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Depression: HELP
Articles by Albert Hofman
Based on 56 articles published since 2010
(Why 56 articles?)
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Between 2010 and 2020, A. Hofman wrote the following 56 articles about Depression.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Vitamin D serum levels are cross-sectionally but not prospectively associated with late-life depression. 2017

Jovanova, O / Aarts, N / Noordam, R / Zillikens, M C / Hofman, A / Tiemeier, H. ·Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands. · Department of Psychiatry, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands. ·Acta Psychiatr Scand · Pubmed #28120398.

ABSTRACT: OBJECTIVE: The evidence for a prospective association of vitamin D deficiency with the occurrence of late-life depression is limited. We aimed to study the long-term association between vitamin D serum levels and depression in a large population-based study of older adults. METHOD: We included 3251 participants from the Rotterdam Study, aged 55 and older with 32 400 person-years follow-up for depression. Baseline 25-hydroxyvitamin D (25(OH)D) serum levels were analyzed continuously and categorically. Repeated depressive symptoms' questionnaire assessments were used to assess the change of depressive symptoms. Semistructured psychiatric interviews, and GP records were used to assess incident major depressive disorder according to DSM-IV criteria. RESULTS: Low serum vitamin D levels were cross-sectionally associated with more depressive symptoms. However, low 25(OH)D serum levels were not prospectively associated with change of depressive symptoms (unstandardized beta = 0.02, 95% CI = -0.23; 0.26) or incident MDD (hazard ratio = 0.95, 95% CI = 0.86; 1.05). CONCLUSION: We observed a cross-sectional but no prospective association between serum vitamin D levels and depression. A cross-sectional association in the absence of the longitudinal association can mostly be attributed to reverse causality or residual confounding. Probably, vitamin D deficiency is not an independent risk factor for depression but co-occurs with late-life depression.

2 Article The Longitudinal and Cross-Sectional Associations of Grief and Complicated Grief With Sleep Quality in Older Adults. 2019

Milic, Jelena / Saavedra Perez, Heidi / Zuurbier, Lisette A / Boelen, Paul A / Rietjens, Judith A / Hofman, Albert / Tiemeier, Henning. ·a Department of Epidemiology , Erasmus Medical Center , Rotterdam , The Netherlands. · b Department of Clinical and Health Psychology , Utrecht University , Utrecht , The Netherlands. · c Department of Public Health , Erasmus Medical Center , Rotterdam , The Netherlands. · d Department of Psychiatry , Erasmus Medical Center , Rotterdam , The Netherlands. · e Department of Child and Adolescent Psychiatry , Erasmus Medical Center , Rotterdam , The Netherlands. ·Behav Sleep Med · Pubmed #28107032.

ABSTRACT: OBJECTIVE/BACKGROUND: About 15% of grievers experience complicated grief. We determined cross-sectional and longitudinal relations of grief and complicated grief with sleep duration and quality in the general population of elderly adults. PARTICIPANTS: We included 5,421 men and women from the prospective population-based Rotterdam Study. METHODS: The Inventory of Complicated Grief was used to define grief and complicated grief. We assessed sleep with the Pittsburgh Sleep Quality Index. RESULTS: After 6 years, 3,511 (80% of survivors) underwent the follow-up interview. Complicated grief was cross-sectionally associated with shorter sleep duration and lower sleep quality. These associations were explained by the presence of depressive symptoms. The prospective analyses showed that sleep duration and sleep quality did not decline further during follow-up of persons who experienced grief or complicated grief. CONCLUSION: In community-dwelling, middle-aged and older adults, persons with normal and complicated grief had both a shorter sleep duration and a lower sleep quality, mainly explained by depressive symptoms. However, prospective analyses showed that sleep quality and sleep duration do not decline further in persons with normal grief and complicated grief.

3 Article Depressive symptoms prior to and after incident cardiovascular disease and long-term survival. A population-based study of older persons. 2018

Freak-Poli, Rosanne / Ikram, M Arfan / Franco, Oscar H / Hofman, Albert / Tiemeier, Henning. ·Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Epidemiology, Harvard University, Cambridge, MA, USA. · Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands. ·Depress Anxiety · Pubmed #29172249.

ABSTRACT: BACKGROUND: Depression after a cardiovascular disease event (post-CVD) is associated with increased mortality. However, little is known about how pre-existing depression affects survival after CVD incidence. AIM: To evaluate whether depressive symptoms preceding first incident CVD (pre-CVD) affects survival. METHODS: From the Rotterdam Study, 6,932 persons aged 55+ and free of dementia and CVD completed the Center for Epidemiological Studies Depression (CES-D) scale every 4 to 5 years from 1993. CES-D subdomains were positive affect, negative affect, somatic symptoms, and interpersonal affect. Persons were followed for mortality and CVD. RESULTS: During 15-year follow-up, 22% of participants suffered their first incident CVD. Pre-CVD depressive symptoms was not associated with mortality after adjustment for smoking status and physical function (HR per 10-point score: 1.05, 95%CI: 0.99-1.10). After first incident CVD, depressive symptoms increased. Higher post-CVD depressive symptoms was associated with increased mortality (HR: 1.13, 95%CI: 1.06, 1.22). The relation between post-CVD depressive symptoms and mortality was no longer statistically significant after adjustment for pre-CVD depressive symptoms. Pre-CVD and post-CVD measures of somatic symptoms and positive affect were associated with mortality. CONCLUSIONS: During 15 years follow-up in community-dwelling older adults, the relation between higher depressive symptoms measured before first incident CVD and mortality was not independent of health status. Whereas, higher depressive symptoms measured after CVD was associated with increased mortality, was not independent of pre-CVD depressive symptoms. Given the associations observed between positive affect and mortality, positive affect may be the reason we observed a relation between depressive symptoms and mortality.

4 Article 12 Year Trajectories of Depressive Symptoms in Community-Dwelling Older Adults and the Subsequent Risk of Death Over 13 Years. 2018

Saeed Mirza, Saira / Ikram, M Arfan / Freak-Poli, Rosanne / Hofman, Albert / Rizopoulos, Dimitris / Tiemeier, Henning. ·Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Medicine, Division of Neurology, University of Toronto, Toronto, Canada. · Department of Neurology, Sunnybrook Health Sciences Center, Toronto, Canada. · Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Department of Biostatistics, Erasmus Medical Center, The Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus Medical Center, The Netherlands. · Department of Psychiatry, Erasmus Medical Center, The Netherlands. ·J Gerontol A Biol Sci Med Sci · Pubmed #29099907.

ABSTRACT: Background: Populations of depressed persons are typically comprised of individuals with different courses of depression and thus might carry different risks of death. This study aimed to identify different trajectories of depressive symptoms in community-dwelling older adults and study the risk of death across these trajectories. Methods: In the population-based Rotterdam Study, depressive symptoms (Center for Epidemiological Studies-Depression scale) at three examination rounds (1993-2004) from 3,325 dementia-free participants (mean age 64.6 ± 6.1 years) were used to identify depression trajectories by latent-class trajectory modeling. Mortality rates by trajectory were calculated over a subsequent 13 year period (2002-2015), that is using 23 years of follow-up data. Results: Five trajectories of depressive symptoms characterized by low (73.4%), decreasing (11.1%), remitting (5.1%), increasing (7.7%), and high (2.7%) depressive symptoms were identified. Compared with persons in the low symptoms trajectory, persons with a trajectory of increasing depressive symptoms (hazard ratio [HR]: 1.21 [95% CI = 1.02, 1.44]) had a higher risk of death, but not those with remitting depressive symptoms, HR: 1.06 (95% CI = 0.85, 1.32). The estimates for the high symptoms trajectory were also suggestive of a higher risk of mortality, HR: 1.20 (95% CI = 0.91, 1.58). Conclusions: Repeated measures of depression can help predict long-term health outcomes in persons with depressive symptoms. Participants with increasing symptoms over time had a higher risk of death than those with low or no depressive symptoms. Transient high depressive symptoms that remitted were not associated with a higher risk compared with those with no symptoms. Our results open avenues for etiological and prognostic research to focus upon risk factors' key to a particular trajectory.

