Anterior hippocampal dysfunction in early psychosis: a 2-year follow-up study

Abstract

Background: Cross-sectional studies indicate that hippocampal function is abnormal across stages of psychosis. Neural theories of psychosis pathophysiology suggest that dysfunction worsens with illness stage. Here, we test the hypothesis that hippocampal function is impaired in the early stage of psychosis and declines further over the next 2 years.

Methods: We measured hippocampal function over 2 years using a scene processing task in 147 participants (76 individuals in the early stage of a non-affective psychotic disorder and 71 demographically similar healthy control individuals). Two-year follow-up was completed in 97 individuals (50 early psychosis, 47 healthy control). Voxelwise longitudinal analysis of activation in response to scenes was carried out within a hippocampal region of interest to test for group differences at baseline and a group by time interaction.

Results: At baseline, we observed lower anterior hippocampal activation in the early psychosis group relative to the healthy control group. Contrary to our hypothesis, hippocampal activation remained consistent and did not show the predicted decline over 2 years in the early psychosis group. Healthy controls showed a modest reduction in hippocampal activation after 2 years.

Conclusions: The results of this study suggest that hippocampal dysfunction in early psychosis does not worsen over 2 years and highlight the need for longer-term longitudinal studies.

Keywords: Early psychosis; fMRI; hippocampus; longitudinal; schizophrenia.

Figure 1.

(A) Scene processing task. The same task was presented at baseline and follow-up, with unique stimuli presented at each timepoint. Participants viewed nine 16s blocks of scene, face, or scrambled images. Each block contained 16 images presented for 750ms each, followed by a 250ms fixation period. Participants were instructed to respond by buttonpress when an image was repeated (example indicated by bold outline). (B) Hippocampal activation in response to scenes is present in the healthy control and early psychosis groups at baseline and follow-up.

Figure 2.

Voxelwise analyses of scene activation in a hippocampal region of interest. (A) At baseline, a between-group comparison confirms lower activation in the anterior hippocampus in early psychosis. (B) A group-by-time interaction shows that scene activation over time differs between groups. (C) Contrary to our hypothesis, the healthy control group had reduced activation at follow-up compared to baseline. (D) Simultaneous display of the thresholded maps from B and C indicates that reduced activation in healthy controls is driving the group by time interaction in the anterior hippocampus.

Figure 3.

(A) We observed lower anterior hippocampal scene activation in early psychosis participants relative to healthy individuals only at baseline, not at follow-up. Unexpectedly, this resulted from a decrease in activation over two years in the healthy control group rather than a change in the early psychosis group. Asterisk denotes a significant between-group post-hoc test at corrected p<0.05. Error bars indicate the 95% confidence interval of the estimated marginal mean. Patterns of anterior hippocampal scene activation across time vary across individual participants in the Healthy Control (B) and Early Psychosis groups (C). Dashed horizontal lines indicate group mean activation at baseline (SPT1); solid horizontal lines indicate group mean activation at follow-up (SPT2). Each vertical line represents the change in activation of an individual participant from SPT1 (open square) to SPT2 (filled square). Within each group there are a subset of individuals showing a decrease in activation from baseline to follow-up, others showing relatively stable activation between visits, and a third subset showing increased activation from baseline to follow-up.