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1.  Theory of Mind in Schizophrenia and Asperger’s Syndrome: Relationship with Negative Symptoms 
Objective
Although previous studies have shown that the theory of mind (ToM) ability is impaired in Asperger’s Syndrome (AS) and in schizophrenia, few controlled studies compared the ToM performance between the two disorders. Besides, the relationship between the degree of ToM impairment and symptom dimensions is unclear, and presence of ToM impairment in remitted patients with schizophrenia is controversial. Here, we tested the hypothesis that schizophrenia patients with prominent negative symptoms were closer to AS patients and different than schizophrenia patients without prominent negative symptoms and healthy controls in terms of ToM functioning.
Method
Fourteen patients with AS, 20 with schizophrenia and 20 healthy controls, matched by age, educational level and IQ scores were enrolled. AS was diagnosed according to the DSM-IV criteria and independently confirmed by two psychiatrists. Schizophrenia patients were diagnosed by the Turkish version of Structured Clinical Interview for DSM-IV Diagnosis (SCID-I) and symptom severity was evaluated with the Scale for the Assessment of Negative and Positive Symptoms. Schizophrenia group consisted of clinically stable patients. The ToM battery included stories to assess first and second order false belief tasks (ToM1 and ToM2). The full-scale IQ, Verbal Comprehension, Freedom from Distractibility and Perceptual Organization scores were assessed by Weschler Adult Intelligence Scale–Revised (WAIS-R). Non-parametric tests were used to compare the neuropsychological performances of the three groups. In order to investigate whether schizophrenia patients with prominent negative symptoms were similar to AS patients, schizophrenia patients were divided into high (Sch-HN) and low (Sch-LN) negative-symptom subgroups by median split. For these four groups (AS, Sch-HN, Sch-LN, and controls) between group comparisons were performed. Correlations between the clinical measures and ToM performance were assessed by Spearman correlation test.
Results
AS and schizophrenia patients performed significantly worse than controls in the ToM2 task, while the AS group had worse ToM1 performance than both schizophrenia patients and healthy controls. The Sch-HN subgroup had significantly lower ToM2 scores than the Sch-LN patients, and worse ToM1 functioning than the controls.
Conclusions
These results suggest that clinically stable schizophrenia patients have ToM impairments. Sch-HN group performed comparably poorly as the AS group, while the Sch-LN group was relatively spared. The most profoundly impaired patients with schizophrenia in terms of ToM functioning were represented by those with high negative symptoms (Sch-HN). Similar to AS, as a neurodevelopmental impairment, these patients may not have developed ToM ability, or they may have lost their ToM capacity as a result of a neurodegenerative process during the illness. Supplementary studies using other methods (e.g., neuroimaging, neurophysiology) may highlight the brain regions that are affected differentially in AS and schizophrenia, the relationship of ToM impairments and negative symptoms, and the role of ToM impairments in the neurodevelopmental or neurodegenerative hypothesis of schizophrenia.
PMCID: PMC4288770  PMID: 25584026
Theory of mind; schizophrenia; Asperger’s syndrome; Asperger’s disorder; negative symptoms; cognitive deficits
2.  Growing Up with Asperger’s Syndrome: Developmental Trajectory of Autobiographical Memory 
Autobiographical memory (AM) and social cognition share common properties and both are affected in autism spectrum disorders (ASD). So far, most of the scant research in ASD has concerned adults, systematically reporting impairment of the episodic component. The only study to be conducted with children concluded that they have poorer personal semantic knowledge than typical developing children. The present study explores the development of both components of AM in an 8-year-old boy diagnosed with Asperger’s syndrome, based on three examinations in 2007, 2008, and 2010. On each occasion, he underwent a general neuropsychological assessment including theory of mind (ToM) tasks, and a specially designed AM task allowing us to test both the semantic and the episodic components for three lifetime periods (current year, previous year, and earlier years). We observed difficulties in strategic retrieval and ToM, with a significant improvement between the second and third examinations. Regarding AM, different patterns of performance were noted in all three examinations: (1) relative preservation of current year personal knowledge, but impairment for the previous and earlier years, and (2) impairment of episodic memory for the current and previous year, but performances similar to those of controls for the earlier years. The first pattern can be explained by abnormal forgetting and by the semanticization mechanism, which needs verbal communication and social interaction to be efficient. The second pattern suggests that the development of episodic memory only reached the stage of “event memory.” This term refers to memory for personal events lacking in details or spatiotemporal specificity, and is usually observed in children younger than five. We conclude that the abnormal functioning of social cognition in ASD, encompassing social, and personal points of view, has an impact on both components of AM.
doi:10.3389/fpsyg.2012.00605
PMCID: PMC3542927  PMID: 23335906
autobiographical memory; autism; child; theory of mind; episodic memory; semantic memory
3.  Aberrant functioning of the theory-of-mind network in children and adolescents with autism 
Molecular Autism  2015;6:59.
Background
Theory-of-mind (ToM), the ability to infer people’s thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers.
