Incomplete hippocampal inversion in schizophrenia: prevalence, severity, and impact on hippocampal structure

Abstract

Incomplete hippocampal inversion (IHI) is an anatomical variant of the human brain resulting from an arrest in brain development, especially prevalent in the left hemisphere. We hypothesized that IHI is more common in schizophrenia and contributes to the well-known hippocampal structural differences. We studied 199 schizophrenia patients and 161 healthy control participants with 3 T MRI to establish IHI prevalence and the relationship of IHI with hippocampal volume and asymmetry. IHI was more prevalent (left hemisphere: 15% of healthy control participants, 27% of schizophrenia patients; right hemisphere: 4% of healthy control participants, 10% of schizophrenia patients) and more severe in schizophrenia patients compared to healthy control participants. Severe IHI cases were associated with a higher rate of automated segmentation failure. IHI contributed to smaller hippocampal volume and increased R > L volume asymmetry in schizophrenia. The increased prevalence and severity of IHI supports the neurodevelopmental model of schizophrenia. The impact of this developmental variant deserves further exploration in studies of the hippocampus in schizophrenia.

Fig. 1. Incomplete hippocampal inversion.

A Developmental process of the hippocampus from one layer of cortical mantle through early inversion (rounded, verticalized hippocampus with deep collateral sulcus) and late inversion (flat, horizontal hippocampus with shallow collateral sulcus). Arrest in hippocampal development (at Step 4) results in IHI. B 7 T MRI coronal view of an incomplete (left) and complete (right) hippocampal inversion. The hippocampus (H), subiculum (S), collateral sulcus (CS), and occipitotemporal sulcus (OTS) are used as anatomical landmarks to identify IHI. C Criterion 1 is evaluated by comparing the width of the hippocampus (green, solid line) with the height of the hippocampal body (yellow, solid line). The gray, solid line indicates the lateral limit of the hippocampus, which is used for criterion 2. Criterion 3 is measured by comparing the length of the subiculum not covered by the dentate gyrus (orange, dotted line) with the ventral part of the cornu ammonis/subiculum that is covered by the dentate gyrus (blue, dotted line). Criterion 4 is measured using the thickness of the subiculum. The gray, dotted line located at the deepest portion of the CS or OTS is used to evaluate criterion 5.

Fig. 2. Distribution of IHI scores based on laterality of the hippocampus in both schizophrenia patients and healthy control participants.

The density indicates the percent of total hippocampi that have a specific score attributed to them. The dashed line at a score of 3.75 designates the threshold used to define an IHI based on Cury et al. [20]. The prevalence of IHI in schizophrenia patients compared to healthy control participants is greater in the left hemisphere (left panel; χ² = 7.84, p < 0.01) and right hemisphere (right panel, χ² = 4.17, p = 0.04).