Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study

Lee, Mary R.; Schwandt, Melanie L.; Sankar, Vignesh; Suchankova, Petra; Sun, Hui; Leggio, Lorenzo

doi:10.1016/j.psyneuen.2017.07.481

Cited by 27 publications

(15 citation statements)

References 31 publications

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“…Although these studies and others 59 – 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 humans 35 or in nonhuman primates 39 . This anatomical contradiction is also at odds with the numerous in vivo fMRI studies in humans that report changes in cortical BOLD signal after IN-OXT treatment (see the sixty-six publications using fMRI and IN-OXT that were included in this meta-analysis 62 ).…”

Section: Discussionmentioning

confidence: 94%

Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain

et al. 2018

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The prosocial hormone oxytocin (OXT) has become a new target for research on the etiology and treatment of autism spectrum disorder (ASD), a condition characterized by deficits in social function. However, it remains unknown whether there are alterations in OXT receptor (OXTR) levels in the ASD brain. This study quantified the density of OXTR and of the structurally related vasopressin 1a receptor (AVPR1a) in postmortem brain tissue from individuals with ASD and typically developing individuals. We analyzed two regions known to contain OXTR across all primates studied to date: the nucleus basalis of Meynert (NBM), which mediates visual attention, and the superior colliculus, which controls gaze direction. In the NBM specimens, we also analyzed the neighboring ventral pallidum (VP) and the external segment of the globus pallidus. In the superior colliculus specimens, we also analyzed the adjacent periaqueductal gray. We detected dense OXTR binding in the human NBM and VP and moderate to low OXTR binding in the human globus pallidus, superior colliculus, and periaqueductal gray. AVPR1a binding was negligible across all five regions in all specimens. Compared to controls, ASD specimens exhibited significantly higher OXTR binding in the NBM and significantly lower OXTR binding in the VP, an area in the mesolimbic reward pathway. There was no effect of ASD on OXTR binding in the globus pallidus, superior colliculus, or periaqueductal gray. We also found a significant negative correlation between age and OXTR binding in the VP across all specimens. Further analysis revealed a peak in OXTR binding in the VP in early childhood of typically developing individuals, which was absent in ASD. This pattern suggests a possible early life critical period, which is lacking in ASD, where this important reward area becomes maximally sensitive to OXT binding. These results provide unique neurobiological insight into human social development and the social symptoms of ASD.

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Section: Discussionmentioning

confidence: 94%

Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain

et al. 2018

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“…Oxytocin is also likely involved in the pathophysiology of PTSD and there is reason to believe it could be helpful in its treatment, particularly given its role in stress responsiveness, fear conditioning, and social functioning, all of which are impacted by PTSD ( Van de Kar et al, 2001 ; Olff et al, 2010 ). Post-mortem examination of patients with alcohol disorder showed reduced oxytocin mRNA levels as compared to controls ( Lee et al, 2017 ). In turn, intranasal oxytocin has been shown to reduce withdrawal symptoms in alcoholic patients ( Pedersen et al, 2013 ).…”

Section: Oxytocinmentioning

confidence: 99%

Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

et al. 2018

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Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.

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“…Oxytocin is also involved in cardiovascular regulation and various stress-related neuropsychiatric disorders (Vargas-Martínez et al, 2017, Iovino et al, 2018). Oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of male subjects with alcohol use disorder compared to controls, using post-mortem brain tissue (Lee et al, 2017b). Other studies have also found that oxytocin was associated with nicotine dependence and withdrawal in rats (Lee et al, 2017a, Manbeck et al, 2014), specifically that prenatal ethanol and nicotine exposure affects ethanol consumption, ethanol preference, and oxytocin receptor binding in adolescent and adult rats (Williams et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network

Xiang

Yang

Zhou

et al. 2018

American J of Med Genetics Pt B

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Alcohol dependence (AD) and nicotine dependence (ND) co-occur frequently (AD+ND). We integrated SNP-based, gene-based, and protein-protein interaction (PPI) network analyses to identify shared risk genes or gene subnetworks for AD+ND in African Americans (AAs, N=2094) and European Americans (EAs, N=1207). The DSM-IV criterion counts for AD and ND were modeled as two dependent variables in a multivariate linear mixed model, and analyzed separately for the two populations. The most significant SNP was rs6579845 in EAs (p<1.29×10−8) in GM2A, which encodes GM2 ganglioside activator, and is a cis-expression quantitative locus (eQTL) that affects GM2A expression in blood and brain tissues. However, this SNP was not replicated in another small sample. We identified a subnetwork of 24 genes that contributed to the AD+ND criterion counts. In the gene-set analysis for the subnetwork in an independent sample, the Study of Addiction: Genetics and Environment project (SAGE) (predominately EAs), these 24 genes as a set differed in AD+ND versus control subjects in EAs (p=0.041). Functional enrichment analysis for this subnetwork revealed that the gene enrichment involved primarily nerve growth factor pathways, and cocaine and amphetamine addiction. In conclusion, we identified a genomewide significant variant at GM2A and a gene subnetwork underlying the genetic trait of shared AD+ND. These results increase our understanding of the shared (pleiotropic) genetic risk that underlies AD+ND.

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Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study

Cited by 27 publications

References 31 publications

Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain

Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain

Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network

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