5 Article Maternal depressive symptoms during pregnancy are associated with amygdala hyperresponsivity in children. 2018

van der Knaap, Noortje J F / Klumpers, Floris / El Marroun, Hanan / Mous, Sabine / Schubert, Dirk / Jaddoe, Vincent / Hofman, Albert / Homberg, Judith R / Tiemeier, Henning / White, Tonya / Fernández, Guillén. ·Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. n.vanderknaap@fcdonders.ru.nl. · Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. · Experimental Psychopathology and Treatment Section, Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, 3000 CB, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Centre, 3000 CB, Rotterdam, The Netherlands. · Department of Paediatrics, Erasmus Medical Centre, 3000 CB, Rotterdam, The Netherlands. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Department of Radiology, Erasmus Medical Centre, 3000 CB, Rotterdam, The Netherlands. ·Eur Child Adolesc Psychiatry · Pubmed #28667426.

ABSTRACT: Depression during pregnancy is highly prevalent and has a multitude of potential risks of the offspring. Among confirmed consequences is a higher risk of psychopathology. However, it is unknown how maternal depression may impact the child's brain to mediate this vulnerability. Here we studied amygdala functioning, using task-based functional MRI, in children aged 6-9 years as a function of prenatal maternal depressive symptoms selected from a prospective population-based sample (The Generation R Study). We show that children exposed to clinically relevant maternal depressive symptoms during pregnancy (N = 19) have increased amygdala responses to negative emotional faces compared to control children (N = 20) [F(1,36) 7.02, p = 0.022]. Strikingly, postnatal maternal depressive symptoms, obtained at 3 years after birth, did not explain this relation. Our findings are in line with a model in which prenatal depressive symptoms of the mother are associated with amygdala hyperresponsivity in her offspring, which may represent a risk factor for later-life psychopathology.

6 Article A rare missense variant in RCL1 segregates with depression in extended families. 2018

Amin, N / de Vrij, F M S / Baghdadi, M / Brouwer, R W W / van Rooij, J G J / Jovanova, O / Uitterlinden, A G / Hofman, A / Janssen, H L A / Darwish Murad, S / Kraaij, R / Stedehouder, J / van den Hout, M C G N / Kros, J M / van IJcken, W F J / Tiemeier, H / Kushner, S A / van Duijn, C M. ·Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Department of Psychiatry, Erasmus MC, Rotterdam, The Netherlands. · Department of Cell Biology, Center for Biomics, Erasmus MC, Rotterdam, The Netherlands. · Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands. · Department of Hepatology, University Health Network Toronto Western & General Hospital, Toronto, ON, Canada. · Department of Pathology, Erasmus MC, Rotterdam, The Netherlands. ·Mol Psychiatry · Pubmed #28322274.

ABSTRACT: Depression is the most prevalent psychiatric disorder with a complex and elusive etiology that is moderately heritable. Identification of genes would greatly facilitate the elucidation of the biological mechanisms underlying depression, however, its complex etiology has proved to be a major bottleneck in the identification of its genetic risk factors, especially in genome-wide association-like studies. In this study, we exploit the properties of a genetic isolate and its family-based structure to explore whether relatively rare exonic variants influence the burden of depressive symptoms in families. Using a multistep approach involving linkage and haplotype analyses followed by exome sequencing in the Erasmus Rucphen Family (ERF) study, we identified a rare (minor allele frequency (MAF)=1%) missense c.1114C>T mutation (rs115482041) in the RCL1 gene segregating with depression across multiple generations. Rs115482041 showed significant association with depressive symptoms (N=2393, β

7 Article Happiness, rather than depression, is associated with sexual behaviour in partnered older adults. 2017

Freak-Poli, Rosanne / De Castro Lima, Gustavo / Direk, Nese / Jaspers, Loes / Pitts, Marian / Hofman, Albert / Tiemeier, Henning. ·Department of Epidemiology, Erasmus Medical Centre, The Netherlands. · Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, Commercial Road, Melbourne VIC 3004, Australia. · Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey. · Australian Research Centre in Sex, Health and Society, LaTrobe University, Australia. · Department of Epidemiology, Harvard University, USA. · Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, The Netherlands. · Department of Psychiatry, Erasmus Medical Centre, The Netherlands. ·Age Ageing · Pubmed #28104602.

ABSTRACT: Background: The relation between positive psychological well-being (PPWB) and sexual behaviour is understudied in older adult groups. Objective: To examine the relation between PPWB (positive affect and life satisfaction) and sexual behaviour (sexual activity and physical tenderness) in older adults, and whether it is independent from depressive symptoms and uniform across older age groups. Design: Cross-sectional. Setting: Community-dwelling adults aged 65 years or older, Rotterdam, The Netherlands. Methods: Sexual behaviour, the Cantril Self-Anchoring Striving Scale, the Center for Epidemiological Studies Depression (CES-D) scale and partner status were assessed in 2,373 dementia-free older adults from the Rotterdam Study. Results: For partnered participants, greater positive affect and life satisfaction was associated with more sexual activity and physical tenderness. Although CES-D was negatively associated with sexual behaviour within partnered older adults, there was no association between the negative affect sub-scale and sexual behaviour. The relations were independent of depressive symptoms, physical health and chronic disease status and were observed for both sexes at all older ages. For unpartnered participants, greater life satisfaction and was associated with more physical tenderness. There was low prevalence of sexual behaviour in unpartnered participants, limiting further stratification. Conclusion: Greater PPWB was associated with more sexual behaviour in partnered, community-dwelling older adults. We are the first to demonstrate that sexual behaviour is associated with PPWB, rather than lack of depressive symptoms; and that the association was present at all ages for partnered older adults. Limited conclusions can be drawn for unpartnered older adults as their sexual behaviour was infrequent.

