Hippocampal volume in early psychosis: a 2-year longitudinal study

Abstract

Cross-sectional studies suggest that hippocampal volume declines across stages of psychosis. In contrast, longitudinal studies indicate that hippocampal volume is stable in the critical period following illness onset. How can these seemingly disparate sets of findings be resolved? In the present study, we examine two previously unexplored reasons for this discrepancy. First, only specific subregions of the hippocampus may change during the early stage of psychosis. Second, there is diagnostic heterogeneity in the early stage of psychosis and cross-sectional analysis does not permit examination of illness trajectory. Some early stage individuals will have persistent illness leading to a diagnosis of schizophrenia, whereas in others, psychosis will remit. Hippocampal volume may be reduced only in individuals who will ultimately be diagnosed with schizophrenia. We acquired longitudinal structural MRI data from 63 early psychosis and 63 healthy control participants, with up to 4 time points per participant collected over 2 years. Subfield volumes were measured in the anterior and posterior hippocampus using automated segmentation specialized for longitudinal analysis. We observed a volume deficit in early psychosis participants compared to healthy controls that was most pronounced in the anterior hippocampus, but this deficit did not change over 2 years. Importantly, we found that anterior cornu ammonis volume is smaller at baseline in individuals who were diagnosed with schizophrenia at follow-up, but normal in those who maintained a diagnosis of schizophreniform disorder over 2 years. Smaller hippocampal volume is not diagnostic of psychosis, but is instead prognostic of clinical outcome.

Effect of Season of Birth on Hippocampus Volume in a Transdiagnostic Sample of Patients With Depression and Schizophrenia

“…This fact may hamper to detect specific effects of season of birth within the hippocampus. However, our finding is in line with previous reports showing hippocampal volume reduction in schizophrenia ( Nelson et al, 1998 ; Heckers and Konradi, 2010 ; Adriano et al, 2012 ), even at the onset of the disorder in the first episode ( Adriano et al, 2012 ; McHugo et al, 2020 ), as well as in ad risk subjects who later develop the disorder ( Harrisberger et al, 2016 ). Contrary, and as mentioned in the introduction, previous reports have observed alterations in the brain structure associated with season of birth, which was not the case in our report.…”

Stable habituation deficits in the early stage of psychosis: a 2-year follow-up study

“…Our current longitudinal findings provide further support for this notion, and preliminary evidence that hippocampal inhibitory deficits may not progress in the early years of illness. These results are also consistent with recent findings in a partially-overlapping cohort, which showed hippocampal volume is reduced in the early stage of psychosis 70 but does not further decline over a 2-year follow-up period 71 . Together, these findings suggest that hippocampal deficits are stable in the first 2 years of schizophrenia.…”

Hippocampal structural alterations in early-stage psychosis: Specificity and relationship to clinical outcomes

“…In FEP patients, more robust deficits have been reported for both hippocampal volume and shape ( Adriano et al, 2012 , Borgwardt et al, 2007 , Buehlmann et al, 2010 , Lieberman et al, 2018 , Phillips et al, 2002 , Velakoulis et al, 2006 ), particularly in the anterior portion ( McHugo et al, 2020 ; see also Haukvik et al, 2016 ). Interestingly, the extent of volume loss may be linked with the duration of untreated psychosis ( Briend et al, 2020 ) and reduced hippocampal volume might be prognostic for clinical outcomes ( McHugo et al, 2020 ).…”