Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.     

Debate: Bipolar disorder: extremely rare before puberty and antipsychotics cause serious harms – a commentary on Van Meter et al. (2019)

‘Paediatric bipolar disorder’ (PBD) remains controversial; because it is based on the hypothesis that bipolar disorder (BD) often begins in childhood with atypical forms of mania. A meta-analysis of 12 epidemiological surveys found a high prevalence of PBD among children and adolescents worldwide (1.8%), however, our study of the measurement issues (Child and Adolescent Mental Health, 23, 2018, 14) found that PBD rates were lower than claimed. Our findings are consistent with the developmental trajectory of BD, as described by most longitudinal studies of high-risk offspring. BD is extremely rare in childhood with nearly all index manic/hypomanic episodes being in midadolescence or later. Treatment for BD should not commence until the first well-defined manic/hypomanic episode, because children and younger adolescents are extremely sensitive to the side effects of second-generation antipsychotics including weight gain, metabolic syndrome, extrapyramidal side effects and the risk of cerebral atrophy, as observed in studies of juvenile animals.