Oxytocin receptor mRNA expression in dorsolateral prefrontal cortex in major psychiatric disorders: A human post-mortem study
Open accessAbstract
There is growing interest in oxytocin as a putative treatment for various psychiatric disorders including major depressive disorder, bipolar disorder and schizophrenia/schizoaffective disorder. However, potential alterations in the endogenous brain oxytocin system in these disorders are poorly characterized. Brain expression of oxytocin and its receptor genes in patients with these psychiatric disorders has not been well studied outside the hypothalamus. We measured expression of mRNA for oxytocin and its receptor in the dorsolateral prefrontal cortex of postmortem brains using quantitative polymerase chain reaction in a total of 581 individuals. These individuals either were diagnosed with major depressive disorder (n = 135), bipolar disorder (n = 57), schizophrenia/schizoaffective disorder (n = 169), or were control subjects, defined as individuals with no lifetime history of any of these disorders (n = 220). Diagnoses of major depressive disorder and bipolar disorder were associated with significantly increased oxytocin receptor mRNA levels in the dorsolateral prefrontal cortex. This finding is discussed in light of the extant literature on the dysregulation of oxytocin signaling in individuals with major psychiatric disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Although OXTR mRNA can be measured in some portions of the human cortex, autoradiographic studies of OXTR binding have not generated complementary evidence of functional, cell-surface OXTR in these regions of the cortex in humans or in nonhuman primates.
“Although these studies and others59–61 indicate that OXTR mRNA can be measured in some portions of the human cortex, autoradiographic studies of OXTR binding have not generated complementary evidence of functional, cell-surface OXTR in these regions of the cortex in humans35 or in nonhuman primates39.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [60]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3044 · Cited by 1,688 · see citing works
Diorio, D., Viau, V, & Meaney, M. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-09-03839.1993 · Cited by 1,151 · see citing works
Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells
Rajkowska, G. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00950-1 · Cited by 822 · see citing works
The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings
Strakowski, S. M., DelBello, M. P., & Adler, C. M. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001585 · Cited by 818 · see citing works
Integration of emotion and cognition in the lateral prefrontal cortex
Gray, J. R., Braver, T. S., & Raichle, M. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062381899 · Cited by 792 · see citing works
Raadsheer, F. C., Hoogendijk, W. J. G., Stam, F. C., Tilders, F. J. H., & Swaab, D. F. (2008) · Neuroendocrinology · doi:10.1159/000126778 · Cited by 667 · see citing works
The Peptide That Binds: A Systematic Review of Oxytocin and its Prosocial Effects in Humans
MacDonald, K., & MacDonald, T. M. (2010) · Harvard Review of Psychiatry · doi:10.3109/10673220903523615 · Cited by 585 · see citing works
Purba, J. S. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830020055007 · Cited by 433 · see citing works
Webster, M. J., Knable, M. B., O'Grady, J., Orthmann, J., & Weickert, C. S. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001139 · Cited by 420 · see citing works
Neural circuits mediating stress
López, J. F., Akil, H., & Watson, S. J. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00266-8 · Cited by 373 · see citing works
The role of the prefrontal cortex in higher cognitive functions
Frith, C., & Dolan, R. (1996) · Cognitive Brain Research · doi:10.1016/s0926-6410(96)00054-7 · Cited by 343 · see citing works
Critical Factors in Gene Expression in Postmortem Human Brain: Focus on Studies in Schizophrenia
Lipska, B. K., Deep‐Soboslay, A., Weickert, C. S., Hyde, T. M., Martin, C. E., Herman, M. M., & Kleinman, J. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.019 · Cited by 280 · see citing works
Self-citationWang, S.-S., Kamphuis, W., Huitinga, I., Zhou, J.-N., & Swaab, D. F. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.38 · Cited by 250 · see citing works
Pantazatos, S. P., Huang, Y.-Y., Rosoklija, G. B., Dwork, A. J., Arango, V, & Mann, J. J. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.130 · Cited by 229 · see citing works
Berman, K. F., Illowsky, B. P., & Weinberger, D. R. (1988) · PubMed · doi:10.1001/archpsyc.1988.01800310020002 · Cited by 204 · see citing works
Freeman, S. M., Inoue, K., Smith, A. L., Goodman, M. M., & Young, L. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.03.023 · Cited by 185 · see citing works
SPECT and PET imaging in mood disorders.
