Psychotic Disorder
psychotic disorder
Hallucinating mice, dopamine and immunity; towards mechanistic treatment targets for psychosis
Hallucinations are a core symptom of psychotic disorders and have traditionally been difficult to study biologically. We developed a new behavioral computational approach to measure hallucinations-like perception in humans and mice alike. Using targeted neural circuit manipulations, we identified a causal role for striatal dopamine in mediating hallucination-like perception. Building on this, we currently investigate the neural and immunological upstream regulators of these dopaminergic circuits with the goal to identify new biological treatment targets for psychosis
A predictive-processing account of psychosis
There has been increasing interest in the neurocomputational mechanisms underlying psychotic disorders in recent years. One promising approach is based on the theoretical framework of predictive processing, which proposes that inferences regarding the state of the world are made by combining prior beliefs with sensory signals. Delusions and hallucinations are the core symptoms of psychosis and often co-occur. Yet, different predictive-processing alterations have been proposed for these two symptom dimensions, according to which the relative weighting of prior beliefs in perceptual inference is decreased or increased, respectively. I will present recent behavioural, neuroimaging, and computational work that investigated perceptual decision-making under uncertainty and ambiguity to elucidate the changes in predictive processing that may give rise to psychotic experiences. Based on the empirical findings presented, I will provide a more nuanced predictive-processing account that suggests a common mechanism for delusions and hallucinations at low levels of the predictive-processing hierarchy, but still has the potential to reconcile apparently contradictory findings in the literature. This account may help to understand the heterogeneity of psychotic phenomenology and explain changes in symptomatology over time.
Hallucinating mice and dopamine – towards mechanistic treatment targets for psychosis
Psychotic disorders are devastating conditions without any mechanistic treatment available. One major hurdle in the biological study of psychosis is the challenge of rigorously probing this condition in pre-clinical animal models. The goal of our research is to develop and exploit innovative frameworks for the study of psychosis in mice. In our present work, where we developed a cross-species computational psychiatry approach to probe hallucination-like perception. This enabled us to directly relate human and mouse behavior, and to demonstrate and dissect the causal role of striatal dopamine in hallucination-like perception. Our results suggest a neural circuit mechanism for the long-standing dopamine hypothesis of psychosis, and provide a new translational framework for the biological study of psychosis. This opens up exciting possibilities for advancing the biological understanding of psychosis and to identify mechanistic treatment targets.
Reward processing in psychosis: adding meanings to the findings
Much of our daily behavior is driven by rewards. The ability to learn to pursue rewarding experiences is, in fact, an essential metric of mental health. Conversely, reduced capacity to engage in adaptive goal-oriented behavior is the hallmark of apathy, and present in the psychotic disorder. The search for its underlying mechanisms has resulted in findings of profound impairments in learning from rewards and the associated blunted activation in key reward areas of the brain of patients with psychosis. An emerging research field has been relying on digital phenotyping tools and ecological momentary assessments (EMA) that map patients’ current mood, behavior and context in the flow of their daily lives. Using these tools, we have started to see a different picture of apathy, one that is exquisitely driven by the environment. For one, reward sensitivity appears to be blunted by stressors, and exposure to undue chronic stress in the daily life may result in apathy in those predisposed to psychosis. Secondly, even patients with psychosis who exhibit clinically elevated levels of apathy are perfectly capable of seeking out and enjoying social interactions in their daily life, if their environment allows them to do so. The use of digital phenotyping tools in combination with neuroimaging of apathy not only allows us to add meanings to the neurobiological findings, but could also help design rational interventions.