Depression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but... Show moreDepression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but knowledge on the temporal interplay between cortisol and depressive symptoms is scarce. We aimed to analyze the temporal connectivity between salivary cortisol and momentary affective states in depressed individuals and controls. Thirty pair-matched depressed and non-depressed participants completed questionnaires on momentary positive (PA) and negative (NA) affect and collected saliva three times a day for 30 days. The association between cortisol and affect was analyzed by dynamic time warp (DTW) analyses. These analyses involved lag-1 backward to lag-1 forward undirected analyses and lag-0 and lag-1 forward directed analyses. Large inter- and intra-individual variability in the networks were found. At the group level, with undirected analysis PA and NA were connected in the networks in depressed individuals and in controls. Directed analyses indicated that increases in cortisol preceded specific NA items in controls, but tended to follow upon specific affect items increase in depressed individuals. To conclude, at group level, changes in cortisol levels in individuals diagnosed with a depression may be a result of changes in affect, rather than a cause. Show less
The aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into... Show moreThe aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into the ASM prescription behavior and treatment policy in brain tumor-related epilepsy (part 3).First-line levetiracetam seems to be the most efficacious ASM in glioma patients, with favourable tolerability. This is demonstrated in multicenter retrospective observational cohort studies, a systematic review, and is the opinion among the vast majority of European neuro-oncology professionals. Enzyme-inducing AMSs should be avoided in glioma patients due to the high risk of adverse effects. ASM use was not independently associated with neuropsychiatric symptoms in glioma patients, but alternative factors seem to pose a greater risk for developing neuropsychiatric symptoms. If patients experience uncontrolled seizures on ASM monotherapy, levetiracetam combined with valproic acid has better efficacy than other ASM combinations in glioma patients, while toxicity is similar. Subsequently, potential add-on ASMs in glioma patients experiencing uncontrolled seizures on ASM dual therapy include clobazam, lamotrigine, and lacosamide. Show less
This thesis leads to empirical insights in the relationship between anger and aggression, on the one hand, and psychopathology, on the other hand, using robust study designs and a broad spectrum of... Show moreThis thesis leads to empirical insights in the relationship between anger and aggression, on the one hand, and psychopathology, on the other hand, using robust study designs and a broad spectrum of anger manifestations. It became clear that the occurrence of anger and aggression are common among both psychiatric outpatients, including individuals with depressive-, anxiety-, and bipolar disorders, and psychiatric inpatients, including individuals with psychotic- and personality disorders. Aggressive behaviour regularly leads to a referral to long-stay inpatient care. As supported by this thesis, the costs of aggression within long-stay wards are high. However, despite the increased awareness and efforts to reduce violence in clinical care among healthcare workers and policymakers, aggression incidents remain highly prevalent in psychiatric inpatient facilities. Research suggests diet to be a modifiable factor affecting mood and behaviour. Yet, the promising effects of nutritional supplementation on aggressive incidents found in previous studies were not replicated in psychiatric inpatients. These results strengthen the need for study of additional preventative and treatment options. Furthermore, our results underline the importance of including vulnerable populations, who are often underrepresented in RCTs, to provide evidence-based care for these groups. Show less
Introduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of... Show moreIntroduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2-10 years in patients with recurrent depression. Objective: The aim of the study was to examine the effectiveness of PCT over 20 years on time to first recurrence, cumulative proportion of first recurrences, percentage of depression-free time, mean severity of recurrences, and the number of recurrences within a patient. Methods: Adults remitted from recurrent MDD were randomized to PCT or Treatment As Usual (TAU). Clinical outcomes were assessed using the SCID over 20 years. We used Cox regression analyses, Kaplan-Meier analyses, ANOVA, and negative binomial regression and tested for interaction with the