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Oxitocina intranasal en estrés postraumático: investigación experimental., Resúmenes de Medicina

Una investigación experimental sobre el uso de oxytocina intranasal en el tratamiento de la síndrome de estrés postraumático (PTSD). Se discute la motivación detrás de su uso, el fondo científico, el proceso de producción de oxytocina en el sistema nervioso central y su papel en la modulación de la actividad del sistema nervioso simpático y hipotálamo-hipófisis-adrenal. Se presentan los objetivos, la metodología y las expectativas de resultados de la investigación.

Tipo: Resúmenes

2019/2020

Subido el 22/11/2021

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UNIVERSIDAD DE DURANGO
CAMPUS CD. JUAREZ
FACULTAD DE MEDICINA
L
INTRANASAL OXYTOCIN IN RELATION TO STRESS
PRODUCTION: AN EXPERIMENTAL INVESTIGATION
TOPIC: clinical use of intranasal oxytocin in patients diagnosed with post-traumatic
stress syndrome
MOTIVATION
Oxytocin is known as the love hormone, this hormone intervenes in certain physiological
processes that activate behaviours and influences them at a mechanical level in specific
organs like the uterus and breast. This is due to oxytocin acting as a neurotransmitter in the
sympathetic nervous system (SNS) and a decrease of its activity in the hypothalamic-
pituitary-adrenal axis. This activity in the SNS causes an increase in endogenous levels of
opiates and induces anti-stress effects, such as low blood pressure, heart rate and stress
hormones (Cardoso et al., 2013).
In addition to being a hormone involved in lactation and childbirth, intranasal oxytocin
reduces the activation of areas involved in fear processing, as well as reduces symptoms in
response to stress, it is important to consider the use of intranasal oxytocin in illnesses such
as generalized anxiety disorder and post-traumatic stress syndrome.
BACKGROUND:
Oxytocin (OT) is a nonapeptide hormone formed by nine amino acids, the synthesis of OT
in the central nervous system (CNS) is produced by the predominant expression of the OT
gene in neurons located in the paraventricular (NPV) and supraoptic (NSO) nuclei of the
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CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L

INTRANASAL OXYTOCIN IN RELATION TO STRESS

PRODUCTION: AN EXPERIMENTAL INVESTIGATION

TOPIC: clinical use of intranasal oxytocin in patients diagnosed with post-traumatic stress syndrome MOTIVATION Oxytocin is known as the love hormone, this hormone intervenes in certain physiological processes that activate behaviours and influences them at a mechanical level in specific organs like the uterus and breast. This is due to oxytocin acting as a neurotransmitter in the sympathetic nervous system (SNS) and a decrease of its activity in the hypothalamic- pituitary-adrenal axis. This activity in the SNS causes an increase in endogenous levels of opiates and induces anti-stress effects, such as low blood pressure, heart rate and stress hormones (Cardoso et al., 2013). In addition to being a hormone involved in lactation and childbirth, intranasal oxytocin reduces the activation of areas involved in fear processing, as well as reduces symptoms in response to stress, it is important to consider the use of intranasal oxytocin in illnesses such as generalized anxiety disorder and post-traumatic stress syndrome. BACKGROUND: Oxytocin (OT) is a nonapeptide hormone formed by nine amino acids, the synthesis of OT in the central nervous system (CNS) is produced by the predominant expression of the OT gene in neurons located in the paraventricular (NPV) and supraoptic (NSO) nuclei of the

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L hypothalamus. The release of OT is carried out by the NSO through magnocellular neurons that project to the neurohypophysis; While axonal projections of small NPV parvocellular neurons innervate the amygdala, hippocampus, nucleus accumbens, and lateral septum. Similar to classical neurotransmitters such as dopamine, serotonin, GABA or acetylcholine, OT is conserved in vesicles that can be released by electrical stimulation to the synaptic cleft; but unlike classical neurotransmitters, OT can diffuse through the extracellular space (Florez & Cardenas, 2016) Oxytocin is primarily produced by the paraventricular and supraoptic nuclei of the hypothalamus, where it is released into the bloodstream from the posterior pituitary, and travels through the bloodstream to meet its specific receptor (Cardoso et al., 2013). Function of oxytocin. Studies in non-human and human animals have shown that OT has a modulating role in a wide variety of social interactions that have been relevant in the evolution of mammals such as social recognition, sexual behavior, mating, parental behavior (Florez & Cardenas, 2016). It is also considered a great mediator and controller of emotions in social behaviors such as love, memory, anger, aggression and the establishment of correlations between past and present experiences. It promotes an increase in pain threshold and a decrease in anxiety levels, reduces fear and increases confidence and empathy (Steinman et al., 2016). Oxytocin as a treatment Oxytocin is involved in many of the medications related to stress, among them it is mainly related to patients with post-traumatic stress disorder (PTSD). 10% of people exposed to trauma develop post-traumatic stress disorder (PTSD), its symptoms include intrusions,

