Publications by authors named "Louise Gallagher"

112 Publications

NRXN1α is associated with increased excitability in ASD iPSC-derived neurons.

BMC Neurosci 2021 Sep 15;22(1):56. Epub 2021 Sep 15.

Trinity Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.

Background: NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy, and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ. Previous studies on cultured cells show that the short NRXN1β primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons. We recently derived induced pluripotent stem cells (iPSCs) from five controls and three ASD patients carrying NRXN1α and showed increased calcium transients in patient neurons.

Methods: In this study we investigated the electrophysiological properties of iPSC-derived cortical neurons in control and ASD patients carrying NRXN1α using patch clamping. Whole genome RNA sequencing was carried out to further understand the potential underlying molecular mechanism.

Results: NRXN1α cortical neurons were shown to display larger sodium currents, higher AP amplitude and accelerated depolarization time. RNASeq analyses revealed transcriptomic changes with significant upregulation glutamatergic synapse and ion channels/transporter activity including voltage-gated potassium channels (GRIN1, GRIN3B, SLC17A6, CACNG3, CACNA1A, SHANK1), which are likely to couple with the increased excitability in NRXN1α cortical neurons.

Conclusions: Together with recent evidence of increased calcium transients, our results showed that human NRXN1α isoform deletions altered neuronal excitability and non-synaptic function, and NRXN1α patient iPSCs may be used as an ASD model for therapeutic development with calcium transients and excitability as readouts.
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http://dx.doi.org/10.1186/s12868-021-00661-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442436PMC
September 2021

How does genetic variation modify ND-CNV phenotypes?

Trends Genet 2021 Aug 4. Epub 2021 Aug 4.

Department of Psychiatry, Trinity College Dublin, Dublin, Ireland. Electronic address:

Rare copy-number variants (CNVs) associated with neurodevelopmental disorders (NDDs), i.e., ND-CNVs, provide an insight into the neurobiology of NDDs and, potentially, a link between biology and clinical outcomes. However, ND-CNVs are characterised by incomplete penetrance resulting in heterogeneous carrier phenotypes, ranging from non-affected to multimorbid psychiatric, neurological, and physical phenotypes. Recent evidence indicates that other variants in the genome, or 'other hits', may partially explain the variable expressivity of ND-CNVs. These may be other rare variants or the aggregated effects of common variants that modify NDD risk. Here we discuss the recent findings, current questions, and future challenges relating to other hits research in the context of ND-CNVs and their potential for improved clinical diagnostics and therapeutics for ND-CNV carriers.
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http://dx.doi.org/10.1016/j.tig.2021.07.006DOI Listing
August 2021

Scientists' warning on extreme wildfire risks to water supply.

Hydrol Process 2021 May 16;35(5):e14086. Epub 2021 May 16.

Department of Forest and Rangeland Stewardship Colorado State University Fort Collins Colorado USA.

2020 is the year of wildfire records. California experienced its three largest fires early in its fire season. The Pantanal, the largest wetland on the planet, burned over 20% of its surface. More than 18 million hectares of forest and bushland burned during the 2019-2020 fire season in Australia, killing 33 people, destroying nearly 2500 homes, and endangering many endemic species. The direct cost of damages is being counted in dozens of billion dollars, but the indirect costs on water-related ecosystem services and benefits could be equally expensive, with impacts lasting for decades. In Australia, the extreme precipitation ("200 mm day -1 in several location") that interrupted the catastrophic wildfire season triggered a series of watershed effects from headwaters to areas downstream. The increased runoff and erosion from burned areas disrupted water supplies in several locations. These post-fire watershed hazards via source water contamination, flash floods, and mudslides can represent substantial, systemic long-term risks to drinking water production, aquatic life, and socio-economic activity. Scenarios similar to the recent event in Australia are now predicted to unfold in the Western USA. This is a new reality that societies will have to live with as uncharted fire activity, water crises, and widespread human footprint collide all-around of the world. Therefore, we advocate for a more proactive approach to wildfire-watershed risk governance in an effort to advance and protect water security. We also argue that there is no easy solution to reducing this risk and that investments in both green (i.e., natural) and grey (i.e., built) infrastructure will be necessary. Further, we propose strategies to combine modern data analytics with existing tools for use by water and land managers worldwide to leverage several decades worth of data and knowledge on post-fire hydrology.
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http://dx.doi.org/10.1002/hyp.14086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251805PMC
May 2021

Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium.

J Neurodev Disord 2021 06 21;13(1):25. Epub 2021 Jun 21.

Centre for Applied Psychology, School of Psychology, University of Birmingham, Edgbaston, Birmingham, UK.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org ) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC "Behavior Outcomes Working Group" sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive-compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.
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http://dx.doi.org/10.1186/s11689-021-09373-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215770PMC
June 2021

COVID-19 health and social care access for autistic people: European policy review.

