DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for panic disorder — screening already-approved drugs against its 19-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePanic disorder maps to a 19-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 panic 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
gamma-aminobutyric acid type A receptor subunit alpha4 (GABRA4) — GABRA4 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 px6drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7QN5 · 2.5 Å · ligand 1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE (PX6). Experimental structure, not a prediction.
What the evidence adds up to
A 1999 multicentre double-blind placebo-controlled trial randomly assigned 438 adults with panic disorder to clonazepam (0.25–4.0 mg daily, N=222) or placebo (N=216) for six weeks, followed by a seven-week taper. At the therapeutic endpoint clonazepam was superior to placebo on number of panic attacks, Clinical Global Impressions severity and change scores, patient global impression of change, phobic fear and avoidance, and duration of anticipatory anxiety. Gradual tapering produced no overall evidence of rebound or withdrawal syndrome, though patients taking clonazepam experienced some clinical worsening compared with their endpoint status, particularly in panic attack frequency. Somnolence was the main adverse event; the clonazepam group reported more adverse events overall.
A 2007 randomised controlled trial compared panic-focused psychodynamic psychotherapy with applied relaxation training in 49 adults with DSM-IV panic disorder, treated twice weekly for 12 weeks. On the Panic Disorder Severity Scale, the psychodynamic group showed significantly greater reduction in panic symptoms. At termination, 73% of the psychodynamic group met response criteria versus 39% of the relaxation group. The authors noted the small cohort size and described the findings as preliminary efficacy evidence.
Two review articles from 2007 and 2013 summarise the state of genetic research in panic disorder. Hundreds of candidate genes have been examined, but most results have been negative, inconsistent, or await replication. The 2013 review states that linkage and candidate gene association studies have shown only weak success in identifying reliable genetic substrates. A 2020 systematic review using PathwayStudio identified 55 articles reporting genetic associations and 32 reporting no associations; it names COMT and SLC6A4 as the most promising biomarkers for diagnosis to date, but does not report effect sizes or replication rates. A 2008 treatment review notes that cognitive-behaviour therapy and pharmacotherapy are the major modalities, and identifies unresolved issues including optimal ways to combine medications with CBT and how to minimise recurrence after treatment cessation.
What is still missing are adequately powered genome-wide association studies that account for phenotypic heterogeneity, age of onset, gender, and familial aggregation in panic disorder. The genetic findings remain scattered and unsystematic, with no effective genetic testing available. The psychodynamic psychotherapy trial was small and requires replication. No study in this set examines stratified treatment selection based on biomarkers or genetic profile, and no long-term follow-up data beyond the discontinuation phase of the clonazepam trial are provided.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Psychiatry · 2007 · 320 citations
A Randomized Controlled Clinical Trial of Psychoanalytic Psychotherapy for Panic Disorder
AbstractOBJECTIVE: The purpose of this study was to determine the efficacy of panic-focused psychodynamic psychotherapy relative to applied relaxation training, a credible psychotherapy comparison condition. Despite the widespread clinical use of psychodynamic psychotherapies, randomized controlled clinical trials evaluating such psychotherapies for axis I disorders have lagged. To the authors' knowledge, this is the first efficacy randomized controlled clinical trial of panic-focused psychodynamic psychotherapy, a manualized psychoanalytical psychotherapy for patients with DSM-IV panic disorder. METHOD: This was a randomized controlled clinical trial of subjects with primary DSM-IV panic disorder. Participants were recruited over 5 years in the New York City metropolitan area. Subjects were 49 adults ages 18-55 with primary DSM-IV panic disorder. All subjects received assigned treatment, panic-focused psychodynamic psychotherapy or applied relaxation training in twice-weekly sessions for 12 weeks. The Panic Disorder Severity Scale, rated by blinded independent evaluators, was the primary outcome measure. RESULTS: Subjects in panic-focused psychodynamic psychotherapy had significantly greater reduction in severity of panic symptoms. Furthermore, those receiving panic-focused psychodynamic psychotherapy were significantly more likely to respond at treatment termination (73% versus 39%), using the Multicenter Panic Disorder Study response criteria. The secondary outcome, change in psychosocial functioning, mirrored these results. CONCLUSIONS: Despite the small cohort size of this trial, it has demonstrated preliminary efficacy of panic-focused psychodynamic psychotherapy for panic disorder.
