Exploring electrophysiological markers of auditory predictive processes and pathological ageing in adults with Down's syndrome.

Down's syndrome is associated with pathological ageing and a propensity for early-onset Alzheimer's disease. The early symptoms of dementia in people with Down's syndrome may reflect frontal lobe vulnerability to amyloid deposition. Auditory predictive processes rely on the bilateral auditory cortices with the recruitment of frontal cortices and appear to be impaired in pathologies characterized by compromised frontal lobe. Hence, auditory predictive processes were investigated to assess Down's syndrome pathology and its relationship with pathological ageing. An auditory electroencephalography (EEG) global-local paradigm was presented to the participants, in which oddball stimuli could either violate local or higher level global rules. We characterised predictive processes in individuals with Down's syndrome and their relationship with pathological ageing, with a focus on the EEG event-related potential called Mismatch Negativity (MMN) and the P300. In Down's syndrome, we also evaluated the EEG components as predictor of cognitive decline 1 year later. We found that predictive processes of detection of auditory violations are overall preserved in Down's syndrome but also that the amplitude of the MMN to local deviancies decreases with age. However, the 1-year follow-up of Down's syndrome found that none of the ERPs measures predicted subsequent cognitive decline. The present study provides a novel characterization of electrophysiological markers of local and global predictive processes in Down's syndrome.

Long-term cognitive outcome in adult survivors of an early childhood posterior fossa brain tumour.

PURPOSE: Posterior fossa brain tumours (PFT) and their treatment in young children are often associated with subsequent cognitive impairment. However, reported follow-up periods rarely exceed 10 years. This study reports very long-term cognitive consequences of surviving an early childhood PFT. METHODS: 62 adult survivors of a PFT, ascertained from a national register, diagnosed before 5 years of age, and a sibling control, received a single IQ assessment an average of 32 years (range 18-53) after initial diagnosis, using the Weschler Abbreviated Scale of Intelligence. Regression models were fitted to survivor-sibling pair differences on verbal and performance IQ (VIQ and PIQ) scores to investigate whether increasing time between PFT diagnosis and follow-up IQ assessment contributed to survivor-sibling IQ differences. RESULTS: At follow-up, survivors had, on average, VIQ 15 points and PIQ 19 points lower than their siblings. There was no significant effect of time since diagnosis on survivor-sibling VIQ difference. Survivors who received radiotherapy showed no significant effect of time since diagnosis on survivor-sibling PIQ difference. Survivors who did not receive radiotherapy demonstrated a trend for it to reduce. CONCLUSIONS: VIQ and PIQ deficits persist in adulthood, suggesting the effect of a fixed injury imposing on cognitive development, rather than an ongoing pathological process. IMPLICATIONS FOR CANCER SURVIVORS: The findings will help parents and others supporting survivors of an early life PFT to identify and plan for possible cognitive outcomes, and highlight the importance of early interventions to optimize cognitive function during the developmental period.

How can transition to adult care be best orchestrated for adolescents with epilepsy?

Objective evidence is limited for the value of transition programs for youth with chronic illness moving from pediatric to adult care; however, such programs intuitively "make sense". We describe the strengths and weaknesses of a variety of transition programs from around the world for adolescents with epilepsy. Consequences of poorly organized transition beyond suboptimal seizure control may include an increased risk of sudden unexpected death in epilepsy (SUDEP), poor psychological and social outcome, and inadequate management of comorbidities. The content of transition programs for those with normal intelligence differs from those with intellectual disability, but both groups may benefit from an emphasis on sporting activities. Concerns that may interfere with optimal transition include lack of nursing or social work services, limited numbers of adult neurologists/epileptologists confident in the treatment of complex pediatric epilepsy problems, institutional financial support, and time constraints for pediatric and adult physicians who treat epilepsy and the provision of multidisciplinary care. Successful programs eventually need to rely on a several adult physicians, nurses, and other key healthcare providers and use novel approaches to complex care. More research is needed to document the value and effectiveness of transition programs for youth with epilepsy to persuade institutions and healthcare professionals to support these ventures.

The Dysexecutive Questionnaire Revised (DEX-R): An extended measure of everyday dysexecutive problems after acquired brain injury.

