{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:25:23Z","timestamp":1785414323756,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,26]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01AA025066"],"award-info":[{"award-number":["R01AA025066"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R61AA031029"],"award-info":[{"award-number":["R61AA031029"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Prior neuroimaging suggests brain differences between children with attention deficit hyperactivity disorder due to prenatal alcohol exposure (ADHD+PAE) and non-exposed children with ADHD due to other, e.g., familial, causes (ADHD-PAE). There has been interest in regional brain levels of gamma-aminobutyric acid (GABA) and glutamate (Glu) measured\n                    <jats:italic>in vivo<\/jats:italic>\n                    with magnetic resonance spectroscopy (MRS) as possible indicators of local inhibitory, respectively, excitatory activity in ADHD. For the first time, we report here a comparison of GABA and Glu in ADHD+PAE vs. ADHD-PAE.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>At 3 T, we used J-difference-edited single-voxel MRS to assay GABA and Glu in 28 children with ADHD+PAE, 20 with ADHD-PAE, and 28 typically developing (TD) controls, all aged 8-14 years. MRS was sampled from midline anterior middle cingulate cortex (aMCC), the \u201ccognitive cingulate\u201d considered functionally relevant to ADHD. Spectra were fit with custom software, including a unique technique for isolating the GABA signal from the confounding macromolecular baseline (MMBL).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>aMCC GABA was higher in ADHD+PAE and ADHD-PAE than in TD. GABA increased with age in TD, but not in ADHD+PAE or ADHD-PAE. Similar effects were observed for the ratios GABA\/Glu and GABA\/Glx. For GABA+MMBL (GABA+) these effects were not seen, rather GABA+ and MMBL increased with age for the ADHD+PAE group only. No significant effects were found for Glu or Glx.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>GABA in the aMCC does not distinguish the two etiologies of ADHD, rather elevated GABA that follows an abnormal developmental appears to be common to both. High GABA may reflect increased inhibition of the aMCC impairing its cognitive functions. GABA+ results in ADHD may not tract reliably with underlying GABA values. Negative results for Glu and Glx should be reexamined at shorter echo-times.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.25.26354065","type":"posted-content","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T01:25:23Z","timestamp":1779845123000},"source":"Crossref","is-referenced-by-count":0,"title":["Anterior middle cingulate cortex gamma-aminobutyric acid level is elevated in children with both familial and prenatal alcohol exposure-associated attention deficit hyperactivity disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1699-089X","authenticated-orcid":false,"given":"Jeffry R.","family":"Alger","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA"},{"name":"Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"NeuroSpectroScopics LLC, Sherman Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishika","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Farkouh","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Korthas","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Silverberg","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3520-9467","authenticated-orcid":false,"given":"Noriko","family":"Salamon","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Neuroradiology, University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin N.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-7005","authenticated-orcid":false,"given":"Shantanu H.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA"},{"name":"Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-6139","authenticated-orcid":false,"given":"Mary J.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2216-3903","authenticated-orcid":false,"given":"Joseph","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, University of California Los Angeles, CA, USA"},{"name":"Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052802401031000_2026.05.25.26354065v1.1","unstructured":"Alger, J.R. , O\u2019Neill, J. , Ly, R. , Kalender, G. , Joshi, S. , Narr, K. , O\u2019Connor, M.J. , Levitt, J.G. 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