BMJ Open 2021 05 17;11(6):e045341. Epub 2021 May 17.

Department of Forensic and Neurodevelopmental Sciences, King's College London, London, UK.

Background: The global COVID-19 pandemic has had an unprecedented impact on European health and social care systems, with demands on testing, hospital and intensive care capacity exceeding available resources in many regions. This has led to concerns that some vulnerable groups, including autistic people, may be excluded from services.

Methods: We reviewed policies from 15 European member states, published in March-July 2020, pertaining to (1) access to COVID-19 tests; (2) provisions for treatment, hospitalisation and intensive care units (ICUs); and (3) changes to standard health and social care. In parallel, we analysed survey data on the lived experiences of 1301 autistic people and caregivers.

Results: Autistic people experienced significant barriers when accessing COVID-19 services. First, despite being at elevated risk of severe illness due to co-occurring health conditions, there was a lack of accessibility of COVID-19 testing. Second, many COVID-19 outpatient and inpatient treatment services were reported to be inaccessible, predominantly resulting from individual differences in communication needs. Third, ICU triage protocols in many European countries (directly or indirectly) resulted in discriminatory exclusion from lifesaving treatments. Finally, interruptions to standard health and social care left over 70% of autistic people without everyday support.

Conclusions: The COVID-19 pandemic has further exacerbated existing healthcare inequalities for autistic people, probably contributing to disproportionate increases in morbidity and mortality, mental health and behavioural difficulties, and reduced quality of life. An urgent need exists for policies and guidelines on accessibility of COVID-19 services to be updated to prevent the widespread exclusion of autistic people from services, which represents a violation of international human rights law.
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http://dx.doi.org/10.1136/bmjopen-2020-045341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130751PMC
May 2021

A novel non-viral delivery method that enables efficient engineering of primary human T cells for ex vivo cell therapy applications.

Cytotherapy 2021 Sep 1;23(9):852-860. Epub 2021 May 1.

Avectas Ltd, Maynooth, Ireland. Electronic address:

Background Aims: Next-generation immune cell therapy products will require complex modifications using engineering technologies that can maintain high levels of cell functionality. Non-viral engineering methods have the potential to address limitations associated with viral vectors. However, while electroporation is the most widely used non-viral modality, concerns about its effects on cell functionality have led to the exploration of alternative approaches. Here the authors have examined the suitability of the Solupore non-viral delivery system for engineering primary human T cells for cell therapy applications.

Methods: The Solupore system was used to deliver messenger RNA (mRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) guide RNA ribonucleoprotein (RNP) cargos to T cells, and efficiency was measured by flow cytometry. Cell perturbation was assessed by immune gene expression profiling, including an electroporation comparator. In vitro and in vivo cytotoxicity of chimeric antigen receptor (CAR) T cells generated using the Solupore system was evaluated using a real-time cellular impedance assay and a Raji-luciferase mouse tumor model, respectively.

Results: Efficient transfection was demonstrated through delivery of mRNA and CRISPR CAS9 RNP cargos individually, simultaneously and sequentially using the Solupore system while consistently maintaining high levels of cell viability. Gene expression profiling revealed minimal alteration in immune gene expression, demonstrating the low level of perturbation experienced by the cells during this transfection process. By contrast, electroporation resulted in substantial changes in immune gene expression in T cells. CAR T cells generated using the Solupore system exhibited efficient cytotoxicity against target cancer cells in vitro and in vivo.

Conclusions: The Solupore system is a non-viral means of simply, rapidly and efficiently delivering cargos to primary human immune cells with retention of high cell viability and functionality.
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http://dx.doi.org/10.1016/j.jcyt.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386197PMC
September 2021

Parental stress and adjustment in the context of rare genetic syndromes: A scoping review.

J Intellect Disabil 2021 Apr 19:1744629521995378. Epub 2021 Apr 19.

8809Trinity College Dublin, Ireland; Children Health Ireland at Tallaght Hospital, Ireland; Cherry Orchard Hospital, Ireland.

