Ocitocina, um “medicamento” ainda em potencial terapêutico para distúrbios psiquiátricos

Autores

  • Dayse Maria Vasconcelos de Deus Pós graduação em Medicina Tropical - UFPE Faculdade de Ciências Humanas - ESUDA
  • Pauline Santos de Freitas Faculdade de Ciências Humanas - ESUDA

Resumo

Nos últimos anos, o potencial terapêutico da ocitocina (OT) é discutido como um grande promissor no auxílio dos transtornos psiquiátricos (transtorno de personalidade limítrofe, autismo, esquizofrenia, etc). Embora seu papel como fármaco esteja ainda em adaptação para o devido uso farmacológico e aceitação clínica, uma vez que há discrepâncias quanto a atuação (da ocitocina sintética) entre indivíduos saudáveis vs pacientes psiquiátricos; homens vs mulheres; escasso conhecimento efeitos colaterais entre as doenças pesquisadas; e otimização da dosagem terapêutica, devido às carências de estudos direcionados para estas lacunas. O presente artigo objetiva elencar algumas atuações quanto ao potencial da OT nos transtornos psiquiátricos mais evidentes, bem como evidenciar as lacunas que ainda condicionam a falta da aceitação da OT como medicamento, fazendo uso de uma revisão da literatura sobre o tema.  A atuação da OT é muito promissora, contudo, precisa-se de mais estudos que embasem objetivos ao experimental e clínico, para que a OT tenha melhor reconhecimento como medicamento.

Biografia do Autor

Dayse Maria Vasconcelos de Deus, Pós graduação em Medicina Tropical - UFPE Faculdade de Ciências Humanas - ESUDA

Tem experiência na área de biologia molecular, atuando na buca por fatores de riscos (genéticos e comportamentais) para o agravamento das leucemias agudas (linfóide e mielóide) na infância e nas infecções crônicas transmitidas pelos vírus da hepatite B e C. Na Faculdade ESUDA, pretende desenvolver uma linha de pesquisa na área de doenças neurodegenerativas, buscando associar fatores de riscos comportamentais (variáveis preditoras) precoces, em familiares que já possuem tais doenças, sugerindo assim, uma forte inclinação para o desenvolvimento de certas doenças neurodegenerativas.

Principais áreas de atuação: Doenças tropicais, Biologia molecular, genética humana - fatores de riscos comportamentais, doenças neurodegenerativas.

Pauline Santos de Freitas, Faculdade de Ciências Humanas - ESUDA

Aluna de Graduação - curso Psicologia da Faculadade ESUDA.

Faz iniciação científica nesta Faculdade (desde março/2016), desenvolvendo o tema sobre distúrbios neurocogniticos associados ao HIV,  além investigar outros assuntos dentro da área de neuroanatomia/comportamento.

Referências

AOKI, Y; YAHATA, N; WATANABE, T; et al. Oxytocin improves behavioural and neural deficits in inferring others' social emotions in autism. Brain, v. 137, n. 11, p. 3073-3086, 2014.

AUYEUNG, B; LOMBARDO, MV; HEINRICHS, M; et al. Oxytocin increases eye contact during a real-time, naturalistic social interaction in males with and without autism. Translational Psychiatry, v. 5, p. e507, 2015.

BALES, KL and PERKEYBILE, AM. Developmental experiences and the oxytocin receptor system. Hormones and Behavior, v. 61, p. 313–319, 2012.

BALES, KL; VAN WESTERHUYZEN, JÃ; LEWIS-REESE, AD; et al. Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles. Hormones and Behavior, v.52, p. 274–279, 2007b.

BARTZ, JÃ; ZAKI, J; BOLGER, N; et al. Social effects of oxytocin in humans: con-text and personmatter. Trends in Cognitive Sciences, v.15, p. 301–309, 2011b.

BARTZ, J; SIMEON, D; HAMILTON, H; KIM, S; et al. Oxytocin can hinder trust and cooperation in borderline per-sonality disorder. Social Cognitive & Affective Neurosci, v. 6, p. 556–563, 2011a.

BERTSCH, K; GAMER, M; SCHMIDT, B; et al. Oxytocin and Reduction of Social Threat Hypersensitivity in Women With Borderline Personality Disorder. American Journal of Psychiatry, p. 1169–1177, 2013.

BIRKETT, MA; SHINDAY, NM; KESSLER, EJ; et al. Acute anxiogenic-like effects of selec-tive serotonin reuptake inhibitors are attenuated by the benzodi-azepine diazepam in BALB/c mice. Pharmacology Biochemistry and Behavior, v. 98, p. 544–551, 2011.

