Background: Worldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for... Show moreBackground: Worldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for major depressive disorder (MDD) but may also be a symptom of the disorder. Despite the large number of women who use OC, it is yet unknown whether women with previous or current diagnosis of depression are more likely to experience more severe depressive and insomnia symptoms during concurrent OC use than women without diagnosis of depression. Aim: This study examined associations between OC use and concurrent symptoms of depression (including atypical depression) and insomnia as well as between OC and prevalences of concurrent dysthymia and MDD. Participants were adult women with and without a history of MDD or dysthymia. We hypothesized that OC use is associated with concurrent increased severity of depressive symptoms and insomnia symptoms, as well as with an increased prevalence of concurrent diagnoses of dysthymia and MDD. We also hypothesized that a history of MDD or dysthymia moderates the relationship between OC use and depressive and insomnia symptoms. Methods: Measurements from premenopausal adult women from the Netherlands Study of Depression and Anxiety (NESDA) were grouped, based on whether participants were using OC or naturally cycling (NC). OC use, timing and regularity of the menstrual cycle were assessed with a structured interview, self-reported symptoms of depression (including atypical depression), insomnia with validated questionnaires, and MDD and dysthymia with structured diagnostic interviews. Results: We included a total of 1301 measurements in women who reported OC use and 1913 measurements in NC women (mean age 35.6, 49.8% and 28.9% of measurements in women with a previous depression or current depression, respectively). Linear mixed models showed that overall, OC use was neither associated with more severe depressive symptoms (including atypical depressive symptoms), nor with higher prevalence of diagnoses of MDD or dysthymia. However, by disentangling the amalgamated overall effect, within-person estimates indicated increased depressive symptoms and depressive disorder prevalence during OC use, whereas between-person estimated indicated lower depressive symptoms and prevalence of depressive disorders. OC use was consistently associated with more severe concurrent insomnia symptoms, in the overall estimates as well as in the within-person and between-person estimates. Presence of current or previous MDD or dysthymia did not mod-erate the associations between OC use and depressive or insomnia symptoms. Discussion: The study findings showed consistent associations between OC use and more severe insomnia symptoms, but no consistent associations between OC and depressive symptoms or diagnoses. Instead, post-hoc analyses showed that associations between OC and depression differed between within-and between person -estimates. This indicates that, although OC shows no associations on the overall level, some individuals might experience OC-associated mood symptoms. Our findings underscore the importance of accounting for individual differences in experiences during OC use. Furthermore, it raises new questions about mechanisms underlying associations between OC, depression and insomnia. Show less
Background: Given the strong relationship between depression and anxiety, there is an urge to investigate their shared and specific long-term course determinants. The current study aimed to... Show moreBackground: Given the strong relationship between depression and anxiety, there is an urge to investigate their shared and specific long-term course determinants. The current study aimed to identify and compare the main determinants of the 9-year trajectories of combined and pure depression and anxiety symptom severity. Methods: Respondents with a 6-month depression and/or anxiety diagnosis (n=1,701) provided baseline data on 152 sociodemographic, clinical and biological variables. Depression and anxiety symptom severity assessed at baseline, 2-, 4-, 6- and 9-year follow-up, were used to identify data-driven course-trajectory subgroups for general psychological distress, pure depression, and pure anxiety severity scores. For each outcome (classprobability), a Superlearner (SL) algorithm identified an optimally weighted (minimum mean squared error) combination of machine-learning prediction algorithms. For each outcome, the top determinants in the SL were identified by determining variable-importance and correlations between each SL-predicted and observed outcome (rho pred) were calculated. Results: Low to high prediction correlations (rho pred: 0.41-0.91, median=0.73) were found. In the SL, important determinants of psychological distress were age, young age of onset, respiratory rate, participation disability, somatic disease, low income, minor depressive disorder and mastery score. For course of pure depression and anxiety symptom severity, similar determinants were found. Specific determinants of pure depression included several types of healthcare-use, and of pure-anxiety course included somatic arousal and psychological distress. Limitations: Limited sample size for machine learning. Conclusions: The determinants of depression- and anxiety-severity course are mostly shared. Domain-specific exceptions are healthcare use for depression and somatic arousal and distress for anxiety-severity course. Show less