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L Neuropeptide oxytocin (OT) potential influence on social cognitive ability in individuals with social anxiety raises the question of whether arginine vasopressin (AVP), which is structurally similar to OT, may also impact social cognition in individuals with social anxiety, or whether such an effect may be specific to OT. Like OT, AVP also regulates a broad range of social processes including social cognition (Tabak et al., 2016). A social study indicates that oxytocin is related with social behavior, stress regulation and positive physiological adaptation, in this study social stress was induced in men and women the results were cardiovascular changes, men were less affected while women had more anger issues but better performance to social stress. (Kubzansky et al., 2012). Homeostasis is a form of equilibrium of the body, by interrupting this the psychological stress implied the normal well-being of the body, triggering a potential risk like a coronary heart disease, cancer or major physiological depressions. (Eckstein et al,. 2014) To better understand how the male reproductive system responds to environmental influences and the role of SGs in male germ cells, we review advanced discoveries in this field and provide some perspectives on future research. (Wang et al., 2021) Many studies on the effect of seminal oxidative stress (OS) on male fertile capacity have been reported since Aitken et al first reported reactive oxygen species (ROS) results from a disturbance of homeostatic balance between ROS production and antioxidant capacity in seminal plasma (Takeshima et al., 2016). Stress Stress is a normal response of the human body to an alert situation. During stress, the levels of cortisol and adrenaline hormones increase, which then act in different organs, and produce

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L an increase in sugar, acceleration of the heartbeat, increase in blood pressure, oxygen supply to the muscles, and others. It is also known to decrease cortisol. Intranasal oxytocin has recently been investigated to attenuate cortisol levels during the induction of social stress, by improving the communication of the individual with his environment. Patients have presented an improvement in their social skills, due to intranasal oxytocin elevating their confidence capacity. (Riem et al., 2020). Stress is an environmental factor that can lead negative effects on memory functions, oxytocin that is administered intranasally modifies prosocial behavior and the uncontrollable stress effects on the hippocampal memory so this means oxytocin was effective in preventing stress-induced imparting in memory. (Lee et al., 2015) Social buffering is the fundamental problem behind health effects of a normal and equal relationship. Under stress, the body undergoes a great number of physiological responses to maintain homeostasis in the full body, algo the activation of the sympathoadrenal and the hypothalamic pituitary-adrenomedullary, that give a result resulting of adrenaline and cortisol to all the bloodstream. Social support has been proven that stress-induced any physiological changes in people's lives. (Sicorello et al., 2020). Determination of the effect of intranasal oxytocin The effects of intranasal oxytocin are determined by childhood experiences, it has been shown that in people with adverse experiences in childhood the effect of oxytocin is attenuated. Riem conducted a Social Stress Test in women with a history of a difficult childhood, the study showed that oxytocin improved women's ability to find social support

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L There are some anatomical structures that can't permit the free entrance of oxytocin in the central nervous system; these structures are three barriers that keep the brain protected.

  1. Arachnoid blood-cerebrospinal fluid
  2. Blood-cerebrospinal fluid barrier
  3. Blood-brain barrier The first barrier is a physical barrier that is integrated by the meninges, it is composed of three layers that protect the central nervous system and spinal cord from chemicals, pathogens etc. The innermost layer is the pia mater which is formed by connective tissue, the middle layer or the arachnoid layer is avascular and has a web like structure, and lastly, we have the dura mater layer. Any substance that comes into the blood stops in the arachnoid layer and will not reach its goal, which explains why nasal oxytocin would have to find another way to get inside the brain. The second barrier is a blood cerebrospinal fluid barrier, this cerebrospinal fluid is produced by the choroid plexus and the ventricular ependyma, that create osmotic pressure that prevents substances from entering loosely inside the nervous system. Anything that is in the cerebrospinal fluid can enter to the brain, which means that oxytocin needs to enter the cerebrospinal fluid to reach the brain and for this to happen it first has to pass the third barrier. The last barrier is the blood-brain-barrier, that has tight junctions without intracellular spaces that allows different molecules to pass by through transcellular transport of liposoluble substances, transmembrane transports, and vesicles. Because oxytocin is hydro soluble, some endocrinologists state that oxytocin is able to penetrate blood-brain-barriers in small amounts which pass through and reach the brain. (Lima et al., 2019).