Chromosomal abnormalities are now considered a common cause of intellectual disability. With increased genetic testing, phenotyping and technological advancements, many new syndromes have been identified. This review sought to explore parental stress and adjustment in the context of rare genetic syndromes to evaluate their clinical impact. A systematic review of English peer-reviewed literature across three databases (PsycINFO, Medline, CINAHL) was completed and 69 articles were included. Parents of children with rare genetic syndromes experienced greater distress relative to other disabilities. Differences in parental wellbeing were syndrome-specific relative to ASD thus demonstrating the need to consider the contribution of syndrome-specific phenotypes. Child emotional and behavioural difficulties were the most consistent predictor of parental distress. Research reflecting other factors such as physical health, syndrome-specific behaviours, benefit finding and, parental appraisal in the context of a rare genetic aetiology is required in order to support parental adjustment in these conditions.
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http://dx.doi.org/10.1177/1744629521995378DOI Listing
April 2021

Derivation of four iPSC lines from a male ASD patient carrying a deletion in the middle coding region of NRXN1α gene (NUIGi039-A and NUIGi039-B) and a male sibling control (NUIGi040-A and NUIGi040-B).

Stem Cell Res 2021 05 18;53:102254. Epub 2021 Feb 18.

Regenerative Medicine Institute, School of Medicine, National University of Ireland (NUI), Galway, Ireland; FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin D02, Ireland. Electronic address:

NRXN1 deletions are commonly found in autism spectrum disorder (ASD) and other neurodevelopmental/neuropsychiatric disorders. Derivation of induced pluripotent stem cells (iPSCs) from different diseases involving different deletion regions are essential, as NRXN1 may produce thousands of splicing variants. We report here the derivation of iPSCs from a sibling control and an ASD proband carrying de novo heterozygous deletions in the middle region of NRXN1, using a non-integrating Sendai viral kit. The genotype and karyotype of the iPSCs were validated by whole genome SNP array. All iPSC lines highly expressed pluripotency markers and could be differentiated into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2021.102254DOI Listing
May 2021

Derivation of iPSC lines from two patients with autism spectrum disorder carrying NRXN1α deletion (NUIGi041-A, NUIG041-B; NUIGi045-A) and one sibling control (NUIGi042-A, NUIGi042-B).

Stem Cell Res 2021 04 2;52:102222. Epub 2021 Feb 2.

Regenerative Medicine Institute, School of Medicine, National University of Ireland (NUI) Galway, Ireland; FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin D02, Ireland. Electronic address:

NRXN1 encodes thousands of splicing variants categorized into long NRXN1α, short NRXN1β and extremely short NRXN1γ, which exert differential roles in neuronal excitation/inhibition. NRXN1α deletions are common in autism spectrum disorder (ASD) and other neurodevelopmental/neuropsychiatric disorders. We derived induced pluripotent stem cells (iPSCs) from one sibling control and two ASD probands carrying NRXN1α, using non-integrating Sendai viral method. All iPSCs highly expressed pluripotency markers and could be differentiated into ectodermal/mesodermal/endodermal cells. The genotype and karyotype of the iPSCs were validated by whole genome SNP array. The availability of the iPSCs offers an opportunity for understanding NRXN1α function in human neurons and in ASD.
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http://dx.doi.org/10.1016/j.scr.2021.102222DOI Listing
April 2021

'More than a box of puzzles': Understanding the parental experience of having a child with a rare genetic condition".

Eur J Med Genet 2021 Apr 9;64(4):104164. Epub 2021 Feb 9.

Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin; Linn Dara Regional CAMHS Network, Cherry Orchard Hospital, Dublin 10, Ballyfermot; Children Health Ireland at Tallaght Hospital, Dublin 24.

Background: Chromosomal microarray (CMA) testing has been adopted as the first-tier diagnostic test for developmental disabilities. However, determining the clinical significance of the results is often complex. This qualitative study seeks to explore parental interpretation, adaption and coping in the context of ambiguous rare genetic findings in order to support parental adjustment and wellbeing.

Methods: In-depth interviews were conducted with parents (n = 30) of children identified with a rare genetic chromosomal abnormality.

Results: Three major themes were identified following a thematic analysis: 'Learning of the Genetic Diagnosis', "The Reality of the Rarity' and 'Beyond Genetics: The Child Takes Centre Stage'. Findings demonstrated that parental adjustment to their child's genetic results are mediated by several factors including child difficulties and stage of development, clinician communication, perception of genetics, intrinsic coping strategies, access to practical and emotional support as well as broader contextual experiences.

Conclusion: This study highlights the importance of considering the parental perspective in the context of genetic testing in clinical practice.
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http://dx.doi.org/10.1016/j.ejmg.2021.104164DOI Listing
April 2021

A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants.