George, M. S., Ketter, T. A., & Post, R. M. (1993) · PubMed · Cited by 171 · see citing works
Spencer, S. J., Buller, K. M., & Day, T. A. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.20376 · Cited by 171 · see citing works
Freeman, S. M., Walum, H., Inoue, K., Smith, A. L., Goodman, M. M., Bales, K. L., & Young, L. J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.055 · Cited by 153 · see citing works
Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date
Lee, M. R., Rohn, M. C. H., Tanda, G., & Leggio, L. (2016) · CNS Drugs · doi:10.1007/s40263-016-0313-z · Cited by 97 · see citing works
Self-citationInteraction of prefrontal cortical and hypothalamic systems in the pathogenesis of depression
Swaab, D. F., Fliers, E., Hoogendijk, W. J. G., Veltman, D. J., & Zhou, J. (2000) · Progress in brain research · doi:10.1016/s0079-6123(00)26025-1 · Cited by 81 · see citing works
Hypothalamic oxytocin mRNA expression and melancholic depression
Meynen, G., Unmehopa, U. A., Hofman, M. A., Swaab, D. F., & Hoogendijk, W. J. G. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001911 · Cited by 81 · see citing works
Uhrig, S., Hirth, N., Broccoli, L., von Wilmsdorff, M., Bauer, M., Sommer, C., Zink, M., Steiner, J. H., Frodl, T., Malchow, B., et al. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.04.019 · Cited by 75 · see citing works
Lesse, A., Rether, K., Gröger, N., Braun, K., & Bock, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0043-8 · Cited by 66 · see citing works
Fischer, A. S., Keller, C. J., & Etkin, A. (2016) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2016.02.004 · Cited by 60 · see citing works
Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem
Freeman, S. M., Smith, A. L., Goodman, M. M., & Bales, K. L. (2017) · Social Neuroscience · doi:10.1080/17470919.2016.1156570 · Cited by 51 · see citing works
Dai, D., Li, Q., Zhu, Q., Hu, S., Balesar, R. A., Swaab, D. F., & Bao, A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.76 · Cited by 41 · see citing works
Quintana, D. S. (2018) · OSF Preprints (OSF Preprints) · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 29 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- First MB, Spitzer RL, Gibbon M, Williams JB, 2002. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. SCID-I/P.
Cited by
Sorted by citations
Detection, processing and reinforcement of social cues: regulation by the oxytocin system
Menon, R., & Neumann, I. D. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00759-w · Cited by 100 · see citing works
Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression
Danoff, J. S., Wroblewski, K. L., Graves, A. J., Quinn, G. C., Perkeybile, A. M., Kenkel, W. M., Lillard, T. S., Parikh, H. I., Golino, H. F., Gregory, S. G., et al. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01017-5 · Cited by 85 · see citing works
Freeman, S. M., Palumbo, M. C., Lawrence, R. H., Smith, A. L., Goodman, M. M., & Bales, K. L. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0315-3 · Cited by 82 · see citing works
Oxytocin receptor expression patterns in the human brain across development
Rokicki, J., Kaufmann, T., de Lange, A. G., van der Meer, D., Bahrami, S., Sartorius, A. M., Haukvik, U. K., Steen, N. E., Schwarz, E., Stein, D. J., et al. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01305-5 · Cited by 74 · see citing works
The role of oxytocin and vasopressin dysfunction in cognitive impairment and mental disorders
Abramova, O. V., Zorkina, Y., Ushakova, V. M., Zubkov, E. A., Morozova, A. Y., & Chekhonin, V. P. (2020) · Neuropeptides · doi:10.1016/j.npep.2020.102079 · Cited by 74 · see citing works
Roles of the Oxytocin Receptor (OXTR) in Human Diseases
Pierzynowska, K., Gaffke, L., Żabińska, M., Cyske, Z., Rintz, E., Wiśniewska, K., Podlacha, M., & Węgrzyn, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043887 · Cited by 61 · see citing works
Oxytocin as Treatment for Social Cognition, Not There Yet
Erdozain, A. M., & Peñagarikano, O. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00930 · Cited by 61 · see citing works