BLEVINS, JE and HO, JM. Role of oxytocin signaling in the regulation of body weight. Reviews in Endocrine and Metabolic Disorders, v.14, n.4, p.311-329, 2013.

BURGHY, CA; STODOLA, DE; RUTTLE, PL; et al. Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nature Neuroscience, v.15, p. 1736–1741, 2012.

CHAPMAN, CD and FREY, WH. In___Craft, S., Danielyan, L., Hallschmid, M., Schioth, H. B., et al. Intranasal treatment of central nervous system dysfunction in humans. Pharmaceutical Research. 2ed, 2012, doi: 10.1007/s11095- 012-0915-1.

CHOLERIS, E; DEVIDZE, N; KAVALIERS, M; et al. Steroidal/neuropeptide interactions in hypothalamus and amygdala related to social anxiety. Progress in Brain Research. v. 170, p. 291–303, 2008.

COHEN, H; KAPLAN, Z; KOZLOVSKY, N; et al. Hippocampal microinfusion of oxytocin attenuates the behavioural response to stress by means of dynamic interplay with the glucocorticoid-catecholamine responses. Journal of Neuroendocrinology, v. 22, n. 8, p. 889-904, 2010.

COLAIANNI, G; SUN, L; DI, BENEDETTO, A; et al. Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton. The Journal of Biological Chemistry, v. 17, n.287(34), p. 29159-29167, 2012.

DALE, HH. On some physiological actions of ergot. The Journal of Physiology, v. 34, p. 163–206, 1906.

DAVIS, MC; LEE, J, HORAN, WP; CLARKE AD, et al. Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophrenia Research, v. 147, n. 2-3, p,393-397, 2013.

DELVILLE, Y; MANSOUR, KM and FERRIS, CF. Testosterone facilitates aggression by modulat-ing vasopressin receptors in the hypothalamus. Physiology & Behavior, v. 60, p. 25–29, 1996.

DOMES, G; SIBOLD, M; SCHULZE, L; et al. Intranasal oxytocin increases covert attention to positive social cues. Psychological Medicine, v.43, n.8, p. 1747-1753, 2013.

DOMES, G; KUMBIER, E; HEINRICHS, M; et al. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology, v.39, n.3, p. 698-706, 2014.

DOMES, G; NORMANN, C; HEINRICHS, M. The effect of oxytocin on attention to angry and happy faces in chronic depression. BMC Psychiatry, v. 6, n.16, p. 92, 2016.

EBNER, NC; CHEN, H; PORGES, E; et al. Oxytocin's effect on resting-state functional connectivity varies by age and sex. Psychoneuroendocrinology, v.69, p. 50-59, 2016.

FANG, LY; QUAN, RD; KABA, H. Oxytocin facilitates the induction of long-term potentiation in the accessory olfactory bulb. Neuroscience Letters, v. 20, n. 438(2), p.133-137, 2008.

GAO, S; BECKER, B; LUO, L; et al. Oxytocin, the peptide that bonds the sexes also divides them. Proceedings of the National Academy of Sciences, USA, v. 5, n.113(27), p. 7650-7654, 2016.

GILTAY, EJ; ENTER, D; ZITMAN, FG; et al. Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study. Journal of Psychosomatic Research, v. 72(3), p.205-213, 2012.

GIMPL, G and FAHRENHOLZ, F. The oxytocin receptor system: structure, function, and regulation. Physiological Reviews, v. 81, p. 629–683, 2001.

GOLDMAN, MB; GOMES, AM; CARTER, CS; et al. Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without poly-dipsia. Psychopharmacology, v. 216, p. 101–110, 2011.

GOSSEN, A; HAHN, A; WESTPHAL, L; et al. Oxytocin plasma con-centrations after single intranasal oxytocin administration—A study in healthy men. Neuropeptides, v. 46, p. 211–215, 2012.

GRIMMELIKHUIJZEN, CJ and HAUSER, F. Mini-review: the evolution of neuropeptide signaling. Regulatory Peptides, v. 177(Suppl.), p. S6–S9, 2012.

GUASTELLA, AJ; MITCHELL, PB; DADDS, MR. Oxytocin increases gaze to the eye region of human faces. Biological Psychiatry, v. 63, n.1, p. 3-5, 2008.

GUASTELLA, AJ; WARD, PB; HICKIE, IB; et al. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia. Schizophrenia Research, v. 168, n. 3, p. 628-33, 2015.

GUASTELLA, AJ; EINFELD, SL; GRAY, KM; et al. Intranasal oxytocin improves emo-tion recognition for youth with autism spectrum disorders. Biological Psychiatry, v. 67, p. 692–694, 2010.

