ZNF804A and social cognition in patients with schizophrenia and healthy controls

Hargreaves, April; Morris, Derek W.; Rose, Emma Jane; Fahey, Ciara; Moore, Susan; Cummings, Elizabeth; Tropea, Daniela; Gill, Michael; Corvin, Aiden; Donohoe, Gary

doi:10.1038/mp.2011.102

Cited by 22 publications

(21 citation statements)

References 12 publications

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“…Contrary to a previous study from the same group in healthy volunteers [112], the authors did not find an association between the risk allele in either group, however healthy controls (not schizophrenia patients) with the A risk allele at rs1344706 showed greater personalizing bias scores compared with non-carriers [111]. The study underlines the differences in gene by cognitive (ToM) phenotype results between schizophrenia patients and controls, and emphasizes the need to exercise caution in applying findings based on healthy participants to exploring the neural mechanisms in clinical patients, particularly concerning the influence of ZNF804A.…”

Section: Genetic Contribution Of Theory Of Mind Deficitscontrasting

confidence: 52%

“…Hargreaves et al [111] studied the association between performance on two mental state reasoning tasks (Eyes of the Mind and Hinting tasks) and a common variant within ZNF804A in patients with schizophrenia and healthy controls. Contrary to a previous study from the same group in healthy volunteers [112], the authors did not find an association between the risk allele in either group, however healthy controls (not schizophrenia patients) with the A risk allele at rs1344706 showed greater personalizing bias scores compared with non-carriers [111].…”

Section: Genetic Contribution Of Theory Of Mind Deficitsmentioning

confidence: 99%

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Theory of Mind in the Early Course of Schizophrenia

Vyas

et al. 2017

CPSR

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Theory of mind deficit is a core feature of schizophrenia and is considered a vulnerability marker of the disorder. The majority of studies measuring theory of mind in schizophrenia involve multiple-episode or chronic schizophrenia patients, and therefore it is important to delineate whether these deficits occur before or following illness-onset by assessing high-risk subjects (clinical high risk and ultra-high risk), early-onset psychosis, and first-degree relatives. We address the question of whether theory of mind impairment is specific or a facet of general cognitive impairment in these clinical populations, and incorporate genetic and neuroimaging studies on theory of mind. The review provides a succinct evaluation of the literature, discusses current limitations and proposes future directions.

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Section: Genetic Contribution Of Theory Of Mind Deficitscontrasting

confidence: 52%

Section: Genetic Contribution Of Theory Of Mind Deficitsmentioning

confidence: 99%

Theory of Mind in the Early Course of Schizophrenia

Vyas

et al. 2017

CPSR

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“…Hargreaves et al (2012) found that healthy risk allele carriers exhibited a stronger tendency to attribute negative events to other people rather than to situational factors, pointing to a stronger 'personalizing bias'. As this is associated with paranoid ideation, it undermines the notion that ZNF804A-mediated ToM disturbances might represent one mechanism in the development of delusional symptomatology.…”

Section: Further Evidence For Znf804a Effects On Social Cognitionmentioning

confidence: 99%

“…Additionally, we found genotype-dependent fronto-temporo-parietal connectivity changes. Further support for a role of ZNF804A in social cognition comes from a study showing behavioral effects of the risk variant (Hargreaves et al, 2012). Carriers of at least one risk allele exhibited a stronger tendency to attribute negative events to other people rather than to situational factors.…”

Section: Introductionmentioning

confidence: 99%

Further Evidence for the Impact of a Genome-Wide-Supported Psychosis Risk Variant in ZNF804A on the Theory of Mind Network

Mohnke

Erk

Schnell

et al. 2013

Neuropsychopharmacol

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The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N ¼ 297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal-temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network.

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“…Recent investigations using this technique have examined a number of previously mentioned genome-wide significant risk variants for SCZ and their association to the social-emotion network. For example, during emotion processing and ToM tasks, researchers have found reduced connectivity in those with SCZ risk alleles: MIR137 (Mothersill et al, 2014), ZNF804A Hargreaves et al, 2012;Linden et al, 2013;Walter et al, 2011), COMT (Lo Bianco et al, 2013;Surguladze et al, 2012), 5-HTTLPR (Surguladze et al, 2012), and PPP1R1B (Curcic-Blake et al, 2012). However, as SCZ is a polygenetic disorder, risk profiles combining the effects of these risk alleles should be evaluated on their influence on the social-emotion network.…”

Section: Genetic Association Of Emotion Perception In Schizophreniamentioning

confidence: 99%

The neuroimaging and genetics of emotion perception in schizophrenia

Dzafic¹

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Impaired emotion perception is a core deficit in schizophrenia (SCZ) that is robustly associated with poor functional outcome. Studies to date have failed to delineate the critical cognitive, neural and genetic factors that underlie 'naturalistic' emotion perception deficits in SCZ. Recently it has been proposed that in SCZ reduced precision in prior expectations impairs perception. Normal perception relies on predictive processing from precise prior expectations, which prioritise attention to context-relevant stimuli. However, no studies to date have explored the aberrancy of prior expectations during naturalistic emotion perception in SCZ and the underlying abnormal neural circuitry or involvement of SCZ genes. The present thesis aims to develop a novel dynamic emotion perception (DEP) task, in order to examine (1) the influence of prior expectations on naturalistic emotion perception in healthy individuals, and (2) emotion perception impairment in SCZ by investigating aberrancy in prior expectations, neural circuitry, and genetics.The aim of Study 1 was to create a novel functional magnetic resonance imaging (fMRI) paradigm to examine the mechanisms of prior expectations and delineate the spatiotemporal activity of brain regions that contribute to emotion perception. The newly developed and validated fMRI DEP task has improved ecological validity, using dynamic, audio-visual videos, instead of static pictures as stimuli. The improved method provided new behavioural and neuroimaging insights into the influence of prior expectations on naturalistic emotion perception. Prior expectations facilitated emotion perception after repeated exposure and learning over the course of the experiment, engaging prefrontal regions and right amygdala. In contrast, emotions incongruent with prior expectations engaged neural correlates of automatic change detection, which in a complex dynamic environment allows for adaptive behaviours in potentially advantageous or threatening situations.In Study 2, the DEP task was utilised to delineate, in the healthy brain, the functional networks that subserve rapid recognition of threatening emotions in situations either congruent or incongruent with prior expectations. The results showed that fast detection of threat congruent with prior expectations engaged a right amygdala subcortical network, which has been previously implicated in fear conditioning and coarse processing of emotion. In contrast, there was a trend association between fast detection of threat incongruent with prior expectations and activity in inferior frontoparietal network connected to the right temporoparietal junction; this has been previously implicated in rapid reorienting of attention to Finally, in Study 4, the association between SCZ polygenic risk score (PRS) and brain activity during the DEP task in healthy adults was investigated in order to assess emotion perception as an endophenotype for SCZ. The results demonstrate that PRS is associated with higher recruitment of regions involved in emotion regulat...

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ZNF804A and social cognition in patients with schizophrenia and healthy controls

Cited by 22 publications

References 12 publications

Theory of Mind in the Early Course of Schizophrenia

Theory of Mind in the Early Course of Schizophrenia

Further Evidence for the Impact of a Genome-Wide-Supported Psychosis Risk Variant in ZNF804A on the Theory of Mind Network

The neuroimaging and genetics of emotion perception in schizophrenia

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