Am J Psychiatry 2021 01;178(1):77-86

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom (Chawner, Doherty, Anney, Moss, Hall, Owen, van den Bree); Cardiff University Centre for Human Developmental Science, School of Psychology, Cardiff University, Cardiff, United Kingdom (Chawner); Department of Psychology, Syracuse University, Syracuse, N.Y. (Antshel); Department of Psychiatry and Behavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (Bearden, Kushan); Departments of Psychiatry and Behavioral Sciences, University of Washington, Seattle (Bernier); Departments of Pediatrics and Medicine, Columbia University Irving Medical Center, New York (Chung); Center for Autism Research, Children's Hospital of Philadelphia (Clements, Miller, Schultz); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); South West London and St. George's Mental Health National Health Service Foundation Trust, London (Curran); University Children's Hospital, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia (Cuturilo); Department of Psychiatry, Brain Center, University Medical Center Utrecht, the Netherlands (Fiksinski, Vorstman); Clinical Genetics Research Program, Centre for Addiction and Mental Health, and the Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto (Fiksinski); Department of Psychiatry, Trinity College Dublin, Ireland (Gallagher); Department of Pediatrics, Baylor College of Medicine, Houston (Goin-Kochel); Lifespan Brain Institute, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia (Gur); Department of Psychiatry, Neurodevelopment and Psychosis Section, Perelman School of Medicine, University of Pennsylvania, Philadelphia (Gur); Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia (Gur, Schultz); Developmental Medicine, Children's Hospital Boston/Harvard Medical School, Boston (Hanson); Department of Pediatrics, University of Montreal (Jacquemont, Maillard); Centre de recherche, Centre Hospitalier Universitaire Sainte Justine, Montreal (Jacquemont); Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse (Kates); Service des Troubles du Spectre de l'Autisme et Apparentés, Lausanne University Hospital, Lausanne, Switzerland (Maillard); Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia (McDonald-McGinn); 22q and You Center, Children's Hospital of Philadelphia (McDonald-McGinn); Department of Pediatrics, University of Pennsylvania, Philadelphia (McDonald-McGinn, Schultz); Clinic for Psychiatry, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbia (Mihaljevic); Institute of Mental Health, Belgrade, Serbia, Faculty of Medicine, University of Belgrade, Serbia (Pejovic-Milovancevic); Simons Foundation, New York (Green-Snyder); Program in Genetics and Genome Biology, SickKids Research Institute, Toronto (Vorstman); Department of Psychiatry, Hospital for Sick Children, University of Toronto (Vorstman); Department of Pediatrics, Seattle Children's Hospital, Seattle (Wenger); and Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom (Hall, Owen, van den Bree).

Objective: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.

Methods: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.

Results: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.

Conclusions: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
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http://dx.doi.org/10.1176/appi.ajp.2020.20010015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022239PMC
January 2021

Derivation of iPSC lines from three young healthy donors of Caucasian origin (NUIGi035-A; NUIGi036-A; NUIGi037-A).

Stem Cell Res 2020 12 27;49:102101. Epub 2020 Nov 27.

Regenerative Medicine Institute, School of Medicine, National University of Ireland (NUI) Galway, Ireland; FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin D02, Ireland. Electronic address:

The induced pluripotent stem cell (iPSC) technology has offered an unprecedented opportunity for disease modelling and drug discovery. Here we used non-integrating Sendai viral method and derived iPSCs from three young healthy Caucasian donors. All iPSCs expressed pluripotency markers highly and could be differentiated into three germ lineages. They possess normal karyotype which was confirmed by whole genome SNP array. The availability of the healthy control iPSCs offers an opportunity for phenotypic comparison and genome editing for a variety of diseases.
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http://dx.doi.org/10.1016/j.scr.2020.102101DOI Listing
December 2020

Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation.

PLoS One 2020 18;15(12):e0242773. Epub 2020 Dec 18.

Regenerative Medicine Institute, School of Medicine, Biomedical Science Building, National University of Ireland (NUI) Galway, Galway, Ireland.

Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities. We hypothesised that critical ASD candidates should appear widely across different scoring systems, and that comorbidity pathways should be constituted by genes expressed in the relevant tissues. We analysed the Simons Foundation for Autism Research Initiative (SFARI) database and four independently published scoring systems and identified 292 overlapping genes. We examined their mRNA expression using the Genotype-Tissue Expression (GTEx) database and validated protein expression levels using the human protein atlas (HPA) dataset. This led to clustering of the overlapping ASD genes into 2 groups; one with 91 genes primarily expressed in the central nervous system (CNS geneset) and another with 201 genes expressed in both CNS and peripheral tissues (CNS+PT geneset). Bioinformatic analyses showed a high enrichment of CNS development and synaptic transmission in the CNS geneset, and an enrichment of synapse, chromatin remodelling, gene regulation and endocrine signalling in the CNS+PT geneset. Calcium signalling and the glutamatergic synapse were found to be highly interconnected among pathways in the combined geneset. Our analyses demonstrate that 2/3 of ASD genes are expressed beyond the brain, which may impact peripheral function and involve in ASD co-morbidities, and relevant pathways may be explored for the treatment of ASD co-morbidities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242773PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748153PMC
January 2021

Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4-BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature.

