A Preliminary Validity Study of the Cambridge Neuropsychological Test Automated Battery for the Assessment of Executive Function in Schizophrenia and Bipolar Disorder

Objective

Although the executive function subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) have been used to assess cognitive function in diverse psychiatric illnesses, few studies have verified the validity of this battery for Korean psychiatric patients. Therefore, this preliminary study evaluated the construct and concurrent validity of the executive function subtests of the CANTAB for Korean psychiatric patients by comparing it with subtests of the Computerized Neuropsychological Test (CNT).

Methods

Three subtests of the CANTAB and three subtests of the CNT were administered to 36 patients diagnosed with either schizophrenia or bipolar disorder. Subtests of the CANTAB included the Intra/Extra-Dimensional Set Shift (IED), Stockings of Cambridge (SOC), and Spatial Working Memory (SWM). Differences between groups on each subtest as well as correlations between the subtests of the CANTAB and the CNT were assessed.

Results

The schizophrenia group performed significantly more poorly on the IED and the Wisconsin Card Sorting Test (WCST) compared with the bipolar disorder group. Additionally, correlation analyses revealed a significant correlation between the IED and the WCST; a positive correlation between the SOC and the Trail Making Test, Part B and the Stroop test; and a significant correlation between the SWM and the Stroop test.

Conclusion

This study verified the construct and concurrent validity of the executive function subtests of the CANTAB for Korean psychiatric patients and suggests that the subtests of this battery would be useful and appropriate for assessing deficits in executive function in Korean clinical settings.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Affect recognition as an independent social function determinant in schizophrenia

Introduction

Facial affect recognition deficits may represent specific deficits and contribute to social dysfunction in patients with schizophrenia. Whether their impacts on social dysfunction are independent to those caused by deficits in basic neurocognition and clinical symptoms needs to be further delineated.

Method

Association patterns between affect recognition and basic neurocognitive abilities in 40 acute and 33 stable patients with schizophrenia were compared to explore whether their interrelationships changed across clinical stages. The independent contribution of affect recognition deficits to social dysfunction was explored by multivariate models controlling for general intellectual ability, basic neurocognition, and clinical symptoms.

Results

Affect recognition deficits were associated with social role performances, self-care, and contributed independently to global social functioning in stable patients but not in acute patients. Conversely, affect recognition deficits were associated with impaired basic neurocognitions in acute patients but not in stable patients.

Conclusion

In stabilized community patients with schizophrenia, affect recognition deficits were relatively independent to basic neurocognition and had significant social functional consequences.     

Neurocognitive deficits in schizophrenia are associated with alterations in blood levels of neurosteroids: A multiple regression analysis of findings from a double-blind, randomized, placebo-controlled, crossover trial with DHEA

Background

While neurosteroids exert multiple effects in the central nervous system, their associations with neurocognitive deficits in schizophrenia are not yet fully understood. The purpose of this study was to identify the contribution of circulating levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione, and cortisol to neurocognitive deficits through DHEA administration in schizophrenia.

Methods

Data regarding cognitive function, symptom severity, daily doses, side effects of antipsychotic agents and blood levels of DHEA, DHEAS, androstenedione and cortisol were collected among 55 schizophrenia patients in a double-blind, randomized, placebo-controlled, crossover trial with DHEA at three intervals: upon study entry, after 6 weeks of DHEA administration (200 mg/d), and after 6 weeks of a placebo period. Multiple regression analysis was applied for predicting sustained attention, memory, and executive function scores across three examinations controlling for clinical, treatment and background covariates.

Results

Findings indicated that circulating DHEAS and androstenedione levels are shown as positive predictors of cognitive functioning, while DHEA level as negative predictor. Overall, blood neurosteroid levels and their molar ratios accounted for 16.5% of the total variance in sustained attention, 8-13% in visual memory tasks, and about 12% in executive functions. In addition, effects of symptoms, illness duration, daily doses of antipsychotic agents, side effects, education, and age of onset accounted for variability in cognitive functioning in schizophrenia.

Conclusions

The present study suggests that alterations in circulating levels of neurosteroids and their molar ratios may reflect pathophysiological processes, which, at least partially, underlie cognitive dysfunction in schizophrenia.     

Sexual problems in a sample of the Turkish psychiatric population

Introduction

Sexual functioning has received little attention as an important aspect of patient care for those who have severe mental disorders.

Aim

The aim of this study is to compare sexual difficulties seen in Turkish psychiatric patients and healthy control subjects.

