Circadian functional changes of pain-processing brainstem nuclei and implications for cluster headache: A 7 Tesla imaging study.

BACKGROUND: Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism. OBJECTIVE: This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache. METHODS: This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85 years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high-field (7 Tesla) and high-resolution functional magnetic resonance imaging (MRI) at each visit. Functional connectivity was assessed at the two visits by performing a region-of-interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region-of-interest. RESULTS: Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A-delta-mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T = -40.79). CONCLUSION: The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A-delta-mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks.

Endometriosis features and dienogest tolerability in women with depression: a case-control study.

OBJECTIVE: Primary aim of this study was to investigate endometriosis characteristics of patients with psychiatric conditions or depression. The secondary aim was to study tolerability of dienogest in this context. METHODS: This observational case-control study included endometriosis data from patients visiting our clinic from 2015-2021. We collected information from patient charts and in phone interviews based on a structured survey. Patients with surgical confirmed endometriosis were included. RESULTS: 344 patients fulfilled the inclusion criteria: n = 255 no psychiatric disorder, n = 119 any psychiatric disorder and n = 70 depression. Patients with depression (EM-D, p=.018; p=.035) or psychiatric condition (EM-P, p=.020; p=.048) suffered more often from dyspareunia and dyschezia. EM-P patients had more often primary dysmenorrhoea with higher pain scores (p=.045). rASRM stage or localisation of lesions did not differ. EM-D and EM-P patients discontinued dienogest treatment more often related to worsening of mood (p= .001, p=.002). CONCLUSION: EM-D or EM-P had a higher prevalence of pain symptoms. This could not be attributed to differences in rASRM stage or location of endometriosis lesions. Strong primary dysmenorrhoea might predispose to develop chronic pain-based psychological symptoms. Therefore, early diagnosis and treatment are relevant. Gynaecologist should be aware of the potential impact of dienogest on mood.

Women with endometriosis and psychiatric disorders especially have more dyschezia and dyspareunia, independent from rASRM stage, depth of infiltration and localisation of endometriosis lesions. Dienogest has an impact on mood especially in already prone patients.Trial registration: trial registration number: NCT04816357. https://clinicaltrials.gov/ct2/show/NCT04816357Date of registration: 22.03.2021, date of enrolment of the first subject: 25.03.2021.

Impact of family history for endometriosis, migraine, depression and early menopause on endometriosis symptoms, localization and stage: A case control study.

INTRODUCTION: Endometriosis is a common disabling pain condition in women of childbearing age, frequently showing familial clustering. Nevertheless, little is known about whether familial predispositions influence its severity or presentation. In this study, we investigate disease characteristics in endometriosis patients with a family history (FH) for endometriosis or the comorbidities migraine, depression and early menopause (EMP). MATERIALS AND METHODS: We performed an observational case-control study enrolling women with histologically confirmed endometriosis in a tertiary center. Based on surgical findings, patient records and phone interviews, we examined the relations between a FH for endometriosis, migraine, depression or EMP and endometriotic signs and symptoms, such as response to combined hormonal contraceptives (CHC) and analgesics, disease localization, infiltration depth, Enzian- and rASRM-scores. RESULTS: A positive FH for endometriosis, migraine, depression or EMP was reported by 10.2 %, 33.4 %, 32.6 % and 9.9 % of the 344 patients. A positive FH of endometriosis was associated with an increased risk for high rASRM-scores (rASRM 3 + 4: OR 2.74 (95 % CI 1.16-6.49), p = 0.017) and the presence of endometriomas (OR 2.70 (1.22-5.95), p = 0.011). A positive FH for migraine was associated with less response of endometriosis symptoms to CHC (OR 0.469 (0.27-0.82) p = 0.025). Depression in the family was linked to less severe rASRM-scores (rASRM 3 + 4: OR 0.63 (0.39-0.99), p = 0.046) and less endometriomas (OR 0.58 (0.67-0.92), p = 0.02), but increased the risk of both migraine (OR 1.66 (1.01-2.73), p = 0.043) and depression (OR 3.04 (1.89-4.89), p < 0.001) while showing a better response to CHC (OR 2.0 (1.15-3.48, p < 0.001). Patients with EMP in their family reported more current endometriosis symptoms at present (OR 3.72 (1.67-8.30), p = 0.001), more dysmenorrhea (OR 2.13 (1.04-4.35), p = 0.037), more frequent severe dysmenorrhea (OR 2.32 (1.14-4.74), p = 0.019) and suffered significantly more often > 5 days of non-cyclic pain (OR 3.58 (1.72-7.44), p < 0.001). CONCLUSIONS: Around 30% reported a positive FH for migraine or depression. Patients with a positive FH for endometriosis, migraine, depression or EMP differ in symptoms and surgical findings when compared to controls. While a FH for endometriosis is associated with higher rASRM scores and more endometriomas, women with a FH for depression had lower rASRM scores and less endometriomas while responding better to CHC. In contrast, women with a FH for migraine showed less response to CHC.

