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
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
Wiebenga, J.X.M.; Heering, H.D.; Eikelenboom, M.; Hemert, A.M. van; Oppen, P. van; Penninx, B.W.J.H. 2022
Background: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear.... Show moreBackground: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic-pituitaryadrenal axis (HPA-axis), immune inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far.Methods: Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-alpha), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA).Results: High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose-response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-.Conclusion: Although stress system markers could not differentiate between SI+SA-and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality. Show less
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
Background: Temporality of the association of low omega-3 polyunsaturated fatty acid (n-3 PUFA) plasma levels with depression remains questionable. To determine the underlying nature of these... Show moreBackground: Temporality of the association of low omega-3 polyunsaturated fatty acid (n-3 PUFA) plasma levels with depression remains questionable. To determine the underlying nature of these associations, this study examined the bidirectional longitudinal associations of n-3 PUFA plasma levels with (presence, onset and course of) depressive disorders and symptoms.Methods: Baseline (n = 2912, 28.6% with current depressive disorder) and 6-year follow-up data (n = 1966, 13.0% with current depressive disorder) of the Netherlands Study of Depression and Anxiety (NESDA) were used. Depression diagnoses and symptoms were based on psychiatric interviews and self-report questionnaires. N-3 PUFA levels (ratio of total fatty acids (mmol%)), were assessed using nuclear magnetic resonance.Results: Using two waves of data, n-3 PUFA levels were lower among depressed persons, as compared to healthy controls (Beta = - 0.047, SE = 0.011, p < .001). Nevertheless, baseline n-3 PUFA levels were not consistently associated with subsequent change in depressive symptoms, onset or remission of depressive disorders over 6 years. Furthermore, the difference in n-3 PUFA levels detected at baseline between depressed and non-depressed participants tended to dissipate over 6 years (depression-by-time estimate: p = .011). Finally, subjects depressed both at baseline and at 6-year follow up had consistently lower n-3 PUFA levels over the entire follow-up as compared to those who had never been depressed. Change in depressive disorders across waves was not consistently accompanied by change in n-3 PUFA levels over time.Limitations: No data on intermediate time points and EPA levels were available.Conclusions: Despite significant cross-sectional associations between n-3 PUFA plasma levels and depressive disorders and severity, this 6-year longitudinal study could not confirm an uni- or bidirectional association over time. The association between depression and n-3 PUFA plasma levels is unlikely to be causal. Show less
Struijs, S.Y.; Lamers, F.; Verdam, M.G.E.; Ballegooijen, W. van; Spinhoven, P.; Does, W. van der; Penninx, B.W.J.H. 2020
Background: Signs and symptoms of psychopathology can be chronic but are generally regarded as less stable over time than markers of cognitive vulnerability and personality. Some findings suggest... Show moreBackground: Signs and symptoms of psychopathology can be chronic but are generally regarded as less stable over time than markers of cognitive vulnerability and personality. Some findings suggest that these differences in temporal stability are modest in size but a rigorous examination across concepts is lacking. The current study investigated the temporal stability of affective symptoms, cognitive vulnerability markers and personality traits at various assessments over nine years.Methods: Participants of the Netherlands Study of Depression and Anxiety were assessed at baseline and reassessed after 2, 4, 6 and 9 years. They were grouped on the basis of waves of depression and anxiety CIDI-diagnoses into stable healthy (n = 768), stable patients (n = 352) and unstable patients (n = 821). We determined temporal stability by calculating intraclass correlation coefficients (ICC) and consistency indices of latent state-trait analyses (LST).Results: Temporal stability was moderate to high for symptoms (range ICC's 0.54-0.73; range consistency 0.64-0.74), cognitive vulnerability (range ICC's 0.53-0.76; range consistency 0.60-0.74) and personality (range ICC's 0.57-0.80; range consistency.60 -0.75). Consistency indices for all measures were on average a bit lower in the unstable group (ICC = 0.54) compared to the stable groups (ICC = 0.61). Overall stability was similarly high after 2, 4, 6 and 9 years.Conclusion: The 9-year stability over time of symptoms of affective disorders and that of indices of cognitive vulnerability and personality are remarkably similar and relatively high. Show less
Alshehri, T.; Boone, S.; Mutsert, R. de; Penninx, B.; Rosendaal, F.; Cessie, S. le; ... ; Mook-Kanamori, D. 2019
Background: The role of chronotype, the individual timing of sleep/activity, has been studied in relation todepressive and anxiety disorders. A cross-sectional association between a depressive... Show moreBackground: The role of chronotype, the individual timing of sleep/activity, has been studied in relation todepressive and anxiety disorders. A cross-sectional association between a depressive episode and evening-typehas been identified. However, until now the predicting capacity of chronotype concerning persistence of psy-chiatric disorders remains unclear. Our aim is to examine whether a later chronotype in patients with a de-pressive and/or anxiety disorder can serve as a predictor of a persistent course.Methods: A subsample of patients with a depressive and/or anxiety disorder diagnosis and chronotype data ofthe longitudinal Netherlands Study of Depression and Anxiety (NESDA) was used. Diagnosis of depressive andanxiety disorders (1-month DSM-IV based diagnosis) were determined at baseline (n = 505). From this grouppersistence was determined at 2-year (FU2) (persistent course: n = 248, non-persistent course: n = 208) and 4-year follow-up (FU4) (persistent course: n = 151, non-persistent course: n = 264). Chronotype was assessed atbaseline with the Munich Chronotype Questionnaire.Results: A later chronotype did not predict a persistent course of depressive and/or anxiety disorder at FU2 (OR(95% CI) = 0.99 (0.83–1.19), P = 0.92) or at FU4 (OR (95% CI) = 0.94 (0.77–1.15), P = 0.57).Limitations: Persistence was defined as having a diagnosis of depressive and/or anxiety disorder at the two-yearand four-year follow-up, patients may have remitted and relapsed between assessments.Conclusion: Chronotype, measured as actual sleep timing, of patients with a depressive or anxiety disorder didnot predict a persistent course which suggests it might be unsuitable as predictive tool in clinical settings. Show less
Struijs, S.Y.; Lamers, F.; Spinhoven, P.; Does, W. van der; Penninx, B.W.J.H. 2018
This thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic),... Show moreThis thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic), and a control group of non-carriers that had an a-priori 50% risk for HD. The study started in may 2004 and a second measurement was performed 2 years later. The aim of this study was to study the presence and course of both formal psychiatric disorders and neuropsychiatric symptoms, and to find correlates and predictors associated with the psychiatric phenomena. This cohort study confirms that neuropsychiatric symptoms frequently occur in patients with HD. We expected a diminished insight in patients with a neuropsychiatric symptoms like irritability, but most patients were aware of their irritability. A strong relationship was found between the presence of psychopathology, cognitive functioning and global daily functioning. Irritability may be an early sign of the disease, but only apathy was closely related to the progression of HD indicating a relationship with the progressive neurodegenerative nature of the disease. However, we also found associations with apathy and irritability, and the use of psychotropic medications. Show less