Deficiency of theory of mind in patients with remitted mood disorder

BACKGROUND: Recent researches on theory of mind (ToM) in patients with mood disorders have revealed deficits of ToM ability during episodes. In this study, we aimed to test ToM ability among patients with unipolar or bipolar depression currently in remission. METHODS: ToM ability and IQ obtained by Wechsler Adult Intelligence Scale-Revised (WAIS-R) were evaluated in 50 patients with remitted depression, who met the criteria of mood disorders of DSM-IV, and 50 matched healthy controls. RESULTS: The patients with mood disorders showed statistically significant impairment in a second-order false question (Fisher's Exact Test p < 0.0001). No significant difference was shown in the other three areas of ToM between the patients and the controls. In addition, no correlation of the four areas of ToM with IQ obtained by WAIS-R was found. LIMITATIONS: The relation of ToM deficit to other specific cognitive impairment was not examined. CONCLUSIONS: Our results suggest that depressive patients in symptomatic remission have a lower ability of second-order false belief. The ToM impairment suggests a decline of skillful social relationships. Evaluation of ToM ability in depressive patients in remission may be useful to provide treatment for better social adjustment.     

Integration of emotional and cognitive aspects of theory of mind in schizophrenia and its relation to prefrontal neurocognitive performance

Introduction. There is substantial evidence that patients with schizophrenia present with impaired Theory of Mind (ToM). Whereas previous studies have focused on general ToM abilities, the present study is aimed at testing the underlying behavioural and neurocognitive mechanisms of the impaired integration of affective and cognitive aspects of ToM (the integration of emotional information with mentalising) in patients with schizophrenia.

Methods. Twenty-six patients with schizophrenia and 35 healthy controls were tested on two ToM tasks involving the integration of affective and cognitive ToM abilities: “Faux Pas” and “reading the mind in the eyes” tasks. To assess the neurocognitive bases of impaired ToM, the ID/ED test (intradimensional/extradimensional shifting test from the CANTAB) was administered.

Results. Patients performed poorly on both the cognitive-affective integration ToM tasks and the ID/ED task as compared to controls. Furthermore, patients’ ToM scores were selectively correlated with the reversal trials, which are believed to be associated with orbitofrontal functioning. In addition, more than 50% of the variance in recognising and understanding Faux Pas could be explained by patients’ symptomatology. Performance on orbitofrontal related tasks was correlated with subjects’ Faux Pas scores in the patients group, but not in the healthy control group.

Conclusions. Schizophrenic patients appear to have considerable impairment in affective and cognitive ToM integration, which may be related to orbitofrontal dysfunction. These results are in line with previous findings regarding empathy and the importance of the orbitofrontal area in the integration of cognition and affect.     

Theory of mind impairments in schizophrenia: symptomatology, severity and specificity

BACKGROUND: Several studies have examined the ability of schizophrenic patients to represent mental states ('theory of mind': ToM). There is consensus that some patients have impaired ToM, but there is disagreement about the relation between ToM and symptomatology, and about the severity and specificity of the deficit. METHODS: Two first-order and one second-order false belief tests of ToM were given to groups of schizophrenic patients and psychiatric and normal controls. The relation between ToM and symptomatology was explored using regression and symptom subgroup analyses. Severity was investigated by using the same task methodology as in autism research, to enable direct comparison with that disorder. Specificity was investigated using matched control tasks which were as difficult as the ToM tasks, but did not require ToM. RESULTS: Symptom subgroup analysis showed that schizophrenic patients with behavioural signs were impaired relative to controls on ToM, and that remitted patients and a single case with passivity symptoms performed as well as controls. Regression analysis showed that ratings of behavioural signs predicted impaired ToM in schizophrenia. There was weak evidence that a subgroup with paranoid symptoms had ToM impairments, although these were associated with low IQ. Schizophrenic patients only showed ToM deficits on the second-order task. No impairments appeared on the matched control tasks which did not require ToM. CONCLUSIONS: There is a clear association between ToM impairment and behavioural signs in schizophrenia. Deficits in paranoid patients are harder to detect with current tasks and may be compensated for by IQ-dependent problem-solving skills. ToM impairments in schizophrenia are less severe than in autism, but are specific and not a reflection of general cognitive deficits.     

Social and emotional functions in three patients with medial frontal lobe damage including the anterior cingulate cortex

Introduction. The aim of this study was to explore social and emotional functions in patients with medial frontal damage including the anterior cingulate cortex (ACC).

Methods. Three patients with medial frontal lobe lesions primarily involving the ACC performed tasks on motivational decision making, emotional facial expression recognition, and social cognition, including theory of mind (ToM). Their performance on these tasks was compared with age and education matched healthy controls.

Results. Patient performance on the motivational decision making and social situations tasks did not differ from controls. Selective emotional facial expression recognition impairment for fear was evident in one patient with a unilateral right ACC lesion (patient 3). ToM impairment was present in only one patient with a bilateral ACC lesion (patient 2). In contrast, the two patients with unilateral right ACC lesions had intact ToM (patients 1 and 3).

Conclusions. These findings suggest that medial frontal lobe lesions primarily involving the ACC do not appear to critically disrupt motivational decision making or social situation processing. The ACC plays a role in processing particular types of emotion (fear). Bilateral ACC damage impairs ToM processing, but unilateral damage to the right ACC is not sufficient to disrupt ToM.     

The relations between joint action and theory of mind: a neuropsychological analysis

We examined the relations between joint action and Theory of Mind (ToM) in neurological patients with impairments in ToM, in control patients (who passed ToM tasks) and non-lesioned controls. In two experiments, joint action was assessed in a "social Simon" procedure where spatial compatibility effects were tested under two-alternative forced-choice and under go/nogo conditions, which participants performed in isolation or alongside another participant (the joint action condition). In Experiment 1, patients with impaired ToM showed evidence of increased spatial compatibility effects under standard (two-alternative forced-choice) conditions but, unlike the control participants, these effects disappeared in the joint action condition. In Experiment 2, the ToM patients were asked to pay particular attention to their co-actor. With these instructions, ToM patients with lesions of posterior parietal cortex now showed a sustained spatial compatibility effect in the joint action condition, while ToM patients with lesions primarily involving frontal regions showed an initial effect of spatial compatibility that decreased across trials. The data suggest common processes involved in ToM processing and joint action effects, related to either the ability to attend to appropriate social cues (affected in posterior parietal patients) or the ability to recruit sufficient resources to code another's actions (affected in frontal patients).     

Social reasoning in Tourette syndrome

Introduction. Tourette syndrome (TS) is thought to be associated with striatal dysfunction. Changes within frontostriatal pathways in TS could lead to changes in abilities reliant on the frontal cortex. Such abilities include executive functions and aspects of social reasoning.

Methods. This study aimed to investigate executive functioning and Theory of Mind (ToM; the ability to reason about mental states, e.g., beliefs and emotions), in 18 patients with TS and 20 controls. A range of tasks involving ToM were used. These required participants to make judgements about mental states based on pictures of whole faces or the eyes alone, reason about humour in cartoons that featured sarcasm, irony or “slapstick” style humour, and make economic decisions. The executive measures assessed inhibition and verbal fluency.

Results. Patients with TS exhibited significantly poorer performance than controls on all four tasks involving ToM, even when patients with comorbid obsessive-compulsive disorder were excluded. These difficulties were despite no inhibitory deficits. Patients with TS exhibited impairment on the verbal fluency task but their performance on executive and ToM tasks was not related.

Conclusions. We propose that TS is associated with changes in ToM. The observed deficits could reflect dysfunction in frontostriatal pathways involving ventromedial prefrontal cortex.     

Age-related learning and memory impairments in adult-onset hypothyroidism in Kunming mice

The memory impairment induced by adult-onset hypothyroidism is a common symptom. However, the exact onset time that will influence on memory function is still an issue of debate. The purpose of this study is to determine the onset effect of hypothyroidism on the memory during adulthood. Three age groups of Kunming (KM) mice were used, including 2, 8, and 15-month-old mice. Adult-onset hypothyroidism was made by adding PTU to drinking water and hypothyroid states were documented by the measurement of serum thyroid hormones level. A battery of tasks, i.e. novel-object recognition, olfactory discrimination, Morris water maze, was used to test mice's memory. The results showed that adult-onset hypothyroidism induced the impairment of odor and spatial memory consolidation whereas it did not affect visual memory encoding or consolidated spatial memory retention. Age at onset of hypothyroidism was an important factor for the memory impairment induced by hypothyroidism. The 2-month-old hypothyroid mice had significantly impaired abilities in both the olfactory discrimination and the spatial cognitive tasks relative to the 2-month-old controls. The 8-month-old hypothyroid mice had only impaired ability in the spatial cognitive task relative to the same age controls. The 15-month-old hypothyroid mice retained these cognitive abilities relative to the same age controls. These results suggested that adult-onset hypothyroidism could induce an age- and task-dependent impairment of memory in female KM mice.     