The Journal of Clinical Psychiatry · 1999 · 69 citations
Efficacy, Safety, and Gradual Discontinuation of Clonazepam in Panic Disorder
AbstractBACKGROUND: The purpose of this multicenter, double-blind, placebo-controlled study was to evaluate the efficacy and safety of optimized dosages of clonazepam for the treatment of panic disorder and assess the tolerability of a schedule for gradual discontinuation. METHOD: Adult patients with panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to receive either placebo or clonazepam in individually adjusted doses over 3 weeks to approximate an optimal dosage, which was then maintained for an additional 3 weeks, amounting to a 6-week therapeutic phase. The daily dose range was 0.25 to 4.0 mg administered in 2 divided doses. In the following 7-week discontinuance phase, the doses were tapered gradually to cessation. RESULTS: At the therapeutic endpoint, clonazepam (N = 222) proved clinically and statistically superior to placebo (N = 216) in change in the number of panic attacks and in Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Change scores, Patient's Global Impression of Change scores, amount of fear and avoidance associated with phobic symptoms, and duration of anticipatory anxiety. The gradual tapering of clonazepam was not associated with symptoms suggestive of withdrawal syndrome. Although patients taking clonazepam experienced some clinical worsening compared with the status achieved at endpoint, particularly in terms of number of panic attacks, no deterioration was observed using their condition at baseline as point of reference. No overall evidence of rebound was found. All regimens were generally well tolerated. Somnolence was the main adverse event associated with clonazepam therapy. The percentage of patients who reported adverse events was higher in the clonazepam group than in the placebo group, as was the mean number of adverse events per patient. CONCLUSION: In this placebo-controlled trial, clonazepam was an efficacious and safe shortterm treatment of the symptoms of panic disorder. Discontinuance during and after slow tapering was well tolerated.
Candidate genes for panic disorder: insight from human and mouse genetic studies
AbstractPanic disorder is a major cause of medical attention with substantial social and health service cost. Based on pharmacological studies, research on its etiopathogenesis has been focused on the possible dysfunction of specific neurotransmitter systems. However, recent work has related the genes involved in development, synaptic plasticity and synaptic remodeling to anxiety disorders. This implies that learning processes and changes in perception, interpretation and behavioral responses to environmental stimuli are essential for development of complex anxiety responses secondary to the building of specific brain neural circuits and to adult plasticity. The focus of this review is on progress achieved in identifying genes that confer increased risk for panic disorder through genetic epidemiology and the use of genetically modified mouse models. The integration of human and animal studies targeting behavioral, systems-level, cellular and molecular levels will most probably help identify new molecules with potential impact on the pathogenetic aspects of the disease.
Expert Review of Neurotherapeutics · 2008 · 14 citations
Treatment of panic disorder: recent developments and current status
AbstractPanic disorder is a commonly encountered condition in general medical practice and in various medical settings. It is important for all medical practitioners to be able to recognize this disorder, provide patients with basic information and medical advice, and depending on the specific circumstances, to refer patients for appropriate treatment by primary care physicians, psychiatrists and/or clinical psychologists. This article reviews the developments in the treatment of panic disorder, focusing on the major treatment modalities of pharmacotherapy and cognitive-behavior therapy, as well as their combinations. In addition to providing information on current treatments for panic disorder and the main underlying treatment issues, the article identifies areas where improvements need to be made and areas where much research has been conducted in recent years. These include simplified modes of delivery of cognitive-behavior therapy, optimal ways of combining medications with cognitive-behavior therapy, and minimizing the risk of recurrence after the cessation of treatment.
