{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T01:07:24Z","timestamp":1768784844297,"version":"3.49.0"},"reference-count":49,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"NIMH Grant","award":["R01MH59990A (JDC)"],"award-info":[{"award-number":["R01MH59990A (JDC)"]}]},{"name":"NIMH Grant","award":["R21MH066748 (JMG)"],"award-info":[{"award-number":["R21MH066748 (JMG)"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Chronic Stress"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p> Using proton magnetic resonance spectroscopy imaging, the effects of early life stress on nonhuman primate striatal neuronal integrity were examined as reflected by N-acetyl aspartate (NAA) concentrations. NAA measures were interrogated through examining their relationship to previously documented early life stress markers\u2014cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and behavioral timidity. Rodent models of depression exhibit increases in neurotrophic effects in the nucleus accumbens. We hypothesized that rearing under conditions of early life stress (variable foraging demand, VFD) would produce persistent elevations of NAA concentrations (in absolute or ratio form) in ventral striatum\/caudate nucleus (VS\/CN) with altered correlation to early life stress markers. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> Eleven bonnet macaque males reared under VFD conditions and seven age-matched control subjects underwent proton magnetic resonance spectroscopy imaging during young adulthood. Voxels were placed over VS\/CN to capture nucleus accumbens. Cisternal cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and response to a human intruder had been previously determined. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> VFD-reared monkeys exhibited significantly increased NAA\/creatine concentrations in right VS\/CN in comparison to normally reared controls, controlling for multiple comparisons. In comparison to controls, VFD cerebrospinal fluid corticotropin-releasing factor concentrations were directly associated with right VS\/CN absolute NAA. Left hippocampal volume was inversely associated with left VS\/CN NAA\/creatine in VFD reared but not in controls. Disruption of a normative inverse correlation between left VS\/CN NAA and body mass was noted in VFD. Only non-VFD subjects exhibited a direct relationship between timidity response to an intruder and right VS\/CN NAA. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Early life stress produced persistent increases in VS\/CN NAA, which demonstrated specific patterns of association (or lack thereof) to early life stress markers in comparison to non-VFD subjects. The data are broadly consistent with a stable nonhuman primate phenotype of anxiety and mood disorder vulnerability whereby in vivo indicators of neuronal integrity, although reduced in hippocampus, are increased in striatum. The findings may provide a catalyst for further studies in humans and other species regarding a reciprocal hippocampal\/nucleus accumbens relationship in affective disorders. <\/jats:p><\/jats:sec>","DOI":"10.1177\/2470547018768450","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T05:14:09Z","timestamp":1524114849000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Early Life Stress Associated With Increased Striatal <i>N<\/i>-Acetyl-Aspartate: Cerebrospinal Fluid Corticotropin-Releasing Factor Concentrations, Hippocampal Volume, Body Mass, and Behavioral Correlates"],"prefix":"10.1177","volume":"2","author":[{"given":"Jeremy D.","family":"Coplan","sequence":"first","affiliation":[{"name":"Department of Psychiatry & Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dunyue","family":"Lu","sequence":"additional","affiliation":[{"name":"McLaren Behavioral Health Services, Flint Township, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander M.","family":"El Sehamy","sequence":"additional","affiliation":[{"name":"State University of New York Downstate College of Medicine, Brooklyn, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheuk","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA"},{"name":"Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA"},{"name":"Department of Radiology, Mount Sinai School of Medicine, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea P.","family":"Jackowski","sequence":"additional","affiliation":[{"name":"Departamento de Psiquiatria, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5783-6181","authenticated-orcid":false,"given":"Chadi G.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles B.","family":"Nemeroff","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of Miami Health Systems, Miami, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Owens","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay J.","family":"Mathew","sequence":"additional","affiliation":[{"name":"Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, TX, USA"},{"name":"Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack M.","family":"Gorman","sequence":"additional","affiliation":[{"name":"Franklin Behavioral Health Care Consultants and Critica LLC, Bronx, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,4,18]]},"reference":[{"key":"bibr1-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(03)00004-0"},{"key":"bibr2-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2010.11.006"},{"key":"bibr3-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.08.021"},{"key":"bibr4-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.4.1619"},{"key":"bibr5-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/S0193-953X(18)30020-0"},{"key":"bibr6-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(93)90189-V"},{"key":"bibr7-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1017\/S109285290001018X"},{"key":"bibr8-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(01)01175-1"},{"key":"bibr9-2470547018768450","doi-asserted-by":"publisher","DOI":"10.4306\/pi.2010.7.4.236"},{"key":"bibr10-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.02.013"},{"key":"bibr11-2470547018768450","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.10m06745"},{"key":"bibr12-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb02141.x"},{"key":"bibr13-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00035-7"},{"key":"bibr14-2470547018768450","doi-asserted-by":"publisher","DOI":"10.3758\/CABN.6.1.79"},{"key":"bibr15-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.07.009"},{"key":"bibr16-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1080\/14660820310006689"},{"key":"bibr17-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.08.018"},{"key":"bibr18-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1002\/dev.1026"},{"key":"bibr19-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2003.08.003"},{"key":"bibr20-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1126\/science.1120972"},{"key":"bibr21-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1037\/a0018464"},{"key":"bibr22-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.7.786"},{"key":"bibr23-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2012.05.009"},{"key":"bibr24-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.49"},{"key":"bibr25-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00653-0"},{"key":"bibr26-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018114"},{"key":"bibr27-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001650404"},{"key":"bibr28-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-10-02908.1986"},{"key":"bibr29-2470547018768450","doi-asserted-by":"publisher","DOI":"10.2165\/11587790-000000000-00000"},{"issue":"2","key":"bibr30-2470547018768450","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.psyneuen.2010.07.011","volume":"36","author":"Coplan JD","year":"2011","journal-title":"Psychoneuroendocrinology"},{"issue":"2","key":"bibr31-2470547018768450","first-page":"185","volume":"33","author":"Heim C","year":"1997","journal-title":"Psychopharmacol Bull"},{"key":"bibr32-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00207-Y"},{"key":"bibr33-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2012.01031.x"},{"key":"bibr34-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0452"},{"key":"bibr35-2470547018768450","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1409"},{"key":"bibr36-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852900002121"},{"key":"bibr37-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1126\/science.6334362"},{"key":"bibr38-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1297-04.2004"},{"key":"bibr39-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1016\/0377-2217(84)90282-0"},{"key":"bibr40-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1177\/001316447303300111"},{"key":"bibr41-2470547018768450","doi-asserted-by":"publisher","DOI":"10.1109\/TAC.1974.1100705"},{"key":"bibr42-2470547018768450","doi-asserted-by":"crossref","unstructured":"Burnham KP, and Anderson DR. 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