Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous... Show moreDepression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an “atypical/energy-related” symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An ‘AES profile’ score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (β = 0.13, p = 1.35*10-12), isoleucine (β = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10-9) and saturated fatty acid levels (β = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (β = −0.07, p = 1.14*10-4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature—commonly linked to cardiometabolic disorders—associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression’s detrimental impact on health. Show less
Bralten, J.; Mota, N.R.; Klemann, C.J.H.M.; Witte, W. de; Laing, E.; Collier, D.A.; ... ; Poelmans, G. 2021
Levels of sociability are continuously distributed in the general population, and decreased sociability represents an early manifestation of several brain disorders. Here, we investigated the... Show moreLevels of sociability are continuously distributed in the general population, and decreased sociability represents an early manifestation of several brain disorders. Here, we investigated the genetic underpinnings of sociability in the population. We performed a genome-wide association study (GWAS) of a sociability score based on four social functioning-related self-report questions from 342,461 adults in the UK Biobank. Subsequently we performed gene-wide and functional follow-up analyses. Robustness analyses were performed in the form of GWAS split-half validation analyses, as well as analyses excluding neuropsychiatric cases. Using genetic correlation analyses as well as polygenic risk score analyses we investigated genetic links of our sociability score to brain disorders and social behavior outcomes. Individuals with autism spectrum disorders, bipolar disorder, depression, and schizophrenia had a lower sociability score. The score was significantly heritable (SNP h(2) of 6%). We identified 18 independent loci and 56 gene-wide significant genes, including genes like ARNTL, DRD2, and ELAVL2. Many associated variants are thought to have deleterious effects on gene products and our results were robust. The sociability score showed negative genetic correlations with autism spectrum, disorders, depression, schizophrenia, and two sociability-related traits-loneliness and social anxiety-but not with bipolar disorder or Alzheimer's disease. Polygenic risk scores of our sociability GWAS were associated with social behavior outcomes within individuals with bipolar disorder and with major depressive disorder. Variation in population sociability scores has a genetic component, which is relevant to several psychiatric disorders. Our findings provide clues towards biological pathways underlying sociability. 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
Marees, A.T.; Hammerschlag, A.R.; Bastarache, L.; Kluiver, H. de; Vorspan, F.; Brink, W. van den; ... ; Derks, E.M. 2018