8 Article An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. 2017

Direk, Nese / Williams, Stephanie / Smith, Jennifer A / Ripke, Stephan / Air, Tracy / Amare, Azmeraw T / Amin, Najaf / Baune, Bernhard T / Bennett, David A / Blackwood, Douglas H R / Boomsma, Dorret / Breen, Gerome / Buttenschøn, Henriette N / Byrne, Enda M / Børglum, Anders D / Castelao, Enrique / Cichon, Sven / Clarke, Toni-Kim / Cornelis, Marilyn C / Dannlowski, Udo / De Jager, Philip L / Demirkan, Ayse / Domenici, Enrico / van Duijn, Cornelia M / Dunn, Erin C / Eriksson, Johan G / Esko, Tonu / Faul, Jessica D / Ferrucci, Luigi / Fornage, Myriam / de Geus, Eco / Gill, Michael / Gordon, Scott D / Grabe, Hans Jörgen / van Grootheest, Gerard / Hamilton, Steven P / Hartman, Catharina A / Heath, Andrew C / Hek, Karin / Hofman, Albert / Homuth, Georg / Horn, Carsten / Jan Hottenga, Jouke / Kardia, Sharon L R / Kloiber, Stefan / Koenen, Karestan / Kutalik, Zoltán / Ladwig, Karl-Heinz / Lahti, Jari / Levinson, Douglas F / Lewis, Cathryn M / Lewis, Glyn / Li, Qingqin S / Llewellyn, David J / Lucae, Susanne / Lunetta, Kathryn L / MacIntyre, Donald J / Madden, Pamela / Martin, Nicholas G / McIntosh, Andrew M / Metspalu, Andres / Milaneschi, Yuri / Montgomery, Grant W / Mors, Ole / Mosley, Thomas H / Murabito, Joanne M / Müller-Myhsok, Bertram / Nöthen, Markus M / Nyholt, Dale R / O'Donovan, Michael C / Penninx, Brenda W / Pergadia, Michele L / Perlis, Roy / Potash, James B / Preisig, Martin / Purcell, Shaun M / Quiroz, Jorge A / Räikkönen, Katri / Rice, John P / Rietschel, Marcella / Rivera, Margarita / Schulze, Thomas G / Shi, Jianxin / Shyn, Stanley / Sinnamon, Grant C / Smit, Johannes H / Smoller, Jordan W / Snieder, Harold / Tanaka, Toshiko / Tansey, Katherine E / Teumer, Alexander / Uher, Rudolf / Umbricht, Daniel / Van der Auwera, Sandra / Ware, Erin B / Weir, David R / Weissman, Myrna M / Willemsen, Gonneke / Yang, Jingyun / Zhao, Wei / Tiemeier, Henning / Sullivan, Patrick F. ·Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey. · Department of Genetics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. · Department of Epidemiology, University of Michigan, Ann Arbor, Michigan. · Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston; Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin. · Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia. · Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia. · Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam. · Rush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois. · Division of Psychiatry, University of Edinburgh, Edinburgh. · Department of Biological Psychology, VU University, Amsterdam, The Netherlands. · MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London. · Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus. · Queensland Brain Institute, University of Queensland, St. Lucia, Queensland. · Department of Biomedicine and Centre for Integrative Sequencing, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus. · Department of Psychiatry, Lausanne University Hospital, Lausanne. · Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn; Institute of Neuroscience and Medicine, Research Centre Jülich, Jülich; Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland. · Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Psychiatry and Psychotherapy, University of Münster, Münster. · Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge; Department of Neurology, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Neurology, Harvard Medical School, Boston. · Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland; Centre for Integrative Biology, University of Trento, Trento, Italy. · Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge; Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki; Unit of General Practice, Helsinki University Central Hospital, Helsinki; Folkhalsan Research Centre, Helsinki; Vasa Central Hospital, Vasa, Finland. · Program in Medical and Populational Genetics, The Broad Institute of Harvard and MIT, Cambridge; Division of Endocrinology, Boston Children's Hospital, Cambridge; Department of Genetics, Harvard Medical School, Boston; Estonian Genome Center, University of Tartu, Tartu, Estonia. · Institute for Social Research, University of Michigan, Ann Arbor, Michigan. · Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland. · Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas. · Department of Psychiatry, Trinity Centre for Health Science, Dublin, Ireland. · QIMR Berghofer Medical Research Institute, Brisbane. · Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, Munich; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich. · Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands. · Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco. · Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen. · Department of Psychiatry, Washington University, St. Louis, Missouri. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam. · Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Munich. · Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland. · Max Planck Institute of Psychiatry, Munich. · Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York. · Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne. · Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich; Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg. · Folkhalsan Research Centre, Helsinki; Institute of Behavioural Sciences, University of Helsinki, Helsinki. · Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. · Division of Psychiatry, University College London, London. · Janssen Research & Development LLC, New Brunswick, New Jersey. · University of Exeter Medical School, Exeter. · Department of Biostatistics, Boston University School of Public Health, Framingham, Massachusetts; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. · The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus; Research Department P, Aarhus University Hospital, Risskov, Denmark. · Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. · Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts. · Max Planck Institute of Psychiatry, Munich; Munich Cluster for Systems Neurology, Munich; University of Liverpool, Institute of Translational Medicine, Liverpool. · Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn. · QIMR Berghofer Medical Research Institute, Brisbane; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland. · MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom. · Department of Psychiatry, Washington University, St. Louis, Missouri; Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida. · Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston. · Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa. · Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York. · Solid GT, Boston; Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland. · Institute of Behavioural Sciences, University of Helsinki, Helsinki. · Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim. · MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; CIBERSAM-Universidad de Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University, Munich; Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. · Group Health, Seattle, Washington. · Department of Psychiatry and Psychiatric Neuroscience, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. · Unit of Genetic Epidemiology & Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Munich. · MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; Dalhousie University, Halifax, Nova Scotia, Canada. · Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich. · Department of Epidemiology, University of Michigan, Ann Arbor, Michigan; Institute for Social Research, University of Michigan, Ann Arbor, Michigan. · College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute, New York, New York. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam. Electronic address: h.tiemeier@erasmusmc.nl. · Department of Psychiatry, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Center for Psychiatric Genomics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden. ·Biol Psychiatry · Pubmed #28049566.

ABSTRACT: BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10 CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

9 Article Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. 2017

Amin, Najaf / Belonogova, Nadezhda M / Jovanova, Olivera / Brouwer, Rutger W W / van Rooij, Jeroen G J / van den Hout, Mirjam C G N / Svishcheva, Gulnara R / Kraaij, Robert / Zorkoltseva, Irina V / Kirichenko, Anatoly V / Hofman, Albert / Uitterlinden, André G / van IJcken, Wilfred F J / Tiemeier, Henning / Axenovich, Tatiana I / van Duijn, Cornelia M. ·Departments of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: n.amin@erasmusmc.nl. · Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. · Departments of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. · Center for Biomics, Erasmus University Medical Center, Rotterdam, the Netherlands. · Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia. · Departments of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Departments of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. · Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia; Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia. ·Biol Psychiatry · Pubmed #27745872.

ABSTRACT: BACKGROUND: Despite high heritability, little success was achieved in mapping genetic determinants of depression-related traits by means of genome-wide association studies. METHODS: To identify genes associated with depressive symptomology, we performed a gene-based association analysis of nonsynonymous variation captured using exome-sequencing and exome-chip genotyping in a genetically isolated population from the Netherlands (n = 1999). Finally, we reproduced our significant findings in an independent population-based cohort (n = 1604). RESULTS: We detected significant association of depressive symptoms with a gene NKPD1 (p = 3.7 × 10 CONCLUSIONS: Our study suggests that nonsynonymous variation in the gene NKPD1 affects depressive symptoms in the general population. NKPD1 is predicted to be involved in the de novo synthesis of sphingolipids, which have been implicated in the pathogenesis of depression.

10 Article Mild cognitive impairment and risk of depression and anxiety: A population-based study. 2017

Mirza, Saira Saeed / Ikram, M Arfan / Bos, Daniel / Mihaescu, Raluca / Hofman, Albert / Tiemeier, Henning. ·Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: h.tiemeier@erasmusmc.nl. ·Alzheimers Dement · Pubmed #27520773.

ABSTRACT: INTRODUCTION: Many people with mild cognitive impairment (MCI) suffer from concomitant depression or anxiety. Whether MCI increases the risk of future depression or anxiety is unknown. METHODS: In the Rotterdam Study, cross-sectional (n = 4168) and longitudinal associations (n = 2967) of MCI with Diagnostic and Statistical Manual of Mental Disorders-depressive and anxiety disorders-were assessed (2002-2005 to 2009-2011). RESULTS: At baseline, 413 persons had MCI; 125 (22 MCI and 103 non-MCI) had a depressive disorder and 330 had an anxiety disorder (46 MCI and 284 non-MCI). In longitudinal depression analysis, of the 212 persons with prevalent MCI, 6 (2.8%) developed depression compared with 29 (1%) in the nonexposed group. In longitudinal anxiety analysis, 11 (7.3%) of the 151 with prevalent MCI developed anxiety, compared with 75 (3.4%) in nonexposed group. Persons with MCI had more depressive and anxiety disorders and also a higher risk of developing depressive disorder, odds ratio (OR) 3.13 (95% confidence interval [CI]: 1.26, 7.77), and anxiety disorder, OR 2.59 (95% CI: 1.31, 5.12). DISCUSSION: MCI is a risk factor for dementia and for depressive and anxiety disorders, suggesting common pathological pathways for cognitive and psychiatric outcomes.

11 Article Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms. 2017

Amin, N / Jovanova, O / Adams, H H H / Dehghan, A / Kavousi, M / Vernooij, M W / Peeters, R P / de Vrij, F M S / van der Lee, S J / van Rooij, J G J / van Leeuwen, E M / Chaker, L / Demirkan, A / Hofman, A / Brouwer, R W W / Kraaij, R / Willems van Dijk, K / Hankemeier, T / van Ijcken, W F J / Uitterlinden, A G / Niessen, W J / Franco, O H / Kushner, S A / Ikram, M A / Tiemeier, H / van Duijn, C M. ·Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Department of Radiology, Erasmus MC, Rotterdam, The Netherlands. · Rotterdam Thyroid Center, Erasmus MC, Rotterdam, The Netherlands. · Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Department of Psychiatry, Erasmus MC, Rotterdam, The Netherlands. · Department of Human Genetics, Leiden University Medical Center, RC Leiden, The Netherlands. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. · Center for Biomics, Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands. · Division of Endocrinology, Department of Medicine, Leiden University Medical Center, RC Leiden, The Netherlands. · Leiden Academic Center for Drug Research, Division of Analytical Biosciences, Leiden University, Leiden, The Netherlands. · The Netherlands Metabolomics Centre, Leiden University, Leiden, The Netherlands. · Departments of Radiology and Medical Informatics, Erasmus MC, Rotterdam, The Netherlands. · Department of Imaging Physics, Delft University of Technology, Delft, The Netherlands. ·Mol Psychiatry · Pubmed #27431295.