Methods

Study group consisted of outpatients in remission with schizophrenia (n = 84), bipolar affective disorders (n = 90), heroin addiction (n = 88), and healthy control group (n = 98). A sociodemographical data form and the Golombok Rust Inventory of Sexual Satisfaction were applied to all groups (N = 360).

Results

Half of the patient groups and 72.8% of control subjects reported that they had regular sexual life. The patients with heroin addiction complained about more problems in their sexual life than in the other groups. Controls (86.2%) felt more satisfied with their sexual life. Female patients with heroin addiction had statistically significant higher scores in nonsensuality subscale of Golombok Rust Inventory of Sexual Satisfaction. Female patients with schizophrenia and bipolar disorder had statistically significant higher scores in vaginismus subscale than in control group. Between the groups, male patients with bipolar disorder had higher score in most of the items except noncommunication and erectile dysfunction and also had higher total score than in the controls. More men (especially with heroin addiction) thought that their illness and drugs were responsible for their sexual problems, knew the effect of the illness and drugs on their sexual life, and asked questions to their psychiatrists about the problems more than women.

Conclusion

Patients with bipolar disorders and schizophrenia were unaware of effects of their medication on their sexual life. Finally, it was also found that clinicians in our country do not pay sufficient attention to the sexual problems of psychiatric patients.     

Prepulse inhibition of the startle reflex in schizophrenia remains stable with short-term quetiapine

Purpose

To study the short-term effect of treatment with quetiapine on prepulse inhibition (PPI) deficits of the startle reflex in schizophrenia patients.

Subjects and methods

Using PPI, we studied a group of 21 schizophrenia patients and 16 controls. Seventeen of the patients were re-tested with PPI after 21 days of treatment with quetiapine.

Results

At baseline, an almost significant decrease in PPI was found in the patients as compared to the controls. PPI measurements did not change in the patients after 21 days of treatment with quetiapine, despite their clinical improvement.

Conclusion

Our results suggest that short-term quetiapine treatment may not modify PPI measures in schizophrenia patients.     

Functional neural substrates of self-reported physical anhedonia in non-clinical individuals and in patients with schizophrenia

Background

Anhedonia is a negative symptom of schizophrenia that has a detrimental impact on functioning and quality of life. Anhedonia also represents a vulnerability marker for schizophrenia when measured in non-clinical individuals. The investigation of the neural correlates of anhedonia in schizophrenia and non-clinical individuals could provide key insights on the pathophysiology of negative symptoms, as well as on the characterization of neural markers of vulnerability.

Methods

Thirty patients with schizophrenia and twenty-six non-clinical individuals were recruited. We used an event-related functional Magnetic Resonance Imaging paradigm involving an emotional picture viewing task. For each group, separately, we correlated the regional BOLD signal changes during hedonic processing with the Chapman Physical Anhedonia Scale scores. An interaction analysis identified the neural correlates of anhedonia specific to schizophrenia.

Results

We found that anhedonia severity in both groups was inversely correlated with the activity of a limited number of emotion-related regions, including the medial prefrontal cortex. The orbitofrontal cortex and putamen/ventral striatum activity was negatively correlated with anhedonia severity in people with schizophrenia only.

Conclusions

The data first suggest that anhedonia severity is linked to a poor modulation of emotional/attentional brain regions during the processing of hedonic information. The link between anhedonia and the activity of the ventral striatum and orbitofrontal cortex found in schizophrenia could reflect the specific impairment of indirect factors, such as reward anticipation deficits, that influence the measurement of anhedonia severity through self-report questionnaires.     

Depression and cognitive deficits in geriatric schizophrenia

Objective

Past reports have found patients with comorbid depression and schizophrenia spectrum disorders exhibit greater deficits in memory and attention compared to schizophrenia spectrum disorder patients without depressive symptoms. However, in contrast to younger schizophrenia patients, the few past studies using cognitive screens to examine the relationship between depression and cognition in inpatient geriatric schizophrenia have found that depressive symptomatology was associated with relatively enhanced cognitive performance. In the current study we examined the relationship between depressive symptoms and cognitive deficits in geriatric schizophrenia spectrum disorder patients (n = 71; mean age = 63.7) on an acute psychiatric inpatient service.

Method

Patients completed a battery of cognitive tests assessing memory, attention and global cognition. Symptom severity was assessed via the PANSS and Calgary Depression Scale for Schizophrenia.

Results

Results revealed that geriatric patients' depression severity predicted enhancement of their attentional and verbal memory performance. Patients' global cognitive functioning and adaptive functioning were not associated with their depression severity.

