Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Operational message
There are currently operational disruptions. Troubleshooting is in progress.
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Beating of hammers
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and Neuroscience.ORCID iD: 0000-0001-5775-0185
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

I've been investigating the connection between migraine and depression—two debilitating disorders with high comorbidity. My overarching goal is to unravel their pathophysiology and pinpoint associated risk factors to pave the way for more effective therapeutic interventions. The fruits of my labor is discussed in the introductory part of the thesis and comprises four first-author publications in international peer-reviewed journals.

In the first two projects, I worked mostly on the comorbid aspects of migraine and depression. I conducted a meta-analysis on the efficacy of onabotulinumtoxinA injections as a treatment for those grappling with both migraine and depression. The findings were promising, showing not only the treatment's safety and effectiveness but also hinting at a shared pathophysiology between the two conditions. The second project delved into the structural brain anatomy, utilizing voxel-based magnetic resonance imaging measures to explore subcortical volumes in migraine and depression patients. The distinct patterns observed suggest a nuanced relationship at the subcortical level.

Expanding beyond comorbidity, my research ventured into the occupational determinants of migraine, scrutinizing the impact of job-related factors on migraine prevalence. Leveraging data from the UK Biobank, the third project identified strong associations between migraine and specific job categories, setting the stage for future interventions and policies to enhance workers' well-being. Additionally, my exploration into the role of the cerebellum and brainstem in migraine pathophysiology, using the UK Biobank data, unveiled larger gray matter volumes in multiple cerebellar regions in individuals with migraines. This sheds light on potential mechanisms underlying migraine attacks, contributing significantly to our understanding and potential treatments for these challenging disorders.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2024. , p. 44
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2045
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-526438ISBN: 978-91-513-2115-8 (print)OAI: oai:DiVA.org:uu-526438DiVA, id: diva2:1850641
Public defence
2024-06-03, H:son Holmdahlsalen, Akademiska Sjukhuset, Ingång 100, Dag Hammarskjölds Väg 8, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2024-05-08 Created: 2024-04-11 Last updated: 2024-05-08
List of papers
1. High efficacy of onabotulinumtoxinA treatment in patients with comorbid migraine and depression: a meta-analysis
Open this publication in new window or tab >>High efficacy of onabotulinumtoxinA treatment in patients with comorbid migraine and depression: a meta-analysis
Show others...
2021 (English)In: Journal of Translational Medicine, E-ISSN 1479-5876, Vol. 19, no 1, article id 133Article, review/survey (Refereed) Published
Abstract [en]

Background: Migraine and depression are highly prevalent and partly overlapping disorders that cause strong limitations in daily life. Patients tend to respond poorly to the therapies available for these diseases. OnabotulinumtoxinA has been proven to be an effective treatment for both migraine and depression. While many studies have addressed the effect of onabotulinumtoxinA in migraine or depression separately, a growing body of evidence suggests beneficial effects also for patients comorbid with migraine and depression. The current meta-analysis systematically investigates to what extent onabotulinumtoxinA is efficient in migraineurs with depression.

Methods: A systematic literature search was performed based on PubMed, Scopus and Web of Science from the earliest date till October 30th, 2020. Mean, standard deviation (SD) and sample size have been used to evaluate improvement in depressive symptoms and migraine using random- effects empirical Bayes model.

Results: Our search retrieved 259 studies, eight of which met the inclusion criteria. OnabotulinumtoxinA injections administered to patients with both chronic migraine and major depressive disorder led to mean reduction of - 8.94 points (CI [ - 10.04,- 7.84], p < 0.01) in the BDI scale, of - 5.90 points (CI [ - 9.92,- 1.88], p < 0.01) in the BDI-II scale and of - 6.19 points (CI [ - 9.52,- 2.86], p < 0.01) in the PHQ-9 scale, when evaluating depressive symptoms. In the case of the migraine-related symptoms, we found mean reductions of - 4.10 (CI [ - 7.31,- 0.89], p = 0.01) points in the HIT6 scale, - 32.05 (CI [ - 55.96,- 8.14], p = 0.01) in the MIDAS scale, - 1.7 (CI [ - 3.27,- 0.13], p = 0.03) points in the VAS scale and of - 6.27 (CI [ - 8.48,- 4.07], p < 0.01) migraine episodes per month. Comorbid patients showed slightly better improvements in BDI, HIT6 scores and migraine frequency compared to monomorbid patients. The latter group manifested better results in MIDAS and VAS scores.

