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
De uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische... Show moreDe uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische onderbouwing, overwogen dient te worden. Inmiddels wordt adipositas in de dagelijkse praktijk op meer dan alleen het BMI beoordeeld, namelijk ook de tailleomtrek en het lipidenprofiel. Echter, dergelijke aandacht bestaat nog niet voor de heterogeniteit van depressie. Een grotere bewustwording van de verschillende manifestaties van depressie-symptomatologie, die het gevolg kunnen zijn van uiteenlopende pathofysiologische mechanismen, is van essentieel belang. Wanneer een patiënt met depressie een atypisch energie-gerelateerd symptoomprofiel heeft, kan het nuttig zijn om diens metabole biomarkers te controleren om mogelijke ontwikkeling van cardiometabole ziekten te voorkomen. In de klinische praktijk moeten wij ons bij de behandeling van patiënten met depressie ook meer bewust worden van de correlatie tussen symptoomprofielen van depressie en afzonderlijke biologische en klinische manifestaties. Het is cruciaal om goed te kijken naar de symptomen die bij elke patiënt tot uiting komen. De resultaten van dit proefschrift tonen aan dat patiënten met een depressie die atypische energie-gerelateerde depressieve symptomen vertonen, genetisch en klinisch kwetsbaar zijn voor aan insulineresistentie gerelateerde ziekten (namelijk adipositas, metabole ontregelingen en diabetes mellitus type 2). Een gepersonaliseerde aanpak kan behulpzaam zijn in preventie van deze chronische en complexe ziekten. Hierbij dient er rekening gehouden worden met de heterogeniteit van depressie en de associatie tussen atypische energie-gerelateerde symptomen van depressie en deze ziekten. Show less
Kivelae, L.M.M.; Antypa, N.; Fried, E.I.; Schoevers, R.; Hemert, A.M. van; Penninx, B.W.J.H.; Does, A.J.W. van der 2023
BackgroundDepression is a highly recurrent disorder, with more than 50% of those affected experiencing a subsequent episode. Although there is relatively little stability in symptoms across... Show moreBackgroundDepression is a highly recurrent disorder, with more than 50% of those affected experiencing a subsequent episode. Although there is relatively little stability in symptoms across episodes, some evidence indicates that suicidal ideation may be an exception. However, these findings warrant replication, especially over longer periods and across multiple episodes.AimsTo assess the relative stability of suicidal ideation in comparison with other non-core depressive symptoms across episodes.MethodWe examined 490 individuals with current major depressive disorder (MDD) at baseline and at least one subsequent episode during 9-year follow-up within the Netherlands Study of Depression and Anxiety (NESDA). The Inventory of Depressive Symptomatology (IDS) was used to assess DSM-5 non-core MDD symptoms (fatigue, appetite/weight change, sleep disturbance, psychomotor disturbance, concentration difficulties, worthlessness/guilt, suicidal ideation) at baseline and 2-, 4-, 6- and 9-year follow-up. We examined consistency in symptom presentation (i.e. whether the symptom met the diagnostic threshold, based on a binary categorisation of the IDS) using kappa (κ) and percentage agreement, and stability in symptom severity using Spearman correlation, based on the continuous IDS scores.ResultsOut of all non-core depressive symptoms, insomnia appeared the most stable across episodes (r = 0.55–0.69, κ = 0.31–0.47) and weight decrease the least stable (r = 0.03–0.33, κ = 0.06–0.19). For suicidal ideation, correlations across episodes ranged from r = 0.36 to r = 0.55 and consistency ranged from κ = 0.28 to κ = 0.49.ConclusionsSuicidal ideation is moderately stable in recurrent depression over 9 years. Contrary to prior reports, however, it does not exhibit substantially more stability than most other non-core symptoms of depression. Show less
Major Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations... Show moreMajor Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations between enduring depression and brain functioning during regulation of negative and positive emotions using cognitive reappraisal.We used fMRI-data from the longitudinal Netherlands Study of Depression and Anxiety acquired during an emotion regulation task in 77 individuals with MDD. Task-related brain activity was related to disease load, calculated from presence and severity of depression in the preceding nine years. Additionally, we explored task related brain-connectivity. Brain functioning in individuals with MDD was further compared to 35 controls to explore overlap between load-effects and general effects related to MDD history/presence.Disease load was not associated with changes in affect or with brain activity, but with connectivity between areas essential for processing, integrating and regulating emotional information during downregulation of negative emotions. Results did not overlap with general MDD-effects. Instead, MDD was generally associated with lower parietal activity during downregulation of negative emotions. During upregulation of positive emotions, disease load was related to connectivity between limbic regions (although driven by symptomatic state), and connectivity between frontal, insular and thalamic regions was lower in MDD (vs controls).Results suggest that previous depressive load relates to brain connectivity in relevant networks during downregulation of negative emotions. These abnormalities do not overlap with disease-general abnormalities and could foster an incremental vulnerability to recurrence or chronicity of MDD. Therefore, optimizing emotion regulation is a promising therapeutic target for improving long-term MDD course. Show less
