DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for neurotic 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 moduleNeurotic 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 neurotic 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
BAR/IMD domain containing adaptor protein 2 (BAIAP2) — BAIAP2 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 bis-carboxymethyl-aminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3RNJ · 1.5 Å · ligand {[-(BIS-CARBOXYMETHYL-AMINO)-ETHYL]-CARBOXYMETHYL-AMINO}-ACETIC ACID (EDT). Experimental structure, not a prediction.
What the evidence adds up to
In a 2006 fMRI study of 14 unmedicated depressed individuals, those with low sustained reactivity in the subgenual cingulate cortex and high amygdala reactivity showed the strongest improvement after 16 sessions of cognitive behaviour therapy, suggesting that emotion regulation disruptions targeted by CBT may predict recovery. A 2011 randomised controlled trial of 52 patients with unipolar depression found that adding resource activation to cognitive behavioural therapy produced comparable overall improvement to CBT alone, with no additional efficacy from the resource focus on cognitive, emotional or interpersonal outcomes. A 2005 systematic review of treatments for depression in people aged 60 or over rated antidepressants, electroconvulsive therapy, cognitive behaviour therapy, psychodynamic psychotherapy, reminiscence therapy, problem-solving therapy, bibliotherapy and exercise as having the best evidence, while transcranial magnetic stimulation, dialectical behaviour therapy, interpersonal therapy, light therapy, St John's wort and folate had only limited supporting evidence.
A 2022 pilot randomised controlled trial of 78 participants with treatment-resistant depression compared repetitive transcranial magnetic stimulation (rTMS) alone with rTMS plus internet-delivered cognitive behaviour therapy (iCBT). After adjusting for baseline scores, the study found no significant difference between the two interventions on the Hamilton depression rating scale, the Columbia suicide severity rating scale, the Quick inventory of depressive symptomatology, or the EQ-5D quality of life measure. However, for the combined study population there was a significant reduction from baseline to six weeks of 42% on the HAMD-17, 41% on the CSSRS and 35% on the QIDS-SR16, with a 62% improvement in quality of life as recorded on the EQ-VAS. The same paper's scoping reviews concluded that rTMS is efficacious for treatment-resistant depression, PTSD, bipolar disorder and obsessive-compulsive disorder, and that iCBT appears an effective and accessible internet-based intervention for major depressive disorder and treatment-resistant depression.
A 2007 review noted that nearly 60% of patients with depression may not achieve adequate response following antidepressant treatment, and positioned transcranial magnetic stimulation as a less invasive somatic option than electroconvulsive therapy for resistant depression. A 2022 overview of drugs for mood disorders states that medications and/or psychotherapy are indicated for moderate to severe depressive symptoms, while somatic treatments such as electroconvulsive therapy and transcranial magnetic stimulation are reserved for severe refractory cases. A 1989 clinical review reported that specialised psychotherapy (interpersonal, cognitive or behavioural) is as effective as standard tricyclic antidepressants in treating depression and can be used as an alternative to medication, and that combined use may enhance compliance and efficacy.
A 1964 paper argued that behaviour therapy is effective in neuroses, and that common qualifications limiting its use to monosymptomatic cases such as phobias, or claiming it leaves the deep cause untouched, are erroneous. Across these studies, the evidence base for neurotic disorders is dominated by depression trials, with modest sample sizes and no consistent demonstration that adding one active treatment to another improves outcomes beyond the single intervention. What remains missing is large-scale randomised evidence comparing treatment sequences, head-to-head trials of psychotherapy versus somatic treatments in resistant neurotic disorders, and reliable biomarkers or neural predictors that could stratify patients to CBT, rTMS or medication rather than relying on trial and error.
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 · 2006 · 373 citations
Use of fMRI to Predict Recovery From Unipolar Depression With Cognitive Behavior Therapy
AbstractObjective: In controlled treatment trials, 40%–60% of unmedicated depressed individuals respond to cognitive behavior therapy (CBT). The authors examined whether pretreatment neural reactivity to emotional stimuli accounted for this variation. Method: Unmedicated depressed individuals (N=14) and never depressed comparison subjects (N=21) underwent fMRI during performance of a task sensitive to sustained emotional information processing. Afterward, depressed participants completed 16 sessions of CBT. Results: Participants whose sustained reactivity to emotional stimuli was low in the subgenual cingulate cortex (Brodmann’s area 25) and high in the amygdala displayed the strongest improvement with CBT. Conclusions: The presence of emotion regulation disruptions, which are targeted in CBT, may be the key to recovery with this intervention.
