Migraine and depression: what relates these complex disorders?
Published in Neuroscience, Genetics & Genomics, and Behavioural Sciences & Psychology
In many ways, migraine and Major Depressive Disorder look very different. Migraine is a disorder with repeated attacks that usually have acute triggers and unfold over a relatively short timespan (hours to days). Triggers can include foods, sounds, smells, atmospheric pressure, lighting (too bright, too much contrast, or blinking), irregular sleep, hormones and more. Migraine attacks unfold in characteristic phases including a prodrome phase (characterized by mood changes, cognitive impairments, yawning, and other symptoms), in some patients aura (visual hallucinations and/or partial paralysis), headache (including extreme sensory hypersensitivity), and a post-drome phase (lingering symptoms, fatigue, depressive mood).
By contrast, depression tends to last much longer (weeks, months, or even years) and is much less time-specific in how symptoms may present. Patients display at least five symptoms that include depressed mood, diminished interest or pleasure, changes in weight or sleep, psychomotor agitation or slowed thinking, fatigue, feelings of worthlessness or excessive guilt, diminished concentration, or recurrent thoughts of death or suicide).
We (as authors) have known people personally who have suffered from both migraine and depression and have thought a lot about what might be the relationship, if any, between these seemingly very different conditions. Does one disorder predispose a person to the other? Are there shared underlying relationships in brain or nervous system physiology that might provide a causal link?
We surveyed what is currently known about the mechanistic contributors to each disorder and examined what they have in common across treatment and physiological mechanisms from genetics through brain-wide communication.
Common Threads:
Our literature search found several emergent themes of mechanistic overlap between migraine and MDD spanning multiple levels of analysis, including:
- Key genetic risk variants and genes common to both disorders
- Overlap in the mechanisms of therapeutics used to treat each disorder, including the effects of these treatments on neurotransmitters and peptides
- Shared disruptions in the regulation of sensory sensation and mood
- Key brain regions and circuits
- Common physiological responses to environmental factors
- The critical role of sex differences and clues from hormones
Why Now?
With emerging therapies for each of these disorders, there are new opportunities to consider for patients. Having a better understanding of where mechanisms between these two disorders overlap and differ can shed light on 1) therapeutics that may not have been thought of for the opposite disorder, or that may work for both conditions, 2) unexplored mechanisms that are worth further probing for each disorder and 3) for creating therapeutics with the least likelihood of unwanted side-effects. Focusing on the mechanisms that these disorders have in common provides a strategy for scientists to consider for developing therapeutics to best target the comorbid condition.
An example of an emerging therapy in migraine with relevance to depression includes anti-CGRP therapies. Calcitonin gene-related peptide (CGRP) is a peptide involved in inflammation, blood vessel dilation, and many other physiological functions and provides one of the most exciting recent examples of a therapeutic derived from neuroscience research. A promising new development is that a recent clinical trial showed success for one such anti-CGRP therapy in the treatment of migraine with comorbid depression (https://jamanetwork.com/journals/jamaneurology/fullarticle/2833452). Given that historically, patients living with migraine and comorbid depression have been excluded from many such studies, this finding represents an important step forward .
By contrast, an example of an emerging therapy in depression with relevance to migraine is ketamine. Ketamine impacts a wide range of biology but is best characterized for its role as a glutamate receptor antagonist, thus impacting excitatory/inhibitory balance, a mechanism important in migraine. Several small studies have found success with ketamine for treating migraine, opening the door to larger studies that can ask whether there are specific patients that may especially be good candidates for ketamine.
Overall, such findings may pave the way for development of novel therapeutics designed to target both disorders instead of treating them as separate problems. Our review provides a roadmap for future studies to truly understand these two disorders and the comorbid condition. We hope it will ignite conversation and provide fresh insight into patients with a dual diagnosis.
Have further thoughts or questions on this topic? Leave us a comment below!
For more information about the Laboratory for Brain-Network Based Molecular Medicine, please visit our lab website here: https://hultman.lab.uiowa.edu/
Artwork credit: Jeff MacInnes https://www.decimalpoint.studio/
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The Journal of Headache and Pain
The Journal of Headache and Pain is a peer-reviewed open access journal specifically dedicated to researchers involved in all aspects of headache and related pain syndromes, including epidemiology, public health, basic science, translational medicine, clinical trials and real-world data.
