This thesis aimed to lay the foundation for a new set of Dutch mental health instruments to measure depression and anxiety in an efficient, reliable, valid, and responsive manner. More specifically... Show moreThis thesis aimed to lay the foundation for a new set of Dutch mental health instruments to measure depression and anxiety in an efficient, reliable, valid, and responsive manner. More specifically, the Dutch-Flemish PROMIS adult v1.0 item banks for Depression and Anxiety were psychometrically evaluated for computerized adaptive test (CAT) administration in the Dutch clinical and general population. CAT is a modern methodology that can be used to develop instruments that measure both efficiently and reliably as only the most appropriate questions are administered, and assessment terminates as soon as sufficient reliability is achieved. For the PROMIS CAT instruments, this was demonstrated in the thesis: measuring depression and anxiety in Dutch persons was highly efficient and reliable. Moreover, the CAT instruments were shown to measure depression and anxiety sufficiently responsive and valid as well. This even includes longitudinal validity, which has barely been studied for other Dutch mental health instruments. Overall, it was concluded that the new instruments are an improvement over available instruments. Therefore, using the PROMIS CAT instruments in clinical practice may lead to more efficient and reliable measurement that supports professionals and patients in evaluating patients' treatment. 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
This dissertation describes the findings of six studies on mental health problems in the family context, specifically focusing on the associations with the parent-child relationship, parenting... Show moreThis dissertation describes the findings of six studies on mental health problems in the family context, specifically focusing on the associations with the parent-child relationship, parenting behaviors and experiences of childhood maltreatment. The aim is to better understand the risk factors, development and transmission of common psychological problems in order to contribute to prevention and treatment strategies for common psychological problems such as anxiety and depression.Overall, the findings underline the importance of the family context in the development and levels of mental health problems. In addition to the impact of one's own negative parenting experiences, including lack of warmth and experiences of emotional or physical abuse, negative parenting experiences of one's siblings are also associated with elevated anxiety and depressive symptom levels.We also found that externalizing problems of fathers and children have a negative impact on the parent-child interactions. In addition, we found that children with behavioral problems during early adolescence experience harsher parental discipline, even three years later.In the current treatment guidelines for common mental disorders, most therapies focus on the individual. An (additional) systemic approach and considering past and present family relationships in therapy, can be of additional value. For example, supporting families with interventions to improve the parent-child relationship can be helpful in the short and long term. Moreover, (early) treatment of psychological and behavioral problems of the parent or child might be beneficial for all family members. 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
Background and Aims: Observational studies have suggested a bidirectional association between depression and inflammatory bowel disease [IBD], including Crohn's disease [CD] and ulcerative colitis ... Show moreBackground and Aims: Observational studies have suggested a bidirectional association between depression and inflammatory bowel disease [IBD], including Crohn's disease [CD] and ulcerative colitis [UC]. However, it remains unclear whether the observed associations are causal due to the difficulties of determining sequential temporality. We investigated the association between depression and IBD by using bidirectional two-sample Mendelian randomization [MR]. Methods: Independent genetic variants for depression and IBD were selected as instruments from published genome-wide association studies [GWAS] among individuals of predominantly European ancestry. Summary statistics for instrument-outcome associations were retrieved from three separate databases for both depression [Psychiatric Genomics Consortium, FinnGen and UK Biobank] and IBD [the largest GWAS meta-analysis, FinnGen and UK Biobank], respectively. MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger regression, and sensitivity analyses of Steiger filtering and MR PRESSO. From either direction, analyses were performed per outcome database and were subsequently meta-analysed using a fixed-effect model. Results: Genetically predicted depression [per log-odds ratio increase] was associated with a higher risk of IBD; odds ratios [95% confidence interval] for IBD, CD and UC were 1.20 [1.05, 1.36], 1.29 [1.07, 1.56] and 1.22 [1.01, 1.47] in a combined sample size of 693 183 [36 507 IBD cases], 212 172 [13 714 CD cases] and 219 686 [15 691 UC cases] individuals, respectively. In contrast, no association was observed between genetically influenced IBD and depression in 534 635 individuals [71 466 depression cases]. Conclusions: Our findings corroborated a causal association of depression on IBD, which may impact the clinical decision on the management of depression in patients with IBD. Though our results did not support a causal effect of IBD on depression, further investigations are needed to clarify the effect of IBD activity on depression [with different symptomology]. Show less
