DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for personality disorder — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePersonality disorder maps to a 3-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 personality 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
phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma (PIK3C2G) — PIK3C2G 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2WWE · 1.25 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Fifteen studies of psychotherapy for personality disorders, including three randomised controlled trials, reported mean pre-post effect sizes of 1.11 on self-report measures and 1.29 on observational measures. In four studies, 52% of patients remaining in therapy no longer met full criteria for personality disorder after a mean of 1.3 years. A heuristic model estimated 25.8% recovery per year of therapy, compared with 3.7% per year in a natural history model of borderline personality disorder, which projected 50% recovery after 10.5 years. The authors concluded psychotherapy is effective and may be associated with up to a sevenfold faster rate of recovery than natural history.
A separate review identified a substantial number of treatment outcome studies for Axis II disorders, contrary to contemporary assumptions. It found evidence that effective treatments exist to alleviate symptoms and reduce symptomatic behaviours accompanying personality disorders, but considered what these results mean for the idea of remission from personality disorder. The best evidence for effective treatment supports specialised forms of psychotherapy, but these are generally unavailable in health care systems, partly due to the expense of long-term therapies, though there is evidence they are cost-effective. One proposed solution is to treat most patients more briefly.
Among 82 depressed outpatients receiving routine antidepressant medication and psychosocial intervention, followed over five visits at three-month intervals, only those with cluster B or mixed personality disorders took significantly longer for reduction in Hamilton Depression Rating Scale scores. The impact of personality disorders on treatment outcomes varied with how personality disorder variables were described and used as independent predictors, because outcomes were influenced by the impact weight of each personality disorder even within the same cluster.
A commentary on personality disorder genetics called for harnessing advances in assessment rather than relying on politically derived top-down nosologies. It highlighted the joint hierarchical structure of PD traits and psychopathology, and personality dynamics, as fruitful avenues for exploring genetics. It stressed the need to better understand the role of environment, the need for more research and larger samples to arrive at stronger conclusions, and how advances in gene-environment research could help determine targets for prevention and treatment. What is still missing are larger genetic samples, consistent assessment methods that capture personality dynamics, and trial designs that test specific therapies for specific personality disorders with uniform outcome measures, as well as health system investment to make specialised psychotherapies routinely available.
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 · 1999 · 426 citations
Effectiveness of Psychotherapy for Personality Disorders
AbstractOBJECTIVE: The authors examined the evidence for the effectiveness of psychotherapy for personality disorders in psychotherapy outcome studies. METHOD: Fifteen studies were located that reported data on pretreatment-to-posttreatment effects and/or recovery at follow-up, including three randomized, controlled treatment trials, three randomized comparisons of active treatments, and nine uncontrolled observational studies. They included psychodynamic/interpersonal, cognitive behavior, mixed, and supportive therapies. RESULTS: All studies reported improvement in personality disorders with psychotherapy. The mean pre-post effect sizes within treatments were large: 1.11 for self-report measures and 1.29 for observational measures. Among the three randomized, controlled treatment trials, active psychotherapy was more effective than no treatment according to self-report measures. In four studies, a mean of 52% of patients remaining in therapy recovered--defined as no longer meeting the full criteria for personality disorder--after a mean of 1.3 years of treatment. A heuristic model based on these findings estimated that 25.8% of personality disorder patients recovered per year of therapy, a rate sevenfold larger than that in a published model of the natural history of borderline personality disorder (3.7% recovered per year, with recovery of 50% of patients requiring 10.5 years of naturalistic follow-up). CONCLUSIONS: Psychotherapy is an effective treatment for personality disorders and may be associated with up to a sevenfold faster rate of recovery in comparison with the natural history of disorders. Future studies should examine specific therapies for specific personality disorders, using more uniform assessment of core pathology and outcome.
The Canadian Journal of Psychiatry · 1998 · 122 citations · open access
Treatment Outcome of Personality Disorders
AbstractOBJECTIVE: To review the treatment outcome of personality disorders. METHOD: A literature search of studies pertaining to personality disorder and outcome was conducted, and studies that focused primarily on Axis II were retained. Of these, naturalistic outcome studies were distinguished from those that addressed treatment outcome specifically. The treatment outcome studies were examined in terms of type of treatment intervention, dependent variables, and outcome. RESULTS: Contrary to contemporary assumptions about Axis II, a substantial number of treatment outcome studies were identified. Trends in the assumptions underlying psychosocial and pharmacologic approaches were identified on the basis of dependent variables. CONCLUSION: There is evidence that effective treatments exist to alleviate symptoms and reduce symptomatic behaviours that accompany personality disorders. What these results hold for the idea of remission from personality disorder is considered.
Neuropsychiatric Disease and Treatment · 2015 · 6 citations · open access
The influence of comorbid personality disorders on recovery from depression
AbstractPURPOSE: The impact of personality disorders on the treatment of and recovery from depression is still a controversial topic. The aim of this paper is to provide more information on what has led to this disagreement. MATERIALS AND METHODS: Clinician-rated Hamilton Depression Rating Scale (HAMD) scores were assessed among 82 depressed outpatients who were receiving a routine treatment combination of antidepressant medication and psychosocial intervention. The participants were followed up over five visits at 3-month intervals: at the baseline, at 3, 6, 9 and 12 months. Personality disorders were assessed after the last visit in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. These repeated measures were used to explore the impact of personality disorders on HAMD scores by using a linear mixed model. RESULTS: Among the four personality clusters that were used (A, B, C, and mixed), only those in cluster B and in the mixed cluster were found to take significantly longer than those without personality disorders, for reduction in HAMD scores over the course of treatment. CONCLUSION: In this study, the impact of personality disorders on treatment outcomes varied with the way that the personality disorder variables were described and used as independent predictors. This is because the outcomes were influenced by the impact weight of each personality disorder, even within the same cluster.
Cambridge University Press eBooks · 2020 · 0 citations
Four Key Areas for Further Investigation: Commentary on Issues and New Directions in Personality Disorder Genetics
AbstractThe following commentary on Jang and Choi’s chapter Issues and New Directions in Personality Disorder (PD) Genetics (This Volume) echoes their call to harness advances in PD assessment rather than rely on politically derived "top down" nosologies. We first discuss how recent work in the joint hierarchical structure of PD traits and psychopathology, as well as, personality dynamics (i.e., how personality manifests in different situations) likely offer fruitful avenues for exploring the more nuanced role of genetics in the development and maintenance of PD. Second, we highlight the need to better understand the role of environment in PD genetics and discuss emerging models (e.g., common pathway model). Third, we stress the need for more research and larger samples in order to arrive at stronger conclusions. Fourth, we consider how advances in gene-environment research can help to determine targets for PD prevention and treatment.
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.