Int J Environ Res Public Health 2020 12 10;17(24). Epub 2020 Dec 10.

UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.
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http://dx.doi.org/10.3390/ijerph17249253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763014PMC
December 2020

Autism spectrum disorder genomics: The progress and potential of genomic technologies.

Genomics 2020 11 15;112(6):5136-5142. Epub 2020 Sep 15.

Department of Psychiatry, Trinity College Dublin, Ireland; Department of Biology, Maynooth University, Ireland. Electronic address:

Genomic technologies have accelerated research progress in autism spectrum disorder (ASD) genomics and promises to further transform our understanding of the genetic basis of this neurodevelopmental disorder. Here we review the current evidence for the genetic basis of ASD, present the progress of large-scale studies to date and highlight the potential of genomic technologies. In particular, we discuss evidence for the importance of identifying rare genetic variants in family-based studies. Genomics is a key feature of future healthcare and our review illustrates it's potential to improve our biological understanding of neurodevelopmental disorders, and to ultimately aid ASD diagnosis, inform medical decision making and establish genomics as central to personalised medicine.
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http://dx.doi.org/10.1016/j.ygeno.2020.09.022DOI Listing
November 2020

The role of rare compound heterozygous events in autism spectrum disorder.

Transl Psychiatry 2020 06 22;10(1):204. Epub 2020 Jun 22.

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

The identification of genetic variants underlying autism spectrum disorders (ASDs) may contribute to a better understanding of their underlying biology. To examine the possible role of a specific type of compound heterozygosity in ASD, namely, the occurrence of a deletion together with a functional nucleotide variant on the remaining allele, we sequenced 550 genes in 149 individuals with ASD and their deletion-transmitting parents. This approach allowed us to identify additional sequence variants occurring in the remaining allele of the deletion. Our main goal was to compare the rate of sequence variants in remaining alleles of deleted regions between probands and the deletion-transmitting parents. We also examined the predicted functional effect of the identified variants using Combined Annotation-Dependent Depletion (CADD) scores. The single nucleotide variant-deletion co-occurrence was observed in 13.4% of probands, compared with 8.1% of parents. The cumulative burden of sequence variants (n = 68) in pooled proband sequences was higher than the burden in pooled sequences from the deletion-transmitting parents (n = 41, X = 6.69, p = 0.0097). After filtering for those variants predicted to be most deleterious, we observed 21 of such variants in probands versus 8 in their deletion-transmitting parents (X = 5.82, p = 0.016). Finally, cumulative CADD scores conferred by these variants were significantly higher in probands than in deletion-transmitting parents (burden test, β = 0.13; p = 1.0 × 10). Our findings suggest that the compound heterozygosity described in the current study may be one of several mechanisms explaining variable penetrance of CNVs with known pathogenicity for ASD.
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http://dx.doi.org/10.1038/s41398-020-00866-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308334PMC
June 2020

Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

Am J Psychiatry 2020 09 16;177(9):834-843. Epub 2020 Jun 16.

The full list of authors in the ENIGMA working groups, author affiliations, author disclosures, and acknowledgments are provided in online supplements.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.

Methods: Structural T-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).

Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.

Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
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http://dx.doi.org/10.1176/appi.ajp.2020.19030331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296070PMC
September 2020

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Hum Brain Mapp 2020 May 18. Epub 2020 May 18.

Division of Psychological & Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technischen Universität Dresden, Dresden, Germany.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.
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http://dx.doi.org/10.1002/hbm.25029DOI Listing
May 2020

Helpful and challenging aspects of breastfeeding in public for women living in Australia, Ireland and Sweden: a cross-sectional study.

Int Breastfeed J 2020 05 12;15(1):38. Epub 2020 May 12.

Institute of Health Sciences, Medical Faculty, Lund University, Lund, Sweden.

Background: Breastfeeding in public continues to be contentious with qualitative evidence confirming that women face many challenges. It is therefore important to gain understanding of not only the challenges but also what women perceive is helpful to breastfeed in public.

Methods: A cross-sectional study was conducted with women living in Australia, Ireland or Sweden currently breastfeeding or having breastfed within the previous 2 years. Our objective was to explore and compare what women do when faced with having to breastfeed in the presence of someone they are uncomfortable with and what women think is helpful and challenging when considering whether to breastfeed in public. Data were collected in 2018 from an online survey over a 4 week period in each country. Content analysis revealed data similarity and theme names and definitions were negotiated until consensus was reached. How often each theme was cited was counted to report frequencies. Helpful and challenging aspects were also ranked by women to allow international comparison.