Methods
fMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two “interacting” geometrical shapes.
Results
Participants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants.
Conclusions
Overall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity.
Electronic supplementary material
The online version of this article (doi:10.1186/s13229-015-0052-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s13229-015-0052-x
PMCID: PMC4624365  PMID: 26512314
Theory-of-mind; Autism; fMRI; Functional connectivity MRI, mentalizing
4.  Using Fiction to Assess Mental State Understanding: A New Task for Assessing Theory of Mind in Adults 
PLoS ONE  2013;8(11):e81279.
Social functioning depends on the ability to attribute and reason about the mental states of others – an ability known as theory of mind (ToM). Research in this field is limited by the use of tasks in which ceiling effects are ubiquitous, rendering them insensitive to individual differences in ToM ability and instances of subtle ToM impairment. Here, we present data from a new ToM task – the Short Story Task (SST) - intended to improve upon many aspects of existing ToM measures. More specifically, the SST was designed to: (a) assess the full range of individual differences in ToM ability without suffering from ceiling effects; (b) incorporate a range of mental states of differing complexity, including epistemic states, affective states, and intentions to be inferred from a first- and second-order level; (c) use ToM stimuli representative of real-world social interactions; (d) require participants to utilize social context when making mental state inferences; (e) exhibit adequate psychometric properties; and (f) be quick and easy to administer and score. In the task, participants read a short story and were asked questions that assessed explicit mental state reasoning, spontaneous mental state inference, and comprehension of the non-mental aspects of the story. Responses were scored according to a rubric that assigned greater points for accurate mental state attributions that included multiple characters’ mental states. Results demonstrate that the SST is sensitive to variation in ToM ability, can be accurately scored by multiple raters, and exhibits concurrent validity with other social cognitive tasks. The results support the effectiveness of this new measure of ToM in the study of social cognition. The findings are also consistent with studies demonstrating significant relationships among narrative transportation, ToM, and the reading of fiction. Together, the data indicate that reading fiction may be an avenue for improving ToM ability.
doi:10.1371/journal.pone.0081279
PMCID: PMC3820595  PMID: 24244736
5.  Neural processing associated with cognitive and affective Theory of Mind in adolescents and adults 
Theory of Mind (ToM) is the ability to attribute thoughts, intentions and beliefs to others. This involves component processes, including cognitive perspective taking (cognitive ToM) and understanding emotions (affective ToM). This study assessed the distinction and overlap of neural processes involved in these respective components, and also investigated their development between adolescence and adulthood. While data suggest that ToM develops between adolescence and adulthood, these populations have not been compared on cognitive and affective ToM domains. Using fMRI with 15 adolescent (aged 11–16 years) and 15 adult (aged 24–40 years) males, we assessed neural responses during cartoon vignettes requiring cognitive ToM, affective ToM or physical causality comprehension (control). An additional aim was to explore relationships between fMRI data and self-reported empathy. Both cognitive and affective ToM conditions were associated with neural responses in the classic ToM network across both groups, although only affective ToM recruited medial/ventromedial PFC (mPFC/vmPFC). Adolescents additionally activated vmPFC more than did adults during affective ToM. The specificity of the mPFC/vmPFC response during affective ToM supports evidence from lesion studies suggesting that vmPFC may integrate affective information during ToM. Furthermore, the differential neural response in vmPFC between adult and adolescent groups indicates developmental changes in affective ToM processing.
doi:10.1093/scan/nsr023
PMCID: PMC3252629  PMID: 21467048
Theory of Mind; empathy; adolescence; development; fMRI
6.  The neural basis of theory of mind and its relationship to social functioning and social anhedonia in individuals with schizophrenia☆ 
NeuroImage : Clinical  2013;4:154-163.
Theory of mind (ToM), the ability to attribute and reason about the mental states of others, is a strong determinant of social functioning among individuals with schizophrenia. Identifying the neural bases of ToM and their relationship to social functioning may elucidate functionally relevant neurobiological targets for intervention. ToM ability may additionally account for other social phenomena that affect social functioning, such as social anhedonia (SocAnh). Given recent research in schizophrenia demonstrating improved neural functioning in response to increased use of cognitive skills, it is possible that SocAnh, which decreases one's opportunity to engage in ToM, could compromise social functioning through its deleterious effect on ToM-related neural circuitry. Here, twenty individuals with schizophrenia and 18 healthy controls underwent fMRI while performing the False-Belief Task. Aspects of social functioning were assessed using multiple methods including self-report (Interpersonal Reactivity Index, Social Adjustment Scale), clinician-ratings (Global Functioning Social Scale), and performance-based tasks (MSCEIT—Managing Emotions). SocAnh was measured with the Revised Social Anhedonia Scale. Region-of-interest and whole-brain analyses revealed reduced recruitment of medial prefrontal cortex (MPFC) for ToM in individuals with schizophrenia. Across all participants, activity in this region correlated with most social variables. Mediation analysis revealed that neural activity for ToM in MPFC accounted for the relationship between SocAnh and social functioning. These findings demonstrate that reduced recruitment of MPFC for ToM is an important neurobiological determinant of social functioning. Furthermore, SocAhn may affect social functioning through its impact on ToM-related neural circuitry. Together, these findings suggest ToM ability as an important locus for intervention.