The Dysexecutive Questionnaire (DEX) is a tool for measuring everyday problems experienced with the dysexecutive syndrome. This study investigated the psychometric properties of a revised version of the measure (DEX-R), a comprehensive tool, grounded in current theoretical conceptualisations of frontal lobe function and dysexecutive problems. The aim was to improve measurement of dysexecutive problems following acquired brain injury (ABI). Responses to the DEX-R were collected from 136 men and women who had experienced an ABI (the majority of whom had experienced a stroke or subarachnoid haemorrhage) and where possible, one of their carers or family members (n = 71), who acted as an informant. Rasch analysis techniques were employed to explore the psychometric properties of four newly developed, theoretically distinct subscales based on Stuss model of frontal lobe function and to evaluate the comparative validity and reliability of self and informant ratings of these four subscales. The newly developed subscales were well targeted to the range of dysexecutive problems reported by the current sample and each displayed a good level of internal validity. Both self- and independent-ratings were found to be performing reliably as outcome measures for at least a group-level. This new version of the tool could help guide selection of interventions for different types of dysexecutive problems and provide accurate measurement in neurorehabilitation services.

"Sometimes, it just stops me from doing anything": A qualitative exploration of epilepsy management in people with intellectual disabilities and their carers.

PURPOSE: Epilepsy affects 1 in 5 people with an intellectual disability (ID), but little is known about their experiences of living with epilepsy. A qualitative study was conducted to investigate the impact and management of epilepsy in people with ID. MATERIALS AND METHODS: People with epilepsy and ID and their carers were invited to take part in semi-structured interviews. Eleven participants with ID and their carers were interviewed together, one participant with ID and their carer were interviewed separately, two interviews took place with the participant with ID only, and one interview took place with the carer only. The interviews were transcribed verbatim, coded, and analyzed thematically (dual independent coding for 30% of the transcripts). RESULTS: Three themes emerged (participant characteristics, living with epilepsy, epilepsy management and information needs) which indicated the following: 1) diversity regarding health profiles, communication abilities, severity of epilepsy, perceived control of epilepsy, and support needs; 2) a reduction in severity and frequency of seizures for a sizeable proportion of participants through antiepileptic drugs; 3) the lifelong impact of epilepsy and related seizures on participants' activities and quality of life; 4) the perceived burden of epilepsy and difficulty managing the condition for a large proportion of participants; 5) high levels of satisfaction with epilepsy-related services and care; and 6) an overall lack of written accessible information about epilepsy. CONCLUSIONS: This study has highlighted a significant impact of epilepsy and related seizures on the daily lives and quality of life of people with ID. Although a sizeable proportion of participants and their carers considered their epilepsy to be well controlled, the majority reported difficulties managing epilepsy and minimizing its impact on their wellbeing. Excluding care staff and the support provided by epilepsy clinics, the participants had not accessed any adapted self-management or information resources about epilepsy.

A method for identifying associations between seizures and possible trigger events in adults with intellectual disability.

OBJECTIVES: Precipitants of seizures are often reported by patients and carers, but the accuracy of these claims remains unknown. Focusing on epilepsy in people with intellectual disability (ID), the aims of this work were to (1) identify a set of methods for assessing the validity of reported seizure triggers in individual patients; and (2) undertake an initial assessment of the ease of implementation and acceptability of the method by applying it to a series of cases. METHODS: Data collection materials (developed with carer involvement) consisted primarily of carer diaries of seizure and trigger occurrences. Statistical analysis of diary data was using the self-controlled case series method. Unlike previously used methods, the analysis method included a means of choosing the time window, following trigger exposure, during which changes in seizure likelihood are to be assessed. RESULTS: The method developed was trialed in five adults with ID and epilepsy, who had a range of ID severities and living circumstances. Examples of the application of the method in two of the five cases are presented for illustrative purposes. The method was acceptable to participants and most aspects successfully implemented. SIGNIFICANCE: This method may be useful for clinicians and researchers wishing to investigate possible triggers in individual patients with epilepsy and ID. It also supports the identification of a statistically defined time window following exposure to a precipitant, during which the risk of developing a seizure is increased. The identification of such a window has value not just in contributing to clinical management, but also in guiding future work into the mechanisms of seizure precipitation.

Autistic characteristics in adults with epilepsy and perceived seizure activity.