Executive function and theory of mind in 2 year olds: a family affair?

Although numerous studies of preschoolers report robust associations between performance on tests of executive function (EF) and theory of mind (ToM), a lack of developmentally appropriate tasks so far has limited research on these cognitive skills in younger children. Here, we present new batteries of EF and ToM tasks that were administered to 140 two-year-olds from predominantly disadvantaged families, with analyses based on 129 children. Our results showed a strong association between EF and ToM, which remained significant when effects of verbal ability were controlled. Individual differences in EF and ToM were also examined in relation to both distal family factors (social disadvantage, number of siblings) and proximal family factors (quality of child's relationships with parents and siblings). Social disadvantage predicted significant variance in both EF and ToM but did not contribute to the association between these domains. Associations between positive parent-child relationships and both EF and ToM were nonsignificant when verbal ability was controlled. In contrast, positive sibling relationships predicted significant variance in ToM, even controlling for age, verbal ability, EF, social disadvantage, and parent-child relationships.     

Theory of mind and social inference in children and adolescents with bipolar disorder

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 neutral-valenced 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.     

Theory of Mind as a potential trait marker of schizophrenia: A family study

Introduction. Although there is some evidence that Theory of Mind (ToM) deficits may be trait markers of schizophrenia it is not clear yet if ToM deficits are primary deficits, that is, to be independent of deficits in general intellectual abilities and executive function. The aim was to examine if ToM deficits may be trait markers of the illness and the effect of cognitive inhibition, general intellectual abilities and depression on ToM abilities of patients with schizophrenia and their unaffected parents.

Methods. We assessed ToM abilities (first-order and second-order ToM stories, The Revised Eyes Test), cognitive inhibition (Stroop Task), general intellectual ability (Standard Progressive Matrices Test Plus) in patients with schizophrenia (N=21) and their unaffected fathers (N=21) and mothers (N=21) in comparison with healthy control families (healthy control males, N=21, healthy control fathers, N=21, healthy control mothers, N=21)

Results. Patients showed deficits in first-order ToM tasks but some of these deficits were mediated by general intellectual abilities. Impairments in cognitive inhibition mediated only patients’ performance in The Revised Eyes Test. Patients showed deficits in second-order ToM stories independently of deficits in general intellectual abilities and cognitive inhibition. Unaffected parents did not show deficits in first-order ToM tasks, whereas they showed deficits in second-order ToM stories. However, the deficits that unaffected parents showed in second-order ToM stories were mediated by their deficits in general intellectual abilities, and there was an effect of remitted depression on the unaffected mothers’ performance.

Conclusions. The results suggest that intact neurocognitive and general intellectual abilities are necessary in order patients and their unaffected parents to pass successfully ToM tasks. Patients and their unaffected parents show ToM deficits but these deficits are not similar. Patients show ToM deficits but these deficits seem to be a component of the pathophysiology of the illness (e.g., deficits in executive function, general intellectual abilities).     

A Neuropsychological Investigation of Theory of Mind in an Elderly Lady with Frontal Leucotomy

This single case study assessed an elderly lady with prefrontal leucotomy on Theory of Mind (ToM) and executive function tasks. The case subject demonstrated impairment on higher order ToM tasks and executive function tasks. She passed first order ToM tasks and her ability to recognise mental state terms was unimpaired. Results are discussed in terms of the role of the frontal lobes as a potential, common mediating structure for these functions.     

Schizophrenia,theory of mind,and persecutory delusions

Introduction. There is already a substantial body of evidence supporting Frith's (1992 Frith CD (1992) The cognitive neuropsychology of schizophrenia Hove, UK: Psychology Press  ) theory that theory of mind (ToM) is impaired in people with schizophrenia. However, a specific relationship between impaired ToM and paranoid delusions, while intuitively reasonable, has only been demonstrated in two studies to date.

Methods. A total of 25 participants with schizophrenia were classified as paranoid or nonparanoid and compared with 38 healthy controls on a variety of ToM tasks. These tasks included verbal and nonverbal, and first and second order ToM tasks.

Results. Participants with schizophrenia performed significantly more poorly than healthy controls on both the first and second order verbal ToM tasks but not on the nonverbal ToM tasks. However, the ToM deficit was only observed for those participants with schizophrenia who had persecutory delusions. There was also a strong relationship observed between the severity of persecutory delusions and length of illness.

