BackgroundDespite its high prevalence, migraine remains underdiagnosed and undertreated. ID-Migraine is a short, self-administrated questionnaire, originally developed in English by Lipton et al. and later validated in several languages. Our goal was to validate the Hungarian version of the ID-Migraine Questionnaire.MethodsPatients visiting two headache specialty services were enrolled. Diagnoses were made by headache specialists according to the ICHD-3beta diagnostic criteria. There were 309 clinically diagnosed migraineurs among the 380 patients. Among the 309 migraineurs, 190 patients had only migraine, and 119 patients had other headache beside migraine, namely: 111 patients had tension type headache, 3 patients had cluster headache, 4 patients had medication overuse headache and one patient had headache associated with sexual activity also. Among the 380 patients, 257 had only a single type headache whereas 123 patients had multiple types of headache. Test-retest reliability of the ID-Migraine Questionnaire was studied in 40 patients.ResultsThe validity features of the Hungarian version of the ID-Migraine questionnaire were the following: sensitivity 0.95 (95% CI, 0.92–0.97), specificity 0.42 (95% CI, 0.31–0.55), positive predictive value 0.88 (95% CI, 0.84–0.91), negative predictive value 0.65 (95% CI, 0.5–0.78), missclassification error 0.15 (95% CI, 0.12–0.19). The kappa coefficient of the questionnaire was 0.77.ConclusionThe Hungarian version of the ID-Migraine Questionnaire had adequate sensitivity, positive predictive value and misclassification error, but a low specificity and somewhat low negative predictive value.

One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross‐sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID‐Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression‐ and anxiety‐related phenotypes. In addition, a Bayesian systems‐based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.

Objective: The relationship between migraine and psychological distress has been consistently reported in cross-sectional and longitudinal studies. We hypothesised that a stable tendency to perseverative thoughts such as rumination would mediate the relationship between migraine and psychological distress. Design and Main Outcomes Measures: Self-report questionnaires measuring depressive rumination, current psychological distress and migraine symptoms in two independent European population cohorts, recruited from Budapest (N = 1139) and Manchester (N = 2004), were used. Structural regression analysis within structural equation modelling was applied to test the mediational role of brooding and reflection, the components of rumination, between migraine and psychological distress. Sex, age and lifetime depression were controlled for in the analysis. Results: Migraine predicted higher brooding and reflection scores, and brooding proved to be a mediator between migraine and psychological distress in both samples, while reflection mediated the relationship significantly only in the Budapest sample. Conclusions: Elevated psychological distress in migraine is partially attributed to ruminative response style. Further studies are needed to expand our findings to clinical samples and to examine how rumination links to the adjustment to migraine.

BackgroundAlthough migraine is one of the most investigated neurologic disorders, we do not have a perfect neuroimaging biomarker for its pathophysiology. One option to improve our knowledge is to study resting-state functional connectivity in and out of headache pain. However, our understanding of the functional connectivity changes during spontaneous migraine attack is partial and incomplete.Case presentationUsing resting-state functional magnetic resonance imaging we assessed a 24-year old woman affected by migraine without aura at two different times: during a spontaneous migraine attack and in interictal phase. Seed-to-voxel whole brain analysis was carried out using the posterior cingulate cortex as a seed, representing the default mode network (DMN). Our results showed decreased intrinsic connectivity within core regions of the DMN with an exception of a subsystem including the dorsal medial and superior frontal gyri, and the mid-temporal gyrus which is responsible for pain interpretation and control. In addition, increased connectivity between the DMN and pain and specific migraine-related areas, such as the pons and hypothalamus, developed during the spontaneous migraine attack.ConclusionOur preliminary results provide further support for the hypothesis that alterations of the DMN functional connectivity during migraine headache may lead to maladaptive top-down modulation of migraine pain-related areas which might be a specific biomarker for migraine.

The dysfunctions of the mesolimbic cortical reward circuit have been proposed to contribute to migraine pain. Although supporting empirical evidence was mainly found in connection with primary rewards or in chronic migraine where the pain experience is (almost) constant. Our goal however was to investigate the neural correlates of secondary reward/loss anticipation and consumption using the monetary incentive delay task in 29 episodic migraine patients and 41 headache-free controls. Migraine patients showed decreased activation in one cluster covering the right inferior frontal gyrus during reward consumption compared to controls. We also found significant negative correlation between the time of the last migraine attack before the scan and activation of the parahippocampal gyrus and the right hippocampus yielded to loss anticipation. During reward/loss consumption, a relative increase in the activity of the visual areas was observed the more time passed between the last attack and the scan session. Our results suggest intact reward/loss anticipation but altered reward consumption in migraine, indicating a decreased reactivity to monetary rewards. The findings also raise the possibility that neural responses to loss anticipation and reward/loss consumption could be altered by the proximity of the last migraine attack not just during pre-ictal periods, but interictally as well.

IntroductionMigraine and depression frequently occur as comorbid conditions, and it has been hypothesized that migraine with and without depression may have a different genetic background. A distinct personality trait constellation has been described in migraineurs. Less attention, however, was paid to personality differences in migraineurs with and without depression which may also shed light on differences in the neurobiological, background. The aim of our study was to investigate big five personality traits, headaches, and lifetime depression (DEP) in a large European general population sample.MethodsRelationship between DEP, Big Five Inventory personality traits, and headaches identified by the ID-Migraine Questionnaire were investigated in 3,026 individuals from Budapest and Manchester with multivariate and logistic regression analyses.ResultsBoth DEP and migraine(ID) showed differences in personality traits. Neuroticism was an independent risk factor for both conditions while a significant interaction effect appeared between the two in the case of openness. Namely, subjects with migraine(ID) and without DEP scored higher on openness compared to those who had depression.ConclusionWhile we confirmed previous results that high neuroticism is a risk factor for both depression and migraine, openness to experience was significantly lower in the co-occurrence of migraine and depression. Our results suggest that increased openness, possibly manifested in optimal or advantageous cognitive processing of pain experience in migraine may decrease the risk of co-occurrence of depression and migraine and thus may provide valuable insight for newer prevention and intervention approaches in the treatment of these conditions.

Background The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. Methods Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. Results Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8–10 min of citalopram infusion. Conclusions Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine.

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