UNLABELLED: The prevalence of autism spectrum disorders in epilepsy is approximately 15%-47%, with previous research by Wakeford and colleagues reporting higher autistic traits in adults with epilepsy. The aim of this study was to investigate autistic characteristics and their relationship to having seizures by employing two behavioral assessments in two samples: adults with epilepsy and controls. METHOD: The study employed the Social Responsiveness Scale - Shortened (SRS-S) (patients with epilepsy (n=76), control (n=19)) and the brief Repetitive Behavior Scale - Revised (RBS-R) (patients with epilepsy (n=47), control (n=21)). This study employed a unique method to quantify the extent to which autistic characteristics are related to perceived mild seizure activity. Adults with epilepsy were instructed to rate their usual behavior on each assessment and, at the same time, rate their behavior again when they perceived that they were having mild seizure activity. RESULTS: Significantly higher SRS-S scores were related to having a diagnosis of epilepsy and were perceived by adults with epilepsy to increase during mild seizure activity. These scores positively correlated with antiepileptic drug control. No difference was found for RBS-R scores in adults with epilepsy compared with controls. CONCLUSION: Together, these results suggest that adults with epilepsy have higher autistic characteristics measured by the social responsiveness scale, while sameness behaviors remain unimpaired. The autistic characteristics measured by the social responsiveness scale were reported by adults with epilepsy to be more severe during their mild seizure activity.

Measuring coping style following acquired brain injury: a modification of the Coping Inventory for Stressful Situations Using Rasch analysis.

OBJECTIVE: The importance of coping style factors in the process of emotional adjustment following acquired brain injury (ABI) has been gaining increased attention. To assess ways of coping with distress accurately, clear conceptual definitions and measurement precision is vital. The purpose of this study was to investigate the psychometric properties of a well-known measure of coping, the Coping Inventory for Stressful Situations (CISS), for people who have experienced an ABI; and to modify the CISS, where necessary, to create a more reliable and valid measurement tool for this clinical group. METHODS: Psychometric properties were investigated using Rasch analysis of responses from a sample of adults with ABI (n = 207). The internal consistency reliability and construct validity of the scale were examined. RESULTS: All originally proposed subscales were not valid or reliable and, as such, were incapable of interval-level measurement within this sample - Task: χ(2) (32, N = 207) = 105.1, p < .001; Emotion: χ(2) (32, N = 204) = 121.9, p < .001; Avoidance: χ(2) (32, N = 207) = 66.7, p < .001. Three valid and reliable subscales were derived measuring emotion-, task-, and avoidance-oriented coping styles by removing items that provided the most unreliable information and exploring fit to the Rasch model. CONCLUSIONS: The original version of the CISS may not be a valid and reliable measure of coping style following ABI. Modified subscales of the three distinct coping domains have been proposed that would help to improve measurement of coping style following ABI in future research and clinical practice. PRACTITIONER POINTS: How people cope with difficulties following an ABI has been shown to impact upon emotional outcomes and functional recovery. The original version of the CISS was found to be an imprecise measure of coping following ABI. A modified version of the CISS was found to be a valid and reliable measure of three styles of coping (task-focused, emotion-focused, and avoidance-focused) that conforms to the properties of interval-level measurement as represented by the Rasch model. This structure is in keeping with previous theoretical models of coping. We advise caution about including items (1, 6, 7, 22, 24, 28, 29, 33, 34, and 46) that were found to diverge from the expectations of the Rasch measurement model in total subscale scores for measuring change in coping style. A conversion table for the three modified subscales is included in this paper to convert total raw scores into Rasch transformed logit values. Identifying strengths and weaknesses in coping style could be a means of guiding psychological intervention to promote good recovery following ABI. The sample included mainly people who had experienced non-traumatic brain injuries (e.g., a stroke). This research could be extended to include broader sample of people with differing brain injury aetiologies and neurological disorders.

Why do seizures occur when they do? Situations perceived to be associated with increased or decreased seizure likelihood in people with epilepsy and intellectual disability.

Seizure precipitants are commonly reported in the general population of people with epilepsy. However, there has been little research in this area in people with epilepsy and intellectual disability (ID). We conducted a survey of the situations associated with increased or decreased seizure likelihood in this population. The aim of the research was to identify situations of increased seizure likelihood (SISLs) and situations of decreased seizure likelihood (SDSLs) reported by carers of people with an ID and epilepsy. Three study groups were investigated: two groups comprising individuals with ID associated with a specific genetic diagnosis - Rett syndrome or fragile X syndrome - and one group consisting of individuals with a range of other etiologies. Responses relating to 100 people were received: 44 relating to people with Rett syndrome, 25 to people with fragile X syndrome, and 31 to people whose ID had some other etiologies. Ninety-eight percent of the respondents reported at least one SISL, and 60% reported at least one SDSL. Having more seizure types and greater seizure frequency were associated with a higher number of SISLs reported. The most commonly reported SISLs and SDSLs for each of the three groups are presented. The most common SISL overall was illness, which was reported as an SISL by 71% of the respondents. There was less consensus with regard to SDSLs. These findings provide a greater understanding of when seizures occur in those with ID and epilepsy, with possible implications for adjunctive behavioral management of seizures in those with treatment-refractory epilepsy.