HAZLETT, EA; ZHANG, J; NEW, AS; et al. Potentiated amygdala response to repeated emotional pictures in borderline personality disorder. Biological Psychiatry, v.72, p.448–456, 2012.

HOGE, EA; POLLACK, MH; KAUFMAN, RE; et al. Oxytocin levels in social anxiety disorder. CNS Neuroscience & Therapeutics, v. 14, n. 3, p. 165-170, 2008.

HOLLANDER, E; BARTZ, J; CHAPLIN, W; et al. Oxytocin increases retention of social cognition in autism. Biological Psychiatry, v. 61, p. 498–503, 2007.

JESSO, S; MORLOG, D; ROSS, S; et al. The effects of oxytocin on social cognition and behaviour in frontotemporal dementia. Brain, v.134, p. 2493–2501, 2011.

LABUSCHAGNE, I; PHAN, KL; WOOD, A; et al. Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology, v.35, p. 2403–2413, 2010.

LABUSCHAGNE, I; PHAN, KL; WOOD, A; et al. Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. International Journal of Neuropsychopharmacology, v.1–14, 2011.

LIU, JC; GUASTELLA, AJ and DADDS, MR. Effects of oxytocin on human social approach measured using intimacy equilibriums. Hormones and Behavior, v.62, p. 585–591, 2012.

LOUP, F; TRIBOLLET, E; DUBOIS- DAUPHIN, M; et al. Localization of oxytocin binding sites in the human brainstem and upper spinal cord: an autoradiographic study. Brain Research, v. 500, p. 223–230, 1989.

MACDONALD, E; DADDS, MR; BRENNAN, JL; et al. A review of safety, side-effects and subjec-tive reactions to intranasal oxy-tocin in human research. Psychoneuroendocrinology, v.36, p. 1114–1126, 2011.

MAH, BL; VAN, I; JZENDOORN, MH; et al. Oxytocin in postnatally depressed mothers: its influence on mood and expressed emotion. Progress in Neuro-Psychopharmacology & Biological Psychiatry, v.40, p. 267-272, 2013.

MARSH, AA; YU, HH; PINE, DS; et al. Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology (Berl), v.209, n.3, p.225-232, 2010.

MCGONIGLE, P. Peptide ther-apeutics for CNS indications. Biochemical Pharmacology, v.83, p.559–566, 2012.

MERCEDES PEREZ-RODRIGUEZ, M; MAHON, K; RUSSO, M; et al. Oxytocin and social cognition in affective and psychotic disorders. European Neuropsychopharmacology, v.25, n. 2, p. 265-282, 2015.

MODABBERNIA, A; REZAEI, F; SALEHI, B; et al. Intranasal oxytocin as an adjunct to risperidone in patients with schizophrenia : an 8-week, randomized, double-blind, placebo-controlled study. CNS Drugs, v. 27, n.1, p 57–65, 2013.

MORIMOTO, B; DE LANNOY, I; FOX, AW; et al. Davunetide: pharmacokinetics and distribution to brain after intravenous or intranasal admin-istration to rat. Chimica Oggi, v.27, p.16–20. 2009.

NEUMANN, ID; WIGGER, A; TORNER, L; et al. Brain oxytocin inhibits basal and stress-induced activity of the hypothalamo-pituitary-adrenal axis in male and female rats: partial action within the paraventricular nucleus. Journal of Neuroendocrinology, v.12, n.3, p. 235-243, 2000.

NEUMANN, ID and LANDGRAF, R. Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends in Neurosciences, v.35, p. 649–659, 2012.

PEDERSEN, CA; SMEDLEY, KL; LESERMAN, J; et al. Intranasal oxytocin blocks alcohol withdrawal in human subjects. Alcoholism: Clinical and Experimental Research, v.37, p.484–489, 2013.

PEDERSEN, CA; GIBSON, CM; RAU, SW; et al. Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia. Schizophrenia Research, v.132. n.1, p.50-53, 2011.

PINCUS, D; KOSE, S; ARANA, A; et al. Inverse effects of oxytocin on attributing mental activity to others in depressed and healthy subjects: a double-blind placebo controlled FMRI study. Frontiers in Psychiatry, v.1, p.134, 2010.

REN, D; LU, G; MORIYAMA, H. Genetic diversity in oxytocin ligands and receptors in New World monkeys. PLoS One, v.4, n.10(5), p.e0125775, 2015.

RENNER, DB; FREY, WH and HANSON, LR. Intranasal delivery of siRNA to the olfac-tory bulbs of mice via the olfactory nerve pathway. Neuroscience Letters, v. 513, p. 193–197, 2012a.