Background: Tryptophan catabolites ("TRYCATs") produced by the kynurenine pathway (KP) may play a role in depression pathophysiology. Studies comparing TRYCATs levels in depressed subjects and... Show moreBackground: Tryptophan catabolites ("TRYCATs") produced by the kynurenine pathway (KP) may play a role in depression pathophysiology. Studies comparing TRYCATs levels in depressed subjects and controls provided mixed findings. We examined the association of TRYCATs levels with 1) the presence of Major Depressive Disorder (MDD), 2) depressive symptom profiles and 3) inflammatory markers.Methods: The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1100) or remitted (n = 753) MDD DSM-IV diagnosis and healthy controls (n = 642). Plasma levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KynA), quinolinic acid (QA), C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured. Atypical/energy-related symptom (AES), melancholic symptom (MS) and anxious-distress symptom (ADS) profiles were derived from questionnaires.Results: After adjustment for age, sex, education, smoking status, alcohol consumption and chronic diseases, no significant differences in TRYCATs were found comparing MDD cases versus controls. The MS profile was associated (q < 0.05) with lower KynA (beta = -0.05), while AES was associated with higher KYN (beta = 0.05), QA (beta = 0.06) and TRP (beta = 0.06). Inflammatory markers were associated with higher KYN (CRP beta = 0.12, IL-6 beta = 0.08, TNF beta = 0.10) and QA (CRP beta = 0.21, IL-6 beta = 0.12, TNF beta = 0.18). Significant differences against controls emerged after selecting MDD cases with high (top 30%) CRP (KYN d = 0.20, QA d = 0.33) and high TNF (KYN d = 0.24; QA d = 0.39).Conclusions: TRYCATs levels were related to specific clinical and biological features, such as atypical symptoms or a proinflammatory status. Modulation of KP may potentially benefit a specific subset of depressed patients. Clinical studies should focus on patients with clear evidence of KP dysregulations. Show less
This PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological... Show moreThis PhD project revealed that the female hormonal status – including OC use – and stress vulnerability – as defined by the MR-haplotype – have practical implications in experimental psychological research. Furthermore, incorporation of these variables in models of emotional information processing may be of help in understanding and treating mood disorders in women. Namely, even small biases may affect information processing and may contribute to the resilience or proneness to mood-disorders.Our research was among the first to show that the genetic makeup of healthy women may play a role in the influence of the female hormonal status on emotional information processing. Healthy female MR-haplotype 1/3 carriers may be more prone to distress, and may also be more sensitive to (pharmacological) changes which may counteract or sustain their vulnerability. Consistently, we observed subtle markers of depressogenic side-effects of OC only in MR-haplotype 1/3 carriers. Our findings regarding the MR-haplotypes 2 carriers are generally in line with earlier observations. We observed that MR-haplotype 2 carriers – especially homozygotes – are the less susceptible, more optimistic and more rational individuals, also in ‘unstressed’ conditions. However, stress-related psychopathology is very heterogeneous by nature and proteins from multiple genes are likely to interact in the stress-susceptibility phenotype. Last but not least, we should not ignore that the increased vulnerability of women to mood disorders is the result of a plethora of biological, psychological and sociological factors.OC-users had lower affect variability and reduced sensitivity to interpersonal emotional cues. This may be experienced as either a stabilizing or a blunting effect of OC, perhaps depending on the individual’s appraisal. The lower depression scores of OC-users in our longitudinal study suggests a protective effect of monophasic OC on symptoms of reproductive depression. Future studies should investigate (former) OC-users in larger cohorts including novel users, satisfied users and ‘brand-switchers’ in order to control for the survivor effect. Show less
Struijs, S.Y.; Jong, P.J. de; Jeronimus, B.F.; Does, A.J.W. van der; Riese, H.; Spinhoven, P. 2021
Background: Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core... Show moreBackground: Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms. Methods: In 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years. Results: None of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5 alpha-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms. Conclusions: These results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5 alpha-DHT may be associated with some individual MDD symptoms. Show less
