DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for post-traumatic stress disorder — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePost-traumatic stress disorder maps to a 35-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for post-traumatic stress disorder is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
bromodomain PHD finger transcription factor (BPTF) — BPTF is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet ipadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2RI7 · 1.45 Å · ligand ISOPROPYL ALCOHOL (IPA). Experimental structure, not a prediction.
What the evidence adds up to
About half of people with post-traumatic stress disorder also meet criteria for major depressive disorder, and the evidence suggests this is not simply an artefact of overlapping symptoms but may represent a trauma-related subtype of PTSD with distinct biological correlates. One year after traumatic injury, 30% of a sample of 101 patients met symptomatic criteria for PTSD, and in multivariate models adjusting for injury severity, chronic conditions, age, sex, preinjury physical function and alcohol use, PTSD was the strongest predictor of adverse functional outcomes across seven of eight health domains. Problem drinking, present in 25% of the same sample, showed no clinically or statistically significant functional impairment. Understanding of PTSD remains incomplete, and care should be taken not to interfere with spontaneous recovery.
At the molecular level, the stress response involves activation of the hypothalamic-pituitary-adrenal axis and differential expression of genes controlled by the transcription factor NF-kappaB. Stress upregulates genes for cell growth, chromatin structure and nucleic acid biosynthesis, and downregulates cell cycle inhibitors, apoptosis-related genes and the NF-kappaB inhibitor Apo J. It is still unknown what molecular mechanisms trigger progression to PTSD, though genetic factors may account for about 30% of the variance in symptoms. Genome-wide association studies could identify new genes and dysregulated pathways, but this work has not yet delivered validated biomarkers for diagnosis or treatment.
A 2025 review of drug repurposing for PTSD summarises several classes of existing drugs that have been investigated, including alpha-adrenergic modulators, cannabinoids, glutamatergic modulators and antipsychotics. The rationale is that repurposing compounds with established safety and pharmacokinetic profiles could shorten development timelines and allow direct transition to phase II trials. The review does not report any positive trial results or response rates for these drugs; it notes potential drawbacks and negative aspects should be discussed comprehensively, but does not specify them.
What is still missing is a clear molecular target validated in human PTSD, a biomarker that can stratify patients into subgroups that might respond to different repurposed drugs, and funding for the phase II trials that the repurposing strategy is meant to accelerate. Without these, the list of candidate drugs remains a list of possibilities, not a treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Dialogues in Clinical Neuroscience · 2015 · 629 citations · open access
Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations
AbstractApproximately half of people with post-traumatic stress disorder (PTSD) also suffer from Major Depressive Disorder (MDD). The current paper examines evidence for two explanations of this comorbidity. First, that the comorbidity reflects overlapping symptoms in the two disorders. Second, that the co-occurrence of PTSD and MDD is not an artifact, but represents a trauma-related phenotype, possibly a subtype of PTSD. Support for the latter explanation is inferred from literature that examines risk and biological correlates of PTSD and MDD, including molecular processes. Treatment implications of the comorbidity are considered.
Posttraumatic Stress, Problem Drinking, and Functional Outcomes After Injury
AbstractHYPOTHESIS: Patients undergoing trauma surgery for injury who have subsequent posttraumatic stress disorder (PTSD) or problem drinking will demonstrate significant impairments in functional outcomes compared with patients without these disorders. DESIGN: Prospective cohort study. SETTING: Level I academic trauma center. PARTICIPANTS: One hundred one randomly selected survivors of intentional and unintentional injuries were interviewed while hospitalized and again 1 year later. The investigation achieved a 73% 1-year follow-up rate. MAIN OUTCOME MEASURES: Posttraumatic stress disorder was assessed with the Post-traumatic Stress Disorder Checklist and problem drinking was assessed with the Alcohol Use Disorder Identification Test. Functional status was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: One year after injury, 30% of patients (n = 22) met symptomatic criteria for PTSD and 25% (n = 18) had Alcohol Use Disorder Identification Test scores indicative of problem drinking. Patients with PTSD demonstrated significant adverse outcomes in 7 of the 8 domains of the Medical Outcomes Study 36-Item Short-Form Health Survey compared with patients without PTSD. In multivariate models that adjusted for injury severity, chronic medical conditions, age, sex, preinjury physical function, and alcohol use, PTSD remained the strongest predictor of an adverse outcome. Patients with problem drinking did not demonstrate clinically or statistically significant functional impairment compared with patients without problem drinking. CONCLUSIONS: Posttraumatic stress disorder persisted in 30% of patients 1 year after traumatic injury and was independently associated with a broad profile of functional impairment. The development of treatment intervention protocols for trauma patients with PTSD is warranted.
