Abnormal Organization of Brain Networks Predicts Psychosis in At-Risk Youth

Post by Shireen Parimoo

What's the science?

Schizophrenia is a psychiatric disorder that manifests when a psychotic episode occurs, typically in adolescence and young adulthood when the brain is still developing. A prodromal stage of schizophrenia usually occurs prior to the onset of a psychotic episode, where cognitive function or changes in behaviour occur. Previous studies have found that the brain networks are organized differently in individuals with schizophrenia, however it is not known if organization of functional brain networks during the prodromal stage is related to the occurrence of a psychotic episode. This week in Molecular Psychiatry, Collin and colleagues used functional magnetic resonance imaging (fMRI) and graph theory to investigate the organization of brain networks in individuals who were at risk of developing psychosis.

How did they do it?

Participants included 158 adolescents and young adults who were deemed to be at-risk for developing psychosis through the Shanghai At Risk for Psychosis program. They were matched to 93 healthy participants of the same age, sex, and education level. The participants’ brain activity was recorded in an fMRI session at the beginning of the study. Their at-risk status was determined at two time points (roughly a year apart) using the Structured Interview for Prodromal Symptoms, which provides a measure of whether participants are in the prodromal stage. By the second interview, 23 participants had developed psychosis. The authors used graph theory to create functional connectomes of brain networks. Brain regions are said to be functionally connected when their activity is correlated, and a group of functionally connected regions represents a functional network. Functional connectomes were constructed for each participant as well as for each group of participants: these were healthy participants, at-risk participants, and at-risk participants who later developed psychosis. Functional connectomes of those at-risk and at-risk who later developed psychosis were compared to that of the healthy group, which allowed the authors to examine if brain networks are organized differently between groups.

What did they find?

The authors found that functional networks across all groups were organized into five modules consisting of the central-executive, sensorimotor, visual, paralimbic, and default-mode networks, each with different functional roles. An additional cingulo-opercular network was identified in at-risk individuals who later developed psychosis, but not in healthy or at-risk individuals. The functional connectomes of the healthy and at-risk individuals were more similar to each other than to to participants at-risk who later developed psychosis. Moreover, several brain regions that are affected early in schizophrenia were found to be part of different functional networks in the different participant groups. For example, the superior temporal gyrus was part of the sensorimotor network in healthy and at-risk individuals, but this brain region was functionally connected to regions of the paralimbic network in individuals who went on to develop psychosis. Thus, functional networks were organized differently in individuals who later developed psychosis, and this abnormal organization was associated with a three-fold risk of developing psychosis.

What's the impact?

This study found that at-risk adolescents and young adults who exhibit abnormal organization of brain networks early on eventually develop psychosis, whereas at-risk youth with similar functional networks and healthy individuals do not. This novel insight into the predictive value of brain network organization for the onset of psychosis can be used to identify at-risk individuals and potentially establish preventative measures to mitigate the occurrence and severity of psychosis.

Dr. Collin would like to acknowledge support of a Marie Curie Global Fellowship.

Collin et al. Functional connectome organization predicts conversion to psychosis in clinical high-risk youth from the SHARP program. Molecular Psychiatry (2018). Access the original scientific publication here.