Conclusion

Contrary to patterns typically seen in younger patients and non-patient groups, increasing depression severity is associated with enhancement of memory and attention in geriatric schizophrenia spectrum disorder patients. Also, diverging from younger samples, depression severity was unassociated with patients adaptive and global cognitive functioning.     

Perceptual organization and visual search processes during target detection task performance in schizophrenia, as revealed by fMRI

Background

Past studies of perceptual organization in schizophrenia have demonstrated impairments binding fragmented stimulus components into unified representations. ERP and fMRI data indicate that even under conditions of adequate behavioral task performance, significant and meaningful changes in cortical and subcortical activation are present. Here, we examined, using fMRI, activation differences on a visual task wherein feature grouping was a precursor to the formation of distinct groups in the service of target location and identification.

Method

Fourteen schizophrenia patients and 16 healthy controls completed a target detection task with 2 conditions: one in which target-distractor grouping facilitates detection (the Isolated condition) and one in which it hinders detection (the Embedded condition). Stimuli were blocked by condition. Accuracy and RT data were obtained in addition to fMRI data.

Results

Patients and controls did not differ significantly in accuracy or RT in either condition. Within this context, controls demonstrated greater recruitment of brain regions involved in visual-spatial processing, and the groups differed in activity in areas known to support visual search, visual analysis, decision making and response generation.

Conclusion

These findings are consistent with past data indicating reduced processing of stimulus organization, and the subsequent use of inefficient visual search strategies, even under conditions when behavioral performance is at a high level and matches that of healthy controls.     

Do the obsessive-compulsive symptoms have an effect in schizophrenia?

Objective

Schizophrenia presents with different symptom domains and functionality during its course. Obsessive-compulsive (OC) symptoms in schizophrenia have many themes to be clarified. Our aim was to compare schizophrenia patients with and without OC symptoms in terms of symptom domains, cognitive functions, and quality of life.

Method

Sixty-two patients who met schizophrenia diagnosis were assessed with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition consecutively over a period of 12 months in the setting of an outpatient clinic at medical university hospital. Yale-Brown Obsessive-Compulsive Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, and neuropsychologic tests were used. Quality of life was assessed with Quality of Life Scale for Patients with Schizophrenia.

Results

Obsessive-compulsive symptoms along with schizophrenia were present in a considerable number in our sample (35.5%). Level of psychotic symptoms was more severe and quality of life was lower in schizophrenia patients with OC symptoms. A positive correlation was found between obsessions and delusions. Moreover, there was a positive correlation between compulsions and total Scale for the Assessment of Positive Symptoms score and bizarre behaviors subscore. There was no difference between the 2 groups regarding neurocognitive functions. The level of quality of life of schizophrenic patients with OC symptoms was lower. Besides, no correlation was found between OC symptoms and neurocognition and quality of life.

Conclusions

The findings of this study indicate that schizophrenia patients with OC symptoms had severe psychotic symptoms with a distinctive clinical picture including good neurocognition but poor functioning.     

Differential brain activation during facial emotion discrimination in first-episode schizophrenia

Background

Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms.

Methods

Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data.

Results

Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus.

Conclusions

First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.     

Executive control in chronic schizophrenia: A perspective from manual stimulus-response compatibility task performance

Background

Antisaccade deficits are a well-documented pathophysiological characteristic in schizophrenia. However, it is yet unclear whether these findings reflect a specific oculomotor deficit, general psychomotor impairment or disturbance in executive control mechanisms.

Methods

Performance in a manual stimulus-response compatibility (SRC) task and a neuropsychological test-battery covering different cognitive and motor domains were obtained in 28 patients with chronic schizophrenia. It was compared with a normative cohort of healthy subjects and validated by comparison with a sub-sample of that cohort consisting of 28 age, gender and education matched controls.

Results

Patients showed significantly worse performance than controls in tests requiring maintenance or manipulating of multiple components but were unimpaired in simple motor, memory or executive tasks. In the SRC task patients had a significantly worse performance in the congruent condition and also a significantly higher increase in error rate from the congruent to the incongruent condition. There were, however, neither a group difference nor a group-by-condition interaction with respect to reaction times.

Interpretation

: Our results provide evidence against an isolated oculomotor deficit but also against an undifferentiated psychomotor dysfunction in chronic schizophrenia. Rather, in synopsis with previous reports on antisaccade performance, it becomes evident that the degree of impairment follows closely the amount of executive control required in a task, which in turn may relate to dysfunctional top-down bias of the prefrontal cortex arising from unstable task instructions.     