number of previous episodes. Results: There was a significant interaction effect for number of previous episodes with treatment condition on time to first recurrence (Wald[1, n = 172] = 8.840, p = 0.003). For participants with more than 3 previous episodes, the mean time to recurrence was 4.8 years for PCT versus 1.6 years for TAU; the cumulative proportion of first recurrences was 87.5% for PCT and 100% for TAU. For participants with more than 3 previous episodes, exploratory analyses suggest that PCT had 53% less recurrences and percentage of depression-free time was significantly higher compared to TAU. There were no significant effects on mean severity. Conclusions: Up to 20 years, for MDD patients with more than 3 previous episodes, those who received PCT had significantly longer time to a first recurrence and lower recurrence risk and may have less recurrences and more depression-free time compared to TAU. This suggests long term protective effects of PCT up to 20-years. Show less
It is well known that military deployment can lead to mental health problems in veterans, but the long-term impact is still unclear. This thesis discusses the results of the PRISMO-study, a large... Show moreIt is well known that military deployment can lead to mental health problems in veterans, but the long-term impact is still unclear. This thesis discusses the results of the PRISMO-study, a large cohort study in a group of Dutch Afghanistan veterans with a follow-up period of ten years. It shows that at ten years post-deployment, 8% of the cohort reported severe symptoms of posttraumatic stress disorder (PTSD). Agoraphobia, anxiety, depression, and hostility symptoms are also reported more frequently at ten years post-deployment compared to pre-deployment. Furthermore, this thesis demonstrates the large heterogeneity in PTSD symptom development among veterans. Of note is the delayed onset group that experienced increasing symptom levels between five and ten years post-deployment and did not show significant symptom reduction. The results from this thesis also show that various psychological factors, such as social support, and biological factors, such as DNA methylation, are associated with the development of PTSD or other mental health symptoms after deployment. Combining these factors in a prediction model for PTSD symptoms has not led to a useful screening instrument. It does, however, offer important leads for the identification of risk factors for PTSD and the development of intervention programs. Show less
Alshehri, T.; Mook-Kanamori, D.O.; Mutsert, R. de; Penninx, B.W.J.H.; Rosendaal, F.R.; Cessie, S. le; Milaneschi, Y. 2022
Background: Adiposity has been shown to be linked with atypical energy-related symptoms (AES) of depression. We used genomics to separate the effect of adiposity from that of metabolic... Show moreBackground: Adiposity has been shown to be linked with atypical energy-related symptoms (AES) of depression. We used genomics to separate the effect of adiposity from that of metabolic dysregulations to examine whether the link between obesity and AES is dependent on the presence of metabolic dysregulations. Method: Data were from NEO (n = 5734 individuals) and NESDA (n = 2238 individuals) cohorts, in which the Inventory of Depressive Symptomatology (IDS-SR30) was assessed. AES profile was based on four symptoms: increased appetite, increased weight, low energy level, and leaden paralysis. We estimated associations between AES and two genetic risk scores (GRS) indexing increasing total body fat with (metabolically unhealthy adiposity, GRS-MUA) and without (metabolically healthy adiposity, GRS-MHA) metabolic dysregulations. Results: We validated that both GRS-MUA and GRS-MHA were associated with higher total body fat in NEO study, but divergently associated with biomarkers of metabolic health (e.g., fasting glucose and HDL-cholesterol) in both cohorts. In the pooled results, per standard deviation, GRS-MUA was specifically associated with a higher AES score (beta = 0.03, 95%CI: 0.01; 0.05), while there was no association between GRS-MHA and AES (beta =-0.01, 95%CI:-0.03; 0.01). Conclusion: These results suggest that the established link between adiposity and AES profile emerges in the presence of metabolic dysregulations, which may represent the connecting substrate between the two conditions. Show less
Luenen, S. van; Garnefski, N.; Spinhoven, P.; Kraaij, V. 2022
