Publications by authors named "Linda E Campbell"

67 Publications

Parenting stress in mothers with asthma during the postpartum period.

J Asthma 2021 Oct 12:1-13. Epub 2021 Oct 12.

School of Psychology, University of Newcastle, Australia.

Objective: Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, individuals with asthma are at an increased risk of depression and anxiety. We examined whether asthma during pregnancy is related to parenting stress in the first year postpartum and if this relationship varies with level of asthma control.

Methods: This cohort survey-based study included mothers with ( = 157) and without ( = 79) asthma. Mothers with asthma participated in this study following participation in a randomized controlled trial of a novel asthma management strategy during pregnancy. Mothers completed the Parenting Stress Index - Short Form during the first 12 months postpartum. Mothers with asthma also completed the Asthma Control Questionnaire.

Results: Parenting stress did not differ between mothers with and without asthma. Additionally, for mothers with asthma, there were no differences in levels of parenting stress based on asthma control.

Conclusions: This study suggests that mothers with asthma are not at an increased risk for excessive parenting stress. However, due to response and sampling bias, levels of parenting stress in asthmatic mothers may be underreported in our sample.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2021.1993246DOI Listing
October 2021

Experiences of non-invasive prenatal screening: A survey study.

Aust N Z J Obstet Gynaecol 2021 Sep 27. Epub 2021 Sep 27.

School of Psychological Sciences, College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW, Australia.

Background: In Australia, using non-invasive prenatal testing (NIPT) to screen for fetal abnormalities is becoming more commonplace. However, there is a lack of standardised procedures surrounding pre-test counselling. This holds the potential for variability in pregnant people's experiences when undergoing NIPT, which subsequently may impact their ability to make informed decisions surrounding NIPT results.

Aim: This study sought to characterise the experiences of Australian women undergoing NIPT, including perceptions of informed choice, counselling experiences and decision to undergo NIPT.

Materials And Methods: Australian women who had been recently pregnant (n = 94) completed an online survey which assessed: their knowledge of and attitude toward NIPT; satisfaction with counselling; satisfaction with their decision; and decisional conflict to undergo NIPT. The survey also allowed participants to provide qualitative information about their counselling experience and reasons for undergoing NIPT.

Results: Overall, participants had good knowledge of and positive attitudes toward NIPT, experienced low decisional conflict and were overall satisfied with their counselling experience and decision to undergo NIPT. However, some participants expressed dissatisfaction with the lack of information provided, and biased language, by counselling providers. The desire to be informed was the most frequent reason for undergoing NIPT.

Conclusion: The provision of accurate and objective information in pre-test counselling is important to reduce decisional conflict and improve satisfaction with the decision to undergo NIPT. It is recommended counselling providers present pregnant people with neutral, objective, and accurate information at the time of pre-test counselling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajo.13436DOI Listing
September 2021

Domains and measures of social cognition in acquired brain injury: A scoping review.

Neuropsychol Rehabil 2021 Jun 2:1-35. Epub 2021 Jun 2.

Priority Research Centre for Brain and Mental Health, School of Psychology, University of Newcastle, Callaghan, Australia.

In acquired brain injury (ABI), social cognition is a contributing factor to the changes observed in functional outcomes. However, progress in assessing and understanding social cognitive impairments is limited by a lack of consistency in terminology and the proliferation in assessment tools, leading to a lack of consensus on what should be assessed and how. This review aims to examine the domains of social cognition commonly assessed in ABI, the assessment tools used, and the appropriateness of these tools for researchers and clinicians. Using the Arksey and O'Malley scoping review methodology, 367 articles reporting results from 10,930 people with an ABI met our inclusion criteria. The five most commonly assessed domains of social cognition were emotion perception, theory of mind, social communication, identity recognition and empathy. The most commonly used measure of these domains included: the Ekman and Friesen photo series, Faux Pas Recognition Test, La Trobe Communication Questionnaire, Benton Facial Recognition Test and the Interpersonal Reactivity Index. There are well-validated measures readily available that are underused in favour of non-standardized measures clinically or the development of one's own measure in research. The appropriateness of the identified measure for research and clinical use was discussed, including suggestions for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09602011.2021.1933087DOI Listing
June 2021

Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome.

