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1.
Eur Neuropsychopharmacol ; 61: 17-29, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35716404

RESUMO

A sharp increase in the prevalence of neuropsychiatric disorders, including major depression, anxiety, substance use disorders and posttraumatic stress disorder (PTSD) has occurred due to the traumatic nature of the persisting COVID-19 global pandemic. PTSD is estimated to occur in up to 25% of individuals following exposure to acute or chronic trauma, and the pandemic has inflicted both forms of trauma on much of the population through both direct physiological attack as well as an inherent upheaval to our sense of safety. However, despite significant advances in our ability to define and apprehend the effects of traumatic events, the neurobiology and neuroanatomical circuitry of PTSD, one of the most severe consequences of traumatic exposure, remains poorly understood. Furthermore, the current psychotherapies or pharmacological options for treatment have limited efficacy, durability, and low adherence rates. Consequently, there is a great need to better understand the neurobiology and neuroanatomy of PTSD and develop novel therapies that extend beyond the current limited treatments. This review summarizes the neurobiological and neuroanatomical underpinnings of PTSD and discusses the conventional and emerging psychotherapies, pharmacological and combined psychopharmacological therapies, including the use of psychedelic-assisted psychotherapies and neuromodulatory interventions, for the improved treatment of PTSD and the potential for their wider applications in other neuropsychiatric disorders resulting from traumatic exposure.


Assuntos
COVID-19 , Transtorno Depressivo Maior , Transtornos de Estresse Pós-Traumáticos , Humanos , Neurobiologia , Psicoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/epidemiologia
2.
Pharmacol Ther ; 214: 107602, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32512017

RESUMO

Oxytocin (OT) is a neurohypophysial hormone and neuropeptide produced by the hypothalamus and released by the pituitary gland. It has multiple physiological roles including stimulation of parturition and lactation, and promotion of pro-adaptive social behaviors necessary for mammalian survival. OT interacts with one receptor subtype: the OT receptor (OTR) which, upon stimulation, triggers different intracellular signal transduction cascades to mediate its physiological actions. Preclinical studies show that OT regulates social behaviors such as pair bonding, recognition and social interaction. It also coordinates the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the release of corticotrophin-releasing hormone. Further evidence suggests that OT plays an important role in regulating caloric intake and metabolism, and in maintaining electrolyte and cardiovascular homeostasis. OT is also involved in attenuating the neurophysiological and neurochemical effects of trauma on the brain and body by facilitating both physical attachment such as wound healing, and psychological/social attachment, thereby increasing resilience to subsequent traumatic events. Clinical trials have reported that intranasal administration of OT provides therapeutic benefits for patients diagnosed with traumatic stress-related diseases such as major depressive disorders and post-traumatic stress disorder. OT's therapeutic benefits may result from context-dependent interactions with key neural pathways (social, cognitive, and reward), neurotransmitters (dopamine, norepinephrine, serotonin, and endogenous opioids), and biomarkers (adrenocorticotropic hormone, cortisol, and dehydroepiandrosterone sulfate), that lead to a decrease in stress -associated behaviors, and facilitate post-traumatic growth, ultimately leading to increased resilience, through improved social cohesion and attachment. OT induced-augmentation of physical and cognitive resilience may play a significant role in both the prevention of, and improved clinical outcomes for, traumatic stress-related disorders following either acute or enduring traumatic experiences.


Assuntos
Sistema Hipotálamo-Hipofisário/metabolismo , Apego ao Objeto , Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , Resiliência Psicológica , Transtornos de Estresse Traumático/metabolismo , Adaptação Psicológica , Animais , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Ocitocina/uso terapêutico , Resiliência Psicológica/efeitos dos fármacos , Transdução de Sinais , Transtornos de Estresse Traumático/tratamento farmacológico , Transtornos de Estresse Traumático/fisiopatologia , Transtornos de Estresse Traumático/psicologia
3.
Expert Opin Drug Discov ; 14(1): 81-89, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30457395

RESUMO

INTRODUCTION: Vortioxetine is a novel antidepressant drug approved for the treatment of major depressive disorder (MDD) in adults. It is formulated into tablets and has a dose range of 5-20 mg. The recommended starting dose is 10 mg administered orally once daily without the need for food. Areas covered: This review focuses on the preclinical and clinical discovery of vortioxetine. It analyzes the pharmacological, neurochemical, and behavioral mechanisms of the medication and how these contribute to its potential therapeutic advantages as described in published preclinical and clinical studies and product labels. Expert opinion: Vortioxetine displays high affinity for serotonin transporter (SERT), and serotonin 5-HT3, 5HT1A, 5HT7 receptors. Functional studies show that vortioxetine acts as a SERT blocker, a 5-HT3, 5-HT7 receptor antagonist, and a 5-HT1A receptor agonist. The drug is active in animal models predictive of antipsychotic and antidepressant activities and demonstrates procognitive effects in several animal models that assessed memory, cognition, and executive functions. Short- and long-term clinical trials demonstrated the clinical efficacy of vortioxetine in treating depressive symptoms and cognitive deficits in MDD patients. It also displays fairly benign safety and tolerability profiles. Vortioxetine's unique psychopharmacological properties might contribute to an improved clinical outcome in MDD patient populations.


Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Vortioxetina/administração & dosagem , Animais , Antidepressivos/efeitos adversos , Antidepressivos/farmacologia , Transtorno Depressivo Maior/fisiopatologia , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Vortioxetina/efeitos adversos , Vortioxetina/farmacologia
4.
Pharmacol Ther ; 190: 91-104, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29763648

RESUMO

Autism Spectrum Disorder (ASD) refers to a group of neurodevelopmental disorders including autism, Asperger's syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS). The new diagnostic criteria of ASD focuses on two core domains: social communication impairment and restricted interests/repetitive behaviors. The prevalence of ASD has been steadily increasing over the past two decades, with current estimates reaching up to 1 in 36 children. Hereditary factors, parental history of psychiatric disorders, pre-term births, and fetal exposure to psychotropic drugs or insecticides have all been linked to higher risk of ASD. Several scales such as the Childhood Autism Rating Scale (CARS), The Autism Spectrum Disorder-Observation for Children (ASD-OC), The Developmental, Dimensional, and Diagnostic Interview (3di), are available to aid in better assessing the behaviors and symptoms associated with ASD. Nearly 75% of ASD patients suffer from comorbid psychiatric illnesses or conditions, which may include attention-deficit hyperactivity disorder (ADHD), anxiety, bipolar disorder, depression, Tourette syndrome, and others. Both pharmacological and non-pharmacological interventions are available for ASD. Pharmacological treatments include psychostimulants, atypical antipsychotics, antidepressants, and alpha-2 adrenergic receptor agonists. These medications provide partial symptomatic relief of core symptoms of ASD or manage the symptoms of comorbid conditions. Non-pharmacological interventions, which show promising evidence in improving social interaction and verbal communication of ASD patients, include music therapy, cognitive behavioral therapy and social behavioral therapy. Hormonal therapies with oxytocyin or vasopressin receptor antagonists have also shown some promise in improving core ASD symptoms. The use of vitamins, herbal remedies and nutritional supplements in conjunction with pharmacological and behavioral treatment appear to have some effect in symptomatic improvement in ASD, though additional studies are needed to confirm these benefits. Developing novel disease-modifying therapies may prove to be the ultimate intervention for sustained improvement of symptoms in ASD.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Desenvolvimento de Medicamentos/métodos , Psicotrópicos/uso terapêutico , Transtorno do Espectro Autista/classificação , Transtorno do Espectro Autista/tratamento farmacológico , Terapia Comportamental/métodos , Suplementos Nutricionais , Humanos , Musicoterapia/métodos , Prevalência , Escalas de Graduação Psiquiátrica , Psicotrópicos/farmacologia , Fatores de Risco
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