The aim of this study was to investigate the long-term effectiveness (3-4 years later) of an online intervention that was previously found to effectively reduce depressive symptoms in people with... Show moreThe aim of this study was to investigate the long-term effectiveness (3-4 years later) of an online intervention that was previously found to effectively reduce depressive symptoms in people with HIV on the short term. Participants were people with HIV who had participated in the large RCT on the short-term effectiveness of the guided online intervention. The primary outcome measure was depressive symptoms [Patient Health Questionnaire-9 (PHQ-9)] and the secondary outcome measure was anxiety symptoms [Generalized Anxiety Disorder-2 (GAD-2) scale]. Forty-seven participants completed the long-term follow-up. PHQ-9 scores, previously found to have been significantly reduced on the short term, remained low on the long term. GAD-2 scores did not decrease significantly on the short term, however, on the long term, a significant decrease was found. The intervention may not only be effective in lowering depressive symptoms on the short term but also retain the results on the long term. Show less
Depression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the... Show moreDepression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the sum score on psychometric scales as a total indicator for depression severity. The present dissertation aimed to expand our knowledge of depression by researching its symptom-specific longitudinal characteristics, its predictive factors, and methods for predicting depression and anxiety while taking individual symptoms into account. We demonstrated that individual depressive symptoms are not synchronized over time within patients and in groups of patients. We found that individual symptoms of depression are associated to different risk factors, as preceding chronicity, neuroticism, and inflammation were related to individual symptoms with vastly different magnitudes. Taken these findings together we have demonstrated that depressive disorder can not be characterized as an unified syndrome. Addressing depression at the syndrome level may obscure insights into both patient and symptom-specific characteristics. Our findings strengthen the idea that employing a symptom-focused approach in both clinical care and research is of value. With this dissertation, we hope to have contributed to the development of alternative ways to define and study depression and its symptoms. Show less
Background Depression and anxiety are common mental disorders among patients with chronic pain. It is hypothesised that patients suffering from these disorders benefit less from cervical spine... Show moreBackground Depression and anxiety are common mental disorders among patients with chronic pain. It is hypothesised that patients suffering from these disorders benefit less from cervical spine surgery than mentally healthy patients. Therefore, this study aimed to quantify the effect of mental health status on functional outcome after anterior cervical discectomy in a post hoc analysis on RCT data. Methods One hundred eight patients from the NECK trial, with radiculopathy due to a one-level herniated disc, underwent anterior cervical discectomy and were included into this analysis. Functional outcome was quantified using the Neck Disability Index (NDI), and mental health status was measured using the Hospital Anxiety and Depression Score (HADS) questionnaire. NDI differences were assessed using generalised estimated equations (GEE), crude means, a predictive linear mixed model (LMM) using baseline scores and over time with an explanatory LMM. Results At baseline, 24% and 32% of patients were respectively depressed and anxious and had statistically significant and clinically relevant higher NDI scores during follow-up. However, in those patients in which the HADS returned to normal during follow-up, NDI values decreased comparably to the non-depression or non-anxiety cases. Those patients that demonstrated persisting high HADS values had convincingly worse NDI scores. A predictive LMM showed that combining baseline NDI and HADS scores was highly predictive of NDI during follow-up. The R shiny application enabled the effective, visual communication of results from the predictive LMM. Conclusion This study shows that mental health status and disability are strongly associated and provides insight into the size of the effect, as well as a way to use this relation to improve preoperative patient counselling. These findings give rise to the suggestion that incorporating mental health screening in the preoperative assessment of patients could help to adequately manage patients' expectations for functional recovery. Show less