Galbally, M.; Watson, S.J.; Lappas, M.; Kloet, E.R. de; Rossum, E. van; Wyrwoll, C.; ... ; Lewis, A.J. 2021
Placental 11fl-HSD2 has been a focus of research for understanding potential fetal programming associated with maternal emotional disorders. This study examined the pathway from antenatal mental... Show morePlacental 11fl-HSD2 has been a focus of research for understanding potential fetal programming associated with maternal emotional disorders. This study examined the pathway from antenatal mental health via placental 11flHSD2 mRNA to cortisol regulation in the infant offspring. This study reports on data obtained from 236 participants in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS). At term, placental tissue was collected within 30 min of birth from 52 participants meeting current criteria for a depressive disorder, and 184 control participants. Depressive disorders were diagnosed using the SCID-IV. In addition, antidepressant use, depressive and anxiety symptoms were measured in early and late pregnancy. Placental 11fl-HSD2 mRNA expression was measured using qRT-PCR. Infant salivary cortisol samples were taken at 12 months of age. Women on antidepressant medication and with higher trait anxiety had higher placental 11fl-HSD2 expression compared to women not taking medication. Furthermore, the offspring of women taking an antidepressant and who also had a current depressive disorder and high trait anxiety had high cortisol reactivity at 12 months of age and this was mediated through 11fl-HSD2 mRNA expression. In contrast, offspring of women not taking antidepressant medication with depressive disorder and high anxiety there was low cortisol reactivity observed. Our findings suggest that the relationship between maternal antenatal depression and anxiety and infant cortisol reactivity is mediated through placental 11fl-HSD2 mRNA expression. Furthermore, the direction differed for women taking antidepressants, where infant cortisol reactivity was high whereas when compared to those with unmedicated depression and anxiety, where infant cortisol reactivity was low. Show less
Background: Predicting the onset and course of mood and anxiety disorders is of clinical importance but remains difficult. We compared the predictive performances of traditional logistic regression... Show moreBackground: Predicting the onset and course of mood and anxiety disorders is of clinical importance but remains difficult. We compared the predictive performances of traditional logistic regression, basic probabilistic machine learning (ML) methods, and automated ML (Auto-sklearn).Methods: Data were derived from the Netherlands Study of Depression and Anxiety. We compared how well multinomial logistic regression, a naïve Bayes classifier, and Auto-sklearn predicted depression and anxiety diagnoses at a 2-, 4-, 6-, and 9-year follow up, operationalized as binary or categorical variables. Predictor sets included demographic and self-report data, which can be easily collected in clinical practice at two initial time points (baseline and 1-year follow up).Results: At baseline, participants were 42.2 years old, 66.5% were women, and 53.6% had a current mood or anxiety disorder. The three methods were similarly successful in predicting (mental) health status, with correct predictions for up to 79% (95% CI 75?81%). However, Auto-sklearn was superior when assessing a more complex dataset with individual item scores.Conclusions: Automated ML methods added only limited value, compared to traditional data modelling when predicting the onset and course of depression and anxiety. However, they hold potential for automatization and may be better suited for complex datasets. Show less
Meer, P.B. van der; Koekkoek, J.A.F.; Bent, M.J. van den; Dirven, L.; Taphoorn, M.J.B. 2021
Introduction AEDs have been associated with depression, anxiety, and cognitive impairment, all frequent complications of glioma and its subsequent treatment, with considerable morbidity and an... Show moreIntroduction AEDs have been associated with depression, anxiety, and cognitive impairment, all frequent complications of glioma and its subsequent treatment, with considerable morbidity and an adverse effect on health-related quality of life. This study aimed to determine the independent association between AED use and self-reported depression, anxiety, and subjective cognitive impairment in glioma patients. Methods In this multicenter cross-sectional study, depression and anxiety were assessed with the HADS and subjective cognitive impairment was assessed with the MOS-CFS. Univariable logistic regression analyses were performed on all potential confounding predictor variables. Potential confounders were included in the multivariable analyses if p-value < 0.1, to evaluate whether use of AEDs was independently related to depression, anxiety, and/or subjective cognitive impairment. Results A total of 272 patients were included. Prevalence of depression differed significantly between patients not using (10%) and using AEDs (21%, unadjusted Odds Ratio [uOR] = 2.29 [95%CI 1.05-4.97], p = 0.037), but after correction for confounders the statistical significant difference was no longer apparent (adjusted Odds Ratio [aOR] = 1.94 [95%CI 0.83-4.50], p = 0.125). Prevalences of anxiety (aOR = 1.17 [95%CI 0.59-2.29], p = 0.659) and subjective cognitive impairment (aOR = 0.83 [95%CI 0.34-2.04], p = 0.684) did not differ significantly before or after adjustment of confounders between patients not using (19% and 16%, respectively) and using AEDs (26% and 21%, respectively). Conclusions Our results indicate AED use was not independently associated with concurrent depression, anxiety, or subjective cognitive impairment in glioma patients. Alternative factors seem to have a greater contribution to the risk of developing neuropsychiatric symptoms in glioma patients. Show less