Genetic Biomarkers of Panic Disorder: A Systematic Review
Abstract(1) Background: Although panic disorder (PD) is one of the most common anxiety disorders severely impacting quality of life, no effective genetic testing exists; known data on possible genetic biomarkers is often scattered and unsystematic which complicates further studies. (2) Methods: We used PathwayStudio 12.3 (Elsevier, The Netherlands) to acquire literature data for further manual review and analysis. 229 articles were extracted, 55 articles reporting associations, and 32 articles reporting no associations were finally selected. (3) Results: We provide exhaustive information on genetic biomarkers associated with PD known in the scientific literature. Data is presented in two tables. Genes COMT and SLC6A4 may be considered the most promising for PD diagnostic to date. (4) Conclusions: This review illustrates current progress in association studies of PD and may indicate possible molecular mechanisms of its pathogenesis. This is a possible basis for data analysis, novel experimental studies, or developing test systems and personalized treatment approaches.
Berichte des Ohara Instituts für landwirtschaftliche Forschungen · 1930 · 0 citations · open access
Beziehung zwischen der Wassertemperatur und dem Wachstum der Reispftanzen. Erste Mitteilung.
AbstractPanic disorder is a major cause of medical attention with substantial social and health service cost. Based on pharmacological studies, research on its etiopathogenesis has been focused on the possible dysfunction of specific neurotransmitter systems. However, recent work has related the genes involved in development, synaptic plasticity and synaptic remodeling to anxiety disorders. This implies that learning processes and changes in perception, interpretation and behavioral responses to environmental stimuli are essential for development of complex anxiety responses secondary to the building of specific brain neural circuits and to adult plasticity. The focus of this review is on progress achieved in identifying genes that confer increased risk for panic disorder through genetic epidemiology and the use of genetically modified mouse models. The integration of human and animal studies targeting behavioral, systems-level, cellular and molecular levels will most probably help identify new molecules with potential impact on the pathogenetic aspects of the disease.
Encyclopedia of Life Sciences · 2013 · 0 citations
Genetics of Panic Disorder
AbstractAbstract The molecular genetic research on panic disorder (PD) has grown tremendously in the past decade. To date, several hundreds of candidate genes have been examined in association studies, but most of the results have been negative, inconsistent or awaiting replication. Perhaps most intriguing have been findings involving the genes of biological systems known to be pertinent to anxiety phenotypes, such as serotonin, cholecystokinin and adenosine. An array of other genes related to hormonal, neurotrophic and intracellular systems has also been implicated in disposition to PD. The recent advances in bioinformatics and genotyping technologies, including genome‐wide association and gene expression methods, promise more comprehensive discovery in PD. Preliminary findings point to a number of novel gene targets with still unknown pathogenetic relationship to PD. The progress in clinical and neurobiological concepts of PD may further guide genetic research through the current ambiguity to more definitive findings. Key Concepts: The linkage and candidate gene association studies have so far showed only weak success to identify reliable and replicated evidence for the genetic substrate of PD. The genetic research in PD to date has been mostly restricted to small phenotypically and ethnically diverse datasets with genotyping of limited numbers of SNPs. An improved understanding of neurobiological pathways of PD could contribute to a more effective identification of candidate genes. Novel conceptual and analytic approaches, such as pathways‐based analyses, may help to advance GWA studies in PD. Laboratory panic challenge models may provide clues to genetic predisposition to PD. The understanding of genetic underpinnings of PD will not be of full value without a conceptual integration of the clinical phenomena of PD with psychological models and neurobiological or molecular substrates underlying its development and course. The course of PD may depend on the balance between pathogenetic and compensatory or recovery processes, accompanied by activation or inhibition of relevant genes. PD might exist in many distinct genetic forms, each with a different set of genes, but also in one form with certain genes reflecting broader vulnerability to panicogenesis. The heterogeneity in PD phenotypes, age of onset, subtypes and severity of panic attacks, gender and familial aggregation were not sufficiently accounted for in most of published studies and should be more carefully addressed in further analyses. Other comprehensive genetic approaches, including GWA, the analysis of copy number variants and the study of regulatory small noncoding RNAs, may lead to uncovering new genomic mechanisms of PD.
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.
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