Anterior vs Posterior Hippocampal Subfields in an Extended Psychosis Phenotype of Multidimensional Schizotypy in a Nonclinical Sample

Abstract

Numerous studies have implicated involvement of the hippocampus in the etiology and expression of schizophrenia-spectrum psychopathology, and reduced hippocampal volume is one of the most robust brain abnormalities reported in schizophrenia. Recent studies indicate that early stages of schizophrenia are specifically characterized by reductions in anterior hippocampal volume; however, studies have not examined hippocampal volume reductions in subclinical schizotypy. The present study was the first to examine the associations of positive, negative, and disorganized schizotypy dimensions with hippocampal subfield volumes in a large sample (n = 195) of nonclinically ascertained young adults, phenotyped using the Multidimensional Schizotypy Scale (MSS). Hippocampal subfields were analyzed from high-resolution 3 Tesla structural magnetic resonance imaging scans testing anatomical models, including anterior vs posterior regions and the cornu ammonis (CA), dentate gyrus (DG), and subiculum subfields separately for the left and right hemispheres. We demonstrate differential spatial effects across anterior vs posterior hippocampus segments across different dimensions of the schizotypy risk phenotype. The interaction of negative and disorganized schizotypy robustly predicted left hemisphere volumetric reductions for the anterior and total hippocampus, and anterior CA and DG, and the largest reductions were seen in participants high in negative and disorganized schizotypy. These findings extend previous early psychosis studies and together with behavioral studies of hippocampal-related memory impairments provide the basis for a dimensional neurobiological hippocampal model of schizophrenia risk. Subtle hippocampal subfield volume reductions may be prevalent prior to the onset of detectable prodromal clinical symptoms of psychosis and play a role in the etiology and development of such conditions.

Cognitive Functioning and Schizotypy: A Four-Years Study

“…Correct responses potentially reflect semantic information reserve capacities, while semantic intrusion errors could be considered as failures in semantic processing either due to poor strategic search of representations classified according to their meaning or misattribution of meaning to representations. It is of note, that disorganized schizotypy has been associated with a wide neural network encompassing several brain structures, such as the superior longitudinal fasciculus ( 121 ), hippocampus ( 123 ), and superior temporal gyrus ( 124 ), that are crucial for semantic processing ( 125 – 131 ), thus proving a plausible explanation for our finding. The fact that the association of disorganized schizotypy and semantic processing was abolished in the “schizotypy congruent” sub-group is most probably to the smaller sample size of this group resulting in limited variation of semantic fluency intrusion errors that is required for associational analyses.…”

Nonclinical psychotic‐like experiences and schizotypy dimensions: Associations with hippocampal subfield and amygdala volumes

“…Consistent with previous findings suggesting that failure to distinguish between positive and negative schizotypy dimensions could result in reduced estimator robustness (Barrantes-Vidal, Gross, et al, 2013;Barrantes-Vidal, Lewandowski, & Kwapil, 2010), we found differences in the direction between the regressors that reflect the unique explanatory contribution of each schizotypy dimension. The significant main effect of the positive dimension is not confirmed by our previous study (Sahakyan et al, 2021) with the Multidimensional Schizotypy Scale (MSS; Kwapil, Gross, Silvia, Raulin, & Barrantes-Vidal, 2018). This inconsistency may be attributed to differences between psychometric instruments that provide three (MSS) or four (O-LIFE) phenotype dimensions entered as model predictors.…”

“…This study protocol was in agreement with the Declaration of Helsinki (World Medical Association, 2013) healthy adults (Mean age = 23.85, SD = 3.75 years, min = 18, max = 39) included in the analysis. In this study, we extended the sample previously described in Sahakyan et al (2021). Seven (1.91%) participants scored PLE equal to or above the CHR screening criteria applied in previous studies (Chen et al, 2016;Ising et al, 2012).…”

Multidimensional Schizotypy Scale Manual v2.9

“…Association of the MSS subscales with hippocampal volume. Sahakyan et al (2021) examined the associations of MSS positive, negative, and disorganized schizotypy dimensions with hippocampal subfield volumes in a large sample (n = 195) of nonclinically ascertained young adults. Hippocampal subfields were analyzed from high-resolution 3 Tesla structural magnetic resonance imaging scans testing anatomical models, including anterior vs posterior regions and the cornu ammonis (CA), dentate gyrus (DG), and subiculum subfields separately for the left and right hemispheres.…”