ABSTRACT: Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms. We identified a missense Asn396Ser mutation (rs77960347) in the endothelial lipase (LIPG) gene, occurring with an allele frequency of 1% in the general population, which was significantly associated with depressive symptoms (P-value=5.2 × 10

12 Article Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. 2017

Schmaal, L / Hibar, D P / Sämann, P G / Hall, G B / Baune, B T / Jahanshad, N / Cheung, J W / van Erp, T G M / Bos, D / Ikram, M A / Vernooij, M W / Niessen, W J / Tiemeier, H / Hofman, A / Wittfeld, K / Grabe, H J / Janowitz, D / Bülow, R / Selonke, M / Völzke, H / Grotegerd, D / Dannlowski, U / Arolt, V / Opel, N / Heindel, W / Kugel, H / Hoehn, D / Czisch, M / Couvy-Duchesne, B / Rentería, M E / Strike, L T / Wright, M J / Mills, N T / de Zubicaray, G I / McMahon, K L / Medland, S E / Martin, N G / Gillespie, N A / Goya-Maldonado, R / Gruber, O / Krämer, B / Hatton, S N / Lagopoulos, J / Hickie, I B / Frodl, T / Carballedo, A / Frey, E M / van Velzen, L S / Penninx, B W J H / van Tol, M-J / van der Wee, N J / Davey, C G / Harrison, B J / Mwangi, B / Cao, B / Soares, J C / Veer, I M / Walter, H / Schoepf, D / Zurowski, B / Konrad, C / Schramm, E / Normann, C / Schnell, K / Sacchet, M D / Gotlib, I H / MacQueen, G M / Godlewska, B R / Nickson, T / McIntosh, A M / Papmeyer, M / Whalley, H C / Hall, J / Sussmann, J E / Li, M / Walter, M / Aftanas, L / Brack, I / Bokhan, N A / Thompson, P M / Veltman, D J. ·Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. · Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA. · Neuroimaging Core Unit, Max Planck Institute of Psychiatry, Munich, Germany. · Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada. · Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia. · Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA. · Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · Department of Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands. · German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany. · Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. · Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · German Center for Cardiovascular Research (DZHK), partner site Griefswald, Greifswald, Germany. · German Center for Diabetes Research (DZD), partner site Griefswald, Greifswald, Germany. · Department of Psychiatry, University of Muenster, Muenster, Germany. · Department of Psychiatry, University of Marburg, Marburg, Germany. · Department of Clinical Radiology, University of Muenster, Muenster, Germany. · Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia. · Center for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia. · Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia. · Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. · Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA. · Centre for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany. · Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany. · Clinical Research Unit, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia. · Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany. · Department of Psychiatry and Institute of Neuroscience, Trinity College, Dublin, Ireland. · Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany. · Neuroimaging Center, Section of Cognitive Neuropsychiatry, Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. · Department of Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, The Netherlands. · Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia. · Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia. · Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia. · UT Center of Excellence on Mood Disoders, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA. · Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany. · Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany. · Center for Integrative Psychiatry, University of Lübeck, Lübeck, Germany. · Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum Rotenburg, Rotenburg, Germany. · Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany. · Neurosciences Program and Department of Psychology, Stanford University, Stanford, CA, USA. · Department of Psychiatry, University of Calgary, Calgary, AB, Canada. · University Department of Psychiatry, Warneford Hospital, Oxford, UK. · Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. · Centre for Cogntive Ageing and Cogntive Epidemiology, University of Edinburgh, Edinburg, UK. · Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland. · Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK. · Department of Psychiatry, NHS Borders, Melrose, UK. · Leibniz Institute for Neurobiology, Magdeburg, Germany. · Department of Psychiatry, University Tübingen, Tübingen, Germany. · Department of Experimental and Clinical Neuroscience, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia. · Mental Health Research Institute, Tomsk, Russia. · Faculty of Psychology, National Research Tomsk State University, Tomsk, Russia. · Department of General Medicine, Siberian State Medical University, Tomsk, Russia. ·Mol Psychiatry · Pubmed #27137745.

ABSTRACT: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

13 Article The Very Low-Dose Dexamethasone Suppression Test in the General Population: A Cross-Sectional Study. 2016

Direk, Nese / Dekker, Marieke J H J / Luik, Annemarie I / Kirschbaum, Clemens / de Rijke, Yolanda B / Hofman, Albert / Hoogendijk, Witte J G / Tiemeier, Henning. ·Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands. · Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey. · Department of Internal Medicine, VU Medical Centre, Amsterdam, the Netherlands. · Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. · Department of Biological Psychology, Technical University of Dresden, Dresden, Germany. · Department of Clinical Chemistry, Erasmus Medical Centre, Rotterdam, the Netherlands. · Department of Psychiatry, Erasmus Medical Centre, Rotterdam, the Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, Rotterdam, the Netherlands. ·PLoS One · Pubmed #27736954.

ABSTRACT: Determinants of the hypothalamic-pituitary-adrenal (HPA) axis functioning are increasingly explored in population-based studies. However, functional tests measuring the negative feedback of the HPA axis cannot easily be implemented into large observational studies. Furthermore, high doses of dexamethasone often completely suppress the HPA axis in healthy persons. This study aimed to detect the effects of the health, lifestyle and sociodemographic factors, psychiatric problems and cognitive functions on the negative feedback of the HPA axis using a very low-dose (0.25 mg) dexamethasone suppression test (DST).We evaluated the associations of several determinants with the saliva cortisol concentrations after dexamethasone intake in a confounder-adjusted model also corrected for baseline saliva cortisol concentrations in the Rotterdam Study, a large population-based study (N = 1822). We found that female sex, low income, lack of exercise, instrumental disability and smoking were all independently associated with stronger suppression of the HPA axis. Even though there were no linear associations between psychiatric measures and cortisol suppression, we found that depressive symptoms and anxiety disorders were more common in persons with non-suppression of cortisol. Conversely, psychotropic medication use was related to enhanced suppression of cortisol after DST. In this large study, we found that female gender, low socioeconomic status and poor health were all related to suppression of the HPA axis. Non-linear associations were detected between the suppression of the HPA axis and common psychiatric disorders in community-dwelling persons.

14 Article Self-reported indications for antidepressant use in a population-based cohort of middle-aged and elderly. 2016

Aarts, Nikkie / Noordam, Raymond / Hofman, Albert / Tiemeier, Henning / Stricker, Bruno H / Visser, Loes E. ·Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Psychiatry, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. b.stricker@erasmusmc.nl. · Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. b.stricker@erasmusmc.nl. · Inspectorate of Health Care, Utrecht, The Netherlands. b.stricker@erasmusmc.nl. · Apotheek Haagse Ziekenhuizen - HAGA, The Hague, The Netherlands. ·Int J Clin Pharm · Pubmed #27586370.

ABSTRACT: Background Population-based studies investigating indications for antidepressant prescribing mostly rely on diagnoses from general practitioners. However, diagnostic codes might be incomplete and drugs may be prescribed 'off-label' for indications not investigated in clinical trials. Objective We aimed to study indications for antidepressant use based on self-report. Also, we studied the presence of depressive symptoms associated with the self-reported indications. Setting Our study population of antidepressant users was selected based on interview data between 1997 and 2013 from the prospective population-based Rotterdam Study cohort (age >45 years). Method Antidepressant use, self-reported indication for use, and presence of depressive symptoms (Center for Epidemiological Studies Depression Scale) were based on interview. Self-reported indications were categorized by the researchers into officially approved, clinically-accepted and commonly mentioned off-label indications. Main outcome measures A score of 16 and higher on the Center for Epidemiological Studies Depression Scale was considered as indicator for clinically-relevant depressive symptoms. Results The majority of 914 antidepressant users reported 'depression' (52.4 %) as indication for treatment. Furthermore, anxiety, stress and sleep disorders were reported in selective serotonin reuptake inhibitor and other antidepressant users (ranging from 5.9 to 13.3 %). The indication 'pain' was commonly mentioned by tricyclic antidepressant users (19.0 %). Indications were statistically significantly associated with higher depressive symptom scores when compared to non-users (n = 10,979). Conclusions Depression was the main indication for antidepressant treatment. However, our findings suggest that antidepressants are also used for off-label indications, subthreshold disorders and complex situations, which were all associated with clinically-relevant depressive symptoms in the middle-aged and elderly population.

