Academic Center for Population Neuroscience

Last updated: 365 days ago.

Our overall aim is to advance diagnosis, prevention and treatment of neurodevelopmental and neurodegenerative disorders. The specific objectives of the ACE Population Neuroscience are to:

  • Translate novel findings derived from laboratory functional studies into child, adult and elderly populations
  • Advance mechanistic insights from epidemiological association studies using state-of-the-art animal, cell biological and genetic methods by which we will be able to:
    • Unravel etiologic mechanisms and disease pathophysiology.
    • Discover efficacious therapeutic treatments and novel preventative strategies for brain diseases.

To continue building a comprehensive neuroscience research program committed to implementing a multidisciplinary and translational research approach bridging fundamental neurobiological, translational, clinical, and epidemiological methodologies.

In particular, we aim to facilitate the ability of geneticists and biologists at the Erasmus MC to rapidly test their hypotheses in clinical and epidemiological settings. Conversely, we intend to position modern epidemiological research to generate hypotheses that can be further examined using state-of-the-art cellular and molecular biology.

Currently, we already have a workflow to integrate clinical and community-dwelling populations across the whole range of neuroscience as well as covering fundamental, clinical and population-based aspects of neuroscience. We combine state-of-the-art technologies with novel methodology and statistics to quickly generate new hypotheses and find cross-links between fields.

Academic Center of Excellence

Research Activities

The ACE Population Neuroscience has established a research program where epidemiologists and clinical researchers are working side-by-side with neuroscientists, geneticists, and medical ethicists to study mechanisms from their cellular and genetic basis to behavior and cognitive function.

Our ACE is built upon unique strengths of the Erasmus MC. The population-based cohorts Rotterdam Study and Generation R are renowned worldwide for neurodegenerative, mental health and neurodevelopmental research, comprising the world's largest population-based brain imaging datasets in both children and adults.

The neurobiology and human genetics laboratories at the Erasmus MC are internationally leading in the molecular and cellular research of affect, cognition, and movement. Numerous international collaborations are ongoing. Large scale imaging data, genetic data, epigenetic data are all analyzed in several consortia and resulting in many top publications, funded projects and formalized scientist exchange programmes among which are collaborations with Harvard School of Public Health, Karolinska Institute, UCL, UCopenhagen, King's College London, Bristol, UCLA and Columbia University. Present research activities bring together animal researchers, stem-cell researchers, geneticists, medical ethicists, clinical researchers and epidemiologists conducting life course neuroscience and mental health projects. Population Neuroscience is uniquely positioned internationally to make major advances in our understanding of brain disease pathogenesis, therapeutic discovery, and preventative treatment strategies.

Type of

Collaborations

The neurobiology and human genetics laboratories at the Erasmus MC are internationally leading in the molecular and cellular research of affect, cognition, and movement. Numerous international collaborations are ongoing. Large scale imaging data, genetic data, epigenetic data are all analyzed in several consortia and resulting in many top publications, funded projects and formalized scientist exchange programmes among which are collaborations with Harvard School of Public Health, Karolinska Institute, UCL, Columbia, UCopenhagen, King’s College London, Bristol, UCLA and Columbia University. Population Neuroscience is uniquely positioned internationally to make major advances in our understanding of brain disease pathogenesis, therapeutic discovery, and preventative treatment strategies.

Educational

Contributions

The ACE Population Neuroscience is strongly involved in education at different levels, in particular of graduate and postgraduate students. Postgraduate education: The investigators participate in and coordinate NIHES courses (Master Programmes Clinical Epidemiology, Epidemiology, Genetic Epidemiology with several specific courses), Molecular Medicine, and Neuroscience ONWAR Research Schools.

Also, the ACE investigators teach several courses in the Erasmus Summer Program. These MSc programmes have received accreditation by KNAW, NVAO, and Netherlands Epidemiology Society. At the last NIHES graduation (August 2018), 60 students received their MSc. Over 50% of students are from outside the Netherlands. A substantial proportion of the graduating students were trained in this ACE.

Graduate education: coordination and participation in medical student's research electives.

Undergraduate education: Medical students' master methods of education.

Bachelor program: Participation in and organization (Psychiatry, Medical Ethics) of Minor programs.

