http://www.dspace.cam.ac.uk:80/handle/1810/227538 Sat, 18 May 2013 12:02:54 GMT 2013-05-18T12:02:54Z http://www.dspace.cam.ac.uk:80/handle/1810/241995 Title: Assessment of the impact of the scanner-related factors on brain morphometry analysis with Brainvisa Authors: Shokouhi, Mahsa; Barnes, Anna; Suckling, John; Moorhead, Thomas WJ; Brennan, David; Job, Dominic; Lymer, Katherine; Dazzan, Paola; Reis Marques, Tiago; MacKay, Clare; McKie, Shane; Williams, Steven CR; Lawrie, Stephen M; Deakin, Bill; Williams, Steve R; Condon, Barrie Abstract: Abstract Background Brain morphometry is extensively used in cross-sectional studies. However, the difference in the estimated values of the morphometric measures between patients and healthy subjects may be small and hence overshadowed by the scanner-related variability, especially with multicentre and longitudinal studies. It is important therefore to investigate the variability and reliability of morphometric measurements between different scanners and different sessions of the same scanner. Methods We assessed the variability and reliability for the grey matter, white matter, cerebrospinal fluid and cerebral hemisphere volumes as well as the global sulcal index, sulcal surface and mean geodesic depth using Brainvisa. We used datasets obtained across multiple MR scanners at 1.5 T and 3 T from the same groups of 13 and 11 healthy volunteers, respectively. For each morphometric measure, we conducted ANOVA analysis and verified whether the estimated values were significantly different across different scanners or different sessions of the same scanner. The between-centre and between-visit reliabilities were estimated from their contribution to the total variance, using a random-effects ANOVA model. To estimate the main processes responsible for low reliability, the results of brain segmentation were compared to those obtained using FAST within FSL. Results In a considerable number of cases, the main effects of both centre and visit factors were found to be significant. Moreover, both between-centre and between-visit reliabilities ranged from poor to excellent for most morphometric measures. A comparison between segmentation using Brainvisa and FAST revealed that FAST improved the reliabilities for most cases, suggesting that morphometry could benefit from improving the bias correction. However, the results were still significantly different across different scanners or different visits. Conclusions Our results confirm that for morphometry analysis with the current version of Brainvisa using data from multicentre or longitudinal studies, the scanner-related variability must be taken into account and where possible should be corrected for. We also suggest providing some flexibility to Brainvisa for a step-by-step analysis of the robustness of this package in terms of reproducibility of the results by allowing the bias corrected images to be imported from other packages and bias correction step be skipped, for example. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 21 Dec 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241995 2011-12-21T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241973 Title: Involvement of right STS in audio-visual integration for affective speech Authors: Hagan, Cindy Tue, 27 Mar 2012 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241973 2012-03-27T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241590 Title: Profiles of Family-focused Adverse Experiences through Childhood and Early Adolescence: The ROOTS Project, a community investigation of adolescent mental health Authors: Dunn, Valerie J; Abbott, Rosemary A; Croudace, Tim J; Wilkinson, Paul; Jones, Peter B; Herbert, Joe; Goodyer, Ian M Abstract: Abstract Background Adverse family experiences in early life are associated with subsequent psychopathology. This study adds to the growing body of work exploring the nature and associations between adverse experiences over the childhood years. Methods Primary carers of 1143 randomly recruited 14-year olds in Cambridgeshire and Suffolk, UK were interviewed using the Cambridge Early Experiences Interview (CAMEEI) to assess family-focused adversities. Adversities were recorded retrospectively in three time periods (early and later childhood and early adolescence). Latent Class Analysis (LCA) grouped individuals into adversity classes for each time period and longitudinally. Adolescents were interviewed to generate lifetime DSM-IV diagnoses using the K-SADS-PL. The associations between adversity class and diagnoses were explored. Results LCA generated a 4-class model for each time period and longitudinally. In early childhood 69% were allocated to a low adversity class; a moderate adversity class (19%) showed elevated rates of family loss, mild or moderate family discord, financial difficulties, maternal psychiatric illness and higher risk for paternal atypical parenting; a severe class (6%) experienced higher rates on all indicators and almost exclusively accounted for incidents of child abuse; a fourth class, characterised by atypical parenting from both parents, accounted for the remaining 7%. Class membership was fairly stable (~ 55%) over time with escape from any adversity by 14 years being uncommon. Compared to those in the low class, the odds ratio for reported psychopathology in adolescents in the severe class ranged from 8 for disruptive behaviour disorders through to 4.8 for depressions and 2.0 for anxiety disorders. Only in the low adversity class did significantly more females than males report psychopathology. Conclusions Family adversities in the early years occur as multiple rather than single experiences. Although some children escape adversity, for many this negative family environment persists over the first 15 years of life. Different profiles of family risk may be associated with specific mental disorders in young people. Sex differences in psychopathologies may be most pronounced in those exposed to low levels of family adversities. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 06 Jul 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241590 2011-07-06T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241192 Title: General and Specific Components of Depression and Anxiety in an Adolescent Population Authors: Brodbeck, Jeannette; Abbott, Rosemary A; Goodyer, Ian M; Croudace, Tim J Abstract: Abstract Background Depressive and anxiety symptoms often co-occur resulting in a debate about common and distinct features of depression and anxiety. Methods An exploratory factor analysis (EFA) and a bifactor modelling approach were used to separate a general distress continuum from more specific sub-domains of depression and anxiety in an adolescent community sample (n = 1159, age 14). The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale were used. Results A three-factor confirmatory factor analysis is reported which identified a) mood and social-cognitive symptoms of depression, b) worrying symptoms, and c) somatic and information-processing symptoms as distinct yet closely related constructs. Subsequent bifactor modelling supported a general distress factor which accounted for the communality of the depression and anxiety items. Specific factors for hopelessness-suicidal thoughts and restlessness-fatigue indicated distinct psychopathological constructs which account for unique information over and above the general distress factor. The general distress factor and the hopelessness-suicidal factor were more severe in females but the restlessness-fatigue factor worse in males. Measurement precision of the general distress factor was higher and spanned a wider range of the population than any of the three first-order factors. Conclusions The general distress factor provides the most reliable target for epidemiological analysis but specific factors may help to refine valid phenotype dimensions for aetiological research and assist in prognostic modelling of future psychiatric episodes. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 07 Dec 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241192 2011-12-07T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/239127 Title: Self-referential cognition and empathy in autism Authors: Lombardo, Michael V.; Barnes, Jennifer L.; Wheelwright, Sally J.; Baron-Cohen, Simon Abstract: Background. Individuals with autism spectrum conditions (ASC) have profound impairments in the interpersonal social domain, but it is unclear if individuals with ASC also have impairments in the intrapersonal self-referential domain. We aimed to evaluate across several well validated measures in both domains, whether both self-referential cognition and empathy are impaired in ASC and whether these two domains are related to each other. Methodology/Principal Findings. Thirty adults aged 19-45, with Asperger Syndrome or high-functioning autism and 30 age, sex, and IQ matched controls participated in the self-reference effect (SRE) paradigm. In the SRE paradigm, participants judged adjectives in relation to the self, a similar close other, a dissimilar non-close other, or for linguistic content. Recognition memory was later tested. After the SRE paradigm, several other complimentary self-referential cognitive measures were taken. Alexithymia and private self-consciousness were measured via self-report. Self-focused attention was measured on the Self-Focus Sentence Completion task. Empathy was measured with 3 self-report instruments and 1 performance measure of mentalizing (Eyes test). Self-reported autistic traits were also measured with the Autism Spectrum Quotient (AQ). Although individuals with ASC showed a significant SRE in memory, this bias was decreased compared to controls. Individuals with ASC also showed reduced memory for the self and a similar close other and also had concurrent impairments on measures of alexithymia, self-focused attention, and on all 4 empathy measures. Individual differences in self-referential cognition predicted mentalizing ability and self-reported autistic traits. More alexithymia and less self memory was predictive of larger mentalizing impairments and AQ scores regardless of diagnosis. In ASC, more self-focused attention is associated with better mentalizing ability and lower AQ scores, while in controls, more self-focused attention is associated with decreased mentalizing ability and higher AQ scores. Increasing private self-consciousness also predicted better mentalizing ability, but only for individuals with ASC. Conclusions/Significance. We conclude that individuals with ASC have broad impairments in both self-referential cognition and empathy. These two domains are