15 Article Markers of cerebral small vessel disease and severity of depression in the general population. 2016

Direk, Nese / Perez, Heidi Saavedra / Akoudad, Saloua / Verhaaren, Benjamin F J / Niessen, Wiro J / Hofman, Albert / Vernooij, Meike W / Ikram, M Arfan / Tiemeier, Henning. ·Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands. · Biomedical Imaging Group Rotterdam, Erasmus Medical Centre, Rotterdam, The Netherlands; Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands. · Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands. Electronic address: h.tiemeier@erasmusmc.nl. ·Psychiatry Res Neuroimaging · Pubmed #27254084.

ABSTRACT: The vascular depression hypothesis postulates that cerebral small vessel disease can cause or exacerbate depression in elderly persons. Numerous studies explored the association of imaging markers of cerebral small vessel disease including white matter lesions (WMLs) and lacunar infarcts with depressive symptoms or disorders. However, cerebral microbleeds have not been tested in depression. In the current study, we aimed to explore the association of WMLs, lacunar infarcts and cerebral microbleeds with depression continuum in a large population-based sample, the Rotterdam Study. Study population consisted of 3799 participants (aged 45 or over) free of dementia. WML volumes, lacunar infarcts and cerebral microbleeds were measured with brain magnetic resonance imaging. Depressive symptoms, depressive disorders and co-morbid anxiety disorders were assessed with validated questionnaires and clinical interview. WML volumes and lacunar infarcts were associated with depressive symptoms and disorders. Cerebral microbleeds, especially in deep or infratentorial brain regions, were related to depressive disorders only. Our results indicate that WMLs and lacunar infarcts might be non-specific vascular lesions seen in depressive symptoms and disorders. Association of cerebral microbleeds with more severe forms of depression may indicate impaired brain iron homeostasis or minor episodes of cerebrovascular extraversion, which may play a role in depression etiology.

16 Article 10-year trajectories of depressive symptoms and risk of dementia: a population-based study. 2016

Mirza, Saira Saeed / Wolters, Frank J / Swanson, Sonja A / Koudstaal, Peter J / Hofman, Albert / Tiemeier, Henning / Ikram, M Arfan. ·Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands. · Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Child and Adult Psychiatry, Erasmus Medical Center, Rotterdam, Netherlands; Department of Psychiatry, Erasmus Medical Center, Rotterdam, Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, Netherlands. Electronic address: m.a.ikram@erasmusmc.nl. ·Lancet Psychiatry · Pubmed #27138970.

ABSTRACT: BACKGROUND: Late-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a single timepoint. Such an approach neglects the course of depression, which, given its remitting and relapsing nature, might provide further insights into the complex association of depression with dementia. We therefore repeatedly measured depressive symptoms in a population of adults over a decade to study the subsequent risk of dementia. METHODS: Our study was embedded in the Rotterdam Study, a population-based study of adults aged 55 years or older in Rotterdam (Netherlands), ongoing since 1990. The cohort is monitored continuously for major events by data linkage between the study database and general practitioners. We examined a cohort of participants who were free from dementia, but had data for depressive symptoms from at least one examination round in 1993-95, 1997-99, or 2002-04. We assessed depressive symptoms with the validated Dutch version of the Center for Epidemiology Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale-Depression. We used these data to identify 11-year trajectories of depressive symptoms by latent class trajectory modelling. We screened participants for dementia at each examination round and followed up participants for 10 years for incident dementia by latent trajectory from the third examination round to 2014. We calculated hazard ratios (HR) for dementia by assigned trajectory using two Cox proportional hazards models (model 1 adjusted for age and sex only, and model 2 adjusted additionally for APOEɛ4 carrier status, educational level, body-mass index, smoking, alcohol consumption, cognitive score, use of antidepressants, and prevalent disease status at baseline). We repeated the analyses censoring for incident stroke, restricting to Alzheimer's disease as an outcome, and accounting for mortality as a competing risk for dementia. FINDINGS: From 1993-2004, we obtained data for depressive symptoms from at least one examination round for 3325 participants (median age: 74·88 years [IQR 70·62-80·06], 1995 [60%] women). We identified five trajectories of depressive symptoms in these 3325 individuals, characterised by maintained low CES-D scores (low; 2441 [73%]); moderately high starting scores but then remitting (decreasing; 369 [11%]); low starting scores, increasing, then remitting (remitting; 170 [5%]); low starting scores that steadily increased (increasing; 255 [8%]); and maintained high scores (high; 90 [3%]). During 26 330 person-years, 434 participants developed incident dementia. Only the trajectory with increasing depressive symptoms was associated with a higher risk of dementia compared with the low depressive symptom trajectory, using model 2 (HR 1·42, 95% CI 1·05-1·94; p=0·024). Additionally, only the increasing trajectory was associated with a higher risk of dementia compared with the low trajectory after censoring for incident stroke (1·58, 1·15-2·16; p=0·0041), restricting to Alzheimer's disease as an outcome (1·44, 1·03-2·02; p=0·034), and accounting for mortality as a competing risk (1·45, 1·06-1·97; p=0·019). INTERPRETATION: Risk of dementia differed with different courses of depression, which could not be captured by a single assessment of depressive symptoms. The higher risk of dementia only in the increasing trajectory suggests depression might be a prodrome of dementia. FUNDING: Erasmus Medical Center; ZonMw; the Netherlands Ministry of Education Culture and Science; and the Netherlands Ministry for Health, Welfare and Sports.