Autistic characteristics in adults with epilepsy.

INTRODUCTION: The reported prevalence of autism spectrum disorders in people with epilepsy ranges from 15% to 47%. Despite the high comorbidity, there has been a lack of systematic studies of autistic characteristics in epilepsy. Little is known about the relationship of epilepsy to the core characteristics of autism. The aim of this research was to measure autistic traits and characteristics in adults with epilepsy who do not have a diagnosis of any autism disorder. METHOD: We investigated autistic characteristics in adults with epilepsy and those without epilepsy employing the Autism Spectrum Quotient (group with epilepsy, n = 40; control group, n = 38) and systemizing and empathizing abilities employing the Intuitive Physics test and the Adult Eyes Task-Revised (group with epilepsy, n = 19; control group, n = 23). RESULTS: Significantly more autistic behavioral traits, as measured by the AQ, were related to having epilepsy, but intact systemizing and empathizing abilities in these adults suggest that, in adults with epilepsy, autism-like symptoms may be present in the absence of wider cognitive profiles characteristic of autism. CONCLUSION: Increased autistic characteristics found in adults with epilepsy without an ASD diagnosis suggest that epilepsy syndromes may incorporate behavioral aspects of autism in the absence of some of its core cognitive features.

Conceptual distinctions between reflex and nonreflex precipitated seizures in the epilepsies: a systematic review of definitions employed in the research literature.

Seizure precipitation is a defining characteristic of reflex seizures and epilepsies, but seizure precipitants are also commonly reported for patients with epilepsies not considered to be reflex in nature. This raises the questions of exactly how reflex and nonreflex epilepsies with seizure precipitants are defined, and how these concepts are differentiated from one another in current practice. In this systematic literature review, definitions of reflex seizures, reflex epilepsies, and precipitation in a nonreflex context were extracted from published primary research papers. Content analysis was applied to these definitions to identify their main features, allowing comparisons to be made between definitions of the different concepts. Results indicated that there was little consistency within definitions of a given term, and that although some differences in definition content were found between terms, it was evident that clear defining characteristics to differentiate them from one another were lacking. These findings are discussed in the context of current debates regarding classification of the reflex epilepsies and the extent to which the distinction between reflex and nonreflex epilepsies is a meaningful one. Suggestions are made for how clarity might be increased in ongoing research in this area.

Validating independent ratings of executive functioning following acquired brain injury using Rasch analysis.

Assessment of everyday problems with executive functioning following acquired brain injury (ABI) is greatly valued by neurorehabilitation services. Reliance on self-report measures alone is problematic within this client group who may experience difficulties with awareness and memory. The construct validity and reliability of independent ratings (i.e., ratings provided by a carer/relative) on the Dysexecutive Questionnaire (DEX-I) was explored in this study. Consistent with the results recently reported on the self-rated version of the DEX (DEX-S; Simblett & Bateman, 2011 ), Rasch analysis completed on 271 responses to the DEX-I revealed that the scale did not fit the Rasch model and did not meet the assumption of unidimensionality, that is, a single underlying construct could not be found for the DEX-I that would allow development of an interval-level measure as a whole. Subscales, based on theoretical conceptualisations of executive functioning (Stuss, 2007 ) previously suggested for the DEX-S, were able to demonstrate fit to the Rasch model and unidimensionality. Reliability of independent responses to these subscales in comparison to self-reported ratings is discussed. These results contribute to a greater understanding of how assessment of executive functioning can be improved.

An fMRI investigation of detection of semantic incongruities in autistic spectrum conditions.

The aim of this study was to investigate differences in the brain's haemodynamic response to semantically incongruent and congruent sentences in adults with an autistic spectrum condition (ASC) and a typically developing Control group. We used functional magnetic resonance imaging to measure regional variations in neural activity during detection of semantic incongruities within written sentences. Whilst the 12 controls showed a pattern of activity extending from posterior cingulate cortices bilaterally and the left occipitotemporal region to the left superior and inferior temporal lobes, right anterior cingulate and right inferior frontal gyrus, the 12 participants with an ASC presented a more spatially restricted activation pattern, including the left inferior frontal gyrus, left anterior cingulate cortex and right middle frontal gyrus. These results are coherent with the hypothesis that impaired integration of multiple neural networks in people with an ASC is related to previous observations that this group have difficulties in the use of context to predict the final word of sentences.

