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Khandaker G.M.,University of Cambridge | Khandaker G.M.,Cambridgeshire and Peterborough NHS Foundation Trust | Dibben C.R.M.,West Suffolk Hospital | Jones P.B.,University of Cambridge | Jones P.B.,Cambridgeshire and Peterborough NHS Foundation Trust
Obesity Reviews | Year: 2012

Maternal obesity in pregnancy has been linked with several adverse outcomes in offspring including schizophrenia. The rising prevalence of obesity may contribute to an increase in the number of schizophrenia cases in the near future; therefore, it warrants further exploration. We reviewed current evidence regarding maternal body mass index (BMI) in pregnancy and risk of schizophrenia in adult offspring. We searched PubMed and Embase databases and included studies that were based on large and representative population-based datasets. A qualitative review was undertaken due to heterogeneity between studies. Four studies with 305 cases of schizophrenia and 24,442 controls were included. Maternal obesity (pre-pregnant BMI over 29 or 30 compared with mothers with low or average BMI) was associated with two- to threefold increased risk of schizophrenia in the adult offspring in two birth cohorts. High maternal BMI at both early and late pregnancy also increased risk of schizophrenia in the offspring. Discrepant findings from one study could be attributable to sample characteristics and other factors. The area needs more research. Future studies should take into account obstetric complications, diabetes, maternal infections and immune responses that might potentially mediate this association. © 2011 International Association for the Study of Obesity.


Hackett M.L.,University of Sydney | Hackett M.L.,University of Central Lancashire | Kohler S.,Maastricht University | O'Brien J.T.,University of Cambridge | And 2 more authors.
The Lancet Neurology | Year: 2014

The most common neuropsychiatric outcomes of stroke are depression, anxiety, fatigue, and apathy, which each occur in at least 30% of patients and have substantial overlap of prevalence and symptoms. Emotional lability, personality changes, psychosis, and mania are less common but equally distressing symptoms that are also challenging to manage. The cause of these syndromes is not known, and there is no clear relation to location of brain lesion. There are important gaps in knowledge about how to manage these disorders, even for depression, which is the most studied syndrome. Further research is needed to identify causes and interventions to prevent and treat these disorders. © 2014 Elsevier Ltd.


Fornito A.,Monash University | Bullmore E.T.,Monash University | Bullmore E.T.,University of Cambridge | Bullmore E.T.,Glaxosmithkline | Bullmore E.T.,Cambridgeshire and Peterborough NHS Foundation Trust
European Neuropsychopharmacology | Year: 2015

In recent years, pathophysiological models of brain disorders have shifted from an emphasis on understanding pathology in specific brain regions to characterizing disturbances of interconnected neural systems. This shift has paralleled rapid advances in connectomics, a field concerned with comprehensively mapping the neural elements and inter-connections that constitute the brain. Magnetic resonance imaging (MRI) has played a central role in these efforts, as it allows relatively cost-effective in vivo assessment of the macro-scale architecture of brain network connectivity. In this paper, we provide a brief introduction to some of the basic concepts in the field and review how recent developments in imaging connectomics are yielding new insights into brain disease, with a particular focus on Alzheimer's disease and schizophrenia. Specifically, we consider how research into circuit-level, connectome-wide and topological changes is stimulating the development of new aetiopathological theories and biomarkers with potential for clinical translation. The findings highlight the advantage of conceptualizing brain disease as a result of disturbances in an interconnected complex system, rather than discrete pathology in isolated sub-sets of brain regions. © 2014 Elsevier B.V. and ECNP.


Lai M.-C.,University of Cambridge | Lai M.-C.,National Taiwan University | Lombardo M.V.,University of Cambridge | Lombardo M.V.,University of Cyprus | And 2 more authors.
The Lancet | Year: 2014

Autism is a set of heterogeneous neurodevelopmental conditions, characterised by early-onset difficulties in social communication and unusually restricted, repetitive behaviour and interests. The worldwide population prevalence is about 1%. Autism affects more male than female individuals, and comorbidity is common (>70% have concurrent conditions). Individuals with autism have atypical cognitive profiles, such as impaired social cognition and social perception, executive dysfunction, and atypical perceptual and information processing. These profiles are underpinned by atypical neural development at the systems level. Genetics has a key role in the aetiology of autism, in conjunction with developmentally early environmental factors. Large-effect rare mutations and small-effect common variants contribute to risk. Assessment needs to be multidisciplinary and developmental, and early detection is essential for early intervention. Early comprehensive and targeted behavioural interventions can improve social communication and reduce anxiety and aggression. Drugs can reduce comorbid symptoms, but do not directly improve social communication. Creation of a supportive environment that accepts and respects that the individual is different is crucial.


Illingworth J.L.,University of Cambridge | Ring H.,Cambridgeshire and Peterborough NHS Foundation Trust
Epilepsia | Year: 2013

Summary 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.© 2013 International League Against Epilepsy.


Vertes P.E.,University of Cambridge | Vertes P.E.,Cambridgeshire and Peterborough NHS Foundation Trust | Bullmore E.T.,University of Cambridge | Bullmore E.T.,Cambridgeshire and Peterborough NHS Foundation Trust | Bullmore E.T.,Glaxosmithkline
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2015

Background: We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis: We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions: We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. © 2014 The Authors.


Rubinov M.,University of Cambridge | Bullmore E.,University of Cambridge | Bullmore E.,Glaxosmithkline | Bullmore E.,Cambridgeshire and Peterborough NHS Foundation Trust
Dialogues in Clinical Neuroscience | Year: 2013

Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists ncreasingly postulate that schizophrenia is a disorder of brain network organization. In this article we iscuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence or disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence or network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray-and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia. © 2013, AICH.