Results: Ten themes emerged around women facing someone they were uncomfortable to breastfeed in the presence of with the most frequently cited being: 'made the effort to be discreet'; 'moved to a private location'; 'turned away' and 'just got on with breastfeeding'. Nine themes captured challenges to breastfeed in public with the following ranked in the top five across countries: 'unwanted attention'; 'no comfortable place to sit'; 'environment not suitable'; 'awkward audience' and 'not wearing appropriate clothing'. Nine themes revealed what was helpful to breastfeed in public with the top five: 'supportive network'; 'quiet private suitable environment'; 'comfortable seating'; 'understanding and acceptance of others' and 'seeing other mothers' breastfeed'.

Conclusions: When breastfeeding in public women are challenged by shared concerns around unwanted attention, coping with an awkward audience and unsuitable environments. Women want to feel comfortable when breastfeeding in a public space. How women respond to situations where they are uncomfortable is counterproductive to what they share would be helpful, namely seeing other mothers breastfeed. Themes reveal issues beyond the control of the individual and highlight how the support required by breastfeeding women is a public health responsibility.
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http://dx.doi.org/10.1186/s13006-020-00281-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218587PMC
May 2020

A framework for an evidence-based gene list relevant to autism spectrum disorder.

Nat Rev Genet 2020 06 21;21(6):367-376. Epub 2020 Apr 21.

The Centre for Applied Genomics, Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.

Autism spectrum disorder (ASD) is often grouped with other brain-related phenotypes into a broader category of neurodevelopmental disorders (NDDs). In clinical practice, providers need to decide which genes to test in individuals with ASD phenotypes, which requires an understanding of the level of evidence for individual NDD genes that supports an association with ASD. Consensus is currently lacking about which NDD genes have sufficient evidence to support a relationship to ASD. Estimates of the number of genes relevant to ASD differ greatly among research groups and clinical sequencing panels, varying from a few to several hundred. This Roadmap discusses important considerations necessary to provide an evidence-based framework for the curation of NDD genes based on the level of information supporting a clinically relevant relationship between a given gene and ASD.
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http://dx.doi.org/10.1038/s41576-020-0231-2DOI Listing
June 2020

Derivation of two iPSC lines from a sporadic ASD patient (NUIGi033-A) and a paternal control (NUIGi034-A).

Stem Cell Res 2020 04 4;44:101722. Epub 2020 Feb 4.

Regenerative Medicine Institute, School of Medicine, National University of Ireland (NUI), Galway, Ireland; FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin D02, Ireland. Electronic address:

Hundreds of rare risk factors have been identified for ASD, however, the underlying causes for ~70% of sporadic cases are unknown. Sporadic ASD models are thus essential for validating phenotypic commonality and drug suitability to the majority of patients. Here, we derived induced pluripotent stem cells (iPSCs) from one sporadic ASD child and one paternal control, using non-integrating Sendai viral methods. The iPSCs strongly expressed pluripotency markers and could be differentiated into three germ layers. Their normal karyotype was validated by genome SNP array. The availability of sporadic ASD-derived iPSCs offers an opportunity for phenotypic comparison with genetic ASD models.
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http://dx.doi.org/10.1016/j.scr.2020.101722DOI Listing
April 2020

Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism.

Cell 2020 02 23;180(3):568-584.e23. Epub 2020 Jan 23.

Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
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http://dx.doi.org/10.1016/j.cell.2019.12.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250485PMC
February 2020

Identifying schizophrenia patients who carry pathogenic genetic copy number variants using standard clinical assessment: retrospective cohort study.

Br J Psychiatry 2020 05;216(5):275-279

Professor, Head of Discipline, Neuropsychiatric Genetics Research Group, Department of Psychiatry, School of Medicine, Trinity College Dublin, Ireland.

Background: Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia.

Aims: To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort.

Method: Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479).

Results: In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16-34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58-14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28-19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9-86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0-100.0%) for the replication cohort.

Conclusions: These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders.
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http://dx.doi.org/10.1192/bjp.2019.262DOI Listing
May 2020

The clinical relevance of intragenic deletions.

J Med Genet 2020 05 13;57(5):347-355. Epub 2020 Jan 13.

Department of Human Genetics, KU Leuven, Leuven, Belgium

Background: Intragenic deletions are susceptibility variants for neurodevelopmental disorders; however, their clinical interpretation is often unclear. Therefore, a literature study and an analysis of 43 previously unpublished deletions are provided.

Methods: The literature cohort covered 629 heterozygous deletions: 148 in controls, 341 in probands and 140 in carrier relatives, and was used for clinical hypothesis testing. Exact breakpoint determination was performed for 43 in-house deletions.