Hebbrecht, K.; Morrens, M.; Giltay, E.J.; Nuijs, A.L.N. van; Sabbe, B.; Ameele, S. van den 2021
Introduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway... Show moreIntroduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. Methods: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. Results: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03). Conclusion: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship. Show less
Background: Chronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype... Show moreBackground: Chronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype with later chronotypes in adolescents and earlier chronotypes in children and elderly. Additionally, later chronotypes have been associated with more depressive symptoms. Few studies have been able to study longitudinal associations between chronotype and age, while adjusting for depressive symptoms. Methods: Chronotype was assessed twice with the Munich Chronotype Questionnaire 7 years apart in the Netherlands Study of Depression and Anxiety (T1: N = 1842, mean age (SD): 42.63 years (12.66)) and T2: N = 1829, mean age (SD) 50.67 (13.11)). The longitudinal association between change in age and change in chronotype was tested using a generalized estimated equation analysis adjusted for covariates (including level of depressive symptoms). Using age-bins of 5 years (age at T2), change in chronotype between T1 and T2 was analyzed with Linear Mixed Models. Results: We found a change towards an earlier chronotype with higher age (B (95% CI): -0.011 (-0.014-0.008), p < 0.001). For the age-bins, the difference in chronotype was significant for the 25-29 years age-bin. Limitations: The sample did not include individuals younger than 19 years or older than 68 years. Conclusions: In the whole sample chronotype changed towards becoming more morning-type over a period of 7 years, but this change was only significant for those aged 25-29 years. The study was performed in a large naturalistic cohort study with a wide age-range, including patients with a diagnosis of depressive and anxiety disorder and healthy controls. Show less
Struijs, S.Y.; Jong, P.J. de; Jeronimus, B.F.; Does, W. van der; Riese, H.; Spinhoven, P. 2021
Background: The Netherlands Study of Depression and Anxiety (NESDA; Nbaseline=2981) is an ongoing longitudinal, multi-site, naturalistic, cohort study examining the etiology, course, and... Show moreBackground: The Netherlands Study of Depression and Anxiety (NESDA; Nbaseline=2981) is an ongoing longitudinal, multi-site, naturalistic, cohort study examining the etiology, course, and consequences of depression and anxiety. In this article we synthesize and evaluate fifteen years of NESDA research on prominent psychological risk factors for the onset, persistence, recurrence, and comorbidity of affective disorders.Methods: A narrative review of 62 NESDA articles examining the specificity and predictive value of neuroticism, behavioral inhibition, repetitive negative thinking, experiential avoidance, cognitive reactivity, locus of control, (implicit) self-esteem, (implicit) disorder-specific self-associations, and attentional bias for the course of affective disorders.Results: All self-reported risk factors showed cross-sectional relationships with singular and comorbid affective disorders, and prospective relationships with the development and chronicity of depression and anxiety disorders. High neuroticism, low self-esteem, and negative repetitive thinking showed most prominent transdiagnostic relationships, whereas cognitive reactivity showed most pronounced depression-specific associations. Implicit self-esteem showed predictive validity for the persistence and recurrence of anxiety and depression over and above self-reported risk factors. Automatic approach-avoidance behavior and attentional bias for negative, positive, or threat words showed no relationship with affective disorders.Conclusion: NESDA identified both (a) transdiagnostic factors (e.g., neuroticism, low implicit self-esteem, repetitive negative thinking) that may help explain the comorbidity between affective disorders and overlap in symptoms, and (b) indications for disorder-specific risk factors (e.g., cognitive responsivity) which support the relevance of distinct disorder categories and disorder-specific mechanisms. Thus, the results point to the relevance of both transdiagnostic and disorder-specific targets for therapeutic interventions. Show less
Background: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective... Show moreBackground: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity.Method: Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes.Results: Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered.Limitations: 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant.Conclusions: Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of sub-threshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research. Show less