More than 50 PhD students are supervised by the leading investigators of this ACE. International teaching: The investigators teach internationally, e.g. at the Harvard School of Public Heatlh (Child Psychiatry), Koc Uni Turkey (Research Methods) and in the Boston Uni/Bordeaux programme (Neuroepiomics)

Patient

Care Activities

By design this ACE focuses on translational research in clinical and general population research. Although patient care is currently not a primary focus, in the future patient care in adult psychiatry (mood disorders, psychosis), child psychiatry (ADHD, autism) and neurology (Parkinson, dementia) will be incorporated into this ACE.

Thus diagnosis codes have not been included at this stage, in order to remain focused on topics of broad neuropsychiatric clinical relevance. Furthermore, many leading investigators in this ACE have an appointment in patient care, and thus clinical translation of scientific findings remains an important goal with ensured feasibility.

Societal Relevance to Research, Education and Patient Care

The societal relevance of this ACE on prevention is documented by the research agendas, the impact of the publications measures by media coverage, the collaboration with industry and importantly by the societal impact of the diseases studied. Dementia, depression, and neurodevelopmental disorders such as autism and schizophrenia are among the diseases with the highest global burden of disease.

Past research conducted by investigators of this ACE contributed to the World Alzheimer Report, the WHO Alzheimer Report, Deltaplan Dementie, and several Endocrinological guidelines (Endocrine Society, American Thyroid Association, Guidelines for the Management of Subclinical Hypothyroidism).

Publications of the ACE investigators documenting the decrease in incidence of dementia, the use of lithium in post-partum psychosis and the potential side effects of antidepressants during pregnancy have been incorporated in standard textbooks, educational or patient information material.

Viability of Research, Education and Patient Care

The investigators of the Population Neuroscience ACE collaborate on joint projects, organize meetings and seminars, and supervise PhD students across disciplines and departments. Many of the meetings are informal but with the final constitution a yearly symposium and a bi-annual retreat will be held. Strong collaborations have been established within the Medical Delta. Also, a new Master of Population Neuroscience will be established (embedded in NIHES and Neuroscience) to attract and train talent. The investigators are highly internationally visible and well integrated in national and international research consortia.

The ACE has attracted international students from more than 17 countries, partly in the context of European exchange programmes (ERAWEB, Portuguese National exchange, China Scholarship Council, Brazil's Science without Borders). Several of the graduate PhD students have started international careers (e.g. tenure track New York University, assistant professor Montreal University) or have been promoted to associate professor at the EMC or other Dutch institutions.