Nat Med 2020 12 9;26(12):1912-1918. Epub 2020 Nov 9.

Centro de Genética y Genómica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-020-1103-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975627PMC
December 2020

What parents want to know in the first postnatal year: A Delphi consensus study.

Child Care Health Dev 2021 01 21;47(1):47-56. Epub 2020 Sep 21.

School of Psychology, The University of Newcastle, Ourimbah, New South Wales, Australia.

Background: Early postnatal psychoeducation intervention programmes can support new parents in the adjustment to parenthood. However, most psychoeducation programmes focus on pregnancy and the birth and fail to deliver relevant and age-specific information to new parents about what to expect in the postpartum period. Learning more about this intense period in a new parent's life will facilitate a healthy transition to parenthood. Considering the needs of time-poor but tech-savvy new parents, it is also necessary to rethink the delivery methods of such information to maximize impact.

Method: Two panels of experts in perinatal mental health (eight professionals and eight parents with lived experience) participated in a Delphi consensus study to establish what topics of information are most important for parents in the first postnatal year.

Results: A total of 89 topics of information were endorsed by at least 80% of both panels as Essential or Good to Know information for new parents. The topics were grouped under the following themes: sleep, attachment, co-parenting, parental mental health, developmental milestones, feeding, social and community support, safety and health.

Conclusions: This study established consensus between perinatal experts and parents with lived experience in order to produce relevant m-health psychoeducation for parents in the first postnatal year. The study findings will inform the development of perinatal m-health psychoeducation programmes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cch.12806DOI Listing
January 2021

Be Health for Your Heart: A Pilot Randomized Controlled Trial Evaluating a Web-Based Behavioral Intervention to Improve the Cardiovascular Health of Women with a History of Preeclampsia.

Int J Environ Res Public Health 2020 08 10;17(16). Epub 2020 Aug 10.

Priority Research Centre for Physical Activity and Nutrition, School of Health Sciences, Faculty of Health and Medicine, The University of Newcastle, Callaghan, NSW 2308, Australia.

This pilot randomized controlled trial (RCT) aimed to determine the acceptability and preliminary efficacy of a web-based cardiovascular disease (CVD) prevention intervention for women following preeclampsia. Australian women with a recent history (≤4 years post diagnosis) of preeclampsia were randomized into two study arms: (1) Be Health for your Heart, a web-based behavioral intervention or; (2) Control, access to the National Heart Foundation website. Assessments were conducted at baseline, and after three months. Intervention acceptability and impact on absolute CVD 30-year risk score, CVD risk markers and health behaviors were assessed. Twenty-four of 31 (77.4%) women completed the three-month assessment. Eleven out of 13 intervention participants (84.6%) agreed/strongly agreed they were satisfied with the program, with a mean score of 4.2 ± 0.9 (maximum of five). There were no significant between or within group differences in absolute CVD risk, CVD risk markers or health behaviors from baseline to three months. Women with a history of preeclampsia were successfully recruited and retained and they reported high levels of acceptability with the Be Health for your Heart program. Further research is therefore needed from powered trials to determine the impact of web-based lifestyle interventions on CVD risk in this at-risk group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17165779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459885PMC
August 2020

The temperament features associated with autism spectrum disorder in childhood: A systematic review.

Res Dev Disabil 2020 Sep 26;104:103711. Epub 2020 Jun 26.

School of Psychology, University of Newcastle, Callaghan, Australia; Priority Research Centre GrowUpWell®, University of Newcastle, Australia. Electronic address:

Background: Temperament is an important construct that shapes child development. Temperament is suggested to present differently in different groups, such as children with neurodevelopmental disorders. However, it is not known whether there are specific temperament features associated with Autism Spectrum Disorder (ASD).

Aim: This systematic review aimed to synthesise extant literature to determine whether there are temperament features associated with ASD in infancy, toddlerhood and childhood.

Methods And Procedures: Following the PRISMA guidelines for systematic reviews, we searched PsycINFO, CINAHL, Academic Search Ultimate and ProQuest for all available articles from database conception until January 2020. The Joanna Briggs Institute Critical Appraisal checklists were used to assess the methodological quality of included articles.

