Page 21 - The clinical aspects and management of chronic migraine Judith Anne Pijpers

correlation of genome-wide common variant risk for common psychiatric and neurological disorders, strikingly showed a shared heritability between depression and migraine, but no correlation between depression and other neurological disorders (amongst others Alzheimers disease, multiple sclerosis and epilepsy).42 Furthermore, depression is a strong independent risk factor for chronic migraine and medication overuse, and a predictor for a poorer prognosis in therapy of headache with medication overuse.28,29,43 The relationship between migraine and anxiety has also been established,44,45 but is less well studied, especially in the context of migraine progression.
Furthermore, psychological factors have been studied in light of medication overuse and chronic headache. In the light of operant conditioning, medication intake would be both a negative as a positive reinforcement by the avoidance of pain and the psychotropic action of pain medication itself. This theory is supported by changes in reward-related systems in imaging studies at patients with medication overuse.33,46,47 Taking into account pain coping methods, patient with (chronic) headache or high burden of disease seem to use unhealthy pain copings mechanism, score low on pain acceptance, high on catastrophizing, and experience a low rate of control on their diseases.46,48–50 One could imagine that these psychologic factors aggravate or at least maintain migraine chronification processes, but this has not been formally studied.
Genetic factors
Migraine is a complex disease, which has a strong, but not exclusive genetic component. Multiple studies showed an increased familial risk of migraine,51–53 but the inheritance pattern for the common types of migraine is not one of a monogenetic disease. As is the case in multifactorial diseases, genetic factors are increasing the susceptibility of the disease, but the effect size of one genetic factor by itself is too small and insufficient too cause the disease. As such, association studies did not result in a reproducible genetic association between a gene and migraine.51 A relatively new technique, Genome Wide Association Studies (GWAS), can be used to identify genetic variants, underlying complex multifactorial diseases. These studies investigated in a non-hypothesis driven manner the association between migraine and an extremely large number of single nucleotide polymorphisms (SNPs), so far identifying 38 SNPs associated with migraine.54 However, as a large number of patients and healthy controls is needed for GWAS (>350.000 participants), this method is hardly feasible yet
1
General introduction
19