also intrinsically linked and support predictions made by simulation theory. Our results also highlight a specific dysfunction in ASC within cortical midlines structures of the brain such as the medial prefrontal cortex. Mon, 01 Jan 2007 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/239127 2007-01-01T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238681 Title: Variation in the human Cannabinoid Receptor (CNR1) gene modulates gaze duration for happy faces Authors: Chakrabarti, Bhismadev; Baron-Cohen, Simon Abstract: Abstract Background From an early age, humans look longer at preferred stimuli and also typically look longer at facial expressions of emotion, particularly happy faces. Atypical gaze patterns towards social stimuli are common in autism spectrum conditions (ASC). However, it is unknown whether gaze fixation patterns have any genetic basis. In this study, we tested whether variations in the cannabinoid receptor 1 (CNR1) gene are associated with gaze duration towards happy faces. This gene was selected because CNR1 is a key component of the endocannabinoid system, which is involved in processing reward, and in our previous functional magnetic resonance imaging (fMRI) study, we found that variations in CNR1 modulate the striatal response to happy (but not disgust) faces. The striatum is involved in guiding gaze to rewarding aspects of a visual scene. We aimed to validate and extend this result in another sample using a different technique (gaze tracking). Methods A total of 30 volunteers (13 males and 17 females) from the general population observed dynamic emotional expressions on a screen while their eye movements were recorded. They were genotyped for the identical four single-nucleotide polymorphisms (SNPs) in the CNR1 gene tested in our earlier fMRI study. Results Two SNPs (rs806377 and rs806380) were associated with differential gaze duration for happy (but not disgust) faces. Importantly, the allelic groups associated with a greater striatal response to happy faces in the fMRI study were associated with longer gaze duration at happy faces. Conclusions These results suggest that CNR1 variations modulate the striatal function that underlies the perception of signals of social reward, such as happy faces. This suggests that CNR1 is a key element in the molecular architecture of perception of certain basic emotions. This may have implications for understanding neurodevelopmental conditions marked by atypical eye contact and facial emotion processing, such as ASC. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 28 Jun 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238681 2011-06-28T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238554 Title: Improving Mood with Psychoanalytic and Cognitive Therapies (IMPACT): A pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial Authors: Goodyer, Ian M; Tsancheva, Sonya; Byford, Sarah; Dubicka, Bernadka; Hill, Jonathan; Kelvin, Raphael; Reynolds, Shirley; Roberts, Christopher; Senior, Robert; Suckling, John; Wilkinson, Paul; Target, Mary; Fonagy, Peter Abstract: Abstract Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients. Trial Registration Current Controlled Trials ISRCTN83033550 Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 12 Jul 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238554 2011-07-12T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238514 Title: Scale-free statistics of neuronal assemblies predict learning performance Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Sun, 17 Jul 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238514 2011-07-17T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238101 Title: Brief cognitive assessment in a UK population sample - distributional properties and the relationship between the MMSE and an extended mental state examination Authors: Huppert, Felicia A; Cabelli, Sara; Matthews, Fiona E; MRC-CFAS Abstract: Abstract Background Despite the MMSE's known flaws, it is still used extensively as both a screening instrument for dementia and a population measure of cognitive ability. The aim of this paper is to provide data on the distribution of MMSE scores in a representative sample from the UK population and to compare it with an extended cognitive assessment (EMSE) which covers a wider range of cognitive domains and provides a wider range of difficulty levels. Methods The MMSE and the EMSE were administered to over 12,000 participants at the screening stage of the MRC Cognitive Function and Ageing Study (MRC CFAS). MRC CFAS is a multi-centre population-based study in England and Wales with respondents aged 65 years and older. Results Normative values on the MMSE and EMSE are presented by age group, sex and level of education. There are very large differences between age groups, with smaller differences seen between the sexes and by level of education. The EMSE extends the scores at the high end of the ability range, but is no better than the MMSE at differentiating between dementia and non-dementia. Conclusion Population-derived norms are valuable for comparing an individual's score to the score that would be expected among the general population, given the individual's specific demographic characteristics. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 03 May 2005 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238101 2005-05-03T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238099 Title: Hippocampal lesions facilitate instrumental learning with delayed reinforcement but induce impulsive choice in rats Authors: Cheung, Timothy H C; Cardinal, Rudolf N Abstract: Abstract Background Animals must frequently act to influence the world even when the reinforcing outcomes of their actions are delayed. Learning with action-outcome delays is a complex problem, and little is known of the neural mechanisms that bridge such delays. When outcomes are delayed, they may be attributed to (or associated with) the action that caused them, or mistakenly attributed to other stimuli, such as the environmental context. Consequently, animals that are poor at forming context-outcome associations might learn action-outcome associations better with delayed reinforcement than normal animals. The hippocampus contributes to the representation of environmental context, being required for aspects of contextual conditioning. We therefore hypothesized that animals with hippocampal lesions would be better than normal animals at learning to act on the basis of delayed reinforcement. We tested the ability of hippocampal-lesioned rats to learn a free-operant instrumental response using delayed reinforcement, and what is potentially a related ability – the ability to exhibit self-controlled choice, or to sacrifice an immediate, small reward in order to obtain a delayed but larger reward. Results Rats with sham or excitotoxic hippocampal lesions acquired an instrumental response with different delays (0, 10, or 20 s) between the response and reinforcer delivery. These delays retarded learning in normal rats. Hippocampal-lesioned rats responded slightly less than sham-operated controls in the absence of delays, but they became better at learning (relative to shams) as the delays increased; delays impaired learning less in hippocampal-lesioned rats than in shams. In contrast, lesioned rats exhibited impulsive choice, preferring an immediate, small reward to a delayed, larger reward, even though they preferred the large reward when it was not delayed. Conclusion These results support the view that the hippocampus hinders action-outcome learning with delayed outcomes, perhaps because it promotes the formation of context-outcome associations instead. However, although lesioned rats were better at learning with delayed reinforcement, they were worse at choosing it, suggesting that self-controlled choice and learning with delayed reinforcement tax different psychological processes. Thu, 12 May 2005 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238099 2005-05-12T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238061 Title: A randomised controlled trial investigating the effect of n-3 long-chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636] Authors: Dangour, Alan D; Clemens, Felicity; Elbourne, Diana; Fasey, Nicky; Fletcher, Astrid E; Hardy, Pollyanna; Holder, Graham E; Huppert, Felicia A; Knight, Rosemary; Letley, Louise; Richards, Marcus; Truesdale, Ann; Vickers, Madge; Uauy, Ricardo Abstract: Abstract The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK. To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70–79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain. The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 30 Aug 2006 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238061 2006-08-30T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237986 Title: Clinical heterogeneity among people with high functioning autism spectrum conditions: evidence favouring a continuous severity gradient Authors: Ring, Howard; Woodbury-Smith, Marc; Watson, Peter; Wheelwright, Sally; Baron-Cohen, Simon Abstract: Abstract 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. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 20 Feb 2008 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237986 2008-02-20T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237957 Title: Structural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis Authors: Ellison-Wright, Ian; Ellison-Wright, Zoe; Bullmore, Ed Abstract: Abstract Background The authors sought to map gray matter changes in Attention Deficit Hyperactivity Disorder (ADHD) using a novel technique incorporating neuro-imaging and genetic meta-analysis methods. Methods A systematic search was conducted for voxel-based structural magnetic resonance imaging studies of patients with ADHD (or with related disorders) in relation to comparison groups. The authors carried out meta-analyses of the co-ordinates of gray matter differences. For the meta-analyses they hybridised the standard method of Activation Likelihood Estimation (ALE) with the rank approach used in Genome Scan Meta-Analysis (GSMA). This system detects three-dimensional conjunctions of co-ordinates from multiple studies and permits the weighting of studies in relation to sample size. Results For gray matter decreases, there were 7 studies including a total of 114 patients with ADHD (or related disorders) and 143 comparison subjects. Meta-analysis of these studies identified a significant regional gray matter reduction in ADHD in the right putamen/globus pallidus region. Four studies reported gray matter increases in ADHD but no regional increase was identified by meta-analysis. Conclusion In ADHD there is gray matter reduction in the right putamen/globus pallidus region. This may be an anatomical marker for dysfunction in frontostriatal circuits mediating cognitive control. Right putamen lesions have been specifically associated with ADHD symptoms after closed head injuries in children. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Sun, 29 Jun 2008 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237957 2008-06-29T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237919 Title: Osteomalacia and vitamin D deficiency in a psychiatric rehabilitation unit: case report and survey Authors: Cardinal, Rudolf N; Gregory, Carol A Abstract: Abstract Background Vitamin D deficiency is common and predisposes to many serious diseases, yet often goes unrecognized. Findings We describe a case of severe vitamin D deficiency with osteomalacia in a patient resident in a psychiatric hospital for more than 35 years, and discuss causes and complications. We assayed the serum 25-hydroxyvitamin D levels of all patients under our care on one old-age psychiatry rehabilitation unit. Ten of twelve (83%) of patients had vitamin D deficiency, and 92% had suboptimal vitamin D levels. Vitamin D status was strongly predicted by dietary supplementation. Of those not on vitamin D supplements, 100% had vitamin D deficiency, with vitamin D levels significantly below those of historical controls. Age, sex, and duration of admission did not predict vitamin D status in this group. Conclusion We advocate vitamin D screening in all patients admitted to psychogeriatric units, and discuss treatment options given the current problems affecting high-dose vitamin D supply to the United Kingdom. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Fri, 08 May 2009 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237919 2009-05-08T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237863 Title: Molecular Autism: accelerating and integrating research into neurodevelopmental conditions Authors: Buxbaum, Joseph D; Baron-Cohen, Simon Abstract: AbstractWe are delighted to announce the launch of Molecular Autism - a new open-access journal published by BioMed Central. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Mon, 22 Feb 2010 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237863 2010-02-22T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237852 Title: Genetics in psychiatry: Common variant association studies Authors: Buxbaum, Joseph D; Baron-Cohen, Simon; Devlin, Bernie Abstract: Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 25 Mar 2010 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237852 2010-03-25T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237831 Title: Leaving care and mental health: outcomes for children in out-of-home care during the transition to adulthood Authors: Akister, Jane; Owens, Matt; Goodyer, Ian M Abstract: Abstract There were 59,500 Children in out-of-home care in England in 2008. Research into this population points to poor health and quality of life outcomes over the transition to adult independence. This undesirable outcome applies to mental health, education and employment. This lack of wellbeing for the individual is a burden for health and social care services, suggesting limitations in the current policy approaches regarding the transitional pathway from care to adult independence. Although the precise reasons for these poor outcomes are unclear long term outcomes from national birth cohorts suggest that mental health could be a key predictor for subsequent psychosocial adjustment. Researching the wellbeing of children in out-of-home care has proven difficult due to the range and complexity of the factors leading to being placed in care and the different methods used internationally for recording information. This paper delineates the estimated prevalence of mental health problems for adolescents in the care system, organisational factors, influencing service provision, and pathways through the transition from adolescence to independent young adult life. The extent to which being taken into care as a child moderates adult wellbeing outcomes remains unknown. Whether the care system enhances, reduces or has a null effect on wellbeing and specifically mental health cannot be determined from the current literature. Nonetheless a substantial proportion of young people display resilience and experience successful quality of life outcomes including mental capital. A current and retrospective study of young people transitioning to adult life is proposed to identify factors that have promoted successful outcomes and which would be used to inform policy developments and future longitudinal studies. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 11 May 2010 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237831 2010-05-11T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237818 Title: Defining the broader, medium and narrow autism phenotype among parents using the Autism Spectrum Quotient (AQ) Authors: Wheelwright, Sally; Auyeung, Bonnie; Allison, Carrie; Baron-Cohen, Simon Abstract: Abstract Background The Autism Spectrum Quotient (AQ) is a self-report questionnaire for quantifying autistic traits. This study tests whether the AQ can differentiate between parents of children with an autism spectrum condition (ASC) and control parents. In this paper, the use of the AQ to define the broader, medium and narrow autism phenotypes (BAP, MAP, NAP) is reported, and the proportion of parents with each phenotype is compared between the two groups. Methods A sample of 571 fathers and 1429 mothers of children with an ASC completed the AQ, along with 349 fathers and 658 mothers of developing typically children. Results Both mothers and fathers of the diagnosed children scored higher than the control parents on total AQ score and on four out of five of the subscales. Additionally, there were more parents of diagnosed children with a BAP, MAP or NAP. Conclusions The AQ provides an efficient method for quantifying where an individual lies along the dimension of autistic traits, and extends the notion of a broader phenotype among first-degree relatives of those with ASC. The AQ is likely to have many applications, including population and clinical screening, and stratification in genetic studies. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 16 Jun 2010 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237818 2010-06-16T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237815 Title: Foetal testosterone and autistic traits in 18 to 24-month-old children Authors: Auyeung, Bonnie; Taylor, Kevin; Hackett, Gerald; Baron-Cohen, Simon Abstract: Abstract Background Autism spectrum conditions have been characterised as an extreme presentation of certain male-typical psychological traits. In addition, several studies have established a link between prenatal exposure to testosterone and cognitive sex differences in later life, and one study found that foetal testosterone (FT) is positively correlated to autistic traits in 6 to 10 year-old children. In this study, we tested whether FT is positively correlated with autistic traits in toddlers aged 18-24 months. Methods Levels of FT were analysed in amniotic fluid and compared with autistic traits, measured using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in 129 typically developing toddlers aged between 18 and 24 months (mean ± SD 19.25 ± 1.52 months). Results Sex differences were observed in Q-CHAT scores, with boys scoring significantly higher (indicating more autistic traits) than girls. In addition, we confirmed a significant positive relationship between FT levels and autistic traits. Conclusions The current findings in children between 18 and 24 months of age are consistent with observations in older children showing a positive association between elevated FT levels and autistic traits. Given that sex steroid-related gene variations are associated with autistic traits in adults, this new finding suggests that the brain basis of autistic traits may reflect individual differences in prenatal androgens and androgen-related genes. The consistency of findings in early childhood, later childhood and adulthood suggests that this is a robust association. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Sun, 11 Jul 2010 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237815 2010-07-11T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/237671 Title: Improvement and decline of cognitive function in schizophrenia over one year: a longitudinal investigation using latent growth modelling. Authors: Barnett, Jennifer H; Croudace, Tim J; Jaycock, Sue; Blackwell, Candice; Hynes, Fiona; Sahakian, Barbara J; Joyce, Eileen M; Jones, Peter B Abstract: Abstract Background Long-term follow-up studies of people with schizophrenia report stability of cognitive performance; less is known about any shorter-term changes in cognitive function. Methods This longitudinal study aimed to establish whether there was stability, improvement or decline in memory and executive functions over four assessments undertaken prospectively in one year. Cognitive performance was assessed during randomized controlled trials of first- and second-generation antipsychotic medication. Analyses used a latent growth modeling approach, so that individuals who missed some testing occasions could be included and trajectories of cognitive change explored despite missing data. Results Over the year there was significant decline in spatial recognition but no change in pattern recognition or motor speed. Improvement was seen in planning and spatial working memory tasks; this may reflect improved strategy use with practice. There were significant individual differences in the initial level of performance on all tasks but not in rate of change; the latter may have been due to sample size limitations. Age, sex, premorbid IQ and drug class allocation explained significant variation in level of performance but could not predict change. Patients randomized to first-generation drugs improved more quickly than other groups on the planning task. Conclusion We conclude that cognitive change is present in schizophrenia but the magnitude of change is small when compared with the large differences in cognitive function that exist between patients. Analyses that retain patients who drop out of longitudinal studies, as well as those who complete testing protocols, are important to our understanding of cognition in schizophrenia. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 08 May 2007 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/237671 2007-05-08T23:00:00Z