Outcomes And Results: Twenty-six articles met the selection criteria: (1) reported on the temperament of children (0-12 years of age) diagnosed with ASD, (2) peer-reviewed; and (3) published in English. Articles varied in overall methodological quality. Infants later diagnosed with ASD were found to more frequently be described as having 'easy' temperament features in early infancy, compared to typically developing infants and infants with developmental concerns but not ASD. Once diagnosed, children with ASD were reported to, as a group, display more negative affect, less extraversion and less effortful control than typically developing children.

Conclusions And Implications: The literature suggests that more challenging temperament features are associated with ASD in childhood, but less is known about within group variability. Overall, this review highlights the need for further investigation into the variability of temperament in children with ASD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ridd.2020.103711DOI Listing
September 2020

Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness.

Am J Psychiatry 2020 07 12;177(7):589-600. Epub 2020 Feb 12.

Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, Los Angeles (Ching, Villalon Reina, Zavaliangos-Petropulu, Thompson); Department of Biomedical Engineering, Armour College of Engineering, Illinois Institute of Technology, Chicago (Gutman); Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Los Angeles (Ching, Sun, Lin, Jonas, Pacheco-Hansen, Vajdi, Forsyth, Bearden); Department of Psychology, UCLA, Los Angeles (Ching, Forsyth, Bearden); Department of Biomedical Engineering, Oregon Health and Science University, Portland (Ragothaman); Department of Biomedical Engineering, Duke University, Durham, N.C. (Isaev); Graduate Interdepartmental Program in Neuroscience, UCLA School of Medicine, Los Angeles (Lin, Jonas); Department of Psychiatry, University of Pittsburgh, Pittsburgh (Jalbrzikowski); Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands (Bakker, van Amelsvoort); Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam (Bakker); Department of Psychology, Syracuse University, Syracuse, N.Y. (Antshel); Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse (Fremont, Kates); School of Psychology, University of Newcastle, Newcastle, Australia (Campbell, McCabe); MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis (McCabe, Durdle, Goodrich-Hunsaker, Simon); Institute of Psychiatry, Psychology, and Neuroscience, Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, King's College London (Craig, Daly, Gudbrandsen, C.M. Murphy, D.G. Murphy); Bethlem Royal Hospital, National Institute for Health Research Maudsley Biomedical Research Centre, and SLaM NHS Foundation Trust, National Autism Unit, London (Craig); Behavioural Genetics Clinic, Adult Autism Service, Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London (C.M. Murphy, D.G. Murphy); Department of Psychiatry, Royal College of Surgeons in Ireland, and Education and Research Centre, Beaumont Hospital, Dublin (K.C. Murphy); Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands (Fiksinski, Koops, Vorstman); Clinical Genetics Research Program (Bassett, Fiksinski, Chow), Clinical Genetics Service (Chow), Campbell Family Mental Health Research Institute (Bassett), Centre for Addiction and Mental Health, Toronto; Dalglish Family 22q Clinic (Bassett, Fiksinski), Department of Mental Health, and Toronto General Hospital Research Institute (Bassett); University Health Network, Toronto (Fiksinski, Bassett); Department of Psychiatry, University of Toronto, Toronto (Bassett, Vorstman, Chow); Program in Genetics and Genome Biology, Research Institute, and Department of Psychiatry, Hospital for Sick Children, Toronto (Vorstman); Division of Human Genetics and 22q and You Center, Children's Hospital of Philadelphia, Philadelphia (Crowley, Emanuel, McDonald-McGinn, Zackai); Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia (Emanuel, McDonald-McGinn, Zackai); Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia (Gur); Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia (Roalf, Ruparel); Departments of Radiology and Psychiatry, Hospital of the University of Pennsylvania, Philadelphia (Schmitt); Department of Psychological and Brain Sciences, University of California, Santa Barbara (Durdle); Department of Neurology, University of Utah, Salt Lake City (Goodrich-Hunsaker); Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto (Butcher); Department Psychiatry, University of British Columbia, Vancouver (Vila-Rodriguez); MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Cunningham, Doherty, Linden, Moss, Owen, van den Bree); Cardiff University Brain Research Imaging Centre, Cardiff, U.K. (Doherty, Linden); Department of Psychiatry, Pontificia Universidad Católica de Chile, Santiago (Crossley); Clinica Alemana, Universidad del Desarrollo, Centro de Genética y Genomica, Facultad de Medicina, Santiago (Repetto); Departments of Neurology, Psychiatry, Radiology, Engineering, Pediatrics, and Ophthalmology, University of Southern California, Los Angeles (Thompson).

