Personality Neuroscience Ketamine and neuroticism: a double-hit cambridge.org/pen hypothesis of internalizing disorders N. McNaughton1 and P. Glue2 1 2 Shorter Communication Department of Psychology, University of Otago, Dunedin, New Zealand and Department Psychological Medicine, University of Otago, Dunedin, New Zealand Cite this article: McNaughton N. and Glue P. (2020) Ketamine and neuroticism: a double-hit Abstract hypothesis of internalizing disorders. Personality Neuroscience. Vol 3: e2, 1–7. Psychiatric disorders can often be viewed as extremes of personality traits. The primary action doi: 10.1017/pen.2020.2 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 Received: 24 July 2019 important for disorder. Internalizing disorders show important differences in terms of range Revised: 15 January 2020 Accepted: 25 January 2020 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. Key words: In contrast, low-dose ketamine is rapidly effective and improves symptom ratings in all inter- Ketamine; Neuroticism; Internalizing disorders; nalizing disorders. To account for this, we propose a “double hit” model for internalizing Anxiety; Depression; Post-traumatic stress disorder 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 Author for correspondence: linked to high levels of the personality trait of neuroticism. The other hit is disorder-specific: N. McNaughton, dysfunction of one of a set of disorder-specific neural modules, each with its own particular Email:
[email protected] pattern of sensitivity to conventional drugs.