Conclusions. This study represents only the third demonstration of a specific link between paranoid delusions and ToM impairment. Reasons why previous findings on this issue have been so inconsistent are considered. Further research is needed to explore the relationships among paranoia, ToM, and length of illness.     

Making sense of theory of mind and paranoia: The psychometric properties and reasoning requirements of a false belief sequencing task

Introduction. This study used Item–Response Theory (IRT) to model the psychometric properties of a false belief picture sequencing task. Consistent with the mental time travel hypothesis of paranoia, we anticipated that performance on this deductive theory of mind (ToM) task would not be associated with the presence of persecutory delusions but would be related to other clinical, cognitive, and demographic factors.

Method. A large (N=237) and diverse clinical and nonclinical sample differing in levels of depression and paranoid ideation performed 2 ToM tasks: the false belief sequencing task and a ToM stories task that was used to assess the validity of the false belief sequencing task as a measure of ToM.

Results. A unidimensional IRT model was found to fit the data well. Latent ToM ability as measured by the false belief sequencing task was negatively related with age and positively with IQ. In contrast to the ToM stories measure, there was no association between clinical diagnosis or symptoms and false belief picture sequencing after controlling for age and IQ.

Conclusions. In line with mental time travel hypothesis of paranoia (Corcoran, 2010 Corcoran, R. 2010. The allusive cognitive deficit in paranoia: The case for mental time travel or cognitive self-projection. Psychological Medicine, 40: 1–4.  [Google Scholar]), performance on this deductive nonverbal ToM task is not related to the presence of paranoid symptoms. This measure is best suited for assessing ToM functioning where participants’ performance falls just short of the average latent ToM ability. Furthermore, it is sensitive to the effects of increasing age and decreasing IQ.     

Neuropathology does not Correlate with Regional Differences in the Extent of Expansion of CTG Repeats in the Brain with Myotonic Dystrophy Type 1

Myotonic dystrophy (DM1) is known to be an adult-onset muscular dystrophy caused by the expansion of CTG repeats within the 3' untranslated region of the dystrophin myotonin protein kinase (DMPK) gene. The clinical features of DM1 include CNS symptoms, such as cognitive impairment and personality changes, the pathogenesis of which remains to be elucidated. We hypothesized that the distribution of neuropathological changes might be correlated with the extent of the length of the CTG repeats in the DMPK genes in DM1 patients. We studied the neuropathological changes in the brains of subjects with DM1 and investigated the extent of somatic instability in terms of CTG repeat expansion in the different brain regions of the same individuals by Southern blot analysis. The neuropathological changes included état criblé in the cerebral deep white matter and neurofibrillary tangles immunoreactive for phosphorylated tau in the hippocampus and entorhinal cortex, both of which were compatible with the subcortical dementia in DM1 patients. However, the length of the CTG repeats did not correlate with the regional differences in the extent of neuropathological changes. Our data suggested that pathomechanisms of dementia in DM1 might be more multifactorial rather than a toxic gain-of-function due to mutant RNA.     

Making sense of theory of mind and paranoia: the psychometric properties and reasoning requirements of a false belief sequencing task

INTRODUCTION. This study used Item-Response Theory (IRT) to model the psychometric properties of a false belief picture sequencing task. Consistent with the mental time travel hypothesis of paranoia, we anticipated that performance on this deductive theory of mind (ToM) task would not be associated with the presence of persecutory delusions but would be related to other clinical, cognitive, and demographic factors. METHOD. A large (N=237) and diverse clinical and nonclinical sample differing in levels of depression and paranoid ideation performed 2 ToM tasks: the false belief sequencing task and a ToM stories task that was used to assess the validity of the false belief sequencing task as a measure of ToM. RESULTS. A unidimensional IRT model was found to fit the data well. Latent ToM ability as measured by the false belief sequencing task was negatively related with age and positively with IQ. In contrast to the ToM stories measure, there was no association between clinical diagnosis or symptoms and false belief picture sequencing after controlling for age and IQ. CONCLUSIONS. In line with mental time travel hypothesis of paranoia (Corcoran, 2010 ), performance on this deductive nonverbal ToM task is not related to the presence of paranoid symptoms. This measure is best suited for assessing ToM functioning where participants' performance falls just short of the average latent ToM ability. Furthermore, it is sensitive to the effects of increasing age and decreasing IQ.     