Background: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. However, whether CT is more strongly linked to specific clinical features of these disorders remains... Show moreBackground: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. However, whether CT is more strongly linked to specific clinical features of these disorders remains inconclusive. The current study comprehensively examined cross-sectional and longitudinal associations between CT and depressive/anxiety symptomatology in a large adult sample with current and remitted depressive and/or anxiety disorders. Methods: Baseline (n = 1803), 2-year (n = 1735), 4-year (n = 1585), and 6-year follow-up (n = 1475) data from the Netherlands Study of Depression and Anxiety were used. CT (emotional neglect, emotional/physical/sexual abuse) was assessed at baseline, while depressive/anxiety symptomatology with relevant dimensions (e.g., mood/cognitive, melancholic, general distress, and somatic depression) was assessed at each wave using selfreported questionnaires. Linear regressions and linear mixed models determined cross-sectional and longitudinal associations. Results: Individuals with CT, especially, severe CT, compared to those without CT, had significantly higher scores in overall depressive symptomatology (Cohen's d = 0.674), mood/cognitive depression (d = 0.691), melancholic depression (d = 0.587), general distress (d = 0.561), and somatic depression severity (d = 0.549). Differences were lower, but still highly significant for anxiety (d = 0.418), worry (d = 0.362), and fear/phobic symptomatology (d = 0.359). Effects were consistent across CT types and maintained over six years. Limitations: Retrospectively-reported CT. Conclusions: CT is a risk factor for depressive and anxiety symptomatology across all dimensions and enduring over multiple years. Screening for CT is essential to identify individuals at risk for more severe and chronic manifestations of affective disorders. Show less
Fischer, K.; Tieskens, J.M.; Luijten, M.A.J.; Zijlmans, J.; Oers, H.A. van; Groot, R. de; ... ; Popma, A. 2022
The aim of the study was to assess internalizing problems before and during the pandemic with data from Dutch consortium Child and adolescent mental health and wellbeing in times of the COVID-19... Show moreThe aim of the study was to assess internalizing problems before and during the pandemic with data from Dutch consortium Child and adolescent mental health and wellbeing in times of the COVID-19 pandemic, consisting of two Dutch general population samples (GS) and two clinical samples (CS) referred to youth/psychiatric care. Measures of internalizing problems were obtained from ongoing data collections pre-pandemic (N-GS = 35,357; N-CS = 4487) and twice during the pandemic, in Apr-May 2020 (N-GS = 3938; clinical: N-CS = 1008) and in Nov-Dec 2020 (N-GS = 1489; N-CS = 1536), in children and adolescents (8-18 years) with parent (Brief Problem Monitor) and/or child reports (Patient-Reported Outcomes Measurement Information System (R)). Results show that, in the general population, internalizing problems were higher during the first peak of the pandemic compared to pre-pandemic based on both child and parent reports. Yet, over the course of the pandemic, on both child and parent reports, similar or lower levels of internalizing problems were observed. Children in the clinical population reported more internalizing symptoms over the course of the pandemic while parents did not report differences in internalizing symptoms from pre-pandemic to the first peak of the pandemic nor over the course of the pandemic. Overall, the findings indicate that children and adolescents of both the general and clinical population were affected negatively by the pandemic in terms of their internalizing problems. Attention is therefore warranted to investigate long-term effects and to monitor if internalizing problems return to pre-pandemic levels or if they remain elevated post-pandemic. Show less
Verhoeff-Jahja, R.; Kuile, M.M. ter; Weijl, N.I.; Oosterkamp, R.; Cloos, M.; Portielje, J.E.A.; ... ; Hinnen, C. 2022
Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, especially after taxane-based therapy. This study aimed to examine the relationship between... Show moreBackground Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, especially after taxane-based therapy. This study aimed to examine the relationship between symptoms of anxiety and depression before the start of taxane-based chemotherapy and the development of CIPN in women with breast cancer. Methods In this prospective study, women with breast cancer receiving taxane-based (neo)adjuvant chemotherapy were recruited from four hospitals in the Netherlands. Patients completed questionnaires assessing anxiety and depressive symptoms before treatment and CIPN before treatment (T0), 6 weeks after start of treatment (T1), after the last cycle of chemotherapy (T2), and 6 months after the end of treatment (T3). Mixed model analyses were used to investigate whether medium/high levels of anxiety or depression at baseline are associated with the level of CIPN during and after treatment. Results Among the 61 participating women, 14 (23%) reported medium/high levels of anxiety and 29 (47.5%) reported medium/high levels of depressive symptoms at baseline. The group of women with medium/high baseline levels of anxiety showed a significantly higher increase in CIPN during and after chemotherapy than women with low baseline levels of anxiety (p < .001). No relationship between depressive symptoms at baseline and the development of CIPN was found. Conclusion This study showed that baseline medium to high levels of anxiety but not depressive symptoms impacted the development of CIPN during and in the 6 months after treatment. Show less
