Progressive Brain Changes Associated with Persistent Negative Symptoms Following a First Episode of Psychosis

Abstract

Early persistent negative symptoms (ePNS) refer to the presence of potentially idiopathic or primary negative symptoms and have been observed following a first episode of psychosis (FEP). There is evidence for cortical changes associated with ePNS and given that a FEP often occurs during a period of ongoing brain development and maturation, neuroanatomical changes may have a specific age related component. The current study examined cortical thickness (CT), hippocampal/amygdala volume and shape as a function of clinical trajectories and age using longitudinal structural imaging in FEP. T1-MRI scans were acquired for early (n = 21), secondary (n = 30), non-(n = 44) PNS patients with a FEP, and controls (n = 44). Cortical thickness and amygdalar–hippocampal volumes and surface area (SA) metrics were extracted from three time points over a two-year period. Linear mixed models were applied to test for a main effect of group, and age group interactions. Relative to the other groups, ePNS patients showed cortical thinning over time in temporal regions and a thickening with age primarily in prefrontal areas. They also exhibited reduced left amygdalar and right hippocampal volumes. Morphometry revealed decreased surface area in ePNS compared to other groups in left central amygdala. The current study demonstrates that FEP patients with ePNS show significantly different CT trajectories with age. Increased CT may be indicative of disruptions in cortical maturation processes within higher-order brain regions. Amygdalar-hippocampal changes with age are also linked to ePNS with converging results from volumetric and morphometric analyses. Taken together, these results could represent dynamic endophenotypes setting these ePNS patients apart from their non-symptomatic peers.

Disclosure of interest

The authors have not supplied their declaration of competing interest.