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Focus India
Headache disorders, especially migraine, constitute a major neurological health challenge and are increasingly recognized as leading contributors to disability worldwide. Their impact extends beyond episodic pain, influencing cognitive performance, emotional well-being, and overall quality of life. India carries a substantial share of the global migraine burden, yet remains affected by significant gaps in awareness, diagnosis, access to specialist care, and research output. Although global research has clarified many aspects of headache pathophysiology, the expression of these disorders varies across populations due to genetic, environmental, cultural, and healthcare access factors in the Indian context.
Migraine, in particular, demonstrates substantial heterogeneity in symptom patterns, triggers, and response to therapy, underscoring the need for population specific data. India’s vast and heterogeneous population offers a unique opportunity to generate locally relevant epidemiological, clinical, and translational insights. In many regions, underdiagnosis and inadequate treatment remain persistent problems, often compounded by stigma and limited awareness. Understanding the burden of headache disorders within specific communities in India is essential for designing effective public health strategies, improving diagnostic pathways, and tailoring management approaches. Moreover, the chronic nature of recurrent headaches places a significant economic burden on individuals and healthcare systems through lost productivity and frequent medical consultations. Through this Collection, we aim to stimulate nationally driven research, foster collaboration across institutions and care settings, and strengthen India’s contribution to global headache and brain health science.
Topics of interest include but are not limited to:
- Epidemiology of migraine in India
- Management strategies of migraine in Indian patients
- Cultural perceptions of tension-type headache
- Treatment approaches for cluster headaches
- Trigeminal autonomic cephalalgias in diverse populations
- Chronic daily headache management strategies
- Impact of lifestyle factors on headache prevalence
- Public health initiatives for headache awareness
- Innovations in headache research methodologies
We welcome submissions from author groups with their main affiliated institution in India. Cross-international authorship groups are welcome to submit their work to The Journal of Headache and Pain outside of this Collection.
This Collection supports and amplifies research related to SDG 3, Good Health and Well-Being.
All submissions in this collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the Editor-in-Chief. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or the Editor-in-Chief.
Publishing Model: Open Access
Deadline: Dec 01, 2026
Focus China
Headache disorders, particularly migraine, represent a significant and growing public health concern with a major impact on disability and quality of life. While research has advanced our global understanding, the specific manifestations, burdens, and management challenges of these conditions within unique populations require dedicated attention. In China, factors such as vast geographical disparities, rapid urbanization, diverse ethnicities, and a unique healthcare system structure present distinctive opportunities and challenges in the recognition, diagnosis, and treatment of headache disorders.
This thematic Collection, “Focus China”, aims to illuminate the landscape of headache medicine in China by exploring epidemiological patterns, clinical characteristics, healthcare access, traditional and integrative medicine approaches, and the socio-economic impact of headache disorders across the country.
We invite submissions of original research, systematic and narrative reviews, editorials, rapid reviews, and commentaries on topics including, but not limited to:
• The epidemiology, burden, and clinical features of migraine and other headache disorders in specific Chinese populations and regions.
• Advanced neuroimaging studies identifying unique endophenotypes, structural and functional brain alterations, and biomarkers of headache disorders in the Chinese cohort.
• Insights into the pathophysiology of headache disorders from a Chinese perspective, including research on epigenetics, neuron-glia interactions, and multi-omics.
• Studies on the integration of Traditional Chinese Medicine (TCM) with conventional headache management.
• Unique cultural, environmental, and genetic factors influencing headache disorders in China.
• The development and validation of diagnostic tools for the Chinese population.
This Collection provides a dedicated platform for researchers and clinicians primarily affiliated with Chinese institutions to share their insights and contribute to the global knowledge of headache science while addressing the specific needs of their region. By fostering collaboration and knowledge exchange, “Focus China” aims to drive meaningful advancements in headache research and patient care across China.
Therefore, the Collection welcomes submissions from author groups with their main affiliated institution in China. Cross-international authorship groups are welcome to submit their work to The Journal of Headache and Pain outside of this Collection.
This Collection supports and amplifies research related to SDG 3, Good Health and Well-Being.
All submissions in this collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the Editor-in-Chief. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or the Editor-in-Chief.
Publishing Model: Open Access
Deadline: Oct 13, 2026
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