Galbally, M.; Watson, S.J.; Lappas, M.; Kloet, E.R. de; Wyrwoll, C.S.; Mark, P.J.; Lewis, A.J. 2022
In examining maternal depression, placental 11 beta-HSD2 mRNA expression and offspring cortisol regulation as a potential fetal programming pathway in relation to later child emotional disorders,... Show moreIn examining maternal depression, placental 11 beta-HSD2 mRNA expression and offspring cortisol regulation as a potential fetal programming pathway in relation to later child emotional disorders, it has become clear that sex differences may be important to consider. This study reports on data obtained from 209 participants in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) recruited before 20 weeks of pregnancy. Maternal depressive disorders were diagnosed using the SCID-IV and maternal childhood trauma using the Childhood Trauma Questionnaire. Placental 11 beta-HSD2 mRNA was measured using qRT-PCR. For assessment of stressinduced cortisol reactivity, salivary cortisol samples were taken at 12 months of age. At 4 years of age, measurement of Childhood Emotional Disorders (depression and anxiety) was based on maternal report using the Preschool Age Psychiatric Assessment (PAPA) and internalizing symptoms using the Child Behavior Checklist (CBCL). Maternal depression in pregnancy and postpartum, and infant cortisol reactivity, was associated with internalizing symptoms for females only. For female offspring only, increased 12-month cortisol reactivity was also associated with increased emotional disorders at 4 years of age; however, there was no association with placental 11 beta-HSD2 mRNA expression. In females only, the combination of lower placental 11 beta-HSD2 mRNA expression and higher cortisol reactivity at 12 months of age predicted increased internalising problems. These findings suggest there may be sex differences in prenatal predictors and pathways for early childhood depression and anxiety symptoms and disorder. Show less
Objective: To investigate the impact of the coronavirus pandemic on mental health in hemodialysis patients, we assessed depression, anxiety and quality of life with valid mental health measures... Show moreObjective: To investigate the impact of the coronavirus pandemic on mental health in hemodialysis patients, we assessed depression, anxiety and quality of life with valid mental health measures before and after the start of the pandemic.Methods: Data were used from 121 hemodialysis patients from the ongoing prospective multicenter DIVERS-II study. COVID-19 related stress was measured with the Perceived Stress Scale - 10, depression with the Beck Depression Inventory - second edition (BDI-II)), anxiety with the Beck Anxiety Inventory (BAI) and quality of life with the Short Form - 12 (SF-12). Scores during the first and second COVID-19 wave in the Netherlands were compared to data prior to the pandemic with linear mixed models.Results: No significant differences were found in BDI-II, BAI and SF-12 scores between before and during the pandemic. During the first wave, 33% of participants reported COVID-19 related stress and in the second wave 37%. These patients had higher stress levels (mean difference (MD) 4.7 (95%CI 1.5; 8.0), p = 0.005) and BDI-II scores (MD 4.9 (95%CI 0.7; 9.0), p = 0.021) and lower SF-12 mental component summary scores (MD -5.3 (95% CI -9.0, - 1.6), p = 0.006) than patients who did not experienced COVID-19 stress. These differences were already present before the pandemic.Conclusion: The COVID-19 pandemic does not seem to influence mental health in hemodialysis patients. However, a substantial subgroup of patients with pre-existent mental health problems may be more susceptible to experience COVID-19 related stress. Show less
