A unified model of ketamine’s dissociative and psychedelic properties

OKKetamine is an N-methyl-d-aspartate antagonist which is increasingly being researched and used as a treatment for depression. In low doses, it can cause a transitory modification in consciousness which was classically labelled as ‘dissociation’. However, ketamine is also commonly classified as an atypical psychedelic and it has been recently reported that ego dissolution experiences during ketamine administration are associated with greater antidepressant response. Neuroimaging studies have highlighted several similarities between the effects of ketamine and those of serotonergic psychedelics in the brain; however, no unified account has been proposed for ketamine’s multi-level effects – from molecular to network and psychological levels. Here, we propose that the fast, albeit transient, antidepressant effects observed after ketamine infusions are mainly driven by its acute modulation of reward circuits and sub-acute increase in neuroplasticity, while its dissociative and psychedelic properties are driven by dose- and context-dependent disruption of large-scale functional networks. Computationally, as nodes of the salience network (SN) represent high-level priors about the body (‘minimal’ self) and nodes of the default-mode network (DMN) represent the highest-level priors about narrative self-experience (‘biographical’ self), we propose that transitory SN desegregation and disintegration accounts for ketamine’s ‘dissociative’ state, while transitory DMN desegregation and disintegration accounts for ketamine’s ‘psychedelic’ state. In psychedelic-assisted psychotherapy, a relaxation of the highest-level beliefs with psychotherapeutic support may allow a revision of pathological self-representation models, for which neuroplasticity plays a permissive role. Our account provides a multi-level rationale for using the psychedelic properties of ketamine to increase its long-term benefits.publishersversionepub_ahead_of_prin

Experiências adversas da infância e o seu impacto na saúde do adulto

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017Os efeitos a longo prazo na saúde mental da exposição a eventos stressores na infância estão relativamente bem documentados. O termo genérico “Experiências Adversas na Infância” (EAI), do anglo-saxónico Adverse Childhood Experiences, que inclui os conceitos de abuso, negligência e disfunção familiar, é referido na literatura como um indicador de risco para desenvolver não só doença mental como física no adulto. Neste contexto, o presente trabalho pretende, assim: definir EAI, de acordo com as suas referências na literatura e com o parecer da Organização Mundial de Saúde; avaliar a importância da ocorrência de uma ou mais EAI para o desenvolvimento de uma vinculação patológica e caracterizar o risco daí resultante para a manifestação de doença no adulto; caracterizar a relação entre EAI e patologias orgânicas específicas, de acordo com a evidência actual disponível.The long-term effects on mental health of the exposure to stressing events during childhood are relatively well documented. The generic term Adverse Childhood Experiences (ACE), that includes abuse, negligence and family dysfunction, is referred in the literature as a riskfactor to the development of mental and physical disease in the adult. Having this as a background, the current article intends: to define ACE, according to its references in the literature as well as World Health’s Organization’s position on this issue; to evaluate the importance of the occurrence of one or more ACE to the development of a pathological vinculation and to describe its risk to manifest disease in the adult; to define the relationship between ACE and specific organic pathologies, according to recent available evidence