Migraine and major depression: localizing shared genetic susceptibility in different cell types of the nervous systems.

Background: There is a bidirectional relationship between migraine and major depression disorder (MDD). They likely share important risk genes associated with different cell types in the central nervous system (CNS) and peripheral nervous system (PNS). Profiling the expression of these genes in specific cell types is critical in understanding the pathophysiology of the relationship between migraine and MDD. Methods: Associated genes shared by migraine and MDD were identified by consolidating multiple curations of human disease-gene associations. Subsequently, the expression of overlapping genes was profiled and compared across the different cell types in CNS, PNS and neurovascular cells using eight single cell RNA sequencing datasets, including two human CNS datasets, two mouse CNS datasets, one human PNS dataset and three mouse PNS datasets. Results: 45 shared genes between migraine and MDD were identified. Consistently found in all eight datasets, dopaminergic and serotonergic neurotransmitters were broadly expressed in CNS and PNS cell types. Glutamatergic and endocannabinoid genes were specifically expressed in CNS neurons and astrocytes. Synthesis and/or Release and Binding of Neuropeptides were specifically expressed in PNS peptidergic nociceptor (PEP). Genes related to inflammatory factors and immune responses were specifically expressed in CNS microglia. Among which, IL1B and COMT were highly expressed in CNS microglia cells. Conclusion: Single cell RNA sequencing of the CNS and PNS helps to identify the shared genes between migraine and MDD that are enriched in specific cell types. The findings provide new insight in understanding the underlying mechanism of action for the bidirectional co-morbidity between migraine and MDD.

Risks of suicide in migraine, non-migraine headache, back, and neck pain: a systematic review and meta-analysis.

Objective: To conduct a systematic review and meta-analysis on suicidal ideation, attempts, and death in patients with head, neck, and back pain. Method: Search was performed using PubMed, Embase, and Web of Science from the date of the first available article through September 31, 2021. A random effects model was used to estimate the pooled odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between suicidal ideation and/or attempt and head, back/neck pain conditions. Articles describing non-migraine headache disorders and death by suicide were also reviewed but not included in the meta-analysis due to an insufficient number of studies. Results: A total of 20 studies met criteria for systemic review. A total of 186,123 migraine patients and 135,790 of neck/back pain patients from 11 studies were included in the meta-analysis. The meta-analysis showed that the estimated risk of combined suicidal ideation and attempt in migraine [OR 2.49; 95% CI: 2.15-2.89] is greater than that in back/neck pain pain [OR 2.00; 95% CI: 1.63-2.45] compared to non-pain control groups. Risk of suicide ideation/planning is 2 folds higher [OR: 2.03; 95% CI: 1.92-2.16] and risk of suicide attempt is more than 3 folds higher [OR: 3.47; 95% CI: 2.68-4.49] in migraine as compared to healthy controls. Conclusion: There is an elevated risk of suicidal ideation and attempt in both migraine and neck/back pain patients in comparison to healthy controls, and this risk is particularly higher among migraine patients. This study underscores the critical need for suicide prevention in migraine patients.

Relationship Between Headache Characteristics and a Remote History of TBI in Veterans: A 10-Year Retrospective Chart Review.

BACKGROUND AND OBJECTIVES: The objective of this work was to examine the association between deployment-related traumatic brain injury (TBI) severity, frequency, and other injury characteristics with headache outcomes in veterans evaluated at a Veterans Administration (VA) polytrauma support clinic. METHODS: We conducted a retrospective chart review of 594 comprehensive TBI evaluations between 2011 and 2021. Diagnostic criteria were based on the Department of Defense/VA Consensus-Based Classification of Closed TBI. Adjusted odds ratios (AORs) and 95% CIs were estimated for headache prevalence (logistic), headache severity (ordinal), and prevalence of migraine-like features (logistic) with multiple regression analysis. Regression models were adjusted for age, sex, race/ethnicity, time since injury, and mental health diagnoses. RESULTS: TBI severity groups were classified as sub concussive exposure (n = 189) and mild (n = 377), moderate (n = 28), and severe TBI (n = 0). Increased headache severity was reported in veterans with mild TBI (AOR 1.72 [95% CI 1.15, 2.57]) and moderate TBI (AOR 3.89 [1.64, 9.15]) compared to those with subconcussive exposure. A history of multiple mild TBIs was associated with more severe headache (AOR 2.47 [1.34, 4.59]) and migraine-like features (AOR 5.95 [2.55, 13.77]). No differences were observed between blast and nonblast injuries; however, greater headache severity was reported in veterans with both primary and tertiary blast effects (AOR 2.56 [1.47, 4.49]). Alteration of consciousness (AOC) and posttraumatic amnesia (PTA) >30 minutes were associated with more severe headache (AOR 3.37 [1.26, 9.17] and 5.40 [2.21, 13.42], respectively). The length of time between the onset of last TBI and the TBI evaluation was associated with headache severity (AOR 1.09 [1.02, 1.17]) and prevalence of migraine-like features (AOR 1.27 [1.15, 1.40]). Last, helmet use was associated with less severe headache (AOR 0.42 [0.23, 0.75]) and lower odds of migraine-like features (AOR 0.45 [0.21, 0.98]). DISCUSSION: Our data support the notion of a dose-response relationship between TBI severity and headache outcomes. A history of multiple mild TBIs and longer duration of AOC and PTA are unique risk factors for poor headache outcomes in veterans. Furthermore, this study sheds light on the poor headache outcomes associated with subconcussive exposure. Past TBI characteristics should be considered when developing headache management plans for veterans.

Pilot Study on Reducing Symptoms of Anxiety with a Heart Rate Variability Biofeedback Wearable and Remote Stress Management Coach.

We assessed the feasibility of using a consumer friendly, heart rate variability biofeedback (HRVB) wearable device in conjunction with a remote stress management coach to reduce symptoms of anxiety. We utilized a discreet, continuously wearable electrocardiogram device, the Lief Smart Patch, which measures and records heart rate and HRV in real time, and guides HRVB exercises using vibrations and visual cues. During the 8-week study, participants (N = 14) wore the Lief Smart Patch, participated in HRVB with the device, utilized the mobile app, and communicated with a remote stress management coach. We collected self-report survey responses to measure symptoms of anxiety (GAD-2) and depression (PHQ-2) every 2 weeks, as well as HRV data throughout the study. Participants' mean GAD-2 score began at 4.6 out of 6. By the trial's completion, the group's mean GAD-2 score dropped to 1.7 (t(13) = 11.0, p < .001) with only 2 of the 14 subjects remaining over the clinical threshold of high anxiety. Similarly, the group's mean PHQ-2 score dropped from 2.93 to 1.29 (t(13) = 3.54, p < .01). In addition, participants increased their HRV (RMSSD) by an average of + 11.4 ms after participating in a low dose biofeedback exercise. These findings suggest that engaging in HRVB through a discreet wearable device in conjunction with a remote stress management program may be effective for reducing symptoms of anxiety and depression.