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L Stress granules are considered one of the most important structures for normal cellular events; some studies reveal that these granules can improve cell survival under stress conditions. (Wang et al,. 2021) LONG TERM OBJECTIVE To determine the use of intranasal oxytocin as a safe and effective treatment for post- traumatic stress syndrome, in order to reduce the characteristic symptoms of the disease, in turn increasing the quality of life of patients. SHORT-TERM OBJECTIVE to determine the effectiveness of the use of intranasal oxytocin in patients with post-traumatic stress disorder, in addition to providing new alternatives such as the practice of meditation, yoga and regular exercise to increase natural oxytocin and reduce stress-induced behaviours

RESEARCH RATIONALE and DESIGN

Objective 1 : Confirm the clinical use of intranasal oxytocin in patients with Posttraumatic stress disorder (PTSD). Hypothesis : PTSD patients that undergo stressful situations and are administered intranasal oxytocin will experience a decrease in physiological stress levels, which is reflected in the decrease in blood pressure, heart rate and respiratory rate.

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L Variables Quantitative variables; pulse, heart pressure, oxytocin levels, stress level Inclusion criteria:

  • age group: 20 - 30 years old
  • diagnosed with post-traumatic stress syndrome Exclusion criteria :
  • People over the age of 60 years old
  • Untreated PTSD patients
  • Women who are pregnant at the time of the experiment. •Subjects addicted to drugs. Material
  • PTSD test
  • intranasal oxytocin
  • baumanometer
  • pulsometer
  • Computer Methodology
  1. 50 women and men with scores greater than 10 will be studied in the post-traumatic stress disorder test (annex 1)
  2. 25 people will be given a dose of intranasal oxytocin and the other 25 will be given a placebo saline solution

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L

  1. The patients will be asked one by one to eat a room which will be conditioned and in optimal conditions, in addition to the experimenter will be accompanied by psychological help, where they will be asked to tell a little about the situation in the which were involved.
    1. Two hours after administering the treatments, patients’ blood pressure and heart rate will be taken
  2. This is done to determine the efficacy of the treatment using the (The Eight-Item Treatment-Outcome Post-Traumatic Stress Disorder Scale - TOP-8) scale. RESULT ANALYSIS PLAN The data analysis will be carried out in a quantitative way, mainly an analysis of the numbers of the pressure taking, of both groups, will be observed if there is a decrease or difference in patients with intranasal oxytocin or an increase. CHRONOGRAM Activities January February March April May June test application x participant selection X data collection X analysis of data x

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L If the expected results are obtained during the application of the experiment, that is, if intranasal oxytocin has a positive effect in people with post-traumatic stress disorder, it leads to being able to carry out the study in large masses, that is, to apply the experiment in larger groups. big. This in order to be able to determine the use of oxytocin as a treatment for these patients, since the purchase of oxytocin is easier. Another path that could be taken in our study is to apply the experiment in patients suffering from post-traumatic stress disorder to a more serious degree, which limits their social capacity, affecting their quality of life. In addition, this study could serve as support for the development of drugs. ANNEX TEST DE TRASTORNO DE ESTRÉS POSTRAUMÁTICO Si has sido víctima de un suceso traumático y estás experimentando ciertos síntomas, este test puede ayudarte a determinar la posible existencia de un trastorno de estrés postraumático. Consta de 22 preguntas.