RENNER, DB; SVITAK, AL; GALLUS, NJ; et al. Intranasal delivery of insulin via the olfactory nerve pathway. Journal of Pharmacy and Pharmacology, v.64, p.1709–1714, 2012b.

RICH, ME and CALDWELL, HK. A Role for Oxytocin in the Etiology and Treatment of Schizophrenia. Front Endocrinol (Lausanne), v. 3, n.6, p.90, 2015.

ROMANO, A; TEMPESTA, B; DI BONAVENTURA, MVM; et al. From Autism to Eating Disordersand More: The Role of Oxytocinin Neuropsychiatric Disorders. Frontiers in Neuroscience, v.9 , n.497. doi: 10.3389/fnins.2015.00497, 2016.

ROSS, TM; MARTINEZ, PM; RENNER, JC; THORNE, RG; HANSON, LR and FREY, WH. In___Intranasal administration of inter – feronbeta by passes the blood - brain barrier to target the central nervous system and cervical lymphnodes: a non-invasive treatment strategy for multiple sclerosis. Journal of Neuroimmunology, 2ed, v.151, 2004, p. 66–77.

RUBIN, LH; CARTER, CS; DROGOS, L; et al. Sex-specific associations between peripheral oxytocin and emotion perception in schizophrenia. Schizophrenia Research, v.130, n.1-3, p.266-270, 2011.

SAVASKAN, E; EHRHARDT, R; SCHULZ, A; et al. Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology, v.33, n.3, p.368-374, 2008.

SCHARRER, E and SCHARRER, B. Neurosecretion. Physiological Reviews, v.25, p.171–181, 1945.

SIMEON, D; BARTZ, J; HAMILTON, H; et al. Oxytocin administration attenuates stress reactivity in bor-derline personality disorder: a pilot study. Psychoneuroendocrinology, v.36, p.1418–1421, 2011.

SINGH, F; NUNAG, J; MULDOON, G; et al. Effects of intranasal oxytocin on neural processing within a socially relevant neural circuit. European Neuropsychopharmacology, v.26, n.3, p.626-630, 2016.

SRIPADA, CS; PHAN, KL; LABUSCHAGNE, I; et al. Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex. International Journal of Neuropsychopharmacology, v.16, p.255–260, 2013.

STANKOVA, T; EICHHAMMER, P; LANGGUTH, B; et al.Sexually dimorphic effects of oxytocin receptor gene (OXTR) variants on Harm Avoidance. Biology of Sex Differences, v.3, n.17. 2012.

STOOP, R. Neuromodulation by oxytocin and vasopressin. Neuron, v.76, p.142–159, 2012.

STRAUSS GP, KELLER WR, KOENIG JI, et al. Plasma oxytocin levels predict social cue recognition in individuals with schizophrenia. Schizophrenia Research. 162(1-3):47-51. 2015

SWAAB, DF; POOL, CW and NIJVELDT, F. Immunofluorescence of vasopressin and oxytocin in the rat hypothalamo-neurohypophypopseal system. Journal of Neural Transmission, v. 36, p.195–215, 1975.

VAN HONK, J; BOS, PA; TERBURG, D, et al. Neuroendocrine models of social anxiety disorder. Dialogues in Clinical Neuroscience - Vol 17 . No. 3, p. 287–293, 2015.

VAN IJZENDOORN, M; BHANDARI, R; VAN DER VEEN, R; et al. Elevated salivary levels of oxytocin persist more than seven hours after intranasal administra-tion. Frontiers in Neuroscience, v.6, p.174, 2012.

WEISMAN, O; ZAGOORY-SHARON, O; SCHNEIDERMAN, I; et al. Plasma oxytocin distributions in a large cohort of women and men and their gender-specific associations with anxiety. Psychoneuroendocrinology. v.38, n.5, p.694-701, 2012.

WOOLLEY, JD; LAM, O; CHUANG, B; et al. Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia. Psychoneuroendocrinology, v. 53, p.217-222, 2015.

YOUNG, LJ and BARRETT, CE. Can oxytocin treat autism? Science, v.20, p.347(6224), p. 825–826, 2015.

ZINK, CF and MEYER-LINDENBERG, A. Human neuroimaging of oxytocin and vasopressin in social cognition. Hormones and Behavior, v.61, p.400–409, 2012.

Humanae, v. 11, n. 1

Downloads

Publicado

2017-02-06

Edição

v. 11 n. 1 (2017)

Seção

Artigos

Licença

Autores que publicam nesta revista concordam com os seguintes termos:

  1. Autores mantém os direitos autorais e concedem à revista Hum@nae o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Creative Commons Attribution License, permitindo o compartilhamento do trabalho com reconhecimento da autoria do trabalho e publicação inicial nesta revista.

  2. Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.

  3. Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado.