Deviations in early hippocampus development contribute to visual hallucinations in schizophrenia

Arnaud Cachia,Jérôme Brunelin,Claire Cury,Marion Plaze,François Medjkane,Christine Delmaire,Renaud Jardri,Pierre Thomas,Catherine Oppenheim

doi:10.1038/s41398-020-0779-9

Abstract

Auditory hallucinations (AHs) are certainly the most emblematic experiences in schizophrenia, but visual hallucinations (VHs) are also commonly observed in this developmental psychiatric disorder. Notably, several studies have suggested a possible relationship between the clinical variability in hallucinations′ phenomenology and differences in brain development/maturation. In schizophrenia, impairments of the hippocampus, a medial temporal structure involved in mnesic and neuroplastic processes, have been repeatedly associated with hallucinations, particularly in the visual modality. However, the possible neurodevelopmental origin of hippocampal impairments in VHs has never been directly investigated. A classic marker of early atypical hippocampal development is incomplete hippocampal inversion (IHI). In this study, we compared IHI patterns in healthy volunteers, and two subgroups of carefully selected schizophrenia patients experiencing frequent hallucinations: (a) those with pure AHs and (b) those with audio–visual hallucinations (A+VH). We found that VHs were associated with a specific IHI pattern. Schizophrenia patients with A+VH exhibited flatter left hippocampi than patients with pure AHs or healthy controls. This result first confirms that the greater clinical impairment observed in A+VH patients may relate to an increased neurodevelopmental weight in this subpopulation. More importantly, these findings bring crucial hints to better specify the sensitivity period of A+VH-related IHI during early brain development.

Highlights

Hallucinations—erroneous perceptions that are not elicited by external stimuli—may manifest in every sensory modality[1]
Forty-six right-handed participants were included in the study, including 30 outpatients suffering from schizophrenia and 16 healthy controls (HCs) with no personal history of psychiatric disorder or family history of psychosis
Post hoc analyses indicated a specific distribution of left roundness patterns in A+visual hallucinations (VHs) patients, who exhibited significantly flatter left hippocampus patterns than Auditory hallucinations (AHs) patients (Chi2 = 7.864, Table 2 Hippocampal patterns in healthy controls (HC, N = 16), patients with auditory only (AH, N = 16), and patients with audio–visual (A + VH, N = 14) hallucinations

Summary

Introduction

Hallucinations—erroneous perceptions that are not elicited by external stimuli—may manifest in every sensory modality[1]. Visual hallucinations (VHs) have been largely neglected in psychiatric disorders, a systematic review showed evidence of a weighted mean of 27% of VHs in schizophrenia[3]. In contrast to what can be observed in neurological or eye diseases, schizophrenia is characterized by very rare isolated VHs4, which typically co-occur with hallucinations in other sensory modalities[5,6,7,8,9], notably. Impairments of the hippocampus, a medial temporal structure involved in mnesic and neuroplastic processes, have been repeatedly reported in schizophrenia. Such changes include reductions in volume, increases in basal perfusion, activation deficits during declarative memory, and reductions in neurogenesis in the dentate gyrus Beyond a strict local alteration, disrupted hippocampal oscillations were linked to functional changes in hallucinations-related network[16], while we observed specific structural and functional hippocampal dysconnectivity patterns in patients with audio–visual hallucinations[17]

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