Background Anti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on... Show moreBackground Anti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS).Methods Data were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B; NCT01363856). Serum NMDAR1-abs (IgM/IgA/IgG) were measured within 7 days after IS using cell-based assays. We defined seropositivity as titers >= 1:10, thereof low titers as <= 1:100 and high titers as >1:100. We used the Center for Epidemiological Studies-Depression (CES-D) scale to measure depressive symptoms at year one, two and three following IS. We calculated crude and confounder adjusted weighted generalized linear models to quantify the impact of NMDAR1-abs on CES-D assessed at three annual time-points.Results NMDAR1-abs were measured in 583 PROSCIS-B IS patients (mean age = 67 [SD = 13]; 42%female; median NIHSS = 2 [IQR = 1-4]) of whom 76 (13%; IgM: n = 49/IgA: n = 43/IgG: n = 2) were seropositive, 55 (9%) with low and 21 (4%) with high titers. CES-D regarded over all follow-up time-points was higher in seropositive patients (beta(crude) = 2.56 [95%CI = -0.34 to 5.45]; beta(adjusted) = 2.26 [95%CI = -0.68 to 5.20]) and effects were highest in patients with high titer (low titers: beta(crude) = 1.42 [95%CI = -1.79 to 4.62], beta(adjusted) = 0.53 [95%CI = -2.47 to 3.54]; high titers: beta(crude) = 5.85 [95%CI = 0.20 to 11.50]; beta(adjusted) = 7.20 [95%CI = 0.98 to 13.43]).Conclusion Patients with serum NMDAR1-abs (predominantly IgM&IgA) suffer more severe depressive symptoms after mild-to-moderate IS compared to NMDAR1-abs seronegative patients. 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 dissertation focuses on identifying neural mechanisms underlying social evaluations and self-views from a parent-adolescent perspective among adolescents with and without depression, and their... Show moreThis dissertation focuses on identifying neural mechanisms underlying social evaluations and self-views from a parent-adolescent perspective among adolescents with and without depression, and their parents. As part of RE-PAIR, affective and neural responses to praise and criticism about the adolescent child, and neural responses to reliving positive autobiographical memories were assessed, using ecologically valid fMRI-tasks. Particularly criticism seems to be highly salient to parents and adolescents, activating the salience network and decreasing mood. Both praise and reliving positive autobiographical memories activate areas important for self-referential processing in adolescents, which might reflect the ‘positive self’. Aberrant self-related processing when reliving autobiographical memories and increased sensitivity to parental criticism might be key underlying neural mechanisms in adolescent depression. By feeling more negatively, having more negative self-views, interpreting the environment as more negatively, memorizing past experiences in a more negative way, and focusing on negative events more often, adolescents with depression seem to have multiple negativity biases. These negativity biases are likely to negatively impact social relationships, potentially further reinforcing negative feelings and a negative self. Interventions exploring and strengthening the positive self, in particular the positive self aligning with the current self, might be useful for treating, or even preventing adolescent depression. Show less
Kochlik, B.; Herpich, C.; Moreno-Villanueva, M.; Klaus, S.; Müller-Werdan, U.; Weinberger, B.; ... ; Norman, K. 2023
Growth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with... Show moreGrowth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with combined cognitive-frailty-and-depression in older (i.e. ≥ 55 years) and younger adults of the MARK-AGE study. In the present work, samples and data of MARK-AGE (“European study to establish bioMARKers of human AGEing“) participants (N = 2736) were analyzed. Cognitive frailty was determined by the global cognitive functioning score (GCF) and depression by the Self-Rating Depression Scale (SDS score). Adults were classified into three groups: (I) neither-cognitive-frailty-nor-depression, (II) either-cognitive-frailty-or-depression or (III) both-cognitive-frailty-and-depression. Cross-sectional associations were determined by unadjusted and by age, BMI, sex, comorbidities and hsCRP-adjusted linear and logistic regression analyses. Cognitive frailty, depression, age and GDF15 were significantly related within the whole study sample. High GDF15 levels were significantly associated with both-cognitive-frailty-and-depression (adjusted β = 0.177 [0.044 – 0.310], p = 0.009), and with low GCF scores and high SDS scores. High GDF15 concentrations and quartiles were significantly associated with higher odds to have both-cognitive-frailty-and-depression (adjusted odds ratio = 2.353 [1.267 – 4.372], p = 0.007; and adjusted odds ratio = 1.414 [1.025 – 1.951], p = 0.035, respectively) independent of age, BMI, sex, comorbidities and hsCRP. These associations remained significant when evaluating older adults. We conclude that plasma GDF15 concentrations are significantly associated with combined cognitive-frailty-and-depression status and, with cognitive frailty and depressive symptoms separately in old as well as young community-dwelling adults. Show less
Leeuw, M. de; Verhoeve, S.I.; Wee, N.J.A. van der; Hemert, A.M. van; Vreugdenhil, E.; Coomans, C.P. 2023