17 Article Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. 2016

Okbay, Aysu / Baselmans, Bart M L / De Neve, Jan-Emmanuel / Turley, Patrick / Nivard, Michel G / Fontana, Mark Alan / Meddens, S Fleur W / Linnér, Richard Karlsson / Rietveld, Cornelius A / Derringer, Jaime / Gratten, Jacob / Lee, James J / Liu, Jimmy Z / de Vlaming, Ronald / Ahluwalia, Tarunveer S / Buchwald, Jadwiga / Cavadino, Alana / Frazier-Wood, Alexis C / Furlotte, Nicholas A / Garfield, Victoria / Geisel, Marie Henrike / Gonzalez, Juan R / Haitjema, Saskia / Karlsson, Robert / van der Laan, Sander W / Ladwig, Karl-Heinz / Lahti, Jari / van der Lee, Sven J / Lind, Penelope A / Liu, Tian / Matteson, Lindsay / Mihailov, Evelin / Miller, Michael B / Minica, Camelia C / Nolte, Ilja M / Mook-Kanamori, Dennis / van der Most, Peter J / Oldmeadow, Christopher / Qian, Yong / Raitakari, Olli / Rawal, Rajesh / Realo, Anu / Rueedi, Rico / Schmidt, Börge / Smith, Albert V / Stergiakouli, Evie / Tanaka, Toshiko / Taylor, Kent / Thorleifsson, Gudmar / Wedenoja, Juho / Wellmann, Juergen / Westra, Harm-Jan / Willems, Sara M / Zhao, Wei / Anonymous1080865 / Amin, Najaf / Bakshi, Andrew / Bergmann, Sven / Bjornsdottir, Gyda / Boyle, Patricia A / Cherney, Samantha / Cox, Simon R / Davies, Gail / Davis, Oliver S P / Ding, Jun / Direk, Nese / Eibich, Peter / Emeny, Rebecca T / Fatemifar, Ghazaleh / Faul, Jessica D / Ferrucci, Luigi / Forstner, Andreas J / Gieger, Christian / Gupta, Richa / Harris, Tamara B / Harris, Juliette M / Holliday, Elizabeth G / Hottenga, Jouke-Jan / De Jager, Philip L / Kaakinen, Marika A / Kajantie, Eero / Karhunen, Ville / Kolcic, Ivana / Kumari, Meena / Launer, Lenore J / Franke, Lude / Li-Gao, Ruifang / Liewald, David C / Koini, Marisa / Loukola, Anu / Marques-Vidal, Pedro / Montgomery, Grant W / Mosing, Miriam A / Paternoster, Lavinia / Pattie, Alison / Petrovic, Katja E / Pulkki-Råback, Laura / Quaye, Lydia / Räikkönen, Katri / Rudan, Igor / Scott, Rodney J / Smith, Jennifer A / Sutin, Angelina R / Trzaskowski, Maciej / Vinkhuyzen, Anna E / Yu, Lei / Zabaneh, Delilah / Attia, John R / Bennett, David A / Berger, Klaus / Bertram, Lars / Boomsma, Dorret I / Snieder, Harold / Chang, Shun-Chiao / Cucca, Francesco / Deary, Ian J / van Duijn, Cornelia M / Eriksson, Johan G / Bültmann, Ute / de Geus, Eco J C / Groenen, Patrick J F / Gudnason, Vilmundur / Hansen, Torben / Hartman, Catharine A / Haworth, Claire M A / Hayward, Caroline / Heath, Andrew C / Hinds, David A / Hyppönen, Elina / Iacono, William G / Järvelin, Marjo-Riitta / Jöckel, Karl-Heinz / Kaprio, Jaakko / Kardia, Sharon L R / Keltikangas-Järvinen, Liisa / Kraft, Peter / Kubzansky, Laura D / Lehtimäki, Terho / Magnusson, Patrik K E / Martin, Nicholas G / McGue, Matt / Metspalu, Andres / Mills, Melinda / de Mutsert, Renée / Oldehinkel, Albertine J / Pasterkamp, Gerard / Pedersen, Nancy L / Plomin, Robert / Polasek, Ozren / Power, Christine / Rich, Stephen S / Rosendaal, Frits R / den Ruijter, Hester M / Schlessinger, David / Schmidt, Helena / Svento, Rauli / Schmidt, Reinhold / Alizadeh, Behrooz Z / Sørensen, Thorkild I A / Spector, Tim D / Starr, John M / Stefansson, Kari / Steptoe, Andrew / Terracciano, Antonio / Thorsteinsdottir, Unnur / Thurik, A Roy / Timpson, Nicholas J / Tiemeier, Henning / Uitterlinden, André G / Vollenweider, Peter / Wagner, Gert G / Weir, David R / Yang, Jian / Conley, Dalton C / Smith, George Davey / Hofman, Albert / Johannesson, Magnus / Laibson, David I / Medland, Sarah E / Meyer, Michelle N / Pickrell, Joseph K / Esko, Tõnu / Krueger, Robert F / Beauchamp, Jonathan P / Koellinger, Philipp D / Benjamin, Daniel J / Bartels, Meike / Cesarini, David. ·Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. · Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands. · Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands. · EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands. · Saïd Business School, University of Oxford, Oxford, UK. · Department of Economics, Harvard University, Cambridge, Massachusetts, USA. · Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA. · Department of Complex Trait Genetics, Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands. · Amsterdam Business School, University of Amsterdam, Amsterdam, the Netherlands. · Department of Psychology, University of Illinois, Champaign, Illinois, USA. · Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. · Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA. · New York Genome Center, New York, New York, USA. · COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. · Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark. · Steno Diabetes Center, Gentofte, Denmark. · Department of Public Health, University of Helsinki, Helsinki, Finland. · Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. · South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. · USDA-ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. · 23andMe, Inc., Mountain View, California, USA. · Department of Epidemiology and Public Health, University College London, London, UK. · Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany. · Centre for Research in Environmental Epidemiology, Institute for Global Health, Barcelona, Spain. · Universitat Pompeu Fabra, Barcelona, Spain. · CIBER Epidemiología y Salud Pública, Barcelona, Spain. · Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Psychosomatic Medicine and Psychotherapy, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland. · Folkhälsan Research Centre, Helsingfors, Finland. · Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland. · Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Max Planck Institute for Human Development, Berlin, Germany. · Max Planck Institute for Molecular Genetics, Department of Vertebrate Genomics, Berlin, Germany. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. · Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands. · BESC, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. · Public Health Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia. · Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia. · Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA. · Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. · Department of Clinical Physiology, Turku University Hospital, Turku, Finland. · Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Department of Psychology, University of Tartu, Tartu, Estonia. · Department of Psychology, University of Warwick, Coventry, UK. · Department of Computational Biology, University of Lausanne, Lausanne, Switzerland. · Swiss Institute of Bioinformatics, Lausanne, Switzerland. · Icelandic Heart Association, Kopavogur, Iceland. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. · National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA. · Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA, Torrence, California, USA. · Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany. · Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA. · Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA. · RAND Corporation, Santa Monica, California, USA. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. · Department of Psychology, University of Edinburgh, Edinburgh, UK. · German Socio-Economic Panel Study, DIW Berlin, Berlin, Germany. · Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK. · Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. · Farr Institute of Health Informatics, University College London, London, UK. · Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. · Laboratory of Epidemiology, Demography, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Harvard Medical School, Boston, Massachusetts, USA. · Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. · Department of Genomics of Common Disease, Imperial College London, London, UK. · Center for Life Course Health Research, University of Oulu and Oulu University Hospital, Oulu, Finland. · Department of Pediatrics, University of Helsinki, Helsinki, Finland. · National Institute for Health and Welfare, Helsinki, Finland. · Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia. · Institute for Social and Economic Research, University of Essex, Wivenhoe Park, UK. · Neuroepidemiology Section, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA. · Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. · Department of Neurology, General Hospital and Medical University Graz, Graz, Austria. · Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland. · Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK. · Information-Based Medicine Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia. · Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, Florida, USA. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institute of Neurogenetics and Institute of Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany. · Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK. · Neuroscience Campus Amsterdam, Amsterdam, the Netherlands. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitarià di Monserrato, Monserrato, Italy. · Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. · Unit of General Practice, University Central Hospital, Helsinki, Finland. · Department of Health Sciences, Community and Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. · Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, South Australia, Australia. · Population, Policy and Practice, UCL Institute of Child Health, London, UK. · Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. · Biocenter Oulu, University of Oulu, Oulu, Finland. · Unit of Primary Care, Oulu University Hospital, Oulu, Finland. · Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. · Department for Health, THL (National Institute for Health and Welfare), Helsinki, Finland. · Department of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. · Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. · Fimlab Laboratories, Tampere, Finland. · Department of Clinical Chemistry, University of Tampere, School of Medicine, Tampere, Finland. · Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. · Department of Sociology, University of Oxford, Oxford, UK. · Laboratory of Clinical Chemistry and Hematology, Division of Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands. · Social, Genetic and Developmental Psychiatry Centre, King's College London, De Crespigny Park, UK. · Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA. · Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University Graz, Graz, Austria. · Department of Economics, Oulu Business School, Oulu, Finland. · Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, Capital Region, Frederiksberg, Denmark. · Montpellier Business School, Montpellier, France. · Panteia, Zoetermeer, the Netherlands. · Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. · School of Economics and Management, Berlin University of Technology, Berlin, Germany. · University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia. · Department of Sociology, Princeton University, Princeton, New Jersey, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. · Department of Economics, Stockholm School of Economics, Stockholm, Sweden. · Department of Bioethics, Clarkson University, Schenectady, New York, USA. · Icahn School of Medicine at Mount Sinai, New York, New York, USA. · Department of Biological Sciences, Columbia University, New York, New York, USA. · Department of Economics, New York University, New York, New York, USA. · Research Institute for Industrial Economics, Stockholm, Sweden. ·Nat Genet · Pubmed #27089181.