Jiang, J., Zou, Y., Xie, C., Yang, M., Tong, Q., Yuan, M.-M., Pei, X., Deng, S., Tian, M., Xiao, L., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.08.023 · Cited by 59 · see citing works
Lee, M. R., & Jayant, R. D. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2959-y · Cited by 38 · see citing works
Self-citationPossible oxytocin-related biomarkers in anxiety and mood disorders
Yoon, S., & Kim, Y. (2022) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2022.110531 · Cited by 37 · see citing works
Intertwined associations between oxytocin, immune system and major depressive disorder
Jiang, J., Yang, M., Tian, M., Chen, Z., Xiao, L., & Gong, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114852 · Cited by 36 · see citing works
Chen, C., Wu, C.-C., Kim, Y., Hsu, W.-Y., Tsai, Y.-C., & Chiu, S. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2359501 · Cited by 33 · see citing works
D’Addario, C., Pucci, M., Bellia, F., Girella, A., Sabatucci, A., Fanti, F., Vismara, M. E. M., Benatti, B., Ferrara, L., Fasciana, F., et al. (2022) · Clinical Epigenetics · doi:10.1186/s13148-022-01264-0 · Cited by 31 · see citing works
Almeida, D. M., Fiori, L. M., Chen, G. G., Aouabed, Z., Lutz, P.-É., Zhang, T., Mechawar, N., Meaney, M. J., & Turecki, G. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105600 · Cited by 26 · see citing works
Szczepanska‐Sadowska, E. K., Wsół, A., Cudnoch‐Jędrzejewska, A., Czarzasta, K., & Żera, T. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11040908 · Cited by 26 · see citing works
Guo, L., Qi, Y., Tan, H., Dai, D., Balesar, R. A., Sluiter, A. A., van Heerikhuize, J. J., Hu, S., Swaab, D. F., & Bao, A. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104266 · Cited by 21 · see citing works
Bánki, L., Büki, A., Horváth, G., Kékesi, G., Kis, G., Somogyvári, F., Jancsó, G., Vécsei, L., Varga, E., & Tuboly, G. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134561 · Cited by 20 · see citing works
Granata, L. E., Valentine, A. A., Hirsch, J. L., & Brenhouse, H. C. (2022) · Developmental Psychobiology · doi:10.1002/dev.22260 · Cited by 19 · see citing works
Vasopressin and oxytocin beyond the pituitary in the human brain
Møller, M. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-820107-7.00002-1 · Cited by 18 · see citing works
Gene Expression Profiling of the Habenula in Rats Exposed to Chronic Restraint Stress
Yoo, H., Kim, H. J., Yang, S. H., Son, G. H., Gim, J., Lee, H. W., & Kim, H. (2022) · Molecules and Cells · doi:10.14348/molcells.2022.2257 · Cited by 17 · see citing works
Chapter 4. Psychoneuroendocrinology
Sforzini, L., Weston, F. I., & Pariante, C. M. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as04 · Cited by 16 · see citing works
Watanasriyakul, W. T., Scotti, M. L., Carter, C. S., McNeal, N., Colburn, W., Wardwell, J., & Grippo, A. J. (2022) · Autonomic Neuroscience · doi:10.1016/j.autneu.2022.102967 · Cited by 14 · see citing works
Zheng, X., Wang, J., Yang, X., Xu, L., Becker, B., Sahakian, B. J., Robbins, T. W., & Kendrick, K. M. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02590-w · Cited by 14 · see citing works
Xie, S., Hu, Y., Fang, L., Chen, S., Botchway, B. O. A., Tan, X., Fang, M., & Hu, Z. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0128 · Cited by 14 · see citing works
The implications of hypothalamic abnormalities for schizophrenia
Bernstein, H., Keilhoff, G., & Steiner, J. H. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819973-2.00008-3 · Cited by 13 · see citing works
Acosta, H., Tuulari, J. J., Kantojärvi, K., Lewis, J. D., Hashempour, N., Scheinin, N. M., Lehtola, S. J., Fonov, V., Collins, D. L., Evans, A. C., et al. (2020) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2020.111207 · Cited by 13 · see citing works
Rodrigues, F. D. S., Jantsch, J., Fraga, G. D. F., Milczarski, V. L. D. C., Dias, V. S., Scheid, C., Merib, J. D. O., Giovernardi, M., & Guedes, R. P. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.04.010 · Cited by 13 · see citing works
Hofmann, J. P., Huber, C. W., Novak, B., Schreckenbach, M., Schubert, C. F., Touma, C., Rutten, B. P. F., & Schmidt, U. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105242 · Cited by 12 · see citing works
Dorsolateral prefrontal cortex sensing analgesia