Highlights
•Individuals with schizophrenia exhibited reduced recruitment of MPFC for ToM.•MPFC and RTPJ activities correlate with measures of social functioning and ability.•MPFC activity mediates the relationship between social anhedonia and functioning.•Neural circuitry supporting ToM may represent an important area for remediation.
doi:10.1016/j.nicl.2013.11.006
PMCID: PMC3871293  PMID: 24371798
Schizophrenia; Theory of mind; Social functioning; Social anhedonia; fMRI
7.  A Psychometric Evaluation of the Danish Version of the Theory of Mind Storybook for 8–14 Year-Old Children 
Background: Theory-of-Mind (ToM) keeps on developing in late childhood and early adolescence, and the study of ToM development later in childhood had to await the development of sufficiently sensitive tests challenging more mature children. The current study aimed to investigate the psychometric properties of the Danish version of the Theory-of-Mind Storybook Frederik (ToM-Frederik).
Methods: We assessed whether ToM-Frederik scores differed between a group of 41 typically developing (TD) children and a group of 33 children with High Functioning Autism Spectrum Disorder (HFASD). A lower mean ToM-Frederik score was expected in the HFASD group. To determine the convergent validity of ToM-Frederik, potential associations with Strange Stories and Animated Triangles (AT) were analyzed. Furthermore, potential associations between ToM-Frederik and the Social Responsiveness Scale (SRS) and between ToM-Frederik and the Social Emotional Evaluation (SEE) Total score were analyzed.
Results: A significantly higher ToM-Frederik score was observed in the TD group compared to the HFASD group. Furthermore, the convergent validity of ToM-Frederik as a measure of ToM was supported by significant and positive associations with the Strange Stories and the AT scores in the HFASD group, whereas ToM-Frederik was significantly correlated with Strange Stories, but not with AT in the TD group. ToM-Frederik was not significantly associated with SRS in neither the HFASD nor the TD group.
Conclusion: The findings are supportive of ToM-Frederik as a valid indicator of deficits at the group level in children with HFASD between 7 and 14 years of age. Furthermore, the convergent validity is supported.
doi:10.3389/fpsyg.2016.00330
PMCID: PMC4781859  PMID: 27014139
Theory-of-Mind; validation; autism spectrum disorders
8.  Proton MagneƟc Resonance Spectroscopy in Asperger’s Syndrome: CorrelaƟons with Neuropsychological Test Scores 
Objectives
It has been shown that autistic spectrum patients have impaired theory of mind (ToM) performance; however, no study has investigated the relationship between ToM performance and brain neurochemistry in these patients. The present study aimed to investigate the correlations between dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) N-acetyl-aspartate (NAA)/choline (Cho), NAA/creatine (Cr), and Cho/Cr values based on 1H magnetic resonance spectroscopy and ToM tests.
Method
The study sample included 13 adult, right-handed, Caucasian males with Asperger’s syndrome (AS) (age range: 17–37 years) and 20 controls matched by age, gender, handedness, and Wechsler Adult Intelligence Scale, Revised (WAIS-R) full-scale IQ scores.
Results
AS cases had significantly lower ToM performance. DLPFC NAA/Cho levels were inversely correlated to ToM scores (r = −0.738, P = 0.004). On the other hand, ToM performance improved as DLPFC Cho/Cr increased (r = 0.656, P = 0.015). ACC MRS variables were not significantly correlated with ToM performance in the AS group. No significant correlation was observed between ACC or DLPFC MRS variables and ToM performance in the control group. Discussion: Because NAA/Cho was inversely correlated with ToM performance and Cho/Cr was correlated with ToM performance, it can be suggested that the Cho level was related to better ToM test performance in the AS group. An increase in the Cho peak was associated with an increase in membrane breakdown or turnover. The Cho peak was also thought to reflect cellular density and astrocytosis. It is suggested that membrane turnover and astrocytosis might affect cognitive functioning.
