This could be related to a reporting bias, as neurologists may not recognize or describe mild disorganization. Indeed, we were able to observe one patient scoring 4 on the Positive And Negative Syndrome Scale (PANSS) disorganization subscore. The symptom lasted during a relapse of her MS, and was accompanied by a clear reduction in executive attention without confusion or mood disorder. However, more observations arc required in order to conclude. It is even more difficult

Inhibitors,research,lifescience,medical to conclude concerning negative symptoms which are also an important feature of schizophrenia, because they can be misidcntificd with depression or cognitive decline. What kind of white matter lesion is most likely to evoke psychosis? Inhibitors,research,lifescience,medical WM lesions can have two different physiological effects: From reduction to absence of conduction between two areas. This concept is closer to the notion of deconncction. A variation in conduction time between the different axons linking the two areas. This is what we termed “disconnection.” Synapses will not be active in the same time window, resulting in an improper

summation in the postsynaptic neurons. Not only will the message be weakened, but it will also be noisier. MS and MLD essentially result in lengthening and scattering of conduction delays.100 Demyelinating diseases can also induce voltage-gated channel anomalies Inhibitors,research,lifescience,medical that result in conduction bloc (analogous to deconnection).101 However, MS and MLD seem to trigger more psychotic episodes than diffuse axonal injury after a head trauma Inhibitors,research,lifescience,medical that basically results in a deconnection.102- Accordingly, there is modest evidence that a dis-synchrony between axons better accounts for psychosis. Misconnectivity Misconnectivity is perhaps even more difficult to model, because it can involve different neurons. However, multiple neurological diseases come with putative misconnectivity, especially when accompanied by cortical

dysplasia or heterotopia. Some of them have been described Inhibitors,research,lifescience,medical as presenting with psychosis: Schizencephaly-polymicrogyria.103 Ito’s disease.101 Facomatosis as tuberous sclerosis, also termed Bourneville’s disease.105 In another facomatosis, neurofibromatosis type 1, or Recklinghausen’s disease, about 3% to 6% of patients develop psychosis.106,107 However the amount of psychosis in misconncction diseases is mild. It could also not be the causal factor, as most of these disorders are accompanied Edoxaban by epilepsy. But from an other perspective, the psychosis of epilepsy has not been found to be related to dysplasia.108 Another confounding factor could be the presence of WM lesions in most misconnection diseases. As an example, both tuberous sclerosis and neurofibromatosis also come with WM abnormalities that could account for the expression of psychosis.109-110 Interestingly, psychosis related to cortical dysplasia can appear earlier than adolescence.106 According to our previous line of Selleckchem LY3009104 reasoning, this could mean that dopamine is not an important cofactor.