Migraine and Happiness.

Objective: To investigate the association between happiness and migraine. Background: Contemporary operationalizations of happiness include the prevailing positive over negative affect and the satisfaction with life. Generally, extreme events and circumstances influence happiness only temporarily. However, how does periodic cycling between being relatively healthy and relatively disabled-as in migraineurs-affect happiness? Migraine is a primary headache disorder, in which headache attacks intermittently interfere with normal living and cause a significant personal, societal, and potentially irreversible disease burden. Methods: In this cross-sectional observational study, migraineurs completed the satisfaction with life scale (SWLS), the Patient Health Questionnaire, and the Generalized Anxiety Disorder scale and reported their headache frequency as well as recent changes in that frequency. Furthermore, participants answered a free text question on how to remain happy despite migraine attacks. We built a regression model with the SWLS score as the dependent variable. Results: Seventy participants completed the questionnaire. The regression model revealed that happiness increases with headache days, and subsequent analysis showed a U-shaped relationship between headache frequency and happiness. The participants' advice on remaining happy focused on upvaluing the pain-free time or relieving the attacks themselves. The latter was increasingly common with longer disease durations. Conclusions: Both high and low headache frequencies facilitate adaptation to the disorder, while intermediate frequencies resulted in lower life satisfaction. The nonlinear relationship between happiness and headache days may be due to "hedonic habituation" and implies that headache calendars do not necessarily correctly reflect patients' difficulty to feel well despite the disorder. Many patients advised other migraineurs to increase happiness by enjoying pain-free time. However, with increasing disease duration, patients' recommendations focused on coping with attacks.

Examining Side Effect Variability of Antipsychotic Treatment in Schizophrenia Spectrum Disorders: A Meta-analysis of Variance.

Side effects of antipsychotic drugs play a key role in nonadherence of treatment in schizophrenia spectrum disorders (SSD). While clinical observations suggest that side effect variability between patients may be considerable, statistical evidence is required to confirm this. Here, we hypothesized to find larger side effect variability under treatment compared with control. We included double-blind, placebo-controlled, randomized controlled trials (RCTs) of adults with a diagnosis of SSD treated with 1 out of 14 antipsychotics. Standard deviations of the pre-post treatment differences of weight gain, prolactin levels, and corrected QT (QTc) times were extracted. The outcome measure was the variability ratio of treatment to control for individual antipsychotic drugs and the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. We included N = 16 578 patients for weight gain, N = 16 633 patients for prolactin levels, and N = 10 384 patients for QTc time. Variability ratios (VR) were significantly increased for weight gain (VR = 1.08; 95% CI: 1.02-1.14; P = .004) and prolactin levels (VR = 1.38; 95% CI: 1.17-1.62; P < .001) but did not reach significance for QTc time (VR = 1.05; 95% CI: 0.98-1.12; P = 0.135). We found marked differences between individual antipsychotics and increased variability in side effects in patients under treatment with antipsychotics suggesting that subgroups of patients or individual patients may benefit from treatment allocation through stratified or personalized medicine.