PMCID: PMC4818094  PMID: 19306123
Asperger’s syndrome; magnetic resonance spectroscopy; cingulate gyrus; prefrontal cortex
9.  The reciprocal relationship between executive function and theory of mind in middle childhood: a 1-year longitudinal perspective 
There is robust evidence showing a link between executive function (EF) and theory of mind (ToM) in 3- to 5-year-olds. However, it is unclear whether this relationship extends to middle childhood. In addition, there has been much discussion about the nature of this relationship. Whereas some authors claim that ToM is needed for EF, others argue that ToM requires EF. To date, however, studies examining the longitudinal relationship between distinct subcomponents of EF [i.e., attention shifting, working memory (WM) updating, inhibition] and ToM in middle childhood are rare. The present study examined (1) the relationship between three EF subcomponents (attention shifting, WM updating, inhibition) and ToM in middle childhood, and (2) the longitudinal reciprocal relationships between the EF subcomponents and ToM across a 1-year period. EF and ToM measures were assessed experimentally in a sample of 1,657 children (aged 6–11 years) at time point one (t1) and 1 year later at time point two (t2). Results showed that the concurrent relationships between all three EF subcomponents and ToM pertained in middle childhood at t1 and t2, respectively, even when age, gender, and fluid intelligence were partialled out. Moreover, cross-lagged structural equation modeling (again, controlling for age, gender, and fluid intelligence, as well as for the earlier levels of the target variables), revealed partial support for the view that early ToM predicts later EF, but stronger evidence for the assumption that early EF predicts later ToM. The latter was found for attention shifting and WM updating, but not for inhibition. This reveals the importance of studying the exact interplay of ToM and EF across childhood development, especially with regard to different EF subcomponents. Most likely, understanding others’ mental states at different levels of perspective-taking requires specific EF subcomponents, suggesting developmental change in the relations between EF and ToM across childhood.
doi:10.3389/fpsyg.2014.00655
PMCID: PMC4068105  PMID: 25009527
executive function; theory of mind; longitudinal; middle childhood; attention shifting; inhibition; working memory updating
10.  Deficits in Mental State Attributions in Individuals with 22q11.2 Deletion Syndrome (Velo-Cardio-Facial Syndrome) 
Velo-cardio-facial syndrome (VCFS; 22q11.2 deletion syndrome) results from a genetic mutation that increases risk for Autism Spectrum Disorder (ASD). We compared Theory of Mind (ToM) skills in 63 individuals with VCFS (25% with an ASD diagnosis) and 43 typically-developing controls, and investigated the relationship of ToM to reciprocal social behavior. We administered a video-based task to assess mentalizing at two sites (UCLA and SUNY Upstate Medical University). The videos depicted interactions representing complex mental states (ToM condition), or simple movements (Random condition). Verbal descriptions of the videos were rated for Intentionality (i.e., mentalizing) and Appropriateness. Using Repeated Measures ANOVA, we assessed the effects of VCFS and ASD on Intentionality and Appropriateness, and the relationship of mentalizing to Social Responsiveness Scale (SRS) scores. Results indicated that individuals with VCFS overall had lower Intentionality and Appropriateness scores than controls for ToM, but not for Random scenes. In the SUNY sample, individuals with VCFS, both with and without ASD, performed more poorly than controls on the ToM condition; however, in the UCLA sample, only individuals with VCFS without ASD performed significantly worse than controls on the ToM condition. Controlling for site and age, performance on the ToM condition was significantly correlated with SRS scores. Individuals with VCFS, regardless of an ASD diagnosis, showed impairments in the spontaneous attribution of mental states to abstract visual stimuli, which may underlie real-life problems with social interactions. A better understanding of the social deficits in VCFS is essential for the development of targeted behavioral interventions.
doi:10.1002/aur.1252
PMCID: PMC3528795  PMID: 22962003
22q11.2 deletion syndrome; Velo-cardio-facial syndrome; Theory of Mind; Autism Spectrum Disorders; reciprocal social behavior; social cognition
11.  Sequences of Mind Development in Boys with Autism Spectrum Disorder 
ISRN Neurology  2012;2012:637453.
Autism is a pervasive neurodevelopment disorder, primarily encompassing difficulties in the social, language, and communicative domains. One of the most common social cognitive theories of autism is based on theory of mind (ToM), the “mentalizing” ability needed to infer that others have their own beliefs and desires in order to understand their behavior. In the current study, this hypothesis was tested using Wellman and Liu's scaled ToM tasks. These were employed in the assessment of ToM development of verbal, school-aged high-functioning boys with autism spectrum disorder (ASD). The results indicated that children with ASD performed significantly worse than normal children on ToM tasks (Z = 4.7; P < 0 .001). However, it was shown that some of the ASD children were able to pass desire and false-belief tasks whereas none of them could succeed in knowledge and real-apparent emotion tasks.
doi:10.5402/2012/637453
PMCID: PMC3523140  PMID: 23304550
12.  Theory of Mind in Patients at Clinical High Risk for Psychosis 
Schizophrenia research  2011;131(1-3):11-17.
Background
Patients with schizophrenia have a decreased ability to interpret the intentions of other individuals, called Theory of Mind (ToM). As capacity for ToM normally advances with brain maturation, research on ToM in individuals at heightened clinical risk for psychosis may reveal developmental differences independent of disease based differences.
Methods
We examined ToM in at clinical high risk and schizophrenia patients as well as healthy controls: 1) 63 clinical high risk (CHR) patients and 24 normal youths ascertained by a CHR program; and 2) in 13 schizophrenia cases and 14 normal adults recruited through a schizophrenia program. ToM measures included first- and second-order false belief cartoon tasks (FBT) and two “higher order” tasks (“Strange Stories Task” (SST) and the “Reading the Mind in the Eyes” task). In the first study, CHR patients and normal youths were also assessed for cognition, “prodromal” symptoms and social function.