Results: The prevalence of exonic deletions in controls was ~1/3000 as compared with ~1/800 in patients with neurodevelopmental/neuropsychiatric disorders. The differential distribution of deletions across the gene between controls and probands allowed to distinguish distinct areas within the gene. Exon 6-24 deletions appeared only twice in over 100000 control individuals, had an estimated penetrance for neurodevelopmental disorders of 32.43%, a rate of 50% and segregated mainly with intellectual disability (ID) and schizophrenia. In contrast, exon 1-5 deletions appeared in 20 control individuals, had an estimated penetrance of 12.59%, a rate of 32.5% and were reported with a broad range of neurodevelopmental phenotypes. Exact breakpoint determination revealed six recurrent intron 5 deletions.

Conclusion: Exon 6-24 deletions have a high penetrance and are mainly associated with ID and schizophrenia. In contrast, the actual contribution of exon 1-5 deletions to a neurodevelopmental/neuropsychiatric disorder in an individual patient and family remains very difficult to assess. To enhance the clinical interpretation, this study provides practical considerations for counselling and an interactive table for comparing a deletion of interest with the available literature data.
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http://dx.doi.org/10.1136/jmedgenet-2019-106448DOI Listing
May 2020

Increased Ca signaling in neurons derived from ASD induced pluripotent stem cells.

Mol Autism 2019 30;10:52. Epub 2019 Dec 30.

1Regenerative Medicine Institute, School of Medicine, Biomedical Science Building BMS-1021, National University of Ireland Galway, Dangan, Upper Newcastle, Galway, Ireland.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of lesions to human neurons in different diseases.

Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying deletions. Seven control and six iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca) imaging was performed using Fluo4-AM, and the properties of Ca transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with neurons.

Results: neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in neurons identified by STRING and GSEA analyses.

Conclusions: This is the first report to show that human neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca transients, which may facilitate the development of drug screening assays for the treatment of ASD.
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http://dx.doi.org/10.1186/s13229-019-0303-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937972PMC
June 2020

Derivation of familial iPSC lines from three ASD patients carrying NRXN1α and two controls (NUIGi022-A, NUIGi022-B; NUIGi023-A, NUIGi023-B; NUIGi025-A, NUIGi025-B; NUIGi024-A, NUIGi024-B; NUIGi026-A, NUIGi026-B).

Stem Cell Res 2019 12 13;41:101653. Epub 2019 Nov 13.

Regenerative Medicine Institute, School of Medicine, National University of Ireland (NUI) Galway, Biomedical Science Building BMS-1021, Dangan, Upper Newcastle, Galway, Ireland; Future Neuro Research Centre, Royal College of Surgeons in Ireland, Dublin D02, Ireland. Electronic address:

NRXN1 copy number variation is a rare genetic factor commonly shared among autism spectrum disorder (ASD), schizophrenia, intellectual disability, epilepsy and developmental delay. Human induced pluripotent stem cells (iPSCs) are essential for disease modeling and drug discovery, but familial cases are particularly rare. We report here the derivation of familial iPSC lines from two controls and three ASD patients carrying NRXN1α, using a non-integrating Sendai viral kit. The genotype and karyotype of the resulting iPSCs were validated by whole genome SNP array. All iPSC lines expressed comparable levels of pluripotency markers and could be differentiated into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2019.101653DOI Listing
December 2019

Risk factors for reduced fetal movements in pregnancy: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2019 Dec 18;243:72-82. Epub 2019 Oct 18.

School of Nursing and Midwifery, Trinity College Dublin, Ireland.

Maternal perception of reduced fetal movements (RFM) is an important clinical marker to identify women at higher risk of adverse perinatal outcomes. Preventing and reducing stillbirths can only be achieved through better detection and management of women with RFM, however the characteristics of women who present with RFM in pregnancy vary. A systematic review was conducted to explore the risk factors associated with reduced fetal movements (RFM) in pregnancy. PubMed, EMBASE, CINAHL, Maternity and Infant Care, PsycINFO and Science Citation Index were searched, from their inception date, for studies published up to 16 May 2019. Non-randomised observational studies reporting risk factors in pregnant women presenting with a primary complaint of RFM during pregnancy were included. The quality of the included studies was assessed with the Quality in Prognosis Studies (QUIPS) tool. Meta-analyses were performed using RevMan 5.3 software for each identified risk factor where two or more studies reported on the same risk factor. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Twenty-seven studies reporting on risk factors for RFM during pregnancy were included. Women presenting with RFM during pregnancy are more likely to be Caucasian, smokers, and have an anterior placenta, oligohydramnios and polyhydramnios. No difference was found in parity or the mean age of women presenting with RFM and women who did not present with RFM. Previous caesarean section, postdates >42 weeks', and other medical conditions, including diabetes and hypertensive disorders were not predictive for RFM during pregnancy. Modifiable and non-modifiable risk factors associated with RFM in pregnancy were identified. These results can be used to raise awareness of factors associated with RFM, and prompt women to attend their maternity care provider should concerns arise.
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http://dx.doi.org/10.1016/j.ejogrb.2019.09.028DOI Listing
December 2019

Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets.

