Dysconnection and the immunological basis of schizophrenia

Schizophrenia has been cast, from different neuroscientific perspectives, as a sensory processing disorder, a highly heritable genetic disorder as well as a neurodevelopmental disorder. The dysconnection hypothesis attempts to draw together several of these disparate strands of research to create a coherent picture of how schizophrenia arises, implicating neuromodulatory processes governing synaptic gain control as the aetiological core of psychotic symptoms – i.e., a functional (or perhaps Bayesian) synaptopathy. It calls for studies that empirically ‘close the explanatory gap between pathophysiology at the molecular (synaptic) level and the psychopathology experienced by patients’ (Friston et al, 2016). One strand that has not yet been woven into this tapestry is immunology, which has been overwhelmingly linked with schizophrenia in recent years – the reasons for which are not well understood. In this talk I will overview my recent work, which has used a variety of methods with the aim of ‘closing the explanatory gap’. I begin with an exploration of the genetics of mismatch negativity, a key biomarker for schizophrenia. Next, I present experiments of prenatal immunity in neuronal networks grown out of hair samples from patients with schizophrenia and healthy controls. Finally, I introduce inference from the perspective of the immune system – immunoceptive inference – as a new way of understanding interactions between the immune system and the brain.

Presented at the Wellcome Centre for Human Neuroimaging Brain Meeting.

(Watch the recording here. Passcode: Y5AQ+Uww)