Current Opinion in Psychiatry · 2008 · 29 citations
Post-traumatic stress disorder: facts and fiction
AbstractPURPOSE OF REVIEW: This review provides an update on contemporary perspectives on post-traumatic stress disorder and challenges myths about the disorder and its treatment. Post-traumatic stress disorder has recently attracted public attention because of the impact of international terrorism, although the vast majority of post-traumatic stress disorder cases actually relate to civilian events such as car accidents, rape and violent robbery. This disorder requires deeper understanding and consensus among professionals. RECENT FINDINGS: Advances have been made in elucidating the neurobiology of this disorder, partly by using an animal model of post-traumatic stress disorder. Recent studies have focused on memory processes and the therapeutic role played by plasticity of the hypothalamic-pituitary-adrenal axis, and how this fits (or does not fit) in with the current therapeutic interventions. Guidelines have been established by various bodies in an attempt to streamline treatment options. SUMMARY: Understanding of post-traumatic stress disorder is incomplete. Future research should attempt to determine what treatments given during the 'window of opportunity' - the time from exposure until post-traumatic stress disorder develops - are effective. Care should be taken not to interfere with spontaneous recovery.
Psychological Stress – Cellular and Molecular Mechanisms
AbstractPathophysiological regulation of the stress response involves a number of complex interactions at the organismal, cellular and molecular levels. A salient feature of the stress response is the activation of the hypothalamic-pituitary-adrenal axis. Molecular studies of this phenomenon have found a number of genes which are differentially expressed in stressed individuals and control subjects. The transcription factor NF-kappaB controls many of these genes, which is evidence of the key role it plays in the cellular stress response. Stress upregulates a number of genes such as the transcription factor genes that control cell growth, chromatin structure, cell cycle activation and enzymes involved in the biosynthesis of nucleic acids and proteins. The genes that are down-regulated in stress are cell cycle inhibitors, apoptosis related genes, antiproliferative cytokines and Apo J, the NF-kappaB inhibitor. Post-traumatic stress disorder (PTSD) is an anxiety disorder which develops as a reaction to an extreme traumatic event but only in a small proportion of the population. It is still unknown what molecular mechanisms trigger its progression. Both genetic and epigenetic factors play a role in this condition. Although the environmental component is necessary for developing PTSD, it has been suggested that 30% of the variance in PTSD symptoms could be attributed to genetic influences. Utilizing genome wide association studies, it would be possible to identify new genes involved in PTSD development and elucidate the molecular pathways which are dysregulated. This will facilitate the identification of novel biomarkers that may help in PTSD diagnosis and treatment.
Theory and Practice of Psychological Counseling · 2023 · 0 citations · open access
Review and Prospect of Research on Post-traumatic Stress Disorder
AbstractPost traumatic stress disorder (PTSD) refers to the mental disorder that occurs and persists for a long time after the body encounters an unusual threat or disaster. Its clinical manifestations are mainly characterized by pathological recurrence, continuous increased alertness, continuous avoidance and selective forgetting of traumatic experience. The course of PTSD is prolonged, which seriously affects the psychology and society of patients function. In the increasingly competitive modern society, sudden stress events are increasing day by day, and the occurrence of PTSD shows an obvious upward trend. Therefore, how to prevent the occurrence of PTSD, especially how to prevent the occurrence of PTSD, is particularly important. This paper focuses on the psychological mechanism, treatment of post-traumatic stress disorder and research the prospect.
Repurposing Existing Drugs for the Treatment of Post-Traumatic Stress Disorder
AbstractChronic stress and traumatic events affect the psychological and physiological state of a person. Post-traumatic stress disorder (PTSD) is a type of psychological stress that occurs in critical situations that pose a direct threat to the life of the person and/or his or her loved ones. The prevalence of PTSD is increasing every year due to growing exposure to traumatic factors such as wars, natural disasters, and other crises. These events lead to severe psychological consequences, affecting a rising number of people worldwide. Currently, PTSD can be challenging to treat due to the complex nature of the disorder, variability in individual responses to treatment, and limitations in available therapeutic options. Considering the emergency need for effective PTSD treatment, a drug repurposing strategy presents a promising avenue to accelerate the availability of therapies. Here, we summarized and described drugs that were repurposed for alleviating PTSD symptoms. Moreover, we discussed the potential of some drugs, including alpha-adrenergic modulators, cannabinoids, glutamatergic modulators, and antipsychotics, for being repurposed for PTSD treatment. Drug repurposing implies the rapid identification of compounds with an established safety profile and known therapeutic effects that may be effective in PTSD. Repurposing existing drugs with already established pharmacokinetics and pharmacodynamics may shorten development timelines, facilitate a direct transition to the second phase of clinical trials, and lower costs. However, potential drawbacks and negative aspects should be discussed comprehensively.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