L’enfance des schizophrènes : revue de la littérature

Introduction

Pre-morbid antecedents in schizophrenia have been studied for some time now more particularly as potential markers of vulnerability. What are the tell-tale signs in some of the patient's childhood? The authors suggest a non-exhaustive review of the literature on this subject.

Method

The authors reviewed the literature (English and French) of prospective and retrospective studies.

Results

Many fields appear to be impaired during the childhood of some schizophrenic patients, fields such as: developmental abnormalities, speech impairments, social interactions, behaviour, cognitive functioning. The authors also noticed the presence of neurological soft signs and para-clinical abnormalities.

Discussion

The authors suggest a critical and synthetic review of existing data: what can be retained of this data? The authors also discuss the evolution of these signs and their interaction with the evolution of the disease itself.

Conclusion

Many of these signs were noticed in several children who later developed schizophrenia. For many authors, the more important these signs are, the more severe the disease will be. These pre-morbid antecedents give rise to theoretical questions and open perspectives concerning an early diagnosis of schizophrenia.     

Reduced prepulse inhibition as an early vulnerability marker of the psychosis prodrome in adolescence

Background

The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing and nature of these changes have not been established. The aim of the present study was to determine whether three “classic” neurophysiological markers of schizophrenia are also characteristic of young adolescents (12-18 years) at ultra-high risk for psychosis (UHR).

Methods

63 young UHR individuals and 68 typically developing, age-, sex- and IQ-matched controls were recruited for neurophysiological assessment. Data for P50 suppression, prepulse inhibition (PPI) and smooth pursuit eye movements (SPEM) were gathered and compared.

Results

UHR individuals showed reduced PPI compared to controls, which became more pronounced when controls were directly compared to medication-naive UHR individuals (N = 39). There were no group differences in P50 or SPEM measures.

Conclusions

These results suggest that PPI is a relatively early vulnerability marker, while changes in other neurophysiological measures may only be detected or affected later during the illness course. Antipsychotic and antidepressant medication may aid in elevating PPI levels and potentially have a neuroprotective effect.     

Altered associative learning and emotional decision making in fibromyalgia

Objective

The present study examines the possibility that a chronic pain condition, such as fibromyalgia, was associated with deficits in decision making and associative learning.

Methods

Fifteen patients with fibromyalgia (aged 42-59 years) and 15 healthy controls (aged 39-61 years) participated in the experiment. Subjects completed anxiety (STAI) and depression (BDI) questionnaires, as well as standardized neuropsychological tests (Stroop and WAIS subscales). In addition, an emotional decision-making task (Iowa Gambling Task) and a conditional associative learning task (CALT) were administered to all participants.

Results

Results indicated that fibromyalgia had a poorer performance than healthy controls in both tasks, showing more perseveration errors in the learning task, and more disadvantageous decisions, as well as a more random behavior in the gambling task. Moreover, we observed that poor performance on the associative learning task was mediated by depression, whereas performance on the gambling task was not influenced by depression. No group differences were found on the standardized neuropsychological tests.

Conclusion

These findings indicate that pain and depressive symptoms in fibromyalgia might lead to significant deficits in emotionally charged cognitive tasks. Furthermore, it suggests that chronic pain might impose a high cost on executive control, undermining mainly affective processes involved in learning, memory, attention, and decision-making.     

Hippocampal volume in borderline personality disorder with and without comorbid posttraumatic stress disorder: A meta-analysis

Background

Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients.

Methods

In order to investigate the degree to which comorbid posttraumatic stress disorder (PTSD) could account for reduction in hippocampal volume in these patients, we conducted a systematic review and meta-analysis of studies that compared hippocampal volume in BPD patients with and without PTSD relative to healthy controls.

Results

Seven articles, involving 124 patients and 147 controls, were included. We found a statistically significant reduction for the left and right hippocampus. Data from the four studies that discriminated BPD patients with and without PTSD indicate that hippocampal volumes were reduced bilaterally in BPD patients with PTSD, relative to healthy controls, but that results were mixed for BPD patients without PTSD, relative to healthy controls.

Conclusions

Results from this meta-analysis suggest that hippocampal volumes are reduced in patients with BPD, relative to healthy controls, but particularly in cases in which patients are diagnosed with comorbid PTSD.     

A polymorphism of the ABCA1 gene confers susceptibility to schizophrenia and related brain changes

Objective

The ATP-binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux through the transfer of cholesterol from the inner to the outer layer of the cell membrane and regulates extracellular cholesterol levels in the central nervous system. Several lines of evidence have indicated lipid and myelin abnormalities in schizophrenia.

