{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:00:39Z","timestamp":1784721639852,"version":"3.55.0"},"reference-count":86,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["01KU2004"],"award-info":[{"award-number":["01KU2004"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["403694598"],"award-info":[{"award-number":["403694598"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["GR 1912\/13-1"],"award-info":[{"award-number":["GR 1912\/13-1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["ERAPERMED2019-108"],"award-info":[{"award-number":["ERAPERMED2019-108"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsche Forschungsgemeinschaft","award":["01KU2004"],"award-info":[{"award-number":["01KU2004"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["403694598"],"award-info":[{"award-number":["403694598"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["GR 1912\/13-1"],"award-info":[{"award-number":["GR 1912\/13-1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["ERAPERMED2019-108"],"award-info":[{"award-number":["ERAPERMED2019-108"]}]},{"name":"German Federal State of Mecklenburg-West Pomerania","award":["01KU2004"],"award-info":[{"award-number":["01KU2004"]}]},{"name":"German Federal State of Mecklenburg-West Pomerania","award":["403694598"],"award-info":[{"award-number":["403694598"]}]},{"name":"German Federal State of Mecklenburg-West Pomerania","award":["GR 1912\/13-1"],"award-info":[{"award-number":["GR 1912\/13-1"]}]},{"name":"German Federal State of Mecklenburg-West Pomerania","award":["ERAPERMED2019-108"],"award-info":[{"award-number":["ERAPERMED2019-108"]}]},{"name":"Siemens Healthcare","award":["01KU2004"],"award-info":[{"award-number":["01KU2004"]}]},{"name":"Siemens Healthcare","award":["403694598"],"award-info":[{"award-number":["403694598"]}]},{"name":"Siemens Healthcare","award":["GR 1912\/13-1"],"award-info":[{"award-number":["GR 1912\/13-1"]}]},{"name":"Siemens Healthcare","award":["ERAPERMED2019-108"],"award-info":[{"award-number":["ERAPERMED2019-108"]}]},{"name":"ERA PerMed","award":["01KU2004"],"award-info":[{"award-number":["01KU2004"]}]},{"name":"ERA PerMed","award":["403694598"],"award-info":[{"award-number":["403694598"]}]},{"name":"ERA PerMed","award":["GR 1912\/13-1"],"award-info":[{"award-number":["GR 1912\/13-1"]}]},{"name":"ERA PerMed","award":["ERAPERMED2019-108"],"award-info":[{"award-number":["ERAPERMED2019-108"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to disentangle the effects of various genetic factors on hippocampal subfield volumes using three different approaches: a biologically driven candidate gene approach, a hypothesis-free GWAS approach, and a polygenic approach, where AD risk alleles are combined with a polygenic risk score (PRS). The impact of these genetic factors was investigated in a large dementia-free general population cohort from the Study of Health in Pomerania (SHIP, n = 1806). Analyses were performed using linear regression models adjusted for biological and environmental risk factors. Hippocampus subfield volume alterations were found for APOE \u03b54, BDNF Val, and 5-HTTLPR L allele carriers. In addition, we were able to replicate GWAS findings, especially for rs17178139 (MSRB3), rs1861979 (DPP4), rs7873551 (ASTN2), and rs572246240 (MAST4). Interaction analyses between the significant SNPs as well as the PRS for AD revealed no significant results. Our results confirm that hippocampal volume reductions are influenced by genetic variation, and that different variants reveal different association patterns that can be linked to biological processes in neurodegeneration. Thus, this study underlines the importance of specific genetic analyses in the quest for acquiring deeper insights into the biology of hippocampal volume loss, memory impairment, depression, and neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms24021120","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T01:36:17Z","timestamp":1673228177000},"page":"1120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population"],"prefix":"10.3390","volume":"24","author":[{"given":"Kevin","family":"Kirchner","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9067-8170","authenticated-orcid":false,"given":"Linda","family":"Garvert","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Wittfeld","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Centre for Neurodegenerative Diseases (DZNE), Site Rostock\/Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3095-8362","authenticated-orcid":false,"given":"Sabine","family":"Ameling","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1884-5784","authenticated-orcid":false,"given":"Robin","family":"B\u00fclow","sequence":"additional","affiliation":[{"name":"Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-4579","authenticated-orcid":false,"given":"Henriette","family":"Meyer zu Schwabedissen","sequence":"additional","affiliation":[{"name":"Department Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Nauck","sequence":"additional","affiliation":[{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"},{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"V\u00f6lzke","sequence":"additional","affiliation":[{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"},{"name":"Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Grabe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Centre for Neurodegenerative Diseases (DZNE), Site Rostock\/Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1757-7768","authenticated-orcid":false,"given":"Sandra","family":"Van der Auwera","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Centre for Neurodegenerative Diseases (DZNE), Site Rostock\/Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e591","DOI":"10.1212\/NXG.0000000000000591","article-title":"Genetic Influences on Hippocampal Subfields: An Emerging Area of Neuroscience Research","volume":"7","author":"Evans","year":"2021","journal-title":"Neurol. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13624","DOI":"10.1038\/ncomms13624","article-title":"Novel genetic loci associated with hippocampal volume","volume":"8","author":"Hibar","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1177\/0004867418824021","article-title":"The effects of childhood trauma on adolescent hippocampal subfields","volume":"53","author":"Malhi","year":"2019","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.bbr.2016.09.038","article-title":"Roles of hippocampal subfields in verbal and visual episodic memory","volume":"317","author":"Zammit","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.tins.2021.10.003","article-title":"The many dimensions of human hippocampal organization and (dys)function","volume":"44","author":"Genon","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/hipo.20573","article-title":"Hippocampal volume and asymmetry in mild cognitive impairment and Alzheimer\u2019s disease: Meta-analyses of MRI studies","volume":"19","author":"Shi","year":"2009","journal-title":"Hippocampus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/jnnp-2014-310095","article-title":"Risk factors for predicting progression from mild cognitive impairment to Alzheimer\u2019s disease: A systematic review and meta-analysis of cohort studies","volume":"87","author":"Li","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"705030","DOI":"10.3389\/fnagi.2021.705030","article-title":"Altered Volume and Structural Connectivity of the Hippocampus in Alzheimer\u2019s Disease and Amnestic Mild Cognitive Impairment","volume":"13","author":"Feng","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"146591","DOI":"10.1016\/j.brainres.2019.146591","article-title":"The association between hippocampal subfield volumes in mild cognitive impairment and conversion to Alzheimer\u2019s disease","volume":"1728","author":"Izzo","year":"2020","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101904","DOI":"10.1016\/j.nicl.2019.101904","article-title":"Hippocampal volume across age: Nomograms derived from over 19,700 people in UK Biobank","volume":"23","author":"Nobis","year":"2019","journal-title":"Neuroimage Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1038\/s41380-018-0262-7","article-title":"Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes","volume":"25","author":"Rokicki","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.arr.2016.02.002","article-title":"Apolipoprotein E (APOE) \u03b54 and episodic memory decline in Alzheimer\u2019s disease: A review","volume":"27","author":"Antoine","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jpsychires.2021.09.029","article-title":"ApoE4 increases susceptibility to stress-induced age-dependent depression-like behavior and cognitive impairment","volume":"143","author":"Zhang","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1037\/neu0000750","article-title":"Depression associated with APOE status and hippocampal volume but not cognitive decline in older adults aging with traumatic brain injury","volume":"35","author":"Vervoordt","year":"2021","journal-title":"Neuropsychology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bonk, S., Kirchner, K., Ameling, S., Garvert, L., V\u00f6lzke, H., Nauck, M., V\u00f6lker, U., Grabe, H.J., and Van der Auwera, S. (2022). APOE \u03b54 in Depression-Associated Memory Impairment-Evidence from Genetic and MicroRNA Analyses. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071560"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1007\/s00429-020-02125-3","article-title":"Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-\u03b54 in middle-age cognitively unimpaired individuals from the ALFA study","volume":"225","author":"Operto","year":"2020","journal-title":"Brain Struct. Funct."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"721","DOI":"10.3233\/JAD-200132","article-title":"Interaction Between BDNF Val66Met and APOE4 on Biomarkers of Alzheimer\u2019s Disease and Cognitive Decline","volume":"78","author":"Stonnington","year":"2020","journal-title":"JAD"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1038\/tp.2011.72","article-title":"BDNF val66met affects hippocampal volume and emotion-related hippocampal memory activity","volume":"2","author":"Molendijk","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.neubiorev.2014.03.011","article-title":"The association of the BDNF Val66Met polymorphism and the hippocampal volumes in healthy humans: A joint meta-analysis of published and new data","volume":"42","author":"Harrisberger","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.14715\/cmb\/2022.68.4.6","article-title":"Association of Met\/Val polymorphism of BDNF gene with Alzheimer\u2019s disease in Chinese patients","volume":"68","author":"Li","year":"2022","journal-title":"Cell. Mol. Biol."