Results
Errors on first- and second-order false belief tasks were made primarily by patients. CHR patients and their young comparison group had equivalent performance on higher order ToM, which was not significantly different from the worse ToM performance of schizophrenia patients and the higher performance of normal adult controls. In the combined dataset from both studies, all levels of ToM were associated with IQ, controlling for age and sex. ToM bore no relation to explicit memory, prodromal symptoms, social function, or later transition to psychosis.
Conclusions
Higher order ToM capacity was equally undeveloped in high risk cases and younger controls, suggesting performance on these tasks is not fully achieved until adulthood. This study also replicates the association of IQ with ToM performance described in previous studies of schizophrenia.
doi:10.1016/j.schres.2011.06.005
PMCID: PMC3159813  PMID: 21757324
psychosis; theory of mind; IQ; risk; prodrome
13.  Integrating intention and context: assessing social cognition in adults with Asperger syndrome 
Deficits in social cognition are an evident clinical feature of the Asperger syndrome (AS). Although many daily life problems of adults with AS are related to social cognition impairments, few studies have conducted comprehensive research in this area. The current study examined multiple domains of social cognition in adults with AS assessing the executive functions (EF) and exploring the intra and inter-individual variability. Fifteen adult's diagnosed with AS and 15 matched healthy controls completed a battery of social cognition tasks. This battery included measures of emotion recognition, theory of mind (ToM), empathy, moral judgment, social norms knowledge, and self-monitoring behavior in social settings. We controlled for the effect of EF and explored the individual variability. The results indicated that adults with AS had a fundamental deficit in several domains of social cognition. We also found high variability in the social cognition tasks. In these tasks, AS participants obtained mostly subnormal performance. EF did not seem to play a major role in the social cognition impairments. Our results suggest that adults with AS present a pattern of social cognition deficits characterized by the decreased ability to implicitly encode and integrate contextual information in order to access to the social meaning. Nevertheless, when social information is explicitly presented or the situation can be navigated with abstract rules, performance is improved. Our findings have implications for the diagnosis and treatment of individuals with AS as well as for the neurocognitive models of this syndrome.
doi:10.3389/fnhum.2012.00302
PMCID: PMC3492863  PMID: 23162450
Asperger syndrome; contextual social cognition; executive functions; individual variability
14.  Investigating the Genetic Basis of Theory of Mind (ToM): The Role of Catechol-O-Methyltransferase (COMT) Gene Polymorphisms 
PLoS ONE  2012;7(11):e49768.
The ability to deduce other persons' mental states and emotions which has been termed ‘theory of mind (ToM)’ is highly heritable. First molecular genetic studies focused on some dopamine-related genes, while the genetic basis underlying different components of ToM (affective ToM and cognitive ToM) remain unknown. The current study tested 7 candidate polymorphisms (rs4680, rs4633, rs2020917, rs2239393, rs737865, rs174699 and rs59938883) on the catechol-O-methyltransferase (COMT) gene. We investigated how these polymorphisms relate to different components of ToM. 101 adults participated in our study; all were genetically unrelated, non-clinical and healthy Chinese subjects. Different ToM tasks were applied to detect their theory of mind ability. The results showed that the COMT gene rs2020917 and rs737865 SNPs were associated with cognitive ToM performance, while the COMT gene rs5993883 SNP was related to affective ToM, in which a significant gender-genotype interaction was found (p = 0.039). Our results highlighted the contribution of DA-related COMT gene on ToM performance. Moreover, we found out that the different SNP at the same gene relates to the discriminative aspect of ToM. Our research provides some preliminary evidence to the genetic basis of theory of mind which still awaits further studies.
doi:10.1371/journal.pone.0049768
PMCID: PMC3507837  PMID: 23209597
15.  Theory of mind and social inference in children and adolescents with bipolar disorder 
Psychological medicine  2008;38(6):791-800.
Background
Deficits in theory of mind (ToM), or the ability to infer what another person is thinking or feeling, have been reported in manic and euthymic adults with bipolar disorder. To date, there have been no investigations of ToM in pediatric bipolar disorder (PBD). The aim of the current study was to investigate this ability in PBD patients and healthy controls.
Method
PBD patients (n=26) and intellectually and demographically similar healthy comparison subjects (n=20) were administered two ToM tasks. In the Affective Story Task, subjects were read positive-, negative- and neutralvalenced stories, and were assessed on their ability to recognize that a misleading series of events could lead one character to develop a false belief about another character. On the Hinting Task, subjects were required to infer the real intentions behind subtle hints.
Results
The PBD group performed significantly more poorly than controls on the Hinting Task and the positive and negative conditions of the Affective Story Task. In the PBD group only, younger age, earlier illness onset and manic symptoms were associated with poorer ToM performance.
Conclusions
Consistent with past findings in adult bipolar disorder (BD), PBD youth performed more poorly than controls on ToM tasks. Data suggest that ToM ability may be more impaired in affectively charged contexts. Additionally, an earlier onset of illness among PBD youth may interfere with the development of social-cognitive skills. ToM disturbances may be a useful treatment target in PBD, with the aim of facilitating more accurate assessment of social cues and better interpersonal functioning.
doi:10.1017/S0033291707002541
PMCID: PMC3221606  PMID: 18208632
Pediatric bipolar disorder; social cognition; social inference; theory of mind
16.  Neural bases of Theory of Mind in children with autism spectrum disorders and children with conduct problems and callous-unemotional traits 
Developmental Science  2014;17(5):786-796.
Individuals with autism spectrum disorders (ASD) have difficulty understanding other minds (Theory of Mind; ToM), with atypical processing evident at both behavioural and neural levels. Individuals with conduct problems and high levels of callous-unemotional (CU) traits (CP/HCU) exhibit reduced responsiveness to others' emotions and difficulties interacting with others, but nonetheless perform normally in experimental tests of ToM. The present study aimed to examine the neural underpinnings of ToM in children (aged 10–16) with ASD (N = 16), CP/HCU (N = 16) and typically developing (TD) controls (N = 16) using a non-verbal cartoon vignette task. Whilst individuals with ASD were predicted to show reduced fMRI responses across regions involved in ToM processing, CP/HCU individuals were predicted to show no differences compared with TD controls. The analyses indicated that neural responses did not differ between TD and CP/HCU groups during ToM. TD and CP/HCU children exhibited significantly greater medial prefrontal cortex responses during ToM than did the ASD group. Within the ASD group, responses in medial prefrontal cortex and right temporoparietal junction (TPJ) correlated with symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS). Findings suggest that although both ASD and CP/HCU are characterized by social difficulties, only children with ASD display atypical neural processing associated with ToM.
doi:10.1111/desc.12167
PMCID: PMC4316185  PMID: 24636205
17.  Theory of mind skills are related to gray matter volume in the ventromedial prefrontal cortex in schizophrenia 
Biological psychiatry  2011;70(12):1169-1178.
Background
Among individuals with schizophrenia, deficits in theory of mind (ToM) skills predict poor social functioning. Therefore, identifying the neural basis of ToM may assist the development of treatments that improve social outcomes. Despite growing evidence that the ventromedial prefrontal cortex (VMPFC) facilitates ToM skills among healthy individuals, methodological challenges, such as the influence of general cognitive deficits, have made it difficult to identify the relationship between ToM processing and VMPFC function in schizophrenia.
Methods
We used voxel-based morphometry (VBM) and a multi-method behavioral assessment of ToM processing, including performance-based (Recognition of Faux Pas Test), self-report (Interpersonal Reactivity Index, Perspective-Taking), and interview-rated (Quality of Life Scale–Empathy score) ToM assessments, to investigate whether ToM skills were related to VMPFC gray matter volume (GMV). Standardized neuropsychological measures were used to assess global cognition. 21 schizophrenia and 17 healthy control subjects participated.
Results
Between-group behavioral analyses showed that, as compared to healthy participants, schizophrenia participants had worse ToM performance and lower self-reported ToM processing in daily life. The between-group analysis of GMV showed that schizophrenia participants had less VMPFC GMV than healthy participants. Moreover, among schizophrenia participants, all three measures of ToM processing were associated with VMPFC GMV, such that worse ToM skills were related to less VMPFC GMV. This association remained strong for self-reported and interview-rated ToM skills even when controlling for the influence of global cognition.
Conclusions
The findings suggest that among individuals with schizophrenia, reduced VMPFC GMV is specifically associated with deficits using ToM skills to enhance social relationships.
doi:10.1016/j.biopsych.2011.07.027
PMCID: PMC3432316  PMID: 21917239
mentalizing; theory of mind; empathy; schizophrenia; social functioning; MRI
18.  Theory of Mind Predicts Emotion Knowledge Development in Head Start Children 
Early education and development  2014;25(7):933-948.
Research Findings
Emotion knowledge (EK) enables children to identify emotions in themselves and others and its development facilitates emotion recognition in complex social situations. Social-cognitive processes, such as theory of mind (ToM), may contribute to developing EK by helping children realize the inherent variability associated with emotion expression across individuals and situations. The present study explored how ToM, particularly false belief understanding, in preschool predicts children’s developing EK in kindergarten. Participants were 60 3- to 5-year-old Head Start children. ToM and EK measures were obtained from standardized child tasks. ToM scores were positively related to performance on an EK task in kindergarten after controlling for preschool levels of EK and verbal ability. Exploratory analyses provided preliminary evidence that ToM serves as an indirect effect between verbal ability and EK.
Practice or Policy
Early intervention programs may benefit from including lessons on ToM to help promote socio-emotional learning, specifically EK. This consideration may be the most fruitful when the targeted population is at-risk.
doi:10.1080/10409289.2014.883587
PMCID: PMC4214863  PMID: 25364212
19.  Validity and Reliability of Published Comprehensive Theory of Mind Tests for Normal Preschool Children: A Systematic Review 
Iranian Journal of Psychiatry  2015;10(4):214-224.