Conclusion: Treatment with onabotulinumtoxinA leads to a significant reduction of disease severity of both chronic migraine and major depressive disorder in patients comorbid with both diseases. Comparative analyses suggest an equivalent strong effect in monomorbid and comorbid patients, with beneficial effects specifically seen for certain migraine features.

Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2021
Keywords
OnabotulinumtoxinA, Botox, Migraine, Depression, Meta-analysis
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-442250 (URN)10.1186/s12967-021-02801-w (DOI)000636462700003 ()33789668 (PubMedID)
Funder
Swedish Research Council
Available from: 2021-05-17 Created: 2021-05-17 Last updated: 2024-07-04Bibliographically approved
2. Major sex differences in migraine prevalence among occupational categories: a cross-sectional study using UK Biobank
Open this publication in new window or tab >>Major sex differences in migraine prevalence among occupational categories: a cross-sectional study using UK Biobank
2021 (English)In: Journal of Headache and Pain, ISSN 1129-2369, E-ISSN 1129-2377, Vol. 22, no 1, article id 145Article in journal (Refereed) Published
Abstract [en]

Background Migraine represents one of the most prevalent neurological conditions worldwide. It is a disabling condition with high impact on the working situation of migraineurs. Interestingly, gender-related differences regarding an association of migraine with important occupational characteristics has been hardly studied. Methods The current study scrutinizes gender-specific differences in the prevalence of migraine across a broad spectrum of occupational categories, shedding also light on associations with important job-related features such as shift work, job satisfaction, and physical activity. The study included data from 415 712 participants from the UK Biobank cohort, using the official ICD10 diagnosis of migraine and other health conditions as selection criteria. Prevalence ratios of migraineurs compared to healthy controls among different occupational categories and job-related variables were estimated using log-binomial regression analyses. Statistical models were adjusted for important sociodemographic features such as age, BMI, ethnicity, education and neuroticism. To better highlight specific differences between men and women we stratified by sex. Results We detected a differential prevalence pattern of migraine in relation to different job categories between men and women. Especially in men, migraine appears to be more prevalent in highly physically demanding occupations (PR 1.38, 95% CI [0.93, 2.04]). Furthermore, migraine is also more prevalent in jobs that frequently involve shift or night shift work compared to healthy controls. Interestingly, this prevalence is especially high in women (shift work PR 1.45, 95% CI [1.14, 1.83], night shift work PR 1.46, 95% CI [0.93, 2.31]). Conclusion Our results show that migraine is genderdependently associated with physically demanding jobs and shift working.

Place, publisher, year, edition, pages
Springer NatureSpringer Nature, 2021
Keywords
Migraine, Occupation, Work, Job, Sex differences
National Category
Public Health, Global Health and Social Medicine Neurosciences
Identifiers
urn:nbn:se:uu:diva-461712 (URN)10.1186/s10194-021-01356-x (DOI)000726269000002 ()34863088 (PubMedID)
Funder
Swedish Research Council
Available from: 2022-01-31 Created: 2022-01-31 Last updated: 2025-02-20Bibliographically approved
3. Assessing volumetric brain differences in migraine and depression patients: a UK Biobank study
Open this publication in new window or tab >>Assessing volumetric brain differences in migraine and depression patients: a UK Biobank study
Show others...
2023 (English)In: BMC Neurology, E-ISSN 1471-2377, Vol. 23, no 1, article id 284Article in journal (Refereed) Published
Abstract [en]

Background: Migraine and depression are two of the most common and debilitating conditions. From a clinical perspective, they are mostly prevalent in women and manifest a partial overlapping symptomatology. Despite the high level of comorbidity, previous studies hardly investigated possible common patterns in brain volumetric differences compared to healthy subjects. Therefore, the current study investigates and compares the volumetric difference patterns in sub-cortical regions between participants with migraine or depression in comparison to healthy controls.