},{"key":"ref_21","first-page":"7117613","article-title":"BDNF Genetic Variant and Its Genotypic Fluctuation in Major Depressive Disorder","volume":"2021","year":"2021","journal-title":"Behav. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00429-009-0203-y","article-title":"Brain volumes and Val66Met polymorphism of the BDNF gene: Local or global effects?","volume":"213","author":"Toro","year":"2009","journal-title":"Brain Struct. Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.neubiorev.2015.04.017","article-title":"BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders: A systematic review and meta-analysis","volume":"55","author":"Harrisberger","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1126\/science.1129837","article-title":"Common Kibra alleles are associated with human memory performance","volume":"314","author":"Papassotiropoulos","year":"2006","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/jnc.12480","article-title":"KIBRA (KIdney\/BRAin protein) regulates learning and memory and stabilizes Protein kinase M\u03b6","volume":"128","author":"Duning","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fncel.2019.00137","article-title":"The Neuroprotection of KIBRA in Promoting Neuron Survival and Against Amyloid \u03b2-Induced Apoptosis","volume":"13","author":"Song","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.psychres.2015.01.012","article-title":"KIBRA genetic polymorphism and cognitive dysfunction in depression","volume":"226","author":"Liu","year":"2015","journal-title":"Psychiatry Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14218","DOI":"10.1523\/JNEUROSCI.3292-11.2011","article-title":"KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing","volume":"31","author":"Kauppi","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13088","DOI":"10.1523\/JNEUROSCI.1406-13.2013","article-title":"KIBRA polymorphism is associated with individual differences in hippocampal subregions: Evidence from anatomical segmentation using high-resolution MRI","volume":"33","author":"Palombo","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/npp.2015.203","article-title":"Impact of KIBRA Polymorphism on Memory Function and the Hippocampus in Older Adults","volume":"41","author":"Witte","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112550","DOI":"10.1016\/j.bbr.2020.112550","article-title":"Interaction of COMT and KIBRA modulates the association between hippocampal structure and episodic memory performance in healthy young adults","volume":"384","author":"Wang","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1503\/jpn.150339","article-title":"COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume","volume":"42","author":"Hayes","year":"2017","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.2147\/NDT.S199598","article-title":"COMT polymorphism regulates the hippocampal subfield volumes in first-episode, drug-naive patients with major depressive disorder","volume":"15","author":"Otsuka","year":"2019","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ibror.2019.05.001","article-title":"COMT val158met is not associated with A\u03b2-amyloid and APOE \u03b54 related cognitive decline in cognitively normal older adults","volume":"6","author":"Porter","year":"2019","journal-title":"IBRO Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neulet.2011.12.060","article-title":"Using a cognitive endophenotype to identify risk genes for depression","volume":"510","author":"Haeffel","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.pscychresns.2007.01.005","article-title":"The COMT Val158Met polymorphism and temporal lobe morphometry in healthy adults","volume":"155","author":"Taylor","year":"2007","journal-title":"Psychiatry Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1097\/WNR.0b013e3282f5f784","article-title":"Impact of catechol-O-methyltransferase Val(108\/158) Met genotype on hippocampal and prefrontal gray matter volume","volume":"19","author":"Cerasa","year":"2008","journal-title":"Neuroreport"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neuroimage.2008.10.064","article-title":"Impact of interacting functional variants in COMT on regional gray matter volume in human brain","volume":"45","author":"Honea","year":"2009","journal-title":"Neuroimage"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1176\/appi.ajp.2018.18070881","article-title":"No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples","volume":"176","author":"Border","year":"2019","journal-title":"Am. J. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000321834","article-title":"Smaller hippocampus volume is associated with short variant of 5-HTTLPR polymorphism in medication-free major depressive disorder patients","volume":"63","author":"Eker","year":"2011","journal-title":"Neuropsychobiology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/mp.2008.62","article-title":"Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression","volume":"13","author":"Frodl","year":"2008","journal-title":"Mol. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9917","DOI":"10.1523\/JNEUROSCI.3113-13.2014","article-title":"Additive gene-environment effects on hippocampal structure in healthy humans","volume":"34","author":"Rabl","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e445","DOI":"10.1038\/tp.2014.85","article-title":"Association between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: A longitudinal prospective study","volume":"4","author":"Little","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1017\/neu.2015.25","article-title":"Impact of monoamine-related gene polymorphisms on hippocampal volume in treatment-resistant depression","volume":"27","author":"Phillips","year":"2015","journal-title":"Acta Neuropsychiatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1017\/neu.2013.3","article-title":"Hippocampal volume and serotonin transporter polymorphism in major depressive disorder","volume":"25","author":"Ahdidan","year":"2013","journal-title":"Acta Neuropsychiatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5973","DOI":"10.1002\/hbm.25662","article-title":"Group-guided individual functional parcellation of the hippocampus and application to normal aging","volume":"42","author":"Zhang","year":"2021","journal-title":"Hum. Brain Mapp."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/nan.12529","article-title":"Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer\u2019s disease","volume":"45","author":"Tzioras","year":"2019","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3389\/fnmol.2018.00156","article-title":"Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders","volume":"11","author":"Tsai","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/14728222.2019.1572747","article-title":"Neuronal and behavioral plasticity: The role of serotonin and BDNF systems tandem","volume":"23","author":"Popova","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Weerasinghe-Mudiyanselage, P.D.E., Ang, M.J., Kang, S., Kim, J.-S., and Moon, C. (2022). Structural Plasticity of the Hippocampus in Neurodegenerative Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063349"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3389\/fnins.2015.00160","article-title":"Functional optical probing of the hippocampal trisynaptic circuit in vitro: Network dynamics, filter properties, and polysynaptic induction of CA1 LTP","volume":"9","author":"Stepan","year":"2015","journal-title":"Front. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2015.12.006","article-title":"Hippocampal neurogenesis: Learning to remember","volume":"138\u2013140","author":"Lazarov","year":"2016","journal-title":"Prog. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s40120-022-00338-8","article-title":"Alzheimer\u2019s Disease: Epidemiology and Clinical Progression","volume":"11","author":"Byrnes","year":"2022","journal-title":"Neurol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3233\/JAD-2012-129001","article-title":"Molecular Mechanisms of Amyloid Oligomers Toxicity","volume":"33","author":"Kayed","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ebiom.2016.03.035","article-title":"The Role of Amyloid-\u03b2 Oligomers in Toxicity, Propagation, and Immunotherapy","volume":"6","author":"Sengupta","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.pnpbp.2011.09.010","article-title":"Genetic epistasis between the brain-derived neurotrophic factor Val66Met polymorphism and the 5-HTT promoter polymorphism moderates the susceptibility to depressive disorders after childhood abuse","volume":"36","author":"Grabe","year":"2012","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"fcaa176","DOI":"10.1093\/braincomms\/fcaa176","article-title":"The genetics of circulating BDNF: Towards understanding the role of BDNF in brain structure and function in middle and old ages","volume":"2","author":"Li","year":"2020","journal-title":"Brain Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5455","DOI":"10.1523\/JNEUROSCI.5123-04.2005","article-title":"ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin","volume":"25","author":"Teng","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13041-018-0411-6","article-title":"proBDNF is modified by advanced glycation end products in Alzheimer\u2019s disease and causes neuronal apoptosis by inducing p75 neurotrophin receptor processing","volume":"11","author":"Fleitas","year":"2018","journal-title":"Mol. Brain"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41398-021-01667-2","article-title":"proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model","volume":"11","author":"Yang","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.nbd.2017.05.007","article-title":"Molecular imaging of serotonin degeneration in mild cognitive impairment","volume":"105","author":"Smith","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.tins.2004.08.001","article-title":"BDNF and 5-HT: A dynamic duo in age-related neuronal plasticity and neurodegenerative disorders","volume":"27","author":"Mattson","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2014.10.002","article-title":"Integrating the monoamine, neurotrophin and cytokine hypotheses of depression--a central role for the serotonin