Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study

Uhrig, Stefanie; Hirth, Natalie; Broccoli, Laura; Wilmsdorff, Martina von; Bauer, Manfred; Sommer, Clemens; Zink, Mathias; Steiner, Johann; Frodl, Thomas; Malchow, Berend; Falkai, Peter; Spanagel, Rainer; Hansson, Anita C.; Schmitt, Andrea

doi:10.1016/j.schres.2016.04.019

Cited by 68 publications

(53 citation statements)

References 67 publications

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“…Future studies are needed to determine whether those abnormalities have a developmental origin and to identify the components of the central nervous system that are contributing to them. Our findings raise the possibility that enhanced thyroid hormone action in the central nervous system during development or in adulthood is involved in the etiology of disorders characterized by social deficits, including ASD, schizophrenia and depression (Domes et al 2016;Miller et al 2013;Modahl et al 1998;Neumann & Landgraf 2012;Parker et al 2014;Sasayama et al 2012;Strauss et al 2015a;Thompson et al 2014;Uhrig et al 2016;Wu et al 2005;Zhang et al 2016). Our work further underscores the potential importance of the thyroid hormone state of the brain, and not necessarily the circulating levels of thyroid hormone, when evaluating psychiatric conditions.…”

Section: Discussionsupporting

confidence: 51%

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Stohn

Martı́nez

Zafer

et al. 2017

Genes Brain and Behavior

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Thyroid hormones regulate many aspects of brain development and function, and alterations in the levels of thyroid hormone action lead to abnormal anxiety-and depression-like behaviors. A complement of factors in the brain function independently of circulating levels of hormone to strictly controlled local thyroid hormone signaling. A critical factor is the type 3 deiodinase (DIO3), which is located in neurons and protects the brain from excessive thyroid hormone. Here, we examined whether a local increase in brain thyroid hormone action secondary to DIO3 deficiency is of consequence for social behaviors. Although we did not observe alterations in sociability, Dio3−/− mice of both sexes exhibited a significant increase in aggression-related behaviors and mild deficits in olfactory function. In addition, 85% of Dio3−/− dams manifested no pup-retrieval behavior and increased aggression toward the newborns. The abnormal social behaviors of Dio3−/− mice were associated with sexually dimorphic alterations in the physiology of oxytocin (OXT) and arginine vasopressin (AVP), 2 neuropeptides with important roles in determining social interactions. These alterations included low adult serum levels of OXT and AVP, and an abnormal expression of Oxt, Avp and their receptors in the neonatal and adult hypothalamus. Our results demonstrate that DIO3 is essential for normal aggression and maternal behaviors, and indicate that abnormal local regulation of thyroid hormone action in the brain may contribute to the social deficits associated with neurodevelopmental disorders.

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Section: Discussionsupporting

confidence: 51%

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Stohn

Martı́nez

Zafer

et al. 2017

Genes Brain and Behavior

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“…In humans, OTR-binding sites have been found in specific relays of the fear retrieval pathway in postmortem tissue. For example, Hansson et al (2018) observed OTR expression by autoradiography in the ACC and Uhrig et al (2016) also showed OTR mRNA and OT-binding sites in Brodmann area 10, which is part of the rostrolateral prefrontal cortex, and hence, of the fear retrieval pathway. Furthermore, as in the brain of chimpanzees, OT-positive fibers terminate in the ACC (Rogers et al 2018), indicating a possible divergent evolution of the OT and AVP systems in more evolved primates.…”

Section: Modulation Of Fear Circuits By Oxytocin In Humansmentioning

confidence: 98%

Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction

Río¹,

Burg²,

Stoop³

et al. 2018

Psychopharmacology

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The extinction of conditioned fear responses entrains the formation of safe new memories to decrease those behavioral responses. The knowledge in neuronal mechanisms of extinction is fundamental in the treatment of anxiety and fear disorders. Interestingly, the use of pharmacological compounds that reduce anxiety and fear has been shown as a potent co-adjuvant in extinction therapy. However, the efficiency and mechanisms by which pharmacological compounds promote extinction of fear memories remains still largely unknown and would benefit from a validation based on functional neuronal circuits, and the neurotransmitters that modulate them. From this perspective, oxytocin receptor signaling, which has been shown in cortical and limbic areas to modulate numerous functions (Eliava et al. Neuron 89(6):1291-1304, 2016), among them fear and anxiety circuits, and to enhance the salience of social stimuli (Stoop Neuron 76(1):142-59, 2012), may offer an interesting perspective. Experiments in animals and humans suggest that oxytocin could be a promising pharmacological agent at adjusting memory consolidation to boost fear extinction. Additionally, it is possible that long-term changes in endogenous oxytocin signaling can also play a role in reducing expression of fear at different brain targets. In this review, we summarize the effects reported for oxytocin in corticolimbic circuits and on fear behavior that are of relevance for the modulation and potential extinction of fear memories.

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“…Increased OXTR expression has been reported in the prefrontal cortex of individuals suffering from major depression (29) and alcohol use disorder (30,31). Last, decreased OXTR mRNA was found in several brain areas of subjects with schizophrenia (32). In search for the causal factor of such differences, recent data highlight the role of DNA methylation on the transcription levels of OXTR.…”

Section: Genetic and Postmortem Studiesmentioning

confidence: 99%

Oxytocin as Treatment for Social Cognition, Not There Yet

Erdozain¹,

Peñagarikano²

2020

Front. Psychiatry

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In a short time, oxytocin has progressed from being a regular hormone involved in parturition and breastfeeding to be possibly the neuromodulator that has gathered the most attention. Attributed many positive roles in the modulation of different aspects of social behavior, such as bonding, empathy, cooperation, trust, and generosity, as well as roles as a natural anxiolytic and antidepressant, the expectations on oxytocin becoming a treatment for a number of disorders with associated social deficits have dramatically raised over the last years. However, despite the field has been investigating oxytocin's role in social behavior for over twenty years, there are still many unknowns on oxytocin's mechanisms of action and efficiency and the increasing number of clinical trials administering oxytocin to different clinical groups seem to disagree in its properties and report in most cases conflicting results. This has led to some disappointment among researchers and clinicians as oxytocin might not be the miraculous molecule that works in a "one size fits all" fashion initially considered. Conversely, this down-side of oxytocin might merely reflect the complexity of its neurotransmission system. The current reality is that, although oxytocin seems to have potential therapeutic value, there are key questions that remain unanswered as to decide the optimal target groups and treatment course. Here, we present an overview on critical points regarding the oxytocin system in health and disease that need to be better understood to establish its therapeutic properties and to decide who could benefit the most from its treatment.

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Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study

Cited by 68 publications

References 67 publications

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction

Oxytocin as Treatment for Social Cognition, Not There Yet

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