ABSTRACT: Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

18 Article Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies. 2016

Demirkan, A / Lahti, J / Direk, N / Viktorin, A / Lunetta, K L / Terracciano, A / Nalls, M A / Tanaka, T / Hek, K / Fornage, M / Wellmann, J / Cornelis, M C / Ollila, H M / Yu, L / Smith, J A / Pilling, L C / Isaacs, A / Palotie, A / Zhuang, W V / Zonderman, A / Faul, J D / Sutin, A / Meirelles, O / Mulas, A / Hofman, A / Uitterlinden, A / Rivadeneira, F / Perola, M / Zhao, W / Salomaa, V / Yaffe, K / Luik, A I / Anonymous5731022 / Liu, Y / Ding, J / Lichtenstein, P / Landén, M / Widen, E / Weir, D R / Llewellyn, D J / Murray, A / Kardia, S L R / Eriksson, J G / Koenen, K / Magnusson, P K E / Ferrucci, L / Mosley, T H / Cucca, F / Oostra, B A / Bennett, D A / Paunio, T / Berger, K / Harris, T B / Pedersen, N L / Murabito, J M / Tiemeier, H / van Duijn, C M / Räikkönen, K. ·Genetic Epidemiology Unit,Departments of Epidemiology and Clinical Genetics,Erasmus MC,Rotterdam,The Netherlands. · Institute of Behavioural Sciences, University of Helsinki,Helsinki,Finland. · Department of Epidemiology,Erasmus MC,Rotterdam,The Netherlands. · Department of Medical Epidemiology and Biostatistics,Karolinska Institute,Stockholm,Sweden. · Department of Biostatistics,Boston University School of Public Health,Boston, MA,USA. · National Institute on Aging, National Institutes of Health,Baltimore, MD,USA. · Laboratory of Neurogenetics,National Institute on Aging, National Institutes of Health,Bethesda, MD,USA. · Houston Institute of Molecular Medicine, University of Texas,Houston, TX,USA. · Institute of Epidemiology and Social Medicine, University of Münster,Münster,Germany. · Channing Division of Network Medicine,Brigham and Women's Hospital, Harvard Medical School,Boston, MA,USA. · Public Health Genomics Unit and Institute for Molecular Medicine Finland (FIMM),National Institute for Health and Welfare,Helsinki,Finland. · Department of Neurological Sciences,Rush Alzheimer's Disease Center, Rush University Medical Center,Chicago,IL,USA. · Department of Epidemiology,University of Michigan,Ann Arbor,MI,USA. · University of Exeter Medical School,Exeter,UK. · Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus,Cambridge,UK. · Department of Preventive Medicine and Public Health,School of Medicine, Creighton University,Omaha,NE,USA. · Survey Research Center, Institute for Social Research, University of Michigan,Ann Arbor,MI,USA. · Istituto di Ricerca Genetica e Biomedica, CNR,Monserrato,Cagliari,Italy. · Department of Chronic Disease Prevention,National Institute for Health and Welfare,Helsinki,Finland. · Departments of Psychiatry,University of California,San Francisco, CA,USA. · Center for Human Genomics, Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard,Winston-Salem,NC,USA. · Geriatrics & Gerontology, Sticht Center on Aging, Wake Forest University,Primate Center, Epidemiology & Prevention,Winston-Salem,NC,USA. · Institute for Molecular Medicine Finland (FIMM), University of Helsinki,Helsinki,Finland. · National Institute for Health and Welfare,Helsinki,Finland. · Department of Epidemiology,Mailman School of Public Health, Columbia University,New York,NY,USA. · Department of Medicine,University of Mississippi Medical Center,Jackson,MS,USA. · Laboratory of Epidemiology, Demography, and Biometry,National Institute on Ageing, National Institutes of Health,Bethesda,MD,USA. · Department of Medicine, Section of General Internal Medicine,Boston University School of Medicine,Boston,MA,USA. ·Psychol Med · Pubmed #26997408.

ABSTRACT: BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

19 Article The long-term risk of recognized and unrecognized myocardial infarction for depression in older men. 2016

Jovanova, O / Luik, A I / Leening, M J G / Noordam, R / Aarts, N / Hofman, A / Franco, O H / Dehghan, A / Tiemeier, H. ·Department of Epidemiology,Erasmus MC, University Medical Center Rotterdam,Rotterdam,The Netherlands. ·Psychol Med · Pubmed #26996221.

ABSTRACT: BACKGROUND: The association between myocardial infarction (MI) and depression is well described. Yet, the underlying mechanisms are unclear and the contribution of psychological factors is uncertain. We aimed to determine the risk of recognized (RMI) and unrecognized (UMI) myocardial infections on depression, as both have a similar impact on cardiovascular health but differ in psychological epiphenomena. METHOD: Participants of the Rotterdam Study, 1823 men aged ⩾55 years, were followed for the occurrence of depression. RMI and UMI were ascertained using electrocardiography and medical history at baseline. We determined the strength of the association of RMI and UMI with mortality, and we studied the relationship of RMI and UMI with depressive symptoms and the occurrence of major depression. RESULTS: The risk of mortality was similar in men with RMI [adjusted hazard ratio (aHR) 1.71, 95% confidence interval (CI) 1.45-2.03] and UMI (aHR 1.58, 95% CI 1.27-1.97). Men with RMI had on average [unstandardized regression coefficient (B) 1.14, 95% CI 0.07-2.21] higher scores for depressive symptoms. By contrast, we found no clear association between UMI and depressive symptoms (B 0.55, 95% CI -0.51 to 1.62) in men. Analysis including occurrence of major depression as the outcome were consistent with the pattern of association. CONCLUSION: The discrepant association of RMI and UMI with mortality compared to depression suggests that the psychological burden of having experienced an MI contributes to the long-term risk of depression.

20 Article Antidepressants and heart-rate variability in older adults: a population-based study. 2016

Noordam, R / van den Berg, M E / Niemeijer, M N / Aarts, N / Hofman, A / Tiemeier, H / Kors, J A / Stricker, B H / Eijgelsheim, M / Visser, L E / Rijnbeek, P R. ·Department of Epidemiology,Erasmus MC - University Medical Center Rotterdam,Rotterdam,The Netherlands. · Department of Medical Informatics,Erasmus MC - University Medical Center Rotterdam,Rotterdam,The Netherlands. ·Psychol Med · Pubmed #26679009.

ABSTRACT: BACKGROUND: Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study. METHOD: In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991-2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs. RESULTS: We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes. CONCLUSION: TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.

21 Article Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. 2016

Schmaal, L / Veltman, D J / van Erp, T G M / Sämann, P G / Frodl, T / Jahanshad, N / Loehrer, E / Tiemeier, H / Hofman, A / Niessen, W J / Vernooij, M W / Ikram, M A / Wittfeld, K / Grabe, H J / Block, A / Hegenscheid, K / Völzke, H / Hoehn, D / Czisch, M / Lagopoulos, J / Hatton, S N / Hickie, I B / Goya-Maldonado, R / Krämer, B / Gruber, O / Couvy-Duchesne, B / Rentería, M E / Strike, L T / Mills, N T / de Zubicaray, G I / McMahon, K L / Medland, S E / Martin, N G / Gillespie, N A / Wright, M J / Hall, G B / MacQueen, G M / Frey, E M / Carballedo, A / van Velzen, L S / van Tol, M J / van der Wee, N J / Veer, I M / Walter, H / Schnell, K / Schramm, E / Normann, C / Schoepf, D / Konrad, C / Zurowski, B / Nickson, T / McIntosh, A M / Papmeyer, M / Whalley, H C / Sussmann, J E / Godlewska, B R / Cowen, P J / Fischer, F H / Rose, M / Penninx, B W J H / Thompson, P M / Hibar, D P. ·Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. · Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA. · Max Planck Institute of Psychiatry, Munich, Germany. · Department of Psychiatry, University of Regensburg, Regensburg, Germany. · Department of Psychiatry, University of Dublin, Trinity College, Dublin, Ireland. · Imaging Genetics Center, Department of Neurology, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. · Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · Departments of Radiology and Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands. · Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. · German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany. · Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. · Helios Hospital Stralsund, Stralsund, Germany. · Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, Camperdown, Australia. · Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany. · NeuroImaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. · School of Psychology, University of Queensland, Brisbane, QLD, Australia. · Center for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia. · Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. · Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. · Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. · Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. · Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada. · Department of Psychiatry, Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. · Department of Psychiatry and Institute of Neuroscience, University of Dublin, Trinity College Dublin, Dublin, Ireland. · University of Groningen, University Medical Center Groningen, NeuroImaging Center, Groningen, The Netherlands. · Department of Psychiatry, Leiden University Medical Center, Leiden University, Leiden, The Netherlands. · Leiden Institute for Brain and Cognition, Leiden, The Netherlands. · Department of Psychiatry and Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, Berlin, Germany. · Department of General Psychiatry, University Hospital Heidelberg, Heidelberg, Germany. · Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany. · Department of Psychiatry, University of Bonn, Bonn, Germany. · Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany. · Center for Integrative Psychiatry, University of Lübeck, Lübeck, Germany. · Division of Psychiatry, University of Edinburgh, Edinburgh, UK. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. · University Department of Psychiatry, Warneford Hospital, Oxford, UK. · Department of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Charité Universitätsmedizin, Berlin, Germany. · Institute for Social Medicine, Epidemology and Health Economics, Charité Universitätsmedizin, Berlin, Germany. · Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA. ·Mol Psychiatry · Pubmed #26122586.