Objective: Theory of mind (ToM) or mindreading is an aspect of social cognition that evaluates mental states and beliefs of oneself and others. Validity and reliability are very important criteria when evaluating standard tests; and without them, these tests are not usable. The aim of this study was to systematically review the validity and reliability of published English comprehensive ToM tests developed for normal preschool children.
Method: We searched MEDLINE (PubMed interface), Web of Science, Science direct, PsycINFO, and also evidence base Medicine (The Cochrane Library) databases from 1990 to June 2015. Search strategy was Latin transcription of ‘Theory of Mind’ AND test AND children. Also, we manually studied the reference lists of all final searched articles and carried out a search of their references. Inclusion criteria were as follows: Valid and reliable diagnostic ToM tests published from 1990 to June 2015 for normal preschool children; and exclusion criteria were as follows: the studies that only used ToM tests and single tasks (false belief tasks) for ToM assessment and/or had no description about structure, validity or reliability of their tests. Methodological quality of the selected articles was assessed using the Critical Appraisal Skills Programme (CASP).
Result: In primary searching, we found 1237 articles in total databases. After removing duplicates and applying all inclusion and exclusion criteria, we selected 11 tests for this systematic review.
Conclusion: There were a few valid, reliable and comprehensive ToM tests for normal preschool children. However, we had limitations concerning the included articles. The defined ToM tests were different in populations, tasks, mode of presentations, scoring, mode of responses, times and other variables. Also, they had various validities and reliabilities. Therefore, it is recommended that the researchers and clinicians select the ToM tests according to their psychometric characteristics, validity and reliability.
PMCID: PMC4801491  PMID: 27006666
Theory of Mind Test; Preschool; Normal; Validity; Reliability
20.  Theory-of-mind in individuals with Alström syndrome is related to executive functions, and verbal ability 
Frontiers in Psychology  2015;6:1426.
Objective: This study focuses on cognitive prerequisites for the development of theory-of-mind (ToM), the ability to impute mental states to self and others in young adults with Alström syndrome (AS). AS is a rare and quite recently described recessively inherited ciliopathic disorder which causes progressive sensorineural hearing loss and juvenile blindness, as well as many other organ dysfunctions. Two cognitive abilities were considered; Phonological working memory (WM) and executive functions (EF), both of importance in speech development.
Methods: Ten individuals (18–37 years) diagnosed with AS, and 20 individuals with no known impairment matched for age, gender, and educational level participated. Sensory functions were measured. Information about motor functions and communicative skills was obtained from responses to a questionnaire. ToM was assessed using Happés strange stories, verbal ability by a vocabulary test, phonological WM by means of an auditory presented non-word serial recall task and EF by tests of updating and inhibition.
Results: The AS group performed at a significantly lower level than the control group in both the ToM task and the EF tasks. A significant correlation was observed between recall of non-words and EF in the AS group. Updating, but not inhibition, correlated significantly with verbal ability, whereas both updating and inhibition were significantly related to the ability to initiate and sustain communication. Poorer performance in the ToM and EF tasks were related to language perseverance and motor mannerisms.
Conclusion: The AS group displayed a delayed ToM as well as reduced phonological WM, EF, and verbal ability. A significant association between ToM and EF, suggests a compensatory role of EF. This association may reflect the importance of EF to perceive and process input from the social environment when the social interaction is challenged by dual sensory loss. We argue that limitations in EF capacity in individuals with AS, to some extent, may be related to early blindness and progressive hearing loss, but maybe also to gene specific abnormalities.
doi:10.3389/fpsyg.2015.01426
PMCID: PMC4585138  PMID: 26441796
Alström syndrome (AS); ciliopathy; deafblindness; theory-of-mind; verbal ability; executive functions
21.  Atypical Cross Talk Between Mentalizing and Mirror Neuron Networks in Autism Spectrum Disorder 
JAMA psychiatry  2014;71(7):751-760.
IMPORTANCE
Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition.
OBJECTIVE
To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS).
DESIGN, SETTING, AND PARTICIPANTS
Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ.
MAIN OUTCOMES AND MEASURES
Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures.
RESULTS
Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction.
CONCLUSIONS AND RELEVANCE
Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.
doi:10.1001/jamapsychiatry.2014.83
PMCID: PMC4404406  PMID: 24740586
22.  Theory of Mind Indexes the Broader Autism Phenotype in Siblings of Children with Autism at School Age 
Autism Research and Treatment  2016;2016:6309189.
