{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T12:57:19Z","timestamp":1785589039145,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","award":["4108\u201000004B"],"award-info":[{"award-number":["4108\u201000004B"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013327","name":"H. Lundbeck A\/S","doi-asserted-by":"publisher","award":["R432\u20102023\u201094"],"award-info":[{"award-number":["R432\u20102023\u201094"]}],"id":[{"id":"10.13039\/501100013327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"abstract":"\n Background<\/jats:title>\n Major depressive disorder (MDD) aggregates in families. The neostriatum, key to reward and attachment circuits, has the highest density of serotonin 4 receptors (5\u2010HT4R). Striatal 5\u2010HT4R is low in MDD and linked to familial depression risk. Poor parental bonding increases depression risk, yet whether nature and nurture converge on 5\u2010HT4R is unknown. We investigated whether parental bonding quality is associated with adult neostriatal 5\u2010HT4R levels and could replicate prior findings on familial predisposition.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Familial predisposition, parental bonding instrument, and positron emission tomography data with [\n 11<\/jats:sup>\n C]SB207145 were available from 70 unmedicated MDD patients and 95 healthy controls (64% female; aged 18\u201357\u2009years). 5\u2010HT4R binding was quantified in the neostriatum and, secondarily, the amygdala, ACC, and neocortex. Linear regression models examined associations among 5\u2010HT4R binding, familial predisposition to depression, and parental bonding, adjusting for sex, age, depression, and tracer mass. Sensitivity analyses were conducted with adjustments for hormonal contraceptives and within the healthy subsample only.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Familial predisposition linked to neostriatal 5\u2010HT4R differently by sex (sex interaction,\n P<\/jats:italic>\n \u2009=\u20090.037): predisposed females had 6.8% higher binding than non\u2010predisposed females (\n P<\/jats:italic>\n \u2009=\u20090.024); males showed no significant difference in association. This was consistent across sensitivity analyses and secondary regions. Parental bonding was not associated with 5\u2010HT4R in any region.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Familial predisposition to depression is associated with neostriatal 5\u2010HT4R in a sexually dimorphic manner, suggesting that inherited depression risk influences the serotonergic system through sex\u2010specific mechanisms. The absence of parental bonding effects suggests that the impact on the serotonergic system may be subtle or compensated for.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/pcn.70112","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T12:19:05Z","timestamp":1785586745000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nature, nurture, and 5\u2010\n \n HT\n 4<\/sub>\n R\n <\/scp>\n : Familial predisposition, not parental bonding, is associated with brain 5\u2010\n \n HT\n 4<\/sub>\n R\n <\/scp>\n in a sex\u2010specific manner"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7953-0838","authenticated-orcid":false,"given":"Randi T.","family":"Kj\u00e6r","sequence":"first","affiliation":[{"name":"Neurobiology Research Unit Rigshospitalet Copenhagen Denmark"},{"name":"Bispebjerg\u2010Frederiksberg Hospital Psychiatric Centre Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin B.","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit Rigshospitalet Copenhagen Denmark"},{"name":"Bispebjerg\u2010Frederiksberg Hospital Psychiatric Centre Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian H. R.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit Rigshospitalet Copenhagen Denmark"},{"name":"Bispebjerg\u2010Frederiksberg Hospital Psychiatric Centre Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jad.2022.03.069","article-title":"The relationship between parental bonding and mood, anxiety and related disorders in adulthood: A systematic review and meta\u2010analysis","volume":"307","author":"Kidd KN","year":"2022","journal-title":"J. Affect. Disord."},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1176\/appi.ajp.157.10.1552","article-title":"Genetic epidemiology of major depression: Review and meta\u2010analysis","volume":"157","author":"Sullivan PF","year":"2000","journal-title":"Am. J. 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