The Medical Journal of Australia · 2005 · 154 citations
Effectiveness of treatments for depression in older people
AbstractOBJECTIVE: To conduct a systematic review of the evidence for the effectiveness of a range of possible treatments for depression in older people. DATA SOURCES: Literature search using the PubMed, PsycInfo and Cochrane Library databases. DATA SYNTHESIS: Treatments that have been suggested to be effective for depression were grouped under three categories: medical treatments, psychological treatments, and lifestyle changes/alternative treatments. We describe each treatment, review the studies of its effectiveness in people aged > or = 60 years, and give a rating of the level of evidence. CONCLUSIONS: The treatments with the best evidence of effectiveness are antidepressants, electroconvulsive therapy, cognitive behaviour therapy, psychodynamic psychotherapy, reminiscence therapy, problem-solving therapy, bibliotherapy (for mild to moderate depression) and exercise. There is limited evidence to support the effectiveness of transcranial magnetic stimulation, dialectical behaviour therapy, interpersonal therapy, light therapy (for people in nursing homes or hospitals), St John's wort and folate in reducing depressive symptoms.
The British Journal of Psychiatry · 1964 · 86 citations
Behaviour Therapy in Complex Neurotic States
AbstractIn recent years it has become widely known that behaviour therapy (conditioning therapy) is effective in the treatment of neuroses. However, in many minds, this knowledge has come to be hedged by some erroneous qualifications, of which the commonest are: ( a ) that behaviour therapy leaves the “deep” cause of neurosis untouched, and ( b ) that it is successful with “monosymptomatic” and allegedly simple cases like phobias, but not with more complex neuroses, such as obsessions and “character neuroses”.
Ressourcenorientierte Akutbehandlung unipolarer Depressionen: Eine randomisierte kontrollierte Psychotherapiestudie
AbstractBACKGROUND: Resource activation is considered to be a central mechanism in psychotherapeutic change. However, it is widely unknown whether a special focus on resource activation is associated with higher efficacy in cognitive behavioural therapy. METHOD: 52 patients with unipolar depression took part in a randomized controlled study comparing cognitive behavioural therapy plus resource activation (RFCBT) with cognitive behavioural therapy (CBT) alone. RESULTS: Overall, treatment effects were comparable to published research. In both treatment groups patients equally improved on cognitive, emotional and interpersonal outcome measures. CONCLUSIONS: A combined treatment approach of cognitive behavioural therapy and resource activation was shown to be an effective treatment of unipolar depression. Yet, compared to a standard CBT-treatment an additional focus on resource was not associated with higher efficacy.
The Journal of Clinical Psychiatry · 2007 · 5 citations · open access
Transcranial Magnetic Stimulation: Potential New Treatment for Resistant Depression
AbstractArticle AbstractClick to enlarge pageMajor depression is a common disorder and substantial cause of disease burden worldwide. Nearly 60% of patients with depression may not achieve adequate response following antidepressant treatment. New somatic treatments that are less invasive than electroconvulsive therapy (ECT), such as transcranial magnetic stimulation (TMS), are being added to the repertoire of treatments that have the potential to be effective in depression that is resistant to pharmacologic therapies.
AbstractDepression is a commonly encountered problem in primary medical care. In cases of mild reactive depression, supportive psychotherapy by the primary care physician may be sufficient treatment. Referral for specialized psychotherapy (interpersonal, cognitive, or behavioral therapy) should be considered when psychological risk factors are thought to play an important role in the patient's depression. According to recent clinical trials, specialized psychotherapy is as effective in treating depression as standard tricyclic anti-depressant therapy and can be used as an alternative to medication. When used in conjunction with medication, psychotherapy may enhance compliance and therapeutic efficacy.
AbstractA variety of treatment modalities are available for the management of depression: prescription medications, psychotherapy, and somatic treatments (electroconvulsive therapy, transcranial magnetic stimulation). Medications and/or psychotherapy are indicated for moderate to severe depressive symptoms, while somatic treatments are used for severe refractory cases. Lifestyle and social support are important to decrease the risk of mood disorders and to alleviate their symptoms.
