BackgroundDepression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network... Show moreBackgroundDepression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models.MethodsWe used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later.ResultsThe network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave.ConclusionsThe somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles. Show less
Objectives: The present study examined associations between immunometabolic characteristics (IMCs) and depressive symptom profiles (DSPs) in probands with lifetime diagnoses of depression and/or... Show moreObjectives: The present study examined associations between immunometabolic characteristics (IMCs) and depressive symptom profiles (DSPs) in probands with lifetime diagnoses of depression and/or anxiety disorders and their siblings. Methods: Data were from the Netherlands Study of Depression and Anxiety, comprising 256 probands with lifetime diagnoses of depression and/or anxiety and their 380 siblings. Measured IMCs included blood pressure, waist circumference, and levels of glucose, triglycerides, HDL cholesterol, CRP, TNF-alpha and IL-6. DSPs included mood, cognitive, somatic and atypical-like profiles. We cross-sectionally examined whether DSPs were associated with IMCs within probands and within siblings, and whether DSPs were associated with IMCs between probands and siblings. Results: Within probands and within siblings, higher BMI and waist circumference were associated with higher somatic and atypical-like profiles. Other IMCs (IL-6, glucose and HDL cholesterol) were significantly related to DSPs either within probands or within siblings. DSPs and IMCs were not associated between probands and siblings. Conclusions: The results suggest that there is a familial component for each trait, but no common familial factors for the association between DSPs and IMCs. Alternative mechanisms, such as direct causal effects or non-shared environmental risk factors, may better fit these results. Show less
In this thesis the heterogeneity of late-life depression is being examined. The first part of the thesis focuses on data-driven analyses as a way of identifying subtypes of late-life depression.... Show moreIn this thesis the heterogeneity of late-life depression is being examined. The first part of the thesis focuses on data-driven analyses as a way of identifying subtypes of late-life depression. Through latent class analysis, we have identified three subtypes: a severe melancholic subtype, an atypical subtype, and a moderately severe subtype. These subtypes had different sociodemographic and clinical characteristics, but no specific biological disturbances could be addressed to the different subtypes. This is probably because of the tangle of (patho)physiological processes in aging itself, muddling the results. The stability of these subtypes over a two-year follow-up was however high, strengthening the clinical relevance of found subtypes.The second part of this thesis examines psychomotor disturbances in melancholic depression as a possible predicting symptom of response in electroconvulsive therapy. We have found that psychomotor disturbances predict to a certain amount the response to electroconvulsive therapy, but this effect was overruled by the predictive value of psychotic symptoms in depression. Finally, we have examined the speed of response of different depressive symptoms on electroconvulsive therapy in older depressed persons, and have found that all ten symptoms show response in two weeks, underlining the safety and efficacy of electroconvulsive therapy in older persons. Show less
Kumsta, R.; Kliegel, D.; Linden, M.; DeRijk, R.; Kloet, E.R. de 2019
Recently, the "conceptual endophenotype" approach has been proposed as a means to identify subgroups of patients affected by stress-related psychiatric disorders. Conceptual endophenotypes consist... Show moreRecently, the "conceptual endophenotype" approach has been proposed as a means to identify subgroups of patients affected by stress-related psychiatric disorders. Conceptual endophenotypes consist of patterns of psychological, biological, and symptomatic elements. We studied a sample of patients seeking help for psychosomatic and stress-related disorders (total N = 469), who were evaluated with a diagnostic instrument that integrates psychological and biological data to derive 13 endophenotypes, or Neuropattern. The goal of this study was to explore associations between common variations of the mineralocorticoid receptor gene (MR, NR3C2), and the 13 conceptual endophenotypes of Neuropattem, as well as with the respective biological and symptom measures. A common haplotype of the MR, comprised of two functional single nucleotide polymorphism (rs2070951 G/C & rs5522 A/G), was associated with the conceptual endophenotype CRF-hypoactivity, characterized by low cortisol levels at awakening and a symptom constellation often observed in atypical depression. Homozygous carriers of the G-A haplotype (haplotype 1), previously associated with reduced dispositional optimism, increased levels of rumination and higher risk for depression, more frequently endorsed this Neuropattern. In addition to the overall association between MR variation and CRF hypoactivity, we observed in the whole sample significant associations between MR haplotypes and cortisol awakening response patterns, as well as with symptoms that characterize the CRF hypoactivity endophenotype. If replicated, MR haplotype 1 might serve as a vulnerability marker for a disorder class characterized in biological terms by reduced cortisol levels, and in terms of symptom constellation by features often observed in atypical depression. Show less