Wit, A.E. de; Giltay, E.J.; Boer, M.K. de; Nathan, M.; Wiley, A.; Crawford, S.; Joffe, H. 2021
Objective: Irritability is a highly burdensome complaint, commonly, but not universally, linked with depressive symptoms. While increased variability in estradiol has been associated with... Show moreObjective: Irritability is a highly burdensome complaint, commonly, but not universally, linked with depressive symptoms. While increased variability in estradiol has been associated with depressive symptoms during perimenopause, more insight is needed into reproductive hormone dynamics and other factors that predispose perimenopausal women to irritable mood. Methods: Among 50 mildly depressed perimenopausal women (mean (SD) age 48.4 (3.9) years), severity of irritability symptoms (on Symptom Questionnaire Hostility subscale, range 0-23) was assessed weekly for eight weeks, concurrent with potential predictors. Associations between these were examined using generalized estimating equating models.Results: Most women (82.0%) reported having moderate to severe irritability at least once. However, the severity of irritability was highly variable from week-to-week (between-subject mean coefficient of variation [CV] 72.9% and within-subject mean CV 63.7%). In multivariate analyses, less variable serum estradiol levels (standardized beta within-person CV-0.23 95%CI [-0.32,-0.14], p < 0.001), greater depression severity (0.45 [0.35, 0.56], p < 0.001), younger age (-0.23, [-0.28,-0.09], p < 0.001), and more frequent vasomotor symptoms (0.14 [0.05, 0.23], p = 0.002) were associated with more irritability. Depression severity explained the largest portion of the variance in irritability, but still not more than 20.3%. Neither crude values, weekly change in, or variability of progesterone or FSH levels were associated with irritability.Conclusions: Irritability was highly prevalent among mildly depressed perimenopausal women. In contrast to depressive symptoms, decreased rather than increased variability in estradiol levels was associated with more irritability. This highlights that irritable mood can be disentangled from depressive symptoms in perimenopausal women and might be linked with different estradiol dynamics. Show less
Rationale The impact of prophylactic implantable cardioverter-defibrillator (ICD) implantation on the psychological well-being of patients on dialysis is unknown.Objective We aimed to identify the... Show moreRationale The impact of prophylactic implantable cardioverter-defibrillator (ICD) implantation on the psychological well-being of patients on dialysis is unknown.Objective We aimed to identify the effect of primary ICD implantation on quality of life (QoL), mood and dispositional optimism in patients undergoing dialysis.Methods and results We performed a prespecified subanalysis of the randomized controlled ICD2 trial. In total, 177 patients on chronic dialysis, with an age of 55-81 years, and a left ventricular ejection fraction of >= 35%, were included in the per-protocol analysis. Eighty patients received an ICD for primary prevention, and 91 patients received standard care. The Short Form-36 (SF-36), Geriatric Depression Scale-15 (GDS-15), Revised Life Orientation Test (LOT-R) questionnaires were administered prior to ICD implantation (T0), and at 1-year follow-up (T1) to assess QoL, depression and optimism, respectively. The patients were predominantly male (76.0%), with a median age of 67 years. Hemodialysis was the predominant mode of dialysis (70.2%). The GDS-15 score difference (T1 - T0) was 0.5 (2.1) in the ICD group compared with 0.3 (2.2) in the control group (mean difference - 0.3; 95% CI - 1.1 to 0.6; P = 0.58). The LOT-R score difference was - 0.2 (4.1) in the ICD group compared with - 1.5 (4.0) in the control group (mean difference - 1.1 (0.8); 95% CI - 2.6 to 0.4; P = 0.17). The mean difference scores of all subscales of the SF-36 were not significantly different between randomization groups.Conclusions In our population of patients on dialysis, ICD implantation did not affect QoL, mood or dispositional optimism significantly during 1-year follow-up. Show less