University of Alberta Library · 2022 · 0 citations · open access
Repetitive Transcranial Magnetic Stimulation with and without Internet-delivered Cognitive Behaviour Therapy for the Treatment of Resistant Depression: Patient-centred Randomized Controlled Pilot Trial
AbstractAbstract Background: Major depression is a severe, disabling, and potentially lethal clinical disorder. Only about half of patients respond to an initial course of antidepressant pharmacotherapy. At least 15% of patients with major depression disorder (MDD) remain refractory to any treatment intervention. Repetitive Transcranial Magnetic Stimulation (rTMS) is considered a treatment option for patients with MDD who are refractory to antidepressant treatment as well as cognitive-behavioural therapy (CBT: an evidence-based, structured, intensive, time-limited, symptom-focused form of psychotherapy recommended for the treatment of MDD). It is not known if the addition of iCBT enhances a patient’s response to rTMS treatments. Objectives: The aims of this study are to 1) conduct a scoping review of the literature in support of the use of rTMS for the management of the psychiatric disorders (treatment-resistant depression (TRD), PTSD, bipolar disorder, and obsessive-compulsive disorder (OCD)) 2) conduct a general review of the literature in relation to iCBT for the management of TRD. 3) evaluate the initial comparative clinical effectiveness of rTMS with and without iCBT as an innovative patient-centred intervention for the treatment of participants diagnosed with TRD. Methods: Five databases were searched (MEDLINE, CINAHL, PsychINFO, SCOPUS, and EMBASE) to identify empirical studies and randomized controlled trials (RCTs) aimed at the treatment of TRD, PTSD, bipolar disorder, and OCD with rTMS. Again, a general search was conducted in the afore-mentioned databases to generate a general review of literature on the use of iCBT for the management of TRD. Regarding the prospective RCT, overall, 78 participants diagnosed with TRD were randomized to one of two treatment interventions; rTMS sessions alone and rTMS sessions plus iCBT. Participants in each group completed evaluation measures at baseline and 6 weeks (discharge) from treatment. The primary outcome measure was the mean change in the 17-item Hamilton depression rating scale (HAMD-17) from baseline to six weeks. Secondary outcomes included mean changes from baseline to six weeks in the Columbia suicide severity rating scale (CSSRS), which rates suicidal ideations, Quick inventory of depressive symptomatology-self rated scale (QIDS-SR16) for subjective depression, and the EQ-5D-5L to assess the quality of health in participants. Results: The major findings from the scoping reviews conducted on the efficacy of rTMS were that rTMS application is efficacious in the management of TRD, PTSD, bipolar disorder, and OCD. From the reviewed papers, iCBT seems an effective and promising internet-based intervention for the management of MDD and TRD, with a greater accessibility for the target population. Regarding the prospective RCT, the majority of participants were females 50(64.1%), aged ≥40 39(50.0%), and had college/university education 54(73.0%). After adjusting for baseline scores, the study failed to find a significant difference in the changes in mean scores for participants from baseline to six weeks between the two interventions under study on the HAMD-17 scale; F (1, 53) = 0.15, p = 0.70, partial eta squared = 0.003, CSSRS; F (1, 56) = 0.04 p = 0.85, partial eta squared = .001, QIDS-SR16 scale; F (1, 53) = 0.04 p = 0.61, partial eta squared = 0.005, and EQ-5D-VAS; F (1,51) = 0.46 p = 0.50, partial eta squared = .009. However, it found a significant reduction in means scores at week six compared to baseline scores for the combined study population on the HAMD-17 scale (42%), CSSRS (41%) and QIDS-SR16 scale (35%). Additionally, it noted an improvement of about 62% in the quality of life of all participants, as recorded via the EQ-VAS scale. Conclusion: The scoping reviews suggest that rTMS is effective for management of TRD, PTSD, bipolar disorder, and OCD. Future narratives on effective implementation strategies of iCBT interventions for the management of TRD should consider issues on specific predictors and impediments of their usage, and address them in future studies and practices. The RCT failed to demonstrate a significant difference regarding the management of MDD symptoms, subjective MDD, suicidal ideations, and the quality of health between rTMS alone and rTMS plus unguided iCBT on all scales.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, 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.
