ArticlePersonality neuroscience2020
Ketamine and neuroticism: a double-hit hypothesis of internalizing disorders.
Article in Personality neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 41 citations in OpenAlex.
- Ketamine Dose and Duration Effects in Internalizing Disorders.Journal of clinical pharmacology · 2026Trial
- Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex.Translational psychiatry · 2024Trial
- Ketamine for treatment-resistant major depressive disorder: Double-blind active-controlled crossover study.Journal of psychopharmacology (Oxford, England) · 2024Trial
- Ketamine effects on EEG and their links to therapy differ across treatment-resistant major depression, post-traumatic stress disorder, and obsessive-compulsive disorder.The international journal of neuropsychopharmacology · 2026Article
- Ketamine Dosing Across Clinical Indications: A Narrative Review Organized by Proposed NMDA-Related Mechanisms.Journal of clinical pharmacology · 2026Review
- Hope for Neurotic Disorders: A Summary of New Zealand Research on the Development of Biomarkers and Novel Treatments.Journal of the Royal Society of New Zealand · 2026Article
- Is lack of goal-conflict-specific rhythmicity a biomarker for treatment resistance in generalised anxiety but not social anxiety or major depression?Journal of psychopharmacology (Oxford, England) · 2024Article
- Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review.BJPsych open · 2023Review
- Editorial: an emerging field with bright prospects.Personality neuroscience · 2023Article
- Right Frontal Theta: Is It a Response Biomarker for Ketamine's Therapeutic Action in Anxiety Disorders?Frontiers in neuroscience · 2022Article
- Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review.BJPsych open · 2021Review
- Right frontal anxiolytic-sensitive EEG 'theta' rhythm in the stop-signal task is a theory-based anxiety disorder biomarker.Scientific reports · 2021Article
- Therapeutic Potentials of Ketamine and Esketamine in Obsessive-Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature.Brain sciences · 2021Article
- Personality neuroscience and psychopathology: should we start with biology and look for neural-level factors?Personality neuroscience · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Psychiatric disorders can often be viewed as extremes of personality traits. The primary action of drugs that ameliorate these disorders may, thus, be to alter the patient's position on a relevant trait dimension. Here, we suggest that interactions between such trait dimensions may also be important for disorder. Internalizing disorders show important differences in terms of range of activity and speed of response of medications. Established antidepressant and anxiolytic medications are slow in onset and have differing effects across different internalizing disorders. In contrast, low-dose ketamine is rapidly effective and improves symptom ratings in all internalizing disorders. To account for this, we propose a "double hit" model for internalizing disorders: generation (and maintenance) require two distinct forms of neural dysfunction to coincide. One hit, sensitive to ketamine, is disorder-general: dysfunction of a neural system linked to high levels of the personality trait of neuroticism. The other hit is disorder-specific: dysfunction of one of a set of disorder-specific neural modules, each with its own particular pattern of sensitivity to conventional drugs. Our hypothesis applies only to internalizing disorders. So, we predict that ketamine will be effective in simple phobia and (perhaps partially) in anorexia nervosa, but would make no such prediction about other disorders where neuroticism might also be important secondarily (e.g. attention deficit hyperactivity disorder and schizophrenia).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.