Nat Commun 2019 10 31;10(1):4958. Epub 2019 Oct 31.

Department of Psychiatry, School of Medicine, Trinity College, Dublin, Ireland.

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.
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http://dx.doi.org/10.1038/s41467-019-13005-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823355PMC
October 2019

Antenatal and intrapartum interventions for reducing caesarean section, promoting vaginal birth, and reducing fear of childbirth: An overview of systematic reviews.

PLoS One 2019 24;14(10):e0224313. Epub 2019 Oct 24.

School of Nursing & Midwifery, Trinity College Dublin, Dublin, Ireland.

Concern has been expressed globally over rising caesarean birth rates. Recently, the International Federation of Gynaecology and Obstetrics (FIGO) called for help from governmental bodies, professional organisations, women's groups, and other stakeholders to reduce unnecessary caesareans. As part of a wider research initiative, we conducted an overview of systematic reviews of antenatal and intrapartum interventions, and reports of evidence based recommendations, to identify and highlight those that have been shown to be effective for reducing caesarean birth, promoting vaginal birth and reducing fear of childbirth. Following registration of the review protocol, (PROSPERO 2018 CRD42018090681), we searched The Cochrane Database of Systematic Reviews, PubMed, CINAHL and EMBASE (Jan 2000-Jan 2018) and searched for grey literature in PROSPERO, and on websites of health professional and other relevant bodies. Screening and selection of reviews, quality appraisal using AMSTAR-2, and data extraction were performed independently by pairs of at least two reviewers. Excluding reviews assessed as 'critically low' on AMSTAR-2 (n = 54), 101 systematic reviews, and 10 reports of evidence based recommendations were included in the overview. Narrative synthesis was performed, due to heterogeneity of review methodology and topics. The results highlight twenty-five interventions, across 17 reviews, that reduced the risk of caesarean, nine interventions across eight reviews that increased the risk of caesarean, eight interventions that reduced instrumental vaginal birth, four interventions that increased spontaneous vaginal birth, and two interventions that reduced fear of childbirth. This overview of reviews identifies and highlights interventions that have been shown to be effective for reducing caesarean birth, promoting vaginal births and reducing fear of childbirth. In recognising that clinical practices change over time, this overview includes reviews published from 2000 onwards only, thus providing contemporary evidence, and a valuable resource for clinicians when making decisions on practices that should be implemented for reducing unnecessary caesarean births safely. Protocol Registration: PROSPERO 2018 CRD42018090681. Available from: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018090681.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224313PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812784PMC
March 2020

A qualitative exploration of breastfeeding support groups in Ireland from the women's perspectives.

Midwifery 2019 Nov 1;78:71-77. Epub 2019 Aug 1.

School of Nursing & Midwifery, Trinity College Dublin, 24 D'Olier Street, Dublin 2, Ireland.

Objective: Volunteer breastfeeding support groups are deemed effective in promoting breastfeeding initiation and duration, but women's views are not well reported. The aim of this study was to explore women's experiences of Breastfeeding Support Groups in Ireland from their perspective.

Design And Participants: Semi-structured interviews with 15 breastfeeding mothers were conducted with participants recruited as part of a larger mixed-methods study.

Methods: Interviews were conducted online. Interviews were audiorecorded, transcribed, and analysed using Thematic Analysis. Cultural Historical Activity Theory was used as the theoretical framework.

Findings: Six key themes were identified: 'complexity of breastfeeding support', 'community and connection', 'impact of culture on breastfeeding needs', 'the journey', 'passing on', and 'what mothers want'. Mothers primarily attend in order to meet other mothers, and not necessarily with a problem, getting practical suggestions to meet their individual and changing needs. The social aspect of support groups fosters a sense of community and inclusion, long-standing friendships, a social outlet, and ongoing support.

Conclusions: Mothers attend breastfeeding support groups in order to meet other mothers and continue to attend for this reason to get mothering and breastfeeding support, as well as passing on their knowledge and experiences to other mothers, while meeting their social needs.

Implications For Practice: More resources, acknowledgement and funding are needed to provide breastfeeding support groups in local communities. Breastfeeding support groups and health professionals need to emphasise the social aspects of the interactions at these group rather than attending for a breastfeeding problem.
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http://dx.doi.org/10.1016/j.midw.2019.08.001DOI Listing
November 2019
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