We have assessed the validity and reliability of a self-administered headache questionnaire used in the 'Nord-Trøndelag Health Survey 1995-97 (HUNT)' in Norway, by blindly comparing questionnaire-based headache diagnoses with those made in a clinical interview of a sample of the participants. Restrictive questionnaire-based diagnostic criteria for migraine, assessed according to modified criteria of the International Headache Society, performed excellently in selecting 'definite' migraine patients (100% positive predictive value). The best agreement concerning migraine diagnoses was achieved by using a liberal set of criteria (kappa 0.59). Similar agreement was found evaluating patient status as headache sufferers, and as sufferers from frequent headaches (>6 days per month) (kappa 0.57 and 0.50, respectively). The kappa values of non-migrainous headache and chronic headache (> 14 days per month) were 0.43 and 0.44, respectively. The results suggest that our self-administered questionnaire may be suitable in identifying a population with 'definite' migraine, and the questionnaire is an acceptable instrument in determining the prevalence in Nord-Trøndelag of headache sufferers, migraine, non-migrainous headache, and frequent or chronic headache sufferers.

Some data indicate that migraine with aura (MA) is more strongly associated with anxiety disorder and depression than migraine without aura (MoA), but the evidence is not conclusive. In the Nord-Trøndelag Health study 1995-1997, a total of 49 205 (75% of the participants) subjects gave valid answers to both HADS (Hospital Anxiety and Depression Scale) and a validated headache questionnaire. Associations between anxiety disorder/depression and MA/MoA were evaluated by multiple logistic regression analysis. Depression (DEP) [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.2, 2.6] and depression with comorbid anxiety disorder (COM) (OR 1.6; 95% CI 1.2, 2.1) were more likely in women having MA than in those with MoA. No stronger association was found for pure anxiety disorder (ANX) in MA vs. MoA (OR 0.9; 95% CI 0.7, 1.5). Among men, we found no difference in prevalence of depression and anxiety disorders between MA and MoA. This is a new finding that might have relevance for both research and clinical treatment.

The objective was to assess the placebo response in randomized clinical trials of analgesics in the treatment of migraine attacks. We included placebo-controlled studies that used the criteria of the International Headache Society for the diagnosis of migraine and headache response as the primary efficacy parameter. In the 11 studies that qualified for inclusion, headache response occurred after placebo treatment in 7-50% of the migraineurs with an average placebo response rate of 30% (95% confidence interval (CI) 23-36). Two hours after treatment with placebo an average of 9% (95% CI 7-12, range 7-17%) of the patients were found to be pain free. In conclusion, the average headache response rate to placebo was 30% in randomized clinical trials of analgesics in migraine with a tremendous variation among studies. Placebo response rates vary with the choice of primary efficacy measure as well as patient characteristics and study design.

Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes-sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.