Hyperfunctioning of the right posterior superior temporal sulcus in response to neutral facial expressions presents an endophenotype of schizophrenia

Zhimin Yan,Stephanie N L Schmidt,Daniela Mier,Stephanie H Witt,Joachim Hass,Peter Kirsch,Josef Frank

doi:10.1038/s41386-020-0637-8

Abstract

Deficits in social cognition have been proposed as a marker of schizophrenia. Growing evidence suggests especially hyperfunctioning of the right posterior superior temporal sulcus (pSTS) in response to neutral social stimuli reflecting the neural correlates of social-cognitive impairments in schizophrenia. We characterized healthy participants according to schizotypy (n = 74) and the single-nucleotide polymorphism rs1344706 in ZNF804A (n = 73), as they represent risk variants for schizophrenia from the perspectives of personality traits and genetics, respectively. A social-cognitive fMRI task was applied to investigate the association of right pSTS hyperfunctioning in response to neutral face stimuli with schizotypy and rs1344706. Higher right pSTS activation in response to neutral facial expressions was found in individuals with increased positive (trend) and disorganization symptoms, as well as in carriers of the risk allele of rs1344706. In addition, a positive association between right–left pSTS connectivity and disorganization symptoms during neutral face processing was revealed. Although these findings warrant replication, we suggest that right pSTS hyperfunctioning in response to neutral facial expressions presents an endophenotype of schizophrenia. We assume that right pSTS hyperfunctioning is a vulnerability to perceive neutral social stimuli as emotionally or intentionally salient, probably contributing to the emergence of symptoms of schizophrenia.

Highlights

Social-cognitive impairments have been proposed to present a marker of schizophrenia [1,2,3,4]
Confirming our hypothesis, we found a positive association of right posterior superior temporal sulcus (pSTS) activation for neutral face processing with schizotypy, and with a risk allele for schizophrenia
A recent study reported increased pSTS activation in response to the emotionally and intentionally neutral control condition in their social-cognitive task and increased pSTS connectivity [18]. These results add to the idea that pSTS dysfunction for neutral social stimuli might be regarded as neural basis for hypermentalizing, which may constitute a vulnerability to the emergence of delusion [6]. How could this pSTS hyperfunctioning in response to neutral facial expressions cause symptoms of schizophrenia? Kapur [47, 48] proposed that psychosis, delusions, result from aberrant attribution of novelty and salience to objects and associations, and that faulty attributions of salience arise due to chaotic, context-inappropriate firing of dopamine neurons

Summary

Introduction

Social-cognitive impairments have been proposed to present a marker of schizophrenia [1,2,3,4]. The impairments occur in different domains of social cognition, ranging from deficits in neutral face processing [5, 6], emotion recognition [7], up to complex socialcognitive processes [8], like inferring others’ mental states, known as theory of mind (ToM) [9], and are highly important for social functioning [10] The association of these deficits to enhanced activity and connectivity of the right posterior superior temporal sulcus (pSTS [6, 11]) makes aberrant pSTS functioning during social cognition a highly promising endophenotype candidate for schizophrenia. Since the pSTS is a core area of social cognition and prominently involved in inferring other’s intentions [20] ( Schmidt et al, unpublished data), increased pSTS activation during NFP might be interpreted as a vulnerability for false-positive perceptions of intentions, called hypermentalizing [21]

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