Subclinical variants of the social-communicative challenges and rigidity that define autism spectrum disorder (ASD) are known as the broader autism phenotype (BAP). The BAP has been conceptualized categorically (as specific to a subset of relatives of individuals with ASD) and dimensionally (as continuously distributed within the general population). The current study examined the compatibility of these two approaches by assessing associations among autism symptoms and social-communicative skills in young school-age children with ASD, children who have a sibling with ASD, and children without a sibling with ASD. Autism symptoms were associated with reduced Theory of Mind (ToM), adaptive skills, cognitive empathy, and language skills across the full sample. Reduced ToM was a core aspect of the BAP in the current sample regardless of whether the BAP was defined categorically (in terms of siblings of children with ASD who exhibited atypical developmental) or dimensionally (in terms of associations with autism symptoms across the entire sample). Early language skills predicted school-age ToM. Findings support the compatibility of categorical and dimensional approaches to the BAP, highlight reduced ToM as a core aspect of the school-age BAP, and suggest that narrative-based approaches to promoting ToM may be beneficial for siblings of children with ASD.
doi:10.1155/2016/6309189
PMCID: PMC4736958  PMID: 26881074
23.  From Fancy to Reason: Scaling Deaf and Hearing Children’s Understanding of Theory of Mind and Pretence 
We examined deaf and hearing children’s progression of steps in theory-of-mind (ToM) development including their understanding of social pretending. Ninety-three children (33 deaf; 60 hearing) aged 3 to 13 years were tested on a set of six closely-matched ToM tasks. Results showed that deaf children were delayed substantially behind hearing children in understanding pretending, false belief and other ToM concepts, in line with their delayed uptake of social pretend play. By using a scaling methodology, we confirmed previous evidence of a consistent five-step developmental progression for both groups. Moreover, by including social pretence understanding, both deaf and hearing children’s ToM sequences were shown to extend reliably to six sequential developmental steps. Finally and focally, even though both groups’ sequences were six steps long, the placement of pretence relative to other ToM milestones varied with hearing status. Deaf children understood social pretending at an earlier step in the ToM sequence than hearing children, albeit at a later chronological age. Theoretically, the findings are relevant to questions about how universal developmental progressions come together along with culturally-distinctive inputs and biological factors (such as hearing loss) to set the pace for ToM development.
PMCID: PMC3086259  PMID: 19998533
24.  Social Cognition in 22q11.2 Microdeletion Syndrome: Relevance to Psychosis 
Schizophrenia research  2012;142(0):99-107.
22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic risk factors for schizophrenia. Approximately 30% of individuals with 22qDS develop psychotic illness in adolescence or young adulthood. Given that deficits in social cognition are increasingly viewed as a central aspect of idiopathic schizophrenia, we sought to investigate abilities in this domain as a predictor of psychotic symptoms in 22qDS participants. We assessed multiple domains of social and non-social cognition in 22qDS youth to: 1) characterize performance across these domains in 22qDS, and identify whether 22qDS participants fail to show expected patterns of age-related improvements on these tasks; and 2) determine whether social cognition better predicts positive and negative symptoms than does non-social cognition. Task domains assessed were: emotion recognition and differentiation, Theory of Mind (ToM), verbal knowledge, abstract reasoning, working memory, and processing speed. Positive and negative symptoms were measured using scores obtained from the Structured Interview for Prodromal Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of ToM and processing speed. In contrast to controls, 22qDS participants did not show age-related improvements on measures of working memory and verbal knowledge. Notably, ToM performance was the best predictor of positive symptoms in 22qDS, accounting for 39% of the variance in symptom severity. Processing speed emerged as the best predictor of negative symptoms, accounting for 37% of the variance in symptoms. Given that ToM was a robust predictor of positive symptoms in our sample, these findings suggest that social cognition may be a valuable intermediate trait for predicting the development of psychosis.
doi:10.1016/j.schres.2012.10.007
PMCID: PMC3714207  PMID: 23122739
22q11.2 Microdeletion Syndrome; social cognition; schizophrenia; prodromal; psychosis
25.  Insight and theory of mind in schizophrenia 
Psychiatry research  2014;225(0):169-174.
Theory of mind (ToM) impairment is common in individuals with schizophrenia and is associated with poor social functioning. Poor insight has also been linked to poor outcome in schizophrenia. Social developmental research has shown representations of self (insight) and representations of others (ToM) are related. In schizophrenia, contradictory reports of associations between insight and ToM have emerged, possibly due to a failure to account for neurocognitive impairments and symptoms associated with both mentalization constructs. This study investigated the relationships between ToM (intentions of others on the Hinting task) and clinical and cognitive insight, while accounting for shared variance with neurocognitive impairment and symptom severity in 193 individuals with schizophrenia. Clinical, but not cognitive, insight was associated with ToM. A unique association between Awareness of Mental Illness and Hinting Task performance was found, independent of shared variance with neurocognition and symptoms. Importantly, ToM was found to mediate Awareness of Mental Illness and neurocognition. Results suggested treatments targeting mentalization abilities that contribute to representations of self and others may improve insight deficits associated with poor outcome in schizophrenia.
doi:10.1016/j.psychres.2014.11.010
PMCID: PMC4269286  PMID: 25467703
Schizophrenia; Mentalization; Cognitive Insight; Insight; Theory of Mind; Social Cognition

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