transporter?","volume":"147","author":"Haase","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s00213-018-4950-4","article-title":"Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression","volume":"235","author":"Levy","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.euroneuro.2011.10.003","article-title":"Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy","volume":"22","author":"Porcelli","year":"2012","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jad.2021.02.052","article-title":"Developmental Antecedents of Adult Macaque Neurogenesis: Early-Life Adversity, 5-HTTLPR Polymorphisms, and Adolescent Hippocampal Volume","volume":"286","author":"Schoenfeld","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2014.02.008","article-title":"Methionine sulfoxide reductase B3 deficiency inhibits cell growth through the activation of p53-p21 and p27 pathways","volume":"547","author":"Lee","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3233\/JAD-170459","article-title":"Methionine Sulfoxide Reductase-B3 (MsrB3) Protein Associates with Synaptic Vesicles and its Expression Changes in the Hippocampi of Alzheimer\u2019s Disease Patients","volume":"60","author":"Adams","year":"2017","journal-title":"JAD"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/PSY.0000000000000796","article-title":"Association of Plasma DPP4 Activity and Brain-Derived Neurotrophic Factor With Moderate to Severe Depressive Symptoms in Patients With Type 2 Diabetes: Results From a Cross-Sectional Study","volume":"82","author":"Zheng","year":"2020","journal-title":"Psychosom. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"E9717","DOI":"10.1073\/pnas.1809382115","article-title":"ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins","volume":"115","author":"Behesti","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/YPG.0000000000000296","article-title":"Rare copy number variants in ASTN2 gene in patients with neurodevelopmental disorders","volume":"31","author":"Bauleo","year":"2021","journal-title":"Psychiatr. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e372","DOI":"10.1093\/ije\/dyac034","article-title":"Cohort Profile Update: The Study of Health in Pomerania (SHIP)","volume":"51","author":"Schmidt","year":"2022","journal-title":"Int. J. Epidemiol."},{"key":"ref_73","unstructured":"Oswald, W.D., and Fleischmann, U.M. (1999). N\u00fcrnberger-Alters-Inventar: (NAI). NAI-Testmanual und Textband, Hogrefe."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e12737","DOI":"10.1111\/gbb.12737","article-title":"Sex effects for the interaction of dopamine related genetic variants for COMT and BDNF on declarative memory performance","volume":"20","author":"Terock","year":"2021","journal-title":"Genes Brain Behav."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0022-3956(94)90036-1","article-title":"Reliability and Validity Studies of the WHO-Composite International Diagnostic Interview (CIDI: A Critical Review","volume":"28","author":"Wittchen","year":"1994","journal-title":"J. Psychiatr. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1007\/s001270050095","article-title":"Test-retest reliability of the computerized DSM-IV version of the Munich-Composite International Diagnostic Interview (M-CIDI)","volume":"33","author":"Wittchen","year":"1998","journal-title":"Soc. Psychiatry Psychiatr. Epidemiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","article-title":"The PHQ-9: Validity of a Brief Depression Severity Measure","volume":"16","author":"Kroenke","year":"2001","journal-title":"J. Gen. Intern. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.3174\/ajnr.A4805","article-title":"Relationship between APOE Genotype and Structural MRI Measures throughout Adulthood in the Study of Health in Pomerania Population-Based Cohort","volume":"37","author":"Habes","year":"2016","journal-title":"AJNR. Am. J. Neuroradiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1038\/s41467-019-09718-5","article-title":"Polygenic prediction via Bayesian regression and continuous shrinkage priors","volume":"10","author":"Ge","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing","volume":"51","author":"Kunkle","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5932","DOI":"10.1002\/hbm.22595","article-title":"Alexithymia and brain gray matter volumes in a general population sample","volume":"35","author":"Grabe","year":"2014","journal-title":"Hum. Brain Mapp."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Hosten, N., B\u00fclow, R., V\u00f6lzke, H., Domin, M., Schmidt, C.O., Teumer, A., Ittermann, T., Nauck, M., Felix, S.B., and D\u00f6rr, M. (2022). SHIP-MR and Radiology: 12 Years of Whole-Body Magnetic Resonance Imaging in a Single Center. Healthcare, 10.","DOI":"10.3390\/healthcare10010033"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.neuroimage.2015.04.042","article-title":"A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI","volume":"115","author":"Iglesias","year":"2015","journal-title":"Neuroimage"},{"key":"ref_85","first-page":"36","article-title":"Involvement of BDNF in age-dependent alterations in the hippocampus","volume":"2","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"ref_86","unstructured":"StataCorp LLC (2016). STATA 14, StataCorp."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:01:22Z","timestamp":1760119282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":86,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021120"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021120","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]}}}