Objective: To investigate the effectiveness of a guided internet-based self-help intervention for hemodialysis patients with depressive symptoms. Method: Chronic hemodialysis patients from nine... Show moreObjective: To investigate the effectiveness of a guided internet-based self-help intervention for hemodialysis patients with depressive symptoms. Method: Chronic hemodialysis patients from nine Dutch hospitals with a depression score on the Beck Depression Inventory - second edition (BDI-II) of & GE;10, were cluster-randomized into a five modules guided internet-based self-help problem solving therapy intervention or a parallel care-as-usual control group. Clusters were based on hemodialysis shift. The primary outcome depression was measured with the BDI-II. Analysis was performed with linear mixed models. Results: A total of 190 hemodialysis patients were cluster-randomized to the intervention (n = 89) or control group (n = 101). Post-intervention measurement was completed by 127 patients (67%) and more than half of the patients (54%) completed the intervention. No significant differences were found on the BDI-II score between the groups (mean difference -0.1, 95%CI -3.0; 2.7, p = 0.94). Per protocol sensitivity analysis showed comparable results. No significant differences in secondary outcomes were observed between groups. Conclusions: Guided internet-based self-help problem solving therapy for hemodialysis patients with depressive symptoms does not seem to be effective in reducing these symptoms as compared to usual care. Future research should examine how to best design content and accessibility of an intervention for depressive symptoms in hemodialysis patients. Show less
Gartner, M.; Rover, M. de; Vaclavu, L.; Scheidegger, M.; Osch, M.J.P. van; Grimm, S. 2022
Ketamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However,... Show moreKetamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However, imaging studies attempting to characterise ketamine's mechanism of action using blood oxygen level-dependent signal (BOLD) imaging have yielded inconsistent results- at least partly due to intrinsic properties of the BOLD contrast, which measures a complex signal related to neural activity. To circumvent the limitations associated with the BOLD signal, we used arterial spin labelling (ASL) as an unambiguous marker of neuronal activity-related changes in cerebral blood flow (CBF). We measured CBF in 21 MDD patients at baseline and 24 h after receiving a single intravenous infusion of subanesthetic ketamine and examined relationships with clinical outcomes. Our findings demonstrate that increase in thalamus perfusion 24 h after ketamine administration is associated with greater improvement of depressive symptoms. Furthermore, lower thalamus perfusion at baseline is associated both with larger increases in perfusion 24 h after ketamine administration and with stronger reduction of depressive symptoms. These findings indicate that ASL is not only a useful tool to broaden our understanding of ketamine's mechanism of action but might also have the potential to inform treatment decisions based on CBF-defined regional disruptions. Show less
Background: Mismatch between need and mental healthcare (MHC) use (under-and overuse) has mainly been studied with cross-sectional designs, not accurately capturing patterns of persistence or... Show moreBackground: Mismatch between need and mental healthcare (MHC) use (under-and overuse) has mainly been studied with cross-sectional designs, not accurately capturing patterns of persistence or change in clinical burden and MHC-use among persons with depressive and/or anxiety disorders. Aims: Determining and describing [mis]match of longitudinal trajectories of clinical burden and MHC-use. Methods: Six-year longitudinal burden and MHC-use data came from the Netherlands Study of Depression and Anxiety (n=2981). The sample was split into four subgroups: I) no clinical burden but constant MHC use, II) constant clinical burden but no MHC-use, III) changing clinical burden and MHC-use, and IV) healthy non-users. Within subgroups I)-III), specific clinical burden and MHC trajectories were identified (growth mixture modeling). The resulting classes' associations with predisposing, enabling, and need factors were investigated (regression analysis). Results: Subgroups I-III revealed different trajectories. I) increasing MHC without burden (4.1%). II) slightly increasing (1.9%), strongly increasing (2.4%), and decreasing (9.5%) burden without MHC. III) increasing (41.4%) or decreasing (19.4%) burden and concurrently increasing MHC use (first underuse, then matched care), thus revealing delayed MHC-use. Only having suicidal ideation (p<.001, Cohen's d=.6-1.5) was a significant determinant of being in latter classes compared to underusers (strongly increasing burden without MHC-use). Limitations: More explanatory factors are needed to explain [mis]match. Conclusion: Mismatch occurred as constant underuse or as delayed MHC-use in a high-income country (Netherlands). Additionally, no meaningful class revealed constantly matched care on average. Presence of suicidal ideation could influence the probability of symptomatic individuals receiving matched MHC or not. Show less