Background: Brothers and sisters growing up together share a large proportion of their genes and rearing environment. However, some siblings thrive whereas others struggle. This study investigated... Show moreBackground: Brothers and sisters growing up together share a large proportion of their genes and rearing environment. However, some siblings thrive whereas others struggle. This study investigated family-wide childhood bonding experiences with mother and father, in addition to individual-specific recollections, in relation to current depressive and anxiety symptom levels in adulthood. We examined whether extraversion and internal locus of control (iLoC) had a protective effect in this.Methods: The sample consisted of 256 families with at least one lifetime depressed or anxious person (N = 596; ages 20-78). Multilevel modeling with cross-level interactions was used.Results: Adult siblings showed moderate to high agreement in their childhood parental bonding (PB) recollections. Over-and-above the association between individual-specific recollections of PB and adult internalizing symptoms, family-wide poor PB was additionally linked to elevated symptom levels. Within families characterized by poor maternal bonding persons with an iLoC were relatively less anxious (but not less depressed), whereas extraversion was not protective in this context.Limitation: Although evidence exists that poor childhood PB has an impact on (adult) psychopathology, causality cannot be determined and possible recall bias of PB should be noted. Moreover, next to their moderating effects, extraversion and LoC may also act as mediators.Conclusions: Our findings extend prior work by demonstrating the importance of siblings' childhood PB experiences next to a person's own recollections when investigating adult internalizing symptoms, while also elucidating individual differences within families. Show less
Objective: To determine the physical and mental health of very old people (aged 80+) with anaemia.Methods: Individual level meta-analysis from five cohorts of octogenarians (n = 2,392): LiLACS NZ... Show moreObjective: To determine the physical and mental health of very old people (aged 80+) with anaemia.Methods: Individual level meta-analysis from five cohorts of octogenarians (n = 2,392): LiLACS NZ Maori, LiLACS NZ non-Maori, Leiden 85-plus Study, Newcastle 85+ Study, and TOOTH. Mixed models of change in functional ability, cognitive function, depressive symptoms, and self-rated health over time were separately fitted for each cohort. We combined individual cohort estimates of differences according to the presence of anaemia at baseline, adjusting for age at entry, sex, and time elapsed. Combined estimates are presented as differences in standard deviation units (i.e. standardised mean differences-SMDs).Results: The combined prevalence of anaemia was 30.2%. Throughout follow-up, participants with anaemia, on average, had: worse functional ability (SMD -0.42 of a standard deviation across cohorts; CI -0.59, -0.25); worse cognitive scores (SMD -0.27; CI -0.39,-0.15); worse depression scores (SMD -0.20; CI -0.31, -0.08); and lower ratings of their own health (SMD -0.36; CI -0.47,-0.25). Differential rates of change observed were: larger declines in functional ability for those with anaemia (SMD -0.12 over five years; CI -0.21, -0.03) and smaller mean difference in depression scores over time between those with and without anaemia (SMD 0.18 over five years; CI 0.05, 0.30).Conclusion: Anaemia in the very old is a common condition associated with worse functional ability, cognitive function, depressive symptoms, and self-rated health, and a more rapid decline in functional ability over time. The question remains as to whether anaemia itself contributes to worse outcomes or is simply a marker of chronic diseases and nutrient deficiencies. Show less
Najafabadi, A.H.Z.; Meer, P.B. van der; Boele, F.W.; Taphoorn, M.J.B.; Klein, M.; Peerdeman, S.M.; ... ; Dutch Meningioma Consortium 2021
BACKGROUND: Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention.OBJECTIVE: To assess the long... Show moreBACKGROUND: Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention.OBJECTIVE: To assess the long-term (>= 5 yr) disease burden of meningioma patients.METHODS: In this multicenter cross-sectional study, patients >= 5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported.RESULTS: At amedian of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (-2.11, 95% CI: -3.52 to -0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls.CONCLUSION: In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning. Show less
Background Comorbidity between depressive and anxiety disorders is common. A hypothesis of the network perspective on psychopathology is that comorbidity arises due to the interplay of symptoms... Show moreBackground Comorbidity between depressive and anxiety disorders is common. A hypothesis of the network perspective on psychopathology is that comorbidity arises due to the interplay of symptoms shared by both disorders, with overlapping symptoms acting as so-calledbridges, funneling symptom activation between symptom clusters of each disorder. This study investigated this hypothesis by testing whether (i) twooverlappingmental states "worrying" and "feeling irritated" functioned as bridges in dynamic mental state networks of individuals with both depression and anxiety as compared to individuals with either