Deficit in theory of mind is a risk for relapse of major depression

BACKGROUND: Recently, we reported that patients with depression have theory of mind (ToM) deficit during remission from acute episodes. ToM deficit means difficulty in social adjustment and thus may indicate a poorer prognosis. METHODS: We evaluated ToM ability of 50 patients during remission from major depressive episodes. The patients were followed for 1 year and their outcome observed. RESULTS: After 1 year, patients who had ToM deficit in a second order false question relapsed significantly more frequently as compared with patients who did not have a deficit (Fisher's exact test p < 0.0001; relative risk (RR) = 8.105; CI 2.020, 32.524). Significant differences were shown in scores of the Global Assessment of Functioning Scale (p < 0.0001) between the two groups. CONCLUSIONS: Patients with ToM deficit in second order false belief during remission may be a high risk group for recurrence and lower social function 1 year after recovering from a major depressive episode.     

Impairments in theory of mind shortly after traumatic brain injury and at 1-year follow-up

Most studies into acquired theory of mind (ToM) deficits assessed patients once, long after the onset of brain injury. As a result, the time course of acquired ToM impairments is largely unknown. The present study examined whether ToM impairments following traumatic brain injury (TBI) recover, remain stable, or worsen over time. Because of the alleged association between ToM and social communication, ToM impairments may deteriorate because of changes in patients' social environment following injury. ToM ability and executive functioning were assessed shortly after injury and at 1-year follow-up. Compared with the orthopedic control group, the TBI group was impaired on ToM and executive functioning tasks at both assessments. Furthermore, the ToM impairments in the TBI group remained stable over time.     

Delusions and reasoning: A study involving cognitive behavioural therapy

Introduction. Anomalies on probabilistic reasoning, theory of mind (ToM) tasks, and attributional biases have been found in delusional people. Delusions are also effectively modified by cognitive behavioural therapy (CBT). We sought to examine whether CBT reduces delusional conviction by changing such general reasoning anomalies.

Method. Sixteen patients commenced an 8–11 week CBT programme that targeted their delusions. Probabilistic reasoning, attributional biases, and ToM were assessed pre- and post-treatment. Delusional conviction, preoccupation, and distress were rated at each session. Pretreatment task performances were compared to norms. Repeated measures analyses compared pre- and posttreatment task performances and ratings of delusions. Correlational analyses were used to identify factors associated with reduced delusional conviction.

Results. At baseline, 11 patients showed some form of abnormal probabilistic reasoning, 13 excessive attributional biases, and 13 defective ToM compared to norms. Fourteen patients completed the CBT programme and showed significant reductions in delusional conviction and preoccupation. Despite some inconsistent evidence of improvement in verbal ToM tasks, reasoning styles in these 14 patients were largely unchanged by CBT.

Conclusion. Reasoning anomalies associated with delusions in this sample mark a vulnerability that persists and is independent of the effectiveness of CBT.     

Cannabis abuse is associated with decision-making impairment among first-episode patients with schizophrenia-spectrum psychosis

BACKGROUND: Cannabis use appears to be a risk factor for schizophrenia. Moreover, cannabis abusers show impaired decision-making capacities, linked to the orbitofrontal cortex (OFC). Although there is substantial evidence that first-episode schizophrenia patients show impairments in cognitive tasks associated with the dorsolateral prefrontal cortex (DLPFC), it is not clear whether decision making is impaired at schizophrenia onset. In this study, we examined the association between antecedents of cannabis abuse and cognitive impairment in cognitive tasks associated with the DLPFC and the OFC in a sample of first-episode patients with schizophrenia-spectrum disorders.MethodOne hundred and thirty-two patients experiencing their first episode of a schizophrenia-spectrum psychosis were assessed with a cognitive battery including DLPFC-related tasks [backward digits, verbal fluency (FAS) and the Trail Making Test (TMT)] and an OFC-related task [the Iowa Gambling Task (GT)]. Performance on these tasks was compared between patients who had and had not abused cannabis before their psychosis onset. RESULTS: No differences were observed between the two groups on the performance of any of the DLPFC-related tasks. However, patients who had abused cannabis before their psychosis onset showed a poorer total performance on the gambling task and a lower improvement on the performance of the task compared to no-abusers. CONCLUSIONS: Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis. Further studies are needed to examine the direction of causality of this impairment; that is, does the impairment make the patients abuse cannabis, or does cannabis abuse cause the impairment?