Objective: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group.

Methods: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female).

Results: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder.

Conclusions: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ajp.2019.19060583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419015PMC
July 2020

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion.

Mol Psychiatry 2020 Feb 3. Epub 2020 Feb 3.

Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (p = 6.73 × 10). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-020-0654-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396297PMC
February 2020

"She'll be able to live independently… as long as I'm around": The "lived" experience of parenting a child with 22q11.2 deletion syndrome in the transition to adulthood.

J Appl Res Intellect Disabil 2020 May 9;33(3):565-573. Epub 2020 Jan 9.

School of Psychology, University of Newcastle, Ourimbah, NSW, Australia.

Background: 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome. Parents of emerging adults with 22q11DS have an intense and ongoing involvement in their child's life. This study explores the lived experience of parents in relation to their child becoming independent and establishing intimate relationships.

Method: Interpretative phenomenological analysis was used to explore the positive and negative experiences of five parents of emerging adults with 22q11DS.

Results: Supervised independence overarched four subordinate themes. These themes highlighted the difficulties experienced by parents attempting to relinquish control whilst still experiencing a need to keep their child safe as their child negotiated a complex stage of life. Parents waited for "signs" from their child before initiating conversations about intimate relationships.

Conclusions: These findings provide insight into the lived experience of parenting a child through the transition into adulthood, providing a catalyst for further research with the aim of facilitating better services for families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jar.12700DOI Listing
May 2020

Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study.

Mol Psychiatry 2020 11 29;25(11):2818-2831. Epub 2019 Jul 29.

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

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-019-0450-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986984PMC
November 2020

Observational study of mental health in asthmatic women during the prenatal and postnatal periods.

J Asthma 2020 08 31;57(8):829-841. Epub 2019 May 31.

School of Psychology, University of Newcastle, Callaghan, NSW, Australia.

We aimed to examine the prevalence and severity of psychological distress of women with asthma in both the prenatal and postnatal periods, and to determine whether asthmatic women with and without mental health problems differ in self-management, medications knowledge, and asthma symptoms.: We assessed spirometry performance and asthma symptoms in 120 women (mean age 29.8 years) before 23 weeks gestation, as part of the Breathing for Life Trial (Trial ID: ACTRN12613000202763). Prenatal depression data was obtained from medical records. At 6 weeks postpartum, we assessed general health, self-reported asthma control, depression symptoms (with the Edinburgh Postnatal Depression Scale) and adaptive functioning (with the Achenbach System of Empirically Based Assessment scales).: Twenty percent of our sample reported having a current mental health diagnosis, 14% reported currently receiving mental health care, while 47% reported having received mental health care in the past (and may/may not have received a diagnosis). The sample scored high on the Aggressive Behavior, Avoidant Personality, and Attention Deficit/Hyperactivity scales. Poorer self-reported postnatal asthma control was strongly correlated with elevated somatic complaints, externalizing problems, antisocial personality problems, and greater withdrawal. Prenatal spirometry or asthma severity and control were largely not associated with measures of psychopathology.: These findings indicate that pregnant women with asthma frequently report issues with psychopathology during the prenatal and postnatal periods, and that the subjective perception of asthma control may be more related to psychopathology than objective asthma measures. However, due to sample bias, these findings are likely to be understated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2019.1621888DOI Listing
August 2020

Cardiovascular disease lifestyle risk factors in people with psychosis: a cross-sectional study.

BMC Public Health 2018 06 15;18(1):742. Epub 2018 Jun 15.

Faculty Health and Medicine, The University of Newcastle, Callaghan, 2308, Australia.

Background: People with psychosis die on average 25 years earlier than those in the general population, with cardiovascular disease (CVD) contributing to much of the excess mortality. This cross-sectional study aimed to identify the relationship between lifestyle risk factors for CVD - poor nutrition, smoking and low physical activity levels - and dyslipidaemia, hypertension and hyperglycaemia while controlling for potential confounders in 1825 people from the Survey of High Impact Psychosis (SHIP) in Australia. We also aimed to identify clustering patterns of lifestyle risk factors and associated demographic variables.

