6):860-868.
Migraine is a common, often disabling disorder associated with a significant personal and societal burden. The presence of post-traumatic stress disorder (PTSD) may increase this disability substantially. Migraine and PTSD are both up to 3 times more common in women than in men. The divergence in prevalence rates of migraine and PTSD that occurs between the sexes after puberty suggests that gonadal hormones play an important role. In addition, the preponderance of PTSD in women may be related to their higher rates of interpersonal trauma, the most common cause of PTSD. However, recent data suggest that although the odds of PTSD are increased in both women and men with episodic migraine, this association is stronger in men than women. In this paper, we examine the epidemiology of PTSD and migraine, with an emphasis on the known sex differences. We then discuss the neurobiological changes associated with PTSD, the current hypotheses for the mechanisms relating PTSD and migraine, and the treatment implications of these findings.
doi:10.1111/j.1526-4610.2011.01907.x
PMCID: PMC3974501  PMID: 21592096
headache; migraine; post-traumatic stress disorder; anxiety; physical abuse; sexual abuse; maltreatment; sex; women; men
2.  Childhood Abuse and Migraine: Epidemiology, Sex Differences, and Potential Mechanisms 
Headache  2011;51(6):869-879.
Migraine and maltreatment are both common conditions that are more prevalent in women. Epidemiological evidence supports an association between childhood abuse and headache, as well as pain in general, although some controversy exists based on methodological concerns of studying the influence of remote, traumatic, stigmatizing events in an often depressed population. There is a growing scientific body of knowledge regarding the neurobiological effects of abuse on brain function and structure that suggest a possible role of early life stress in the pathogenesis of migraine, and a differential impact based on sex. Advances in our understanding of the basic mechanisms by which an adverse environment interacts with and changes the genome, may suggest new treatment strategies.
doi:10.1111/j.1526-4610.2011.01906.x
PMCID: PMC3972492  PMID: 21631473
headache; migraine; childhood maltreatment; abuse
3.  Ictal Adiponectin Levels in Episodic Migraineurs: A Randomized Pilot Trial 
Headache  2013;53(3):474-490.
Objective
To assess ictal adiponectin (ADP) levels before and after acute abortive treatment in women episodic migraineurs.
Methods
Peripheral blood specimens were collected from women episodic migraineurs before and after acute abortive treatment with sumatriptan/naproxen sodium (suma/nap) versus placebo. Univariate and multivariate models were utilized to examine the relationship between serum total-ADP (T-ADP), ADP oligomers (high molecular weight [HMW], middle molecular weight [MMW], and low molecular weight [LMW]-ADP) and ADP ratio levels and pain severity. Paired-t tests and random intercept longitudinal models were utilized to assess the mean changes in T-ADP, ADP oligomers and ratios over time in treatment responders and non-responders.
Results
Twenty participants (11 responders, 9 non-responders) have been studied to date. In all participants, increases in the HMW:LMW adiponectin ratio were associated with an increase in pain severity. For every 1 point increase in the HMW:LMW ratio, pain severity increased by 0.22 (CI: 0.07, 0.37; p=0.004). In contrast, for every 0.25 µg/mL increase in LMW-ADP, pain severity decreased by 0.20 (CI: -0.41, -0.002; p=0.047). In treatment responders, T-ADP levels were reduced at 30 min (12.52 ± 3.4; p=0.03), 60 min (12.32 ± 3.2; p=0.017) and 120 min (12.65 ± 3.2; p=0.016) after treatment as compared to onset (13.48 ± 3.8). Additionally, in responders, the HMW:LMW ratio level was greater at pain onset (3.70 ±1.9 µg/mL) as compared to non-responders (2.29 ± 0.71 µg/mL), p=0.050. Responders also showed a decrease in the HMW:LMW ratio at 60 min (2.37 ± 1.1; p=0.002) and 120 min (2.76 ± 1.4; p=0.02) after treatment as compared to onset (3.70 ± 1.9). These changes in responders remained significant after adjusting for covariates, including measured BMI (m-BMI). Although non-responders showed no significant changes in unadjusted T-ADP or ADP oligomer or ratio levels, the HMW:LMW ratio was increased in non-responders after adjustments, (p=0.025).
Conclusion
In this pilot study of women episodic migraineurs, the HMW:LMW adiponectin ratio level was associated with migraine severity and predictive of acute treatment response. ADP and the HMW:LMW ratio of adiponectin represent potential novel biomarkers and drug targets for episodic migraine.
doi:10.1111/head.12071
PMCID: PMC3601586  PMID: 23489216
adiponectin; biomarker; headache; migraine
4.  Headache symptoms and indoor environmental parameters: Results from the EPA BASE study 
Annals of Indian Academy of Neurology  2012;15(Suppl 1):S95-S99.
Objective:
The objective of this investigation was to determine the prevalence of migraine and headache symptoms in a national sample of US office employees. Also, we explored the association of headache symptoms with indoor environmental parameters of the work place.
Background:
Sick building syndrome (SBS), which includes headache, is a common global phenomenon, but the underlying environmental cause is uncertain.
Materials and Methods:
We used data from the 1994–1998 US Environmental Protection Agency's (EPA) Building Assessment and Survey Evaluation, a cross-sectional study of workers employed in 100 public and private office buildings across 25 states. The study used a self-administered questionnaire to assess headache frequency and prevalence of self-reported physician-diagnosed (SRPD) migraine. Indoor environmental parameters (IEP) were collected per EPA protocol from each building over a 1-week period and included carbon dioxide, carbon monoxide, temperature, relative humidity, particulate matter, volatile organic compound, illuminance, and sound level. The standards of American Society of Heating, Refrigerating and Air Conditioning Engineers were used to categorize IEP as either within- or out-of-comfort range for human dwelling. These limits delineate whether a parameter value is safe for human dwelling. Out-of-comfort range IEPs are associated with SBS and other human diseases. SRPD migraine and headache frequency were the primary outcome measures of the study. Multivariate logistic regression analyses were employed for the purpose of assessing the association between the outcome variable and IEPs.
Results:
Of the 4326 participants, 66% were females and 60% were between 30 and 49 years. Headache frequency during the last 4 weeks was as follows: None in 31%, 1–3 days in 38%, 1–3 days per week in 18%, and every or almost every workday in 8%. Females had higher SRPD migraine prevalence compared to males (27% vs. 11%, P<0.001) and were more likely to report any headache in the last month compared to males (75% vs. 53%, P<0.001). Odds of SRPD migraine were higher (P<0.05) for those exposed to IEP out-of-comfort range, and odds of exposure to out-of-comfort range IEPs were higher in groups who reported higher headache frequencies.
Conclusions:
Migraine diagnosis and elevated headache frequency are associated with an uncomfortable indoor environment. Periodic assessments and adjustments of IEP may have a beneficial impact on employees who are vulnerable to SBS.
doi:10.4103/0972-2327.100029
PMCID: PMC3444215  PMID: 23024572
EPA BASE study; headache; indoor environmental parameter; migraine; sick building syndrome

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