Khandaker G.M.,University of Cambridge | Khandaker G.M.,Cambridgeshire and Peterborough NHS Foundation Trust | Zimbron J.,University of Cambridge | Zimbron J.,Cambridgeshire and Peterborough NHS Foundation Trust | And 3 more authors.
Psychological Medicine | Year: 2013

Background Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies. Method Electronic and manual searches and rigorous quality assessment yielded 21 studies that included an objective assessment of individual-level prenatal maternal infection and standardized psychotic diagnoses in adult offspring. Methodological differences between studies necessitated a descriptive review. Results Results for prenatal maternal non-specific bacterial, respiratory or genital and reproductive infection differed between studies, which reported up to a two- to fivefold increased risk of schizophrenia. Evidence for herpes simplex virus type 2 (HSV-2) and Toxoplasma gondii was mixed; some studies reported up to a doubling of schizophrenia risk. Prenatal HSV-1 or cytomegalovirus (CMV) infections were not associated with increased risk. Exposure to influenza or other infections during early pregnancy may be more harmful than later exposure. Increased proinflammatory cytokines during pregnancy were also associated with risk. Prenatal infection was associated with structural and functional brain abnormalities relevant to schizophrenia. Conclusions Prenatal exposure to a range of infections and inflammatory responses may be associated with risk of adult schizophrenia. Larger samples, mediation and animal models should be used to investigate whether there is a 'sensitive period' during development, and the effects of prenatal infections on neurodevelopment. Inclusion of genetic and immunological information should help to elucidate to what extent genetic vulnerability to schizophrenia may be explained by vulnerability to infection. Copyright © 2012 Cambridge University Press.


Zimbron J.,Cambridgeshire and Peterborough NHS Foundation Trust
Acta psychiatrica Scandinavica | Year: 2013

To compare clinical and sociodemographic characteristics previously associated with psychosis, between individuals at high-risk for psychosis (HR) and patients experiencing a first episode psychosis (FEP), to achieve a better understanding of factors associated with psychosis. Cross-sectional comparison of 30 individuals at HR with 30 age-gender matched FEP, presenting to an early intervention service for psychosis. Participants were followed-up for 2 years to establish the proportion of HR who made the transition into FEP. Both groups showed similar socio-clinical characteristics, including immigration status, employment history, marital status, family history of psychotic illness, self-harm and alcohol and drug use. The HR group had a lower level of education, higher burden of trauma, earlier onset of psychiatric symptoms and a longer delay in accessing specialised services. A younger onset of symptoms was associated with a longer delay in accessing services in both groups. After a 2 year follow-up, only three (10%) of the HR group made a transition into FEP. The similarities observed between individuals at HR and those with FEP suggest that known variables associated with psychosis may be equally prevalent in people at HR who do not develop a psychotic disorder. © 2012 John Wiley & Sons A/S.


Cassidy S.,University of Cambridge | Bradley P.,Cambridgeshire and Peterborough NHS Foundation Trust | Robinson J.,Cambridgeshire and Peterborough NHS Foundation Trust | Allison C.,University of Cambridge | And 3 more authors.
The Lancet Psychiatry | Year: 2014

Background: Asperger's syndrome in adulthood is frequently associated with depression, but few studies have explored the lifetime experience of self-reported suicidal ideation and suicide plans or attempts in this clinical group. We aimed to assess this prevalence in a clinical cohort of patients in the UK. Method: In a clinical cohort study, we undertook a retrospective analysis of clinical survey data from adults newly diagnosed with Asperger's syndrome at a specialist diagnostic clinic between Jan 23, 2004, and July 8, 2013, in England. Patients completed a self-report questionnaire before clinical assessment, recording lifetime experience of depression, suicidal ideation, and suicide plans or attempts, along with self-reported measures of autistic traits and empathy. We compared the rate of suicidal ideation in the sample with published rates of suicidal ideation in the general population and other clinical groups. We also assessed associations between depression, autistic traits, empathy, and likelihood of suicidal ideation and suicide plans or attempts. Findings: 374 adults (256 men and 118 women) were diagnosed with Asperger's syndrome in the study period. 243 (66%) of 367 respondents self-reported suicidal ideation, 127 (35%) of 365 respondents self-reported plans or attempts at suicide, and 116 (31%) of 368 respondents self-reported depression. Adults with Asperger's syndrome were significantly more likely to report lifetime experience of suicidal ideation than were individuals from a general UK population sample (odds ratio 9·6 [95% CI 7·6-11·9], p<0·0001), people with one, two, or more medical illnesses (p<0·0001), or people with psychotic illness (p=0·019). Compared with people diagnosed with Asperger's syndrome without depression, people with Asperger's syndrome and depression were more likely to report suicidal ideation (p<0·0001) and suicide plans or attempts (p<0·0001). Interpretation: Our findings lend support to anecdotal reports of increased rates of suicidal ideation in adults with Asperger's syndrome, and depression as an important potential risk factor for suicidality in adults with this condition. Because adults with Asperger's syndrome often have many risk factors for secondary depression (eg, social isolation or exclusion, and unemployment), our findings emphasise the need for appropriate service planning and support to reduce risk in this clinical group. Funding: The Three Guineas Trust, the Baily Thomas Foundation, the Medical Research Council, NIHR-CLAHRC-EoE, Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), and the Autism Research Trust. © 2014 Cassidy et al. Open Access article distributed under the terms of CC BY.

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