Table 2 Summary of hypothesized relationship between migraine and its mostly associated psychiatric disorders, involved circuits, neuroimaging evidence, and shared drug response derived by the literature
Psychiatric disorder | Hypothesized relationship | Shared involved circuits and mechanisms | Neuroimaging evidence | Shared treatment response |
|---|---|---|---|---|
Anxiety disorders | - Bidirectional and/or shared genetic predisposition - Facilitates migraine chronification | - Serotonergic dysfunction - Dysregulation of the HPA axis - Hormonal influences - Altered autonomic regulation - Central sensitization - Action on trigeminovascular thalamic neurons - Somatization - Interoceptive conditioning - Fear of pain - Anxiety sensitivity - Avoidance behaviours | - Changes in hippocampal volume | - Tricyclic antidepressants - SSRIs |
Bipolar spectrum disorders | - Common pathophysiology and/or shared genetic predisposition - Comorbidity with migraine seems to be a subtype of bipolar disorder | - Serotonergic dysfunction - Dopaminergic dysfunction - Glutamatergic dysfunction - Calcium and sodium channels alterations - Imbalance between pro-inflammatory and anti-inflammatory cytokines | – | - Anti-seizure (valproate) |
Depression | - Bidirectional and/or shared genetic predisposition - Facilitates migraine chronification | - Serotonergic dysfunction - Dopaminergic dysfunction - Dysregulation of the HPA axis - Hormonal influences - Sensitization of the sensory and emotional neural networks - Probably GABA | - Amygdala, anterior cingulate cortex, and periaqueductal gray present similar connectivity | - Tricyclic antidepressants, SNRIs, onabotulinumtoxinA (chronic migraine) monoclonal CGRP-antibodies |
Abuse (physical or emotional) | - Risk factor for migraine chronification, more disabling migraines, allodynia and earlier onset of migraine | - Cortisol dysfunction - Grater stress reactivity mediated by HPA axis modifications | – | – |
Post-traumatic stress disorder | - Mutual causality and reinforcement - PTSD mediates the association between trauma and migraine | - Stress-induced abnormal activation of the trigeminal nucleus caudalis - Stress-mediated alterations in neurotransmitter balance, neural circuits, autonomic and endocrine responses - Stress-mediated activation of the trigeminovascular system through HPA axis - Impairment of normal limbic response - Prolonged inflammation | - Reduction in hippocampal volume | - Cognitive-behavioral therapy (CBT) |