LAUSR

Abstract Background Schizotypal personality disorder (SPD) is a cluster A personality disorder affecting 1.0% of general population, characterised by disturbances in cognition and reality testing dimensions, affect regulation, and interpersonal function. SPD shares similar but attenuated phenomenological, genetic, and neurobiological abnormalities with schizophrenia (SCZ) and is described as part of the continuum of schizophrenia spectrum disorders. Neuroimaging and neurophysiology are the main non-invasive techniques for the investigation of brain structure and function, so they play a crucial role in psychiatric research and for their applications into clinical practice. The present review aims to systematically identify the major neuroimaging and neurophysiology biomarkers of SPD. Methods The present review has been conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The protocol was prospectively registered in PROSPERO - International prospective register of systematic reviews. The systematic review was performed to summarise the most comprehensive and updated evidence on functional neuroimaging and neurophysiology findings obtained through different techniques (DW-MRI, DTI, PET, SPECT, fMRI, MRS, EEG) in subjects with SPD. Results The search initially yielded 218 records. After study selection and reference screening, the final set comprised 52 studies. Of the 52 studies included in this review, 9 were on DW-MRI and DTI, 11 were on PET and SPECT, 11 were on fMRI and MRS, and 21 were on EEG. Although it was complex to synthesise all the functional abnormalities found in the included studies into a single, unified, pathogenetic pathway, a common theme that emerged was the dysfunction of brain circuits including striatal, frontal, temporal, limbic regions, and their networks. This dysfunction may be the result of a dysregulation along the dopaminergic pathways and lead to deficits or defects in processes that organise a person’s cognitive-perceptual evaluation of the environment and the relatedness to him/herself. As for the limitations, a quantitative data synthesis was not planned for this work, therefore no meta-analytical integrations are presented in this review. The results of individual neuroimaging studies, in fact, are not comparable due to small and heterogeneous samples, analytical flexibility, or differences in imaging modalities and behavioral tasks. Discussion Brain abnormalities in SPD are similar, but less marked, than those found in SCZ, and they do not mirror each other. In fact, different patterns of functional abnormalities in SPD and SCZ have been found in this systematic review, suggesting the ‘presence’ of possible compensatory factors, protecting subjects with SPD from frank psychosis and providing diagnostic specificity. Specifically, SPD differentiates from SCZ by showing: (a) milder frontal-striatal-temporal white matter dysconnectivity in DTI studies, (b) lesser frontal and striatal dysfunction and a decreased striatal dopaminergic activity in PET and SPECT studies, respectively, (c) different patterns of dysfunctional activation of frontal-striatal-thalamic circuitry during attentional processing in fMRI studies, and (d) milder alterations in EEG sensory gating and no evidence of alterations in EEG auditory or visual processing.