  1. Has experimentado o sido expuesto a un suceso traumático? Sí No
  2. ¿Durante el acontecimiento traumático, experimentaste o fuiste testigo de daño físico importante o muertes, o hubo amenazas de daño físico importante o muertes? Sí No
  3. ¿Durante el suceso, sentiste un miedo intenso, impotencia y/o horror? Sí No
  4. ¿Experimentas regularmente pensamientos intrusos o imágenes relacionadas con el suceso? Sí No

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L

  1. ¿Sientes a veces como si volvieras a vivir lo sucedido? Sí No
  2. ¿Tienes pesadillas recurrentes o sueños perturbadores relacionados con el suceso? Sí No
  3. ¿Sientes un malestar intenso cuando algo te recuerda lo sucedido, tanto si es algo que ves u oyes como si es algo que piensas? Sí No
  4. ¿Intentas evitar pensamientos, emociones o conversaciones que te recuerden el suceso traumático? Sí No
  5. ¿Intentas evitar actividades, personas o lugares que te recuerden el suceso traumático? Sí No
  6. ¿Eres incapaz de recordar algo importante relacionado con el suceso? Sí No
  7. Desde que sucedió, ¿sientes menos interés en realizar actividades y aficiones que antes te gustaban? Sí No Enviaste
  8. Desde que sucedió, ¿te sientes distanciado de los demás o tienes problemas para confiar en ellos? Sí No
  9. Desde que sucedió, ¿tienes problemas para expresar o mostrar tus emociones? Sí No
  10. ¿Tienes la sensación de que tu futuro no será "normal", por ejemplo, que no tendrás una carrera, no te casarás, no tendrás hijos, etc.?

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L

CAMPUS CD. JUAREZ FACULTAD DE MEDICINA L BIBLIOGRAPHY

  1. Kumsta , R., & Heinrichs, M. (2013). Oxytocin, stress and social behavior: neurogenetics of the human oxytocin system. Current opinion in neurobiology , 23 (1), 11 - 16. https://doi.org/10.1016/j.conb.2012.09.
  2. Park, S. H., Kim, Y. J., Park, J. C., Han, J. S., & Choi, S. Y. (2017). Intranasal oxytocin following uncontrollable stress blocks impairments in hippocampal plasticity and recognition memory in stressed rats. International Journal of Neuropsychopharmacology , 20 (10), 861- 866 https://doi.org/10.1093/ijnp/pyx
  3. Sippel, L. M., Allington, C. E., Pietrzak, R. H., Harpaz-Rotem, I., Mayes, L. C., & Olff, M. (2017). Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities. Chronic stress , 1 , 2470547016687996. https://doi.org/10.1177/
  4. Van Zuiden, M., Frijling, J. L., Nawijn, L., Koch, S. B., Goslings, J. C., Luitse, J. S., ... & Olff, M. (2017). Intranasal oxytocin to prevent posttraumatic stress disorder symptoms: a randomized controlled trial in emergency department patients. Biological psychiatry , 81 (12), 1030-1040. https://doi.org/10.1016/j.biopsych.2016.11.
  5. Chuang , H. J., Chang, C. Y., Ho, H. P., & Chou, M. Y. (2021). Oxytocin Signaling Acts as a Marker for Environmental Stressors in Zebrafish. International Journal of Molecular Sciences , 22 (14), 7459. https://doi.org/10.3390/ijms
  6. Cardoso, C., Ellenbogen, M. A., Orlando, M. A., Bacon, S. L., & Joober, R. (2013). SteinmanIntranasal oxytocin attenuates the cortisol response to physical stress: a dose– response study. Psychoneuroendocrinology , 38 (3), 399 - 407. https://doi.org/10.1016/j.psyneuen.2012.07.
  7. Steinman, M. Q., Duque-Wilckens, N., Greenberg, G. D., Hao, R., Campi, K. L., Laredo, S. A., ... & Trainor, B. C. (2016). Sex-specific effects of stress on oxytocin neurons correspond with responses to intranasal oxytocin. Biological psychiatry, 80(5), 406-414. https://doi.org/10.1016/j.biopsych.2015.10.

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  1. Takeshima, T., Usui, K., Mori, K., Asai, T., Yasuda, K., Kuroda, S., & Yumura, Y. (2021). Oxidative stress and male infertility. Reproductive Medicine and Biology , 20 (1), 41-
  2. https://doi.org/10.1002/rmb2.
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  4. Kubzansky, L. D., Mendes, W. B., Appleton, A. A., Block, J., & Adler, G. K. (2012). A heartfelt response: oxytocin effects on response to social stress in men and women. Biological psychology , 90 (1), 1-9. https://doi.org/10.1016/j.biopsycho.2012.02.
  5. Flanagan, J. C., & Mitchell, J. M. (2019). Augmenting treatment for posttraumatic stress disorder and co-occurring conditions with oxytocin. Current treatment options in psychiatry , 6 (2), 132-142. https://doi.org/10.1007/s40501- 019 - 00171 - 1
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