Methods: The study included data from 43 930 participants of the large UK Biobank cohort. Using official ICD10 diagnosis, we selected 712 participants with migraine, 1 853 with depression and 23 942 healthy controls. We estimated mean volumetric difference between the groups for the different sub-cortical brain regions using generalized linear regression models, conditioning the model within the levels of BMI, age, sex, ethnical background, diastolic blood pressure, current tobacco smoking, alcohol intake frequency, Assessment Centre, Indices of Multiple Deprivation, comorbidities and total brain volume.

Results: We detected larger overall volume of the caudate (mean difference: 66, 95% CI [-3, 135]) and of the thalamus (mean difference: 103 mm(3), 95% CI [-2, 208]) in migraineurs than healthy controls. We also observed that individuals with depression appear to have also larger overall (mean difference: 47 mm(3), 95% CI [-7, 100]) and gray matter (mean difference: 49 mm(3), 95% CI [2, 95]) putamen volumes than healthy controls, as well as larger amygdala volume (mean difference: 17 mm(3), 95% CI [-7, 40]).

Conclusion: Migraineurs manifested larger overall volumes at the level of the nucleus caudate and of the thalamus, which might imply abnormal pain modulation and increased migraine susceptibility. Larger amygdala and putamen volumes in participants with depression than controls might be due to increased neuronal activity in these regions.

Place, publisher, year, edition, pages
BioMed Central (BMC)BMC, 2023
Keywords
Migraine, Depression, Structural brain MRI, UK Biobank
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:uu:diva-509232 (URN)10.1186/s12883-023-03336-x (DOI)001040412700002 ()37507671 (PubMedID)
Available from: 2023-08-22 Created: 2023-08-22 Last updated: 2024-12-03Bibliographically approved
4. Volumetric Differences in Cerebellum and Brainstem in Patients with Migraine: A UK Biobank Study
Open this publication in new window or tab >>Volumetric Differences in Cerebellum and Brainstem in Patients with Migraine: A UK Biobank Study
2023 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 9, article id 2528Article in journal (Refereed) Published
Abstract [en]

Background: The cerebellum and the brainstem are two brain structures involved in pain processing and modulation that have also been associated with migraine pathophysiology. The aim of this study was to investigate possible associations between the morphology of the cerebellum and brainstem and migraine, focusing on gray matter differences in these brain areas.

Methods: The analyses were based on data from 712 individuals with migraine and 45,681 healthy controls from the UK Biobank study. Generalized linear models were used to estimate the mean gray matter volumetric differences in the brainstem and the cerebellum. The models were adjusted for important biological covariates such as BMI, age, sex, total brain volume, diastolic blood pressure, alcohol intake frequency, current tobacco smoking, assessment center, material deprivation, ethnic background, and a wide variety of health conditions. Secondary analyses investigated volumetric correlation between cerebellar sub-regions.

Results: We found larger gray matter volumes in the cerebellar sub-regions V (mean difference: 72 mm3, 95% CI [13, 132]), crus I (mean difference: 259 mm3, 95% CI [9, 510]), VIIIa (mean difference: 120 mm3, 95% CI [0.9, 238]), and X (mean difference: 14 mm3, 95% CI [1, 27]).

Conclusions: Individuals with migraine show larger gray matter volumes in several cerebellar sub-regions than controls. These findings support the hypothesis that the cerebellum plays a role in the pathophysiology of migraine.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
migraine, cerebellum, brainstem, structural MRI, UK Biobank
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:uu:diva-514061 (URN)10.3390/biomedicines11092528 (DOI)001071288700001 ()37760969 (PubMedID)
Available from: 2023-10-16 Created: 2023-10-16 Last updated: 2024-04-11Bibliographically approved

Open Access in DiVA

UUThesis_Affatato,O-2024(552 kB)429 downloads
File information
File name FULLTEXT01.pdfFile size 552 kBChecksum SHA-512
8a0f8033b14ff7be2ef5bf853a4234f2c2d982337af1bb94f740d05b4d771212561930c24210eac484f2d7d17d4d967cf05490bd99d390b70034e60a167b0759
Type fulltextMimetype application/pdf

Authority records

Affatato, Oreste

Search in DiVA

By author/editor
Affatato, Oreste
By organisation
Functional Pharmacology and Neuroscience
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 431 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1120 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf