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Novel Pharmacological Targets of Post-Traumatic Stress Disorders.

ABSTRACT: Post-traumatic stress disorder (PTSD) is a psychopathological condition with a heterogeneous clinical picture that is complex and challenging to treat. Its multifaceted pathophysiology still remains an unresolved question and certainly contributes to this issue. The pharmacological treatment of PTSD is mainly empirical and centered on the serotonergic system. Since the therapeutic response to prescribed drugs targeting single symptoms is generally inconsistent, there is an urgent need for novel pathogenetic hypotheses, including different mediators and pathways. This paper was conceived as a narrative review with the aim of debating the current pharmacological treatment of PTSD and further highlighting prospective targets for future drugs. The authors accessed some of the main databases of scientific literature available and selected all the papers that fulfilled the purpose of the present work. The results showed that most of the current pharmacological treatments for PTSD are symptom-based and show only partial benefits; this largely reflects the limited knowledge of its neurobiology. Growing, albeit limited, data suggests that the hypothalamic-pituitary-adrenal axis, opioids, glutamate, cannabinoids, oxytocin, neuropeptide Y, and microRNA may play a role in the development of PTSD and could be targeted for novel treatments. Indeed, recent research indicates that examining different pathways might result in the development of novel and more efficient drugs.

SUBMITTER: Marazziti D

PROVIDER: S-EPMC10455314 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Novel Pharmacological Targets of Post-Traumatic Stress Disorders.

Marazziti Donatella D Carmassi Claudia C Cappellato Gabriele G Chiarantini Ilaria I Massoni Leonardo L Mucci Federico F Arone Alessandro A Violi Miriam M Palermo Stefania S De Iorio Giovanni G Dell'Osso Liliana L

Life (Basel, Switzerland) 20230811 8

Post-traumatic stress disorder (PTSD) is a psychopathological condition with a heterogeneous clinical picture that is complex and challenging to treat. Its multifaceted pathophysiology still remains an unresolved question and certainly contributes to this issue. The pharmacological treatment of PTSD is mainly empirical and centered on the serotonergic system. Since the therapeutic response to prescribed drugs targeting single symptoms is generally inconsistent, there is an urgent need for novel ...[more]

PMID: 37629588

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Project description:Significant trauma histories and post-traumatic stress disorder (PTSD) are common in persons with substance use disorders (SUD) and often associate with increased SUD severity and poorer response to SUD treatment. As such, this sub-population has been associated with unique risk factors and treatment needs. Understanding the distinct etiological profile of persons with co-occurring SUD and PTSD is therefore crucial for advancing our knowledge of underlying mechanisms and the development of precision treatments. To this end, we employed supervised machine learning algorithms to interrogate the responses of 160 participants with SUD on the multidimensional NIDA Phenotyping Assessment Battery. Significant PTSD symptomatology was correctly predicted in 75% of participants (sensitivity: 80%; specificity: 72.22%) using a classification-based model based on anxiety and depressive symptoms, perseverative thinking styles, and interoceptive awareness. A regression-based machine learning model also utilized similar predictors, but failed to accurately predict severity of PTSD symptoms. These data indicate that even in a population already characterized by elevated negative affect (individuals with SUD), especially severe negative affect was predictive of PTSD symptomatology. In a follow-up analysis of a subset of 102 participants who also completed neurocognitive tasks, comorbidity status was correctly predicted in 86.67% of participants (sensitivity: 91.67%; specificity: 66.67%) based on depressive symptoms and fear-related attentional bias. However, a regression-based analysis did not identify fear-related attentional bias as a splitting factor, but instead split and categorized the sample based on indices of aggression, metacognition, distress tolerance, and interoceptive awareness. These data indicate that within a population of individuals with SUD, aberrations in tolerating and regulating aversive internal experiences may also characterize those with significant trauma histories, akin to findings in persons with anxiety without SUD. The results also highlight the need for further research on PTSD-SUD comorbidity that includes additional comparison groups (i.e., persons with only PTSD), captures additional comorbid diagnoses that may influence the PTSD-SUD relationship, examines additional types of SUDs (e.g., alcohol use disorder), and differentiates between subtypes of PTSD.

Project description:BackgroundPost-traumatic stress disorder (PTSD), a disease state that has an unclear pathogenesis, imposes a substantial burden on individuals and society. Traumatic brain injury (TBI) is one of the most significant triggers of PTSD. Identifying biomarkers associated with TBI-related PTSD will help researchers to uncover the underlying mechanism that drives disease development. Furthermore, it remains to be confirmed whether different types of traumas share a common mechanism of action.MethodsFor this study, we screened the eligible data sets from the Gene Expression Omnibus (GEO) database, obtained differentially expressed genes (DEGs) through analysis, conducted functional enrichment analysis on the DEGs in order to understand their molecular mechanisms, constructed a PPI network, used various algorithms to obtain hub genes, and finally evaluated, validated, and analyzed the diagnostic performance of the hub genes.ResultsA total of 430 upregulated and 992 down-regulated differentially expressed genes were extracted from the TBI data set. A total of 1919 upregulated and 851 down-regulated differentially expressed genes were extracted from the PTSD data set. Functional enrichment analysis revealed that the differentially expressed genes had biological functions linked to molecular regulation, cell signaling transduction, cell metabolic regulation, and immune response. After constructing a PPI network and introducing algorithm analysis, the upregulated hub genes were identified as VNN1, SERPINB2, and ETFDH, and the down-regulated hub genes were identified as FLT3LG, DYRK1A, DCN, and FKBP8. In addition, by comparing the data with patients with other types of trauma, it was revealed that PTSD showed different molecular processes that are under the influence of different trauma characteristics and responses.ConclusionsBy exploring the role of different types of traumas during the pathogenesis of PTSD, its possible molecular mechanisms have been revealed, providing vital information for understanding the complex pathways associated with TBI-related PTSD. The data in this study has important implications for the design and development of new diagnostic and therapeutic methods needed to treat and manage PTSD.

Project description:Some post-traumatic stress disorder (PTSD) patients do not benefit from imaginal exposure therapy. One possible approach to reach such patients are virtual trauma interventions. Herein, a qualitative scoping review was conducted. Different types of virtual trauma exposure interventions were identified. For each type of virtual trauma exposure interventions it was examined in detail: (1) which in sensu trauma exposure approach serves as therapeutic framework, how it was transferred into virtual reality, and if it was manualized; (2) which hardware and software were used; (3) whether the influence of spatial and social presence on the efficacy of virtual trauma interventions have been measured, and (4) whether the efficacy of virtual trauma interventions for PTSD patients having imagination difficulties was evaluated. These research questions were analyzed qualitatively. Accordingly, an extensive literature search was conducted using the databases Web of Science, PsycINFO, LIVIVO, PTSDpubs, and PubMed for scientific articles published between January 2013 and July 2020. Only studies aimed to reduce PTSD symptoms using virtual trauma interventions were included. The literature search was not limited to a specific study design, treatment/intervention method, or a minimum sample size. Eighteen studies were identified, which reported three different virtual trauma intervention approaches, namely, virtual reality exposure therapy (VRET), multi-modular motion-assisted memory desensitization and reconsolidation (3MDR), and action-centered exposure therapy (ACET). Seven randomized controlled trials (RCTs), two pilot studies, and one case study were focused on VRET; while two RCTs, one pilot study, and three case studies focused on 3MDR, and two case studies on ACET. Regarding the first research question (1), the results show that VRET is based on prolonged exposure, aiming for a virtual re-creation of the patient's traumatic recounting. Several treatment protocols exist for VRET. 3MDR is based on eye movement desensitization and reprocessing, aiming to reduce the patient's avoidance behavior. In 3MDR patients walk toward individualized trauma-related symbolic images in a cave automatic virtual environment (CAVE). One treatment protocol exists for 3MDR. ACET is based on the inhibitory learning theory, aiming for active interactions with a virtual trauma-associated environment to alter the anxiety structure through new secondary inhibitory learning. One treatment protocol exists for ACET. For the second research question (2), the results indicate that all VRET studies used head-mounted displays (HMDs) with a virtual version of the Iraq/Afghanistan or the World Trade Center attacks, while 3MDR studies utilized two different versions of a CAVE with personalized trauma-related images, and the ACET studies used HMDs with virtual street scenarios. For the third research question (3), the results demonstrate that the influence of spatial or social presence on the efficacy of virtual trauma interventions was not examined in any of the included studies. Similarly, for the fourth research question (4), the results show that empirical evidence for the efficacy of virtual trauma interventions on PTSD patients having imagination difficulties was lacking. Therefore, such empirical studies are needed to fill these research gaps.

Project description:BackgroundKidney transplantation (KT) is a life-saving therapy for kidney failure. However, KT recipients can suffer from debilitating depression, post-traumatic stress disorder (PTSD), and suicide. In contrast to PTSD, post-traumatic growth (PTG) is a positive psychologic change in response to a challenging situation. PTG has been studied in other chronic diseases, but less is known about its role in the setting of KT. We sought to elucidate the prevalence, predictors, and the effect of PTSD and PTG on post-KT outcomes. We also considered the roles of benefit finding and resilience.MethodsIn a literature review, we identified publications that examined PTSD, PTG, benefit finding, and/or resilience in KT recipients. We excluded case reports and first-person narratives. Publications meeting the specified criteria after full text review underwent data abstraction and descriptive analysis.ResultsOf the 1013 unique citations identified, 39 publications met our criteria. PTSD was the most common construct evaluated (16 publications). Resilience was studied in 11 publications, PTG in nine, and benefit finding in five. Up to 21% of adult and 42% of pediatric KT recipients may experience PTSD, which is associated with lower quality of life (QOL), impaired sleep, and other psychiatric comorbidity. PTG was associated with improved QOL, kidney function, and reduced risk of organ rejection. Although benefit finding tended to increase post KT, resilience remained stable post KT. Like PTG, resilience was associated with lower psychologic distress and increased treatment adherence and confidence in the health care team.ConclusionsPTG, resilience, and benefit finding appear to reduce the risk of PTSD, promote well-being, and reduce risk of graft failure in KT recipients. Future research to understand these relationships better will allow clinicians and researchers to develop interventions to promote PTG, resilience, and benefit finding, and potentially improve post-transplant outcomes such as adherence and reducing risk of organ rejection.

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Novel Pharmacological Targets of Post-Traumatic Stress Disorders.

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Novel Pharmacological Targets of Post-Traumatic Stress Disorders.

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