Methods: Three logistic regressions were used to predict the effect of nutrition, smoking and physical activity on dyslipidaemia, hypertension and hyperglycaemia while controlling for clozapine use, sex and age. Clustering patterns of nutrition, smoking and physical activity were examined using the two-step cluster method which is based on hierarchical cluster analysis. Demographic variables associated with different clusters were identified using measures of association.

Results: Smoking status had a positive association with dyslipidaemia (adjusted odds ratio = 0.50; 95% confidence interval = 0.32-0.78; p = 0.002). Other cardiovascular disease lifestyle risk factors did not have a significant relationship with dyslipidaemia, hypertension and hyperglycaemia. Clustering patterns of lifestyle risk factors showed that younger men, with low education levels, and relying on a government pension, were most likely to display the poorest lifestyle risk behaviours. The largest cluster (42%) of participants was characterised by a mixed demographic profile and were most likely to display poor nutrition and low physical activity levels but less likely to smoke.

Conclusions: Only smoking status had a significant positive association with dyslipidaemia which could indicate that there are additional factors affecting the relationship between other cardiovascular lifestyle risk factors and dyslipidaemia, hypertension and hyperglycaemia in people with psychosis. Unknown confounders and traditional lifestyle risk factors may explain the high rates of CVD in this group. Clustering of lifestyle risk factors and their demographic profiles could help the design of intervention programs in people with psychosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-018-5649-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003197PMC
June 2018

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

Mol Psychiatry 2020 08 13;25(8):1822-1834. Epub 2018 Jun 13.

Department of Radiology, Division of Neuroradiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-018-0078-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292748PMC
August 2020

The effects of maternal asthma during pregnancy on child cognitive and behavioral development: A systematic review.

J Asthma 2019 02 26;56(2):130-141. Epub 2018 Feb 26.

a School of Psychology , University of Newcastle , Callaghan , NSW , Australia.

Objective: Maternal asthma during pregnancy is associated with a higher risk of negative perinatal outcomes. However, little is known about the direct effects of maternal asthma on infant cognitive development. We examined the evidence for an impact of maternal asthma during pregnancy on cognitive and behavioral development of the child.

Data Sources: We conducted a MEDLINE, PsychINFO, and manual search of the databases for all available studies until January 9th, 2018.

Study Selections: Studies were deemed relevant if they included child cognitive and behavioral development as the outcome, with maternal asthma as the determinant of interest.

Results: Ten articles matched selection criteria. Some studies report that maternal asthma is associated with increased risk for autism and intellectual disability in children. However, these effects are small and are often eliminated when controlling for confounding variables. Other studies have found no association. The only prospective study found that well-managed asthma during pregnancy was not associated with negative developmental outcomes in children.

Conclusions: The evidence suggests that the relationship between maternal asthma during pregnancy and poor developmental and behavioral outcomes of children is weak. Children of mothers with well-managed asthma during pregnancy have similar developmental trajectories to those born to healthy mothers. Prospective, longitudinal studies are needed to confirm these conclusions. Optimal asthma management is important in pregnancy as it may have longer term benefits for the health of the offspring. As the rate of asthma increases in the population, the implications of maternal asthma on child development will be of greater importance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2018.1437174DOI Listing
February 2019

Severity of illness and adaptive functioning predict quality of care of children among parents with psychosis: A confirmatory factor analysis.

Aust N Z J Psychiatry 2018 05 4;52(5):435-445. Epub 2017 Nov 4.

1 The University of Newcastle, Newcastle, NSW, Australia.

Objective: Parenthood is central to the personal and social identity of many people. For individuals with psychotic disorders, parenthood is often associated with formidable challenges. We aimed to identify predictors of adequate parenting among parents with psychotic disorders.

Methods: Data pertaining to 234 parents with psychotic disorders living with dependent children were extracted from a population-based prevalence study, the 2010 second Australian national survey of psychosis, and analysed using confirmatory factor analysis. Parenting outcome was defined as quality of care of children, based on participant report and interviewer enquiry/exploration, and included level of participation, interest and competence in childcare during the last 12 months.