disorder alone, and (ii) overlapping or non-overlapping mental states functioned as stronger bridges. Methods Data come from the Netherlands Study of Depression and Anxiety (NESDA). A total of 143 participants met criteria for comorbid depression and anxiety (65%), 40 participants for depression-only (18.2%), and 37 for anxiety-only (16.8%) during any NESDA wave. Participants completed momentary assessments of symptoms (i.e., mental states) of depression and anxiety, five times a day, for 2 weeks (14,185 assessments). First, dynamics between mental states were modeled with a multilevel vector autoregressive model, using Bayesian estimation. Summed average lagged indirect effects through the hypothesized bridge mental states were compared between groups. Second, we evaluated the role of all mental states as potential bridge mental states. Results While the summed indirect effect for the bridge mental state "worrying" was larger in the comorbid group compared to the single disorder groups, differences between groups were not statistically significant. The difference between groups became more pronounced when only examining individuals with recent diagnoses (< 6 months). However, the credible intervals of the difference scores remained wide. In the second analysis, a non-overlapping item ("feeling down") acted as the strongest bridge mental state in both the comorbid and anxiety-only groups. Conclusions This study empirically examined a prominent network-approach hypothesis for the first time using longitudinal data. No support was found for overlapping mental states "worrying" and "feeling irritable" functioning as bridge mental states in individuals vulnerable for comorbid depression and anxiety. Potentially, bridge mental state activity can only be observed during acute symptomatology. If so, these may present as interesting targets in treatment, but not prevention. This requires further investigation. Show less
Background: Major depressive disorder (MDD) is linked to higher cardio-metabolic comorbidity that may in part be due to the low-grade inflammation and poorer metabolic health observed in MDD.... Show moreBackground: Major depressive disorder (MDD) is linked to higher cardio-metabolic comorbidity that may in part be due to the low-grade inflammation and poorer metabolic health observed in MDD. Heterogeneity of MDD is however large, and immune-inflammatory and metabolic dysregulation is present in only part of the MDD cases. We examined the associations of four depression dimensional profilers (atypical energy-related symptom dimension, melancholic symptom dimension, childhood trauma severity, and anxious distress symptom dimension) with immuno-metabolic outcomes, both cross-sectionally and longitudinally.Methods: Three waves covering a 6-year follow-up (>7000 observations) of the Netherlands Study of Depression and Anxiety (NESDA) were used. Depression profilers were based on the Inventory of Depressive Symptomatology, the Beck Anxiety Inventory, and the Childhood Trauma index. An inflammatory index (based on IL-6 and CRP), a metabolic syndrome index (based on the five metabolic syndrome components), and a combination of these two indices were constructed. Mixed models were used for cross-sectional and longitudinal models, controlling for covariates.Results: Of the four depression profilers, only the atypical, energy-related symptom dimension showed robust associations with higher scores on the inflammatory, metabolic syndrome and combined inflammatory-metabolic indexes cross-sectionally, as well as at follow-up. The melancholic symptom dimension was associated with lower scores on the metabolic syndrome index both cross-sectionally and longitudinally.Conclusion: The atypical energy-related symptom dimension was linked to poorer immune-inflammatory and metabolic health, while the melancholic symptom dimension was linked to relatively better metabolic health. Persons with high atypical energy-related symptom burden, representing an immuno-metabolic depression, may be the most important group to target in prevention programs for cardiometabolic disease, and may benefit most from treatments targeting immuno-metabolic pathways. Show less
Objective: Depression and anxiety often coexist in patients with end -stage -kidney disease. Recently, studies showed that a composite ?general distress score ? which combines depression and... Show moreObjective: Depression and anxiety often coexist in patients with end -stage -kidney disease. Recently, studies showed that a composite ?general distress score ? which combines depression and anxiety symptoms provides a good fit in dialysis and oncology patients. We aim to investigate if the three most frequently used self -report questionnaires to measure depression and anxiety in dialysis patients are sufficiently unidimensional to warrant the use of such a general distress score in two cohorts of dialysis patients. Methods: This study includes two prospective observational cohorts of dialysis patients (total n = 749) which measured depression and anxiety using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Hospital Anxiety and Depression Scale (HADS). Confirmatory factor analyses was used to investigate both a strictly unidimensional model and a multidimensional bifactor model that includes a general distress, depression and anxiety factor. The comparative fit index (CFI) and The Root Mean Square Error of Approximation (RMSEA) were used as model fit indices. Results: Factor analysis did not show a good fit for a strictly unidimensional general distress factor for both the BDI/BAI and HADS (CFI 0.690 and 0.699, RMSEA 0.079 and 0.125 respectively). The multidimensional model performed better with a moderate fit for the BDI/BAI and HADS (CFI 0.873 and 0.839, RMSEA 0.052 and 0.102). Conclusions: This data shows that the BDI/BAI and HADS are insufficiently unidimensional to warrant the use of a general distress score in dialysis patients without also investigating anxiety and depression separately. Future research is needed whether the use of a general distress score might be beneficial to identify patients in need of additional (psychological) support. Show less
Galbally, M.; Watson, S.J.; IJzendoorn, M. van; Saffery, R.; Ryan, J.; Kloet, E.R. de; ... ; Lewis, A.J. 2020
Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early... Show moreUnderstanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes. Show less
Ellis, N.; Tee, A.; McAllister, B.; Massey, T.; McLauchlan, D.; Stone, T.; ... ; Holmans, P. 2020
BACKGROUND: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized examination of motor... Show moreBACKGROUND: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized examination of motor control and often presents with cognitive decline and psychiatric symptoms. Recent studies have detected genetic loci modifying the age at onset of motor symptoms in HD, but genetic factors influencing cognitive and psychiatric presentations are unknown.METHODS: We tested the hypothesis that psychiatric and cognitive symptoms in HD are influenced by the same common genetic variation as in the general population by 1) constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders and of intelligence and 2) testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n = 5160) of patients with HD.RESULTS: Polygenic risk score for major depression was associated specifically with increased risk of depression in HD, as was schizophrenia risk score with psychosis and irritability. Cognitive impairment and apathy were associated with reduced polygenic risk score for intelligence.CONCLUSIONS: Polygenic risk scores for psychiatric disorders, particularly depression and schizophrenia, are associated with increased risk of the corresponding psychiatric symptoms in HD, suggesting a common genetic liability. However, the genetic liability to cognitive impairment and apathy appears to be distinct from other psychiatric symptoms in HD. No associations were observed between HD symptoms and risk scores for other neurodegenerative disorders. These data provide a rationale for treatments effective in depression and schizophrenia to be used to treat depression and psychotic symptoms in HD. Show less
Munter, L. de; Polinder, S.; Haagsma, J.A.; Kruithof, N.; Ree, C.L.P. van de; Steyerberg, E.W.; Jongh, M. de 2020
Objective: To describe the prevalence and prognostic factors of symptoms of anxiety and depression and posttraumatic stress symptoms (PTSS) after injury in the clinical trauma population.Design:... Show moreObjective: To describe the prevalence and prognostic factors of symptoms of anxiety and depression and posttraumatic stress symptoms (PTSS) after injury in the clinical trauma population.Design: Multicenter, prospective, observational cohort study.Setting: Ten hospitals in Noord-Brabant, The Netherlands.Participants: Four thousand two hundred thirty-nine adult patients (N=4239) admitted due to injury between August 2015 and December 2016.Interventions: Patients were asked to complete a questionnaire at 1 week and at 1, 3, 6, and 12 months after injury.Main Outcome Measures: The Hospital Anxiety and Depression Scale was used to assess anxiety and depressive symptoms and the Impact of Event Scale was used to assess PTSS.Results: The prevalence of symptoms of anxiety and depression decreased from 10% and 12%, respectively, at 1 week after injury to 7% and 7% at 12 months after injury. Acute traumatic stress symptoms were present in 13% at 1 week and PTSS was prevalent in 10% of the participants at 12 months after injury. Strong prognostic factors for poor psychological outcome in multivariable logistic mixed models were preinjury frailty, psychological complaints and nonworking status preinjury, female sex, low educational level, and accident category (ie, traffic accident, work-related accident, or accidents at home compared to sport injuries).Conclusions: Psychological distress is a common health problem during the first year after injury. Important prognostic factors for psychological distress include psychological complaints before injury and frailty. Early recognition of psychological problems after injury could facilitate discussion between caregivers and patients and improve recovery. (C) 2019 by the American Congress of Rehabilitation Medicine Show less