Causes of learning disability and epilepsy: a review.

PURPOSE OF REVIEW: Although the association between learning disability and epilepsy is well known, until relatively recently specific processes underlying this association were relatively poorly understood. However, scientific advances in molecular biology are starting to guide researchers towards descriptions of genetic and pathophysiological processes that may explain why syndromes of epilepsy and learning disability often co-exist. RECENT FINDINGS: This article will focus largely on three areas of advancing knowledge: insights gained from wider use of genome-wide array comparative genomic hybridization (aCGH), specific insights gained from detailed study of Rett syndrome and the role of abnormalities of astrocytic function in predisposing to both epilepsy and learning disability. SUMMARY: The enormous complexity of the biological underpinnings of the co-occurrence of epilepsy and learning disability are becoming apparent. In the future it is likely that research into therapeutic approaches will include, amongst other approaches, investigations of gene structure and expression, the role of astrocytes and the stability of dendritic spines.

Computerised cognitive behavioural therapy (cCBT): a possible treatment for mood disorders experienced by people with neurological conditions?

Mood disorders such as depression occur relatively often following the diagnosis of a range of neurological conditions. Recent studies reviewing the prevalence of depression amongst people with a neurological condition have shown that approximately one third report clinically significant levels of depression (Carson, Ringbauer, MacKenzie, Warlow, & Sharpe, 2000; Williams et al., 2003). In particular, people with a diagnosis of a cerebrovascular disorder or a neurological condition with additional cognitive impairments, have been found to be the most likely to report symptoms of depression (Williams et al., 2003). However, despite the evidence that a large proportion of people with neurological conditions experience mood disorders, there are currently limited resources available to treat them.

The effect of ambient sounds on decision-making and heart rate variability in autism.

LAY ABSTRACT: Many autistic people report difficulties making decisions during everyday tasks, such as shopping. To examine the effect of sounds on decision-making, we developed a supermarket task where people watched a film shown from the shopper's perspective and were asked to make decisions between different products. The task was divided into three sections and participants completed each section in a different auditory environment: (1) no sounds, (2) non-social sounds (e.g. fridges humming) and (3) social sounds (e.g. people talking). Thirty-eight autistic and 37 neurotypical adults took part. We measured decision-making by examining how long it took to make a decision and how consistent people were with their decisions. We also measured heart rate variability because this biological response provides a measure of anxiety. After the supermarket shopping task, participants told us in their own words about their experiences. Autistic participants said that they found the non-social and social sound conditions more difficult than the no sound condition, and autistic participants found the social sound condition more negative than neurotypical participants. However, decision-making and heart rate variability were similar for autistic and neurotypical participants across the sound conditions, suggesting that these measures may not have been sensitive enough to reflect the experiences the autistic participants reported. Further research should consider alternative measures to explore the experiences reported by autistic people to help us understand which specific aspects of the environment autistic people are sensitive to. This, in turn, may enable more specific and evidence-based autism-friendly changes to be made.

A survey of the teaching and assessment of undergraduate psychiatry in the medical schools of the United Kingdom and Ireland.

BACKGROUND: Individual medical schools currently decide on the content and delivery of their undergraduate psychiatry curriculum, so there is probably significant variation in the students' experience of the speciality during the medical course and in the extent to which they develop the appropriate skills and knowledge base. AIM: To ascertain how the teaching of undergraduate psychiatry differs across UK and Irish medical schools. METHODS: The educational lead for psychiatry at each medical school in the United Kingdom and Ireland completed a questionnaire providing factual information on the teaching structure, contents and assessment methods in their current psychiatry curriculum. RESULTS: Some aspects of the curriculum were consistent across the medical schools with other areas showing great variability. The course content was broadly similar but the assessment, length of experience and course structure differed. CONCLUSION: There are significant differences in how psychiatry is taught to undergraduate students in the United Kingdom and Ireland and although all the curricula are evaluated by the General Medical Council, further study is required to see if this has any effect on the levels of competency achieved.

Neuromodulation of autism spectrum disorders using vagal nerve stimulation.

Influential theories propose an important role for the autonomic nervous system in social behaviour and emotion regulation. Difficulties with these capabilities occur in autism spectrum disorders (ASD). Vagus nerve stimulation (VNS) is a neuromodulation technique that stimulates autonomic pathways by means of an electrode implanted around the left vagus nerve in the neck. It is a licenced treatment for epilepsy and depression. This study searches the literature for evidence of VNS effects on behaviour in ASD. A literature search was conducted by two independent reviewers using Embase, Medline, PsycInfo and Cochrane using relevant search terms following the principals of the PRISMA guidance. The search strategy utilised a combination of text words and thesaurus terms to retrieve records relating to autism/pervasive developmental disorder and vagus nerve stimulation. No limits were applied. Supplementary searches were carried out on trials registers, and using backwards and forwards citation searching. A predesigned inclusion and exclusion criteria was administered to the identified results. From the 242 results identified search strategy 11 were found to satisfy the full search criteria and used to discuss the hypothesis. Eight studies were case series and three case reports. There is some evidence that VNS, when performed for epilepsy, may improve behaviour in people with ASD. There are indications that this occurs independently of its effects on seizure frequency and mood, although more rigorous studies are required.

Transcutaneous vagus nerve stimulation (t-VNS): A novel effective treatment for temper outbursts in adults with Prader-Willi Syndrome indicated by results from a non-blind study.

Temper outbursts are a severe problem for people with Prader-Willi Syndrome (PWS). Previous reports indicate that vagus nerve stimulation (VNS) may reduce maladaptive behaviour in neurodevelopmental disorders, including PWS. We systematically investigated the effectiveness of transcutaneous VNS (t-VNS) in PWS. Using a non-blind single case repeat measures modified ABA design, with participants as their own controls, t-VNS was evaluated in five individuals with PWS [three males; age 22-41 (M = 26.8)]. After a baseline phase, participants received four-hours of t-VNS daily for 12 months, followed by one month of daily t-VNS for two-hours. The primary outcome measure was the mean number of behavioural outbursts per day. Secondary outcomes included findings from behavioural questionnaires and both qualitative and goal attainment interviews. Four of the five participants who completed the study exhibited a statistically significant reduction in number and severity of temper outbursts after approximately nine months of daily four-hour t-VNS. Subsequent two-hour daily t-VNS was associated with increased outbursts for all participants, two reaching significance. Questionnaire and interview data supported these findings, the latter indicating potential mechanisms of action. No serious safety issues were reported. t-VNS is an effective, novel and safe intervention for chronic temper outbursts in PWS. We propose these changes are mediated through vagal projections and their effects both centrally and on the functioning of the parasympathetic nervous system. These findings challenge our present biopsychosocial understanding of such behaviours suggesting that there is a single major mechanism that is modifiable using t-VNS. This intervention is potentially generalizable across other clinical groups. Future research should address the lack of a sham condition in this study along with the prevalence of high drop out rates, and the potential effects of different stimulation intensities, frequencies and pulse widths.

Clinical heterogeneity among people with high functioning autism spectrum conditions: evidence favouring a continuous severity gradient.

BACKGROUND: Autism Spectrum Conditions (ASCs) are characterized by a high degree of clinical heterogeneity, but the extent to which this variation represents a severity gradient versus discrete phenotypes is unclear. This issue has complicated genetic studies seeking to investigate the genetic basis of the high hereditability observed clinically in those with an ASC. The aim of this study was to examine the possible clustering of symptoms associated with ASCs to determine whether the observed distribution of symptom type and severity supported either a severity or a symptom subgroup model to account for the phenotypic variation observed within the ASCs. METHODS: We investigated the responses of a group of adults with higher functioning ASCs on the fifty clinical features examined in the Autism Spectrum Quotient, a screening questionnaire used in the diagnosis of higher functioning ASCs. In contrast to previous studies we have used this instrument with no a priori assumptions about any underlying factor structure of constituent items. The responses obtained were analyzed using complete linkage hierarchical cluster analysis. For the members of each cluster identified the mean score on each Autism Spectrum Quotient question was calculated. RESULTS: Autism Spectrum Quotient responses from a total of 333 individuals between the ages of 16.6 and 78.0 years were entered into the hierarchical cluster analysis. The four cluster solution was the one that generated the largest number of clusters that did not also include very small cluster sizes, defined as a membership comprising 10 individuals or fewer. Examination of these clusters demonstrated that they varied in total Autism Spectrum Quotient but that the profiles across the symptoms comprising the Autism Spectrum Quotient did not differ independently of this severity factor. CONCLUSION: These results are consistent with a unitary spectrum model, suggesting that the clinical heterogeneity observed in those with an autistic spectrum condition at the higher-IQ end of the spectrum is associated with a gradient in the overall severity of the ASC rather than with the presence of different specific symptom profiles in different individuals. The implications of this for genetic research are considered.