ABSTRACT: The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

22 Article Sleep apnea severity and depressive symptoms in a population-based study. 2015

Luik, Annemarie I / Noteboom, Jenna / Zuurbier, Lisette A / Whitmore, Harry / Hofman, Albert / Tiemeier, Henning. ·Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. · Section of Endocrinology in the Department of Medicine, University of Chicago, Chicago, IL, USA. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: h.tiemeier@erasmusmc.nl. ·Sleep Health · Pubmed #29073376.

ABSTRACT: OBJECTIVES: Sleep apnea and depression often co-occur in clinical studies, but population-based studies demonstrated mixed results. We determined the association of sleep apnea severity and depressive symptoms in a population-based sample. DESIGN: Cross-sectional cohort study. SETTING: Population-based. PARTICIPANTS: Four hundred ninety-one middle-aged and elderly persons of the Rotterdam Study (mean age 61.9 years; standard deviation, 5.4). MEASUREMENTS: Polysomnography recordings were collected to calculate the apnea hypopnea index (AHI). Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. RESULTS: In the total sample, no associations for the severity of sleep apnea with depressive symptoms were found (multivariate adjusted: B = 0.032; 95% confidence interval [CI], -0.057 to 0.122). Only in men we found some evidence for a curvilinear association of the severity of sleep apnea with depressive symptoms (multivariable adjusted: B = -0.126; 95% CI, -0.224 to -0.028); men with an AHI between 5 and 15 (multivariable adjusted: B = 0.378; 95% CI, 0.037-0.718) or between 15 and 30 (multivariable adjusted: B = 0.502; 95% CI, 0.152-0.852) had significantly more depressive symptoms than those with an AHI equal to or greater than 30. CONCLUSIONS: In this population-based sample, the severity of sleep apnea is not consistently related to depressive symptoms, although there was some evidence for an association of AHI with depressive symptoms in men.

23 Article Sex-specific association between antidepressant use and body weight in a population-based study in older adults. 2015

Noordam, Raymond / Aarts, Nikkie / Tiemeier, Henning / Hofman, Albert / Stricker, Bruno H / Visser, Loes E. ·Departments of Internal Medicine, Epidemiology, The Netherlands. ·J Clin Psychiatry · Pubmed #26132681.

ABSTRACT: OBJECTIVE: To investigate the association between antidepressant use and body weight in a population-based study in older adults. METHOD: All participant records (N = 7,269) from the prospective Rotterdam Study with data on anthropometrics and current depressive symptoms were studied post hoc (data were collected between September 1993 and December 2011). The association between antidepressant use, derived from pharmacy records, and change in body mass index (BMI) between repeated examination rounds was analyzed. Current depressive symptoms (assessed by questionnaire) and baseline BMI (for the change in BMI analysis only) were deemed important covariates. Additional analyses were stratified by sex and restricted to long-term use (≥ 90 days) and by level of binding affinity to the serotonin reuptake transporter (denoted as hSERT antidepressants). RESULTS: Participants who used selective serotonin reuptake inhibitors (SSRIs, n = 198) had a larger increase in BMI compared to nonusers (+0.74 and +0.23 kg/m(2), respectively, P < .001) between repeated examination rounds. No change in BMI was observed for users of tricyclic antidepressants (n = 146) and other antidepressants (n = 57) compared to nonusers. Weight gain was observed only in women who were treated for ≥ 90 days with hSERT antidepressants or SSRIs, and not in men (P value for interaction = .002). CONCLUSIONS: Within our study of older adults, hSERT antidepressants were associated with an increased body weight in women, which is supported by the biological function of serotonin in weight control and the differences in serotonergic signaling between males and females.

24 Article Parental depression and child well-being: young children's self-reports helped addressing biases in parent reports. 2015

Ringoot, Ank P / Tiemeier, Henning / Jaddoe, Vincent W V / So, Pety / Hofman, Albert / Verhulst, Frank C / Jansen, Pauline W. ·The Generation R Study Group, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, PO Box 2060, room KP-2822, 3000 CB Rotterdam, The Netherlands. · Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, PO Box 2060, room KP-2822, 3000 CB Rotterdam, The Netherlands; Department of Psychiatry, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: h.tiemeier@erasmusmc.nl. · The Generation R Study Group, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Psychiatry, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Pediatrics, Erasmus University Medical Center, PO Box 2060, 3000 CB Rotterdam, The Netherlands. · Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, PO Box 2060, room KP-2822, 3000 CB Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry, Riagg Rijnmond, PO Box 711, 3000 AS Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. · Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, PO Box 2060, room KP-2822, 3000 CB Rotterdam, The Netherlands. · The Generation R Study Group, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, PO Box 2060, room KP-2822, 3000 CB Rotterdam, The Netherlands; Institute of Psychology, Faculty of Social Sciences, Erasmus University Rotterdam, Woudestein, T13-01, PO Box 1738, 3000 DR Rotterdam, The Netherlands. ·J Clin Epidemiol · Pubmed #25900418.

ABSTRACT: OBJECTIVES: Effects of maternal and paternal depression on child development are typically evaluated using parental reports of child problems. Yet, parental reports may be biased. METHODS: In a population-based cohort, parents reported lifetime depression (N = 3,178) and depressive symptoms (N = 3,131). Child emotional and behavioral problems were assessed at age 6 years by child self-report using the Berkeley Puppet Interview, by mother report using the Child Behavior Checklist (CBCL), and at age 3 years by father and mother reported CBCLs. RESULTS: Both maternal and paternal depression was associated with more child problems. Associations were of similar strength if child problems were obtained by self-reports. However, if parents reported about their own depression or depressive symptoms and about their child's problems, estimates were generally stronger for associations with the reporting parent's depression as the determinant. For instance, if mothers reported child emotional problems, associations were stronger for maternal (B = 0.27; 95% confidence interval (CI) = 0.19, 0.35) than for paternal lifetime depression (B = 0.12; 95% CI = 0.02, 0.21; P-value for difference = 0.02). CONCLUSION: Depression of mothers and fathers affects young children's well-being. However, if parents reported about their own depression and about child problems, associations were inflated. To accurately estimate effects of parental depression, multiple-source data including young children's perspectives must be considered.

25 Article 24-HOUR ACTIVITY RHYTHM AND SLEEP DISTURBANCES IN DEPRESSION AND ANXIETY: A POPULATION-BASED STUDY OF MIDDLE-AGED AND OLDER PERSONS. 2015

Luik, Annemarie I / Zuurbier, Lisette A / Direk, Neşe / Hofman, Albert / Van Someren, Eus J W / Tiemeier, Henning. ·Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, Amsterdam, The Netherlands. · Departments of Integrative Neurophysiology and Medical Psychology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University and Medical Center, Amsterdam, The Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands. ·Depress Anxiety · Pubmed #25693731.

ABSTRACT: BACKGROUND: Disturbed circadian rhythms have been associated with depression and anxiety, but it is unclear if disturbances in the 24-hr activity rhythm and sleep are independently and specifically related to these disorders. METHODS: In 1,714 middle-aged and elderly participants of the Rotterdam Study, we collected actigraphy recordings of at least 96 hr (138 ± 14 hr, mean ± standard deviation). Activity rhythms were quantified calculating the fragmentation of the rhythm, stability of the rhythm over days, and timing of the rhythm. Total sleep time, sleep onset latency, and wake after sleep onset were also estimated with actigraphy. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale, persons with clinically relevant depressive symptoms were interviewed to diagnose DSM-IV-depressive disorder. Anxiety disorders were determined with the Munich version of the Composite International Diagnostic Interview. RESULTS: More fragmented rhythms were associated with clinically relevant depressive symptoms (odds ratio (OR): 1.27, 95% confidence interval (CI): 1.04;1.54) and anxiety disorders (OR: 1.39, 95% CI: 1.14;1.70) after covariate adjustment. Less stable rhythms, longer sleep onset latency, and more wake after sleep onset were related to clinically relevant depressive symptoms or anxiety disorders only if not adjusted for covariates and other activity rhythm and sleep indicators. CONCLUSIONS: Our study in middle-aged and elderly persons suggests that fragmentation of the 24-hr activity rhythm is associated with depression and anxiety. Moreover, this association also largely accounts for the effect of disturbed sleep on these psychiatric disorders.

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