Circadian rhythms have evolved in almost all organisms enabling them to anticipate alternating changes in the environment. As a consequence, the circadian clock controls a broad range of bodily... Show moreCircadian rhythms have evolved in almost all organisms enabling them to anticipate alternating changes in the environment. As a consequence, the circadian clock controls a broad range of bodily functions including appetite, sleep, activity and cortisol levels. The circadian clock synchronizes itself to the external world mainly by environmental light cues and can be disturbed by a variety of factors, including shift-work, jet-lag, stress, ageing and artificial light at night.Interestingly, mood has also been shown to follow a diurnal rhythm. Moreover, circadian disruption has been associated with various mood disorders and patients suffering from depression have irregular biological rhythms in sleep, appetite, activity and cortisol levels suggesting that circadian rhythmicity is crucially involved in the etiology and pathophysiology of depression.The aim of the present review is to give an overview and discuss recent findings in both humans and rodents linking a disturbed circadian rhythm to depression. Understanding the relation between a disturbed circadian rhythm and the etiology of depression may lead to novel therapeutic and preventative strategies. 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
BackgroundChildhood maltreatment is associated with depression and cardiometabolic disease in adulthood. However, the relationships with these two diseases have so far only been evaluated in... Show moreBackgroundChildhood maltreatment is associated with depression and cardiometabolic disease in adulthood. However, the relationships with these two diseases have so far only been evaluated in different samples and with different methodology. Thus, it remains unknown how the effect sizes magnitudes for depression and cardiometabolic disease compare with each other and whether childhood maltreatment is especially associated with the co-occurrence (“comorbidity”) of depression and cardiometabolic disease. This pooled analysis examined the association of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity in adulthood.MethodsWe carried out an individual participant data meta-analysis on 13 international observational studies (N = 217,929). Childhood maltreatment comprised self-reports of physical, emotional, and/or sexual abuse before 18 years. Presence of depression was established with clinical interviews or validated symptom scales and presence of cardiometabolic disease with self-reported diagnoses. In included studies, binomial and multinomial logistic regressions estimated sociodemographic-adjusted associations of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity. We then additionally adjusted these associations for lifestyle factors (smoking status, alcohol consumption, and physical activity). Finally, random-effects models were used to pool these estimates across studies and examined differences in associations across sex and maltreatment types.ResultsChildhood maltreatment was associated with progressively higher odds of cardiometabolic disease without depression (OR [95% CI] = 1.27 [1.18; 1.37]), depression without cardiometabolic disease (OR [95% CI] = 2.68 [2.39; 3.00]), and comorbidity between both conditions (OR [95% CI] = 3.04 [2.51; 3.68]) in adulthood. Post hoc analyses showed that the association with comorbidity was stronger than with either disease alone, and the association with depression was stronger than with cardiometabolic disease. Associations remained significant after additionally adjusting for lifestyle factors, and were present in both males and females, and for all maltreatment types.ConclusionsThis meta-analysis revealed that adults with a history of childhood maltreatment suffer more often from depression and cardiometabolic disease than their non-exposed peers. These adults are also three times more likely to have comorbid depression and cardiometabolic disease. Childhood maltreatment may therefore be a clinically relevant indicator connecting poor mental and somatic health. Future research should investigate the potential benefits of early intervention in individuals with a history of maltreatment on their distal mental and somatic health (PROSPERO CRD42021239288). Show less
PurposeSiblings of probands with depressive and anxiety disorders are at increased risk for psychopathology, but little is known about how risk factors operate within families to increase... Show morePurposeSiblings of probands with depressive and anxiety disorders are at increased risk for psychopathology, but little is known about how risk factors operate within families to increase psychopathology for siblings. We examined the additional impact of psychosocial risk factors in probands—on top of or in combination with those in siblings—on depressive/anxious psychopathology in siblings.MethodsThe sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and their sibling(s) (N = 380 proband-sibling pairs). Sixteen psychosocial risk factors were tested. In siblings, depressive and anxiety disorders were determined with standardized psychiatric interviews; symptom severity was measured using self-report questionnaires. Analyses were performed with mixed-effects models accounting for familial structure.ResultsIn siblings, various psychosocial risk factors (female gender, low income, childhood trauma, poor parental bonding, being single, smoking, hazardous alcohol use) were associated with higher symptomatology and likelihood of disorder. The presence of the same risk factor in probands was independently associated (low income, being single) with higher symptomatology in siblings or moderated (low education, childhood trauma, hazardous alcohol use)—by reducing its strength—the association between the risk factor and symptomatology in siblings. There was no additional impact of risk factors in probands on likelihood of disorder in siblings.ConclusionOur findings demonstrate the importance of weighing psychosocial risk factors within a family context, as it may provide relevant information on the risk of affective psychopathology for individuals. Show less