Background: The relationship between migraine and depression has been thoroughly investigated, indicating a bidirectional comorbidity. The exact temporal relationship between acute depressive... Show moreBackground: The relationship between migraine and depression has been thoroughly investigated, indicating a bidirectional comorbidity. The exact temporal relationship between acute depressive symptoms (mood changes) and the various phases of the migraine attack has not yet been examined. Methods: We performed a prospective diary study in n = 487 participants with migraine. Participants filled out a daily diary on migraine and acute depressive symptoms during a 1-month period. We randomly selected one migraine attack per participant, consisting of six days around an attack, including the interictal, premonitory, ictal, and postdromal phases. Acute depressive symptoms covered five major items from the DSM-5 classification. Primary analysis was performed using a mixed model with post-hoc testing. We also tested whether lifetime depression influenced the presence of acute depressive symptoms. Results: During a migraine headache day, patients scored higher on acute depressive symptoms than on all other days of the migraine attack (p < 0.001). There were no early warning signs for an upcoming headache attack through acute depressive symptomatology. Migraine patients with lifetime depression scored overall higher during the migraine attack than those without lifetime depression (p < 0.001). Limitations: Migraine attacks were based on self-reported migraine and one migraine attack per patient was randomly selected.Conclusion: We now clearly demonstrate that during the migraine headache phase, but not in the prodromal phase, patients report increased depressive symptomatology. No evidence was found for mood changes as an early warning sign for an upcoming migraine attack. Show less
Eveningness is associated with lower daily positive affect (PA). The relationship between negative affect (NA) and chronotype, however, is less consistent in the literature. Eveningness may be... Show moreEveningness is associated with lower daily positive affect (PA). The relationship between negative affect (NA) and chronotype, however, is less consistent in the literature. Eveningness may be further characterized by increased social isolation, which could explain the associations between chronotype and PA/NA. In the present longitudinal study, we used ecological momentary assessment (EMA) to investigate the associations of chronotype with daily PA, NA, and social contact in individuals with current and remitted major depressive disorder (MDD) and healthy controls. As part of the Netherlands Study of Depression and Anxiety (NESDA), 279 participants (n = 49 depressed, n = 172 remitted, n = 58 controls) monitored daily PA, NA, and social contact (i.e., being alone vs. with others) for two weeks, five times per day. Overall, eveningness was associated with less social contact. This effect became nonsignificant, however, after accounting for sociodemographics (gender, age, education, living situation). Chronotype was not related to PA or NA. Less social contact was associated with lower PA and higher NA independent of chronotype. In conclusion, we could not replicate the finding of lower PA among evening types, but found social contact to associate with both daily PA and NA. Show less
Marco, R. de; Ronen, I.; Branzoli, F.; Amato, M.L.; Asllani, I.; Colasanti, A.; ... ; Cercignani, M. 2022
Background: Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently,... Show moreBackground: Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology. In this preliminary study, we applied DW-MRS to measure changes in the apparent diffusion coefficients (ADC) of glial and neuronal metabolites to healthy participants who underwent an LPS administration protocol. We hypothesized that the ADC of glial metabolites will be selectively modulated by LPSinduced glial activation. Methods: Seven healthy male volunteers, (mean 25.3 +/- 5.9 years) were each tested in two separate sessions once after LPS (1 ng/Kg intravenously) and once after placebo (saline). Physiological responses were monitored during each session and serial blood samples and Profile of Mood States (POMS) completed to quantify white blood cell (WBC), cytokine and mood responses. DW-MRS data were acquired 5-51/2 hours after injection from two brain regions: grey matter in the left thalamus, and frontal white matter. Results: Body temperature, heart rate, WBC and inflammatory cytokines were significantly higher in the LPS compared to the placebo condition (p < 0.001). The ADC of the glial metabolite choline (tCho) was also significantly increased after LPS administration compared to placebo (p = 0.008) in the thalamus which scaled with LPS-induced changes in POMS total and negative mood (Adj R-2 = 0.83; p = 0.004). Conclusions: DW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation. Show less