Method

Initially, we examined the possible association of the polymorphisms of the ABCA1 gene (ABCA1) with susceptibility to schizophrenia in 506 patients with schizophrenia (DSM-IV) and 941 controls. The observed association was then subject to a replication analysis in an independent sample of 511 patients and 539 controls. We further examined the possible effect of the risk allele on gray matter volume assessed with magnetic resonance imaging (MRI) in 86 patients with schizophrenia (49 males) and 139 healthy controls (47 males).

Results

In the initial association study, the 1587 K allele (rs2230808) was significantly more common in male patients with schizophrenia than in male controls. Although such a significant difference was not observed in the second sample alone, the increased frequency of the 1587 K allele in male patients remained to be significant in the combined male sample of 556 patients and 594 controls. Male schizophrenia patients carrying the 1587 K allele had a smaller amount of gray matter volume than those who did not carry the allele.

Conclusion

Our data suggest a male-specific association of the 1587 K allele of ABCA1 with susceptibility to schizophrenia and smaller gray matter volume in schizophrenia.     

The impact of the social network, stigma and empowerment on the quality of life in patients with schizophrenia

Objective

The quality of life (QOL) of patients with schizophrenia has been found to be positively correlated with the social network and empowerment, and negatively correlated with stigma and depression. However, little is known about the way these variables impact on the QOL. The study aims to test the hypothesis that the social network, stigma and empowerment directly and indirectly by contributing to depression influence the QOL in patients with schizophrenia and schizoaffective disorders.

Method

Data were collected on demographic and clinical variables, internalized stigma, perceived devaluation and discrimination, empowerment, control convictions, depression and QOL. Structural equation modelling (SEM) was applied to examine the impact of the above-mentioned constructs on QOL.

Results

The influences of the social network, stigma, empowerment and depression on QOL were supported by the SEM. A poor social network contributed to a lack of empowerment and stigma, which resulted in depression and, in turn, in poor QOL. Interestingly, however, the social network and stigma did not show a direct effect on QOL.

Conclusion

Following a recovery approach in mental health services by focusing on the improvement of the social network, stigma reduction and especially on the development of personal strength has the potential to reduce depression in patients with psychosis and improving their QOL.     

Internally vs. externally triggered movements in patients with major depression

Background

Psychomotor retardation is a prominent clinical feature of major depression. While several studies investigated these deficits, differences between internally and externally triggered response selection and initiation are less well understood. In the current study, we delineate internally vs. externally driven response selection and initiation in depression and their relation to basic psychomotor functioning.

Methods

20 inpatients diagnosed with a (unipolar) major depression and 20 closely matched healthy controls performed a computerized motor paradigm assessing differences between internally and externally cued movements. Psychomotor performance and basic memory functions were assessed using a neuropsychological test-battery. To examine within group homogeneity a multivariate clustering approach was applied.

Results

Patients featured a global slowing of internally and externally cued response selection compared to controls, as well as impairments in basic psychomotor functioning. Yet, basic motor speed was preserved. Furthermore, patients were more severely impaired when movements involved internal response selection. The data-driven clustering revealed two patient subgroups, which both showed psychomotor disturbances, while only one featured slowing of response selection.

Interpretation

The results suggest a differential rather than a global psychomotor slowing in major depression with specific impairments of visuospatial and attentional processing as cognitive aspects of psychomotor functioning. As found for depression, in Parkinson's disease internally cued movements are more severely affected than externally cued reactions. Both may therefore be caused by dopaminergic deregulation due to frontostriatal deficits. Finally, multivariate clustering of behavioral data may be a promising future approach to identify subtypes of psychomotor or cognitive disturbances in different patient populations.     

A family history study of intermittent explosive disorder

Background

Intermittent Explosive Disorder (IED) is newly appreciated as a commonly occurring disorder of impulsive aggression. Since aggression and impulsivity are under genetic influence, IED may be familial.

Methods

Blinded and controlled family history study of IED and co-morbid conditions in an outpatient clinical research center for impulsive aggression. The subjects were first-degree relatives of individuals who did and did not meet criteria for IED by DSM-IV and Research Criteria.

Results

Elevated Morbid Risk of IED was observed in relatives of IED Probands compared with relatives of Non-IED Probands. This familial signal of IED was not affected by comorbidity in the IED Probands of comorbidity in the relatives of the IED Probands.

Conclusions

IED, as defined by research criteria, appears to be familial and may not be an artifact of other co-morbid conditions.