Key and relevant publications of the last five years

  • Ikram MA, Fornage M, Smith AV et al. Common variants at 6q22 and 17q21 are associated with intracranial volume. Nature Genetics. 2012;44(5):539-44
  • Van Esbroeck ACM*, Janssen APA*, Cognetta AB 3rd*, Ogasawara D*, Shpak G, van der Kroeg M, Kantae V, Baggelaar MP, de Vrij FMS, Deng H, Allarà M, Fezza F, Lin Z, van der Wel T, Soethoudt M, Mock ED, den Dulk H, Baak IL, Florea BI, Hendriks G, De Petrocellis L, Overkleeft HS, Hankemeier T, De Zeeuw CI, Di Marzo V, Maccarrone M, Cravatt BF, Kushner SAξ, van der Stelt Mξ (2017). Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474. Science, 356(6342): 1084-1087.
  • Gottlieb DJ, Hek K, Chen TH, Watson NF, Eiriksdottir G, Byrne EM, Cornelis M, Warby SC, Bandinelli S, Cherkas L, Evans DS, Grabe HJ, Lahti J, Li M, Lehtimaki T, Lumley T, Marciante KD, Perusse L, Psaty BM, Robbins J, Tranah GJ, Vink JM, Wilk JB, Stafford JM, Bellis C, Biffar R, Bouchard C, Cade B, Curhan GC, Eriksson JG, Ewert R, Ferrucci L, Fulop T, Gehrman PR, Goodloe R, Harris TB, Heath AC, Hernandez D, Hofman A, Hottenga JJ, Hunter DJ, Jensen MK, Johnson AD, Kahonen M (…), Martin NG, O'Connor GT, Stone KL, Tanaka T, Viikari J, Gharib SA, Punjabi NM, Raikkonen K, Volzke H, Mignot E, Tiemeier H. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study. Mol Psychiatry 2015;20(10):1232-9.
  • Bergink V, Armangue T, Titulaer M, Markx S, Dalmau J, Kushner SA (2015). Autoimmune encephalitis in postpartum psychosis. American Journal of Psychiatry, 172(9): 901-908.
  • Bergink V, Burgerhout KM, Koorengevel KM, Lambregtse-van den Berg MP, Kushner SA (2015). Treatment of psychosis and mania in the postpartum period. American Journal of Psychiatry, 172(2): 115-123
  • Blanken LM, Mous SE, Ghassabian A, Muetzel RL, Schoemaker NK, El Marroun H, van der Lugt A, Jaddoe VW, Hofman A, Verhulst FC, Tiemeier H, White T. Cortical morphology in 6- to 10-year old children with autistic traits: a population-based neuroimaging study. Am J Psychiatry 2015;172(5):479-86.
  • Verlinden VJ, van der Geest JN, de Bruijn RF, Hofman A, Koudstaal PJ, Ikram MA. Trajectories of decline in cognition and daily functioning in preclinical dementia. Alzheimer Dementia. 2016;12(2):144-53.
  • Han JH, Kushner SA, Yiu AP, Hsiang HL, Buch T, Waisman A, Bontempi B, Neve RL, Frankland PW, Josselyn SA (2009). Selective erasure of a fear memory. Science, 323(5920): 1492-1496.
  • Amin N*, de Vrij FMS*, Baghdadi M*, Brouwer RW, van Rooij J, Jovanonva O, Uitterlinden AG, Hofman A, Janssen HL, Murad SD, Kraaij R, Stedehouder J, van den Hout MC, Kros JM, van IJcken WF, Tiemeier H, Kushner SAξ, van Duijn CMξ (2018). A rare missense variant in RCL1 segregates with depression in extended families. Molecular Psychiatry, 23(5): 1120-1126.
  • De Vrij FMS*, Bouwkamp CG*, Gunhanlar N*, Shpak G, Lendemeijer B, Baghdadi M, Ghazvini M, Li TM, Quadri M, Olgiati S, Breedveld GJ, Coesmans M, Mientjes E, [...], Amin N, Langen CD, Hofman A, Hoogendijk WJ, van Duijn CM, Ikram MA, Vernooij MW, Tiemeier H, Uitterlinden AG, Elgersma Y, Distel B, Gribnau J, White T, Bonifati V, Kushner SA (2018). Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia. Molecular Psychiatry, doi: 10.1038/s41380-017-0004-2.

PhD theses of the last five years

  • Renée de Bruijn, Emerging determinants of dementia
  • Sandra Thijssen, Neurobiological Correlates of Externalizing and Prosocial Behaviour in School-Age Children
  • Saira Mirza, The Interface of Neurology and Psychiatry. Modern Epidemiological Approaches
  • Eirini Pappa, Genetics and Epigentics of children's behavior problems
  • Sabine Mous, The Distracted brain: The neurobiology and neuropsychology of attention-deficit/hyperactivity problems in the general population
  • Akhgar Ghassabian, Neurobiological Pathways to Childhood Psychopathology
  • Veerle Bergink, First-onset postpartum psychosis
  • Jurate Aleknaviciute, Psychological and Neuroendocrine Determinants of Stress Regulation in Women
  • Richard Wesseloo, Bipolar Spectrum Disorder During Pregnancy and the Postpartum Period
  • Christian Bouwkamp, The Genetics of Familial Psychiatric Disorders: Insights into Genes and Mechanisms

Non-scientific publications related to the ACE

  • Vampire in the belly (Vampir im Bauch, Der Spiegel 23/2017: 104-105, 3 June 2017)
  • Een hersencel kweken: de natuur draait er geen hand voor om (de Volkskrant: 9 Apr 2016)
  • Schizofrenie behandelen begint bij begrip (KennisLink: 12 January 2016)
  • Bonsaihersens in een lab-schaaltje (NRC Handelsblad: 29 September 2018)
  • New clues to why a French drug trial went horribly wrong (Science, 8 June 2017)

Principal coordinator(s)