Ito, E., Oka, K., & Koshikawa, F. (2022) · Biophysics and Physicobiology · doi:10.2142/biophysico.bppb-v19.0014 · Cited by 8 · see citing works
Ludwig, B., Carlberg, L., Kienesberger, K., Swoboda, P., Swoboda, M. M. M., Bernegger, A., Koller, R., Inaner, M., Fuxjäger, M., Zotter, M., et al. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-04031-w · Cited by 7 · see citing works
OXTR-Related Markers in Clinical Depression: a Longitudinal Case–Control Psychotherapy Study
Reiner, I., Gimpl, G., Beutel, M. E., Bakermans‐Kranenburg, M. J., & Frieling, H. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01930-7 · Cited by 5 · see citing works
Das, S. C., Schulmann, A., Callor, W. B., Jerominski, L., Panicker, M. M., Christensen, E. D., Bunney, W. E., Williams, M. E., Coon, H. H., & Vawter, M. P. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.08.144 · Cited by 4 · see citing works
Son, J. J., Suk, J.-W., Garvey, W. F., Edwards, R. T., Leibenluft, E., Blair, J., & Hwang, S. (2025) · Life · doi:10.3390/life15081253 · Cited by 3 · see citing works
Francis, A., Roy, B., & Dwivedi, Y. (2025) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2025.100530 · Cited by 2 · see citing works
Pandamooz, S., Salehi, M. S., Jurek, B., Meinung, C.-P., Azarpira, N., Dianatpour, M., & Neumann, I. D. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10603-4 · Cited by 2 · see citing works
Oxytocin receptor gene single nucleotide polymorphisms in patients with bipolar disorder
Demir, F. Ü., Turan, T., Akalın, H., Özsoy, S., & Dündar, M. (2025) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2025.2472693 · Cited by 1 · see citing works
Das, S. C., Schulmann, A., Callor, W. B., Jerominski, L., Panicker, M. M., Christensen, E. D., Bunney, W. E., Williams, M. E., Coon, H. H., & Vawter, M. P. (2023) · medRxiv · doi:10.1101/2023.01.28.23285121
Okamura, Y., Takayama, S., Namiki, K., Koshikawa, F., & Ito, E. (2024) · Biophysics and Physicobiology · doi:10.2142/biophysico.bppb-v22.0001 · Cited by 1 · see citing works
Wei, S., Tseng, H., Chang, H. H., & Chen, P. S. (2025) · International Journal of Bipolar Disorders · doi:10.1186/s40345-025-00393-8
Ludwig, B., Carlberg, L., Kienesberger, K., Swoboda, P., Swoboda, M. M. M., Bernegger, A., Koller, R., Inaner, M., Fuxjäger, M., Zotter, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20023196
Danoff, J. S., Wroblewski, K. L., Graves, A., Quinn, G. C., Perkeybile, A. M., Kenkel, W. M., Lillard, T. S., Parikh, H. I., Golino, H. F., Gregory, S. G., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13669381
Ludwig, B., Carlberg, L., Kienesberger, K., Swoboda, P., Swoboda, M. M. M., Bernegger, A., Koller, R., Inaner, M., Fuxjäger, M., Zotter, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20023193
Ludwig, B., Carlberg, L., Kienesberger, K., Swoboda, P., Swoboda, M. M. M., Bernegger, A., Koller, R., Inaner, M., Fuxjäger, M., Zotter, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20023190
Williams, A. L., & Blevins, J. E. (2026) · Current Diabetes Reports · doi:10.1007/s11892-026-01640-7
- Authors
- Lee, M. R., Sheskier, M. B., Farokhnia, M., Feng, N., Marenco, S., Lipska, B. K., & Leggio, L.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lee, M.R.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 96
- Pages
- 143-147
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC12258498
- OpenAlex
- W2805402268
- Cited by
- 44
- References
- 29
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 13 · 2021: 8 · 2020: 3 · 2019: 1 · 2018: 2
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NIH) (ZIA-AA000218)
- NIMH IRP (ZIC MH002903-11)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin receptor, oxytocin, dorsolateral prefrontal cortex, major depressive disorder, bipolar disorder, schizophrenia, schizoaffective disorder, gene expression, postmortem brain, oxytocin signaling, mental illness
- MeSH terms
- Adult, Autopsy, Bipolar Disorder, Brain, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Oxytocin, Psychotic Disorders, RNA, Messenger, Schizophrenia, Case-Control Studies, Prefrontal Cortex, Receptors, Oxytocin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