Results: Five hypothesis-driven latent variables were constructed and labelled psychosocial support, illness severity, substance abuse/dependence, adaptive functioning and parenting role. Importantly, 75% of participants were not identified to have any dysfunction in the quality of care provided to their child(ren). Severity of illness and adaptive functioning were reliably associated with quality of childcare. Psychosocial support, substance abuse/dependence and parenting role had an indirect relationship to the outcome variable via their association with either severity of illness and/or adaptive functioning.

Conclusion: The majority of parents in the current sample provided adequate parenting. However, greater symptom severity and poorer adaptive functioning ultimately leave parents with significant difficulties and in need of assistance to manage their parenting obligations. As symptoms and functioning can change episodically for people with psychotic illness, provision of targeted and flexible support that can deliver temporary assistance during times of need is necessary. This would maximise the quality of care provided to vulnerable children, with potential long-term benefits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0004867417731526DOI Listing
May 2018

Men and women with psychosis and the impact of illness-duration on sex-differences: The second Australian national survey of psychosis.

Psychiatry Res 2017 10 13;256:130-143. Epub 2017 Jun 13.

St. Vincent's Hospital Melbourne, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia.

We aimed to examine and compare sex-differences in people receiving treatment for psychotic illnesses in community settings, based on long or short duration of illness; expecting association between longer illness-duration and worse outcomes in women and men. Clinical, demographic and service-use data from the Survey of High Impact Psychosis were analysed by sex and duration of illness (≤5 years; ≥6 years), using independent t-tests, chi-square tests, one-way ANOVA, and Cramer's V. Of the 1825 participants, 47% had schizophrenia, 17.5% bipolar and 16.1% schizo-affective disorders. More women than men had undertaken post-school education, maintained relationships, and been living in their own homes. Women with a shorter-illness-duration showed social functioning equivalent to non-ill women in the general population. Men tended to have an early illness onset, show premorbid dysfunction, be single, show severe disability, and to use illicit substances. Men with a longer-illness-duration were very socially disadvantaged and isolated, often experiencing homelessness and substance use. Men with a short-illness-duration were most likely to be in paid employment, but two-thirds earned less than $AUD500 per fortnight. Men with longer-illness-duration showed most disability, socially and globally. Interventions should be guided by diagnosis, but also by a person's sex and duration of illness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2017.06.024DOI Listing
October 2017

Social Dysfunction and Diet Outcomes in People with Psychosis.

Nutrients 2017 Jan 19;9(1). Epub 2017 Jan 19.

Faculty Health and Medicine, The University of Newcastle, Callaghan 2308, Australia.

This analysis aimed to examine the association of social dysfunction with food security status, fruit intake, vegetable intake, meal frequency and breakfast consumption in people with psychosis from the Hunter New England (HNE) catchment site of the Survey of High Impact Psychosis (SHIP). Social dysfunction and dietary information were collected using standardised tools. Independent binary logistic regressions were used to examine the association between social dysfunction and food security status, fruit intake, vegetable intake, meal frequency and breakfast consumption. Although social dysfunction did not have a statistically significant association with most diet variables, participants with obvious to severe social dysfunction were 0.872 (95% CI (0.778, 0.976)) less likely to eat breakfast than those with no social dysfunction < 0.05. Participants with social dysfunction were therefore, 13% less likely to have breakfast. This paper highlights high rates of social dysfunction, significant food insecurity, and intakes of fruits and vegetables below recommendations in people with psychosis. In light of this, a greater focus needs to be given to dietary behaviours and social dysfunction in lifestyle interventions delivered to people with psychosis. Well-designed observational research is also needed to further examine the relationship between social dysfunction and dietary behaviour in people with psychosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu9010080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295124PMC
January 2017

Calpain 12 Function Revealed through the Study of an Atypical Case of Autosomal Recessive Congenital Ichthyosis.

J Invest Dermatol 2017 02 18;137(2):385-393. Epub 2016 Oct 18.

Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Congenital erythroderma is a rare and often life-threatening condition, which has been shown to result from mutations in several genes encoding important components of the epidermal differentiation program. Using whole exome sequencing, we identified in a child with congenital exfoliative erythroderma, hypotrichosis, severe nail dystrophy and failure to thrive, two heterozygous mutations in ABCA12 (c.2956C>T, p.R986W; c.5778+2T>C, p. G1900Mfs*16), a gene known to be associated with two forms of ichthyosis, autosomal recessive congenital ichthyosis, and harlequin ichthyosis. Because the patient displayed an atypical phenotype, including severe hair and nail manifestations, we scrutinized the exome sequencing data for additional potentially deleterious genetic variations in genes of relevance to the cornification process. Two mutations were identified in CAPN12, encoding a member of the calpain proteases: a paternal missense mutation (c.1511C>A; p.P504Q) and a maternal deletion due to activation of a cryptic splice site in exon 9 of the gene (c.1090_1129del; p.Val364Lysfs*11). The calpain 12 protein was found to be expressed in both the epidermis and hair follicle of normal skin, but its expression was dramatically reduced in the patient's skin. The downregulation of capn12 expression in zebrafish was associated with abnormal epidermal morphogenesis. Small interfering RNA knockdown of CAPN12 in three-dimensional human skin models was associated with acanthosis, disorganized epidermal architecture, and downregulation of several differentiation markers, including filaggrin. Accordingly, filaggrin expression was almost absent in the patient skin. Using ex vivo live imaging, small interfering RNA knockdown of calpain 12 in skin from K14-H2B GFP mice led to significant hair follicle catagen transformation compared with controls. In summary, our results indicate that calpain 12 plays an essential role during epidermal ontogenesis and normal hair follicle cycling and that its absence may aggravate the clinical manifestations of ABCA12 mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2016.07.043DOI Listing
February 2017

"You don't know until you get there": The positive and negative "lived" experience of parenting an adult child with 22q11.2 deletion syndrome.

Health Psychol 2017 Jan 22;36(1):45-54. Epub 2016 Sep 22.

School of Psychology, University of Newcastle.

Objectives: 22q11.2 deletion syndrome (22q11DS), a complex genetic syndrome associated with more than 180 features, presents complex challenges for parents including gaining a diagnosis. This phenomenological study sought the "lived" interpretations of parents supporting an adult child with 22q11DS, a poorly researched area.

Method: Interpretative phenomenological analysis informed a detailed and open exploration of parenting a child through to adult life with 22q11DS. Using in-depth semistructured interviews, 8 parents (2 male, 6 female) of adult children with 22q11DS were individually interviewed; providing the data set for transcription and thematic analysis.

Results: Losing "I" Finding "self," overarched 6 subordinate themes that emerged from participants' articulated descriptions of psychological distress and psychological growth. Distress in parenting a child with 22q11DS was experienced through stigma, loss, grief, and guilt. Progressively, stigma undermined independence, friendships, and instinctual judgement. Ill-informed hierarchical structures experienced as layers of obstruction and lack of awareness of the syndrome triggered angry advocacy for their child. Diagnosis brought opposing relief and grief. In time, they came to value their unique "accomplishments," collected on their journey with 22q11DS, and in turn, consciously valued authentic "self" expressed through empathy, humility, gratitude, and pride.

Conclusion: Parental distress through societal, educational, and health care invalidation persisted for decades for all participants. Conversely, distress facilitated psychological growth for redefining "self" and role as parents over time. Building on this phenomenological cameo, future research can educate against the plight of 22q11DS families. It can enlighten health care professionals in buffering against associated stigma, blame, and self-doubt, and in fostering psychological well-being. (PsycINFO Database Record
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/hea0000415DOI Listing
January 2017

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition.

J Neurodev Disord 2016 17;8:30. Epub 2016 Aug 17.

School of Psychology, University of Newcastle, Callaghan, Australia ; Hunter Medical Research Institute, Newcastle, Australia ; Priority Research Centre GrowUpWell, The University of Newcastle, Callaghan, Australia ; School of Psychology, University of Newcastle, Science Offices, Ourimbah, NSW 2258 Australia.

Background: People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills.

Methods: A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery.

Results: The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group.

Conclusions: The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s11689-016-9164-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988033PMC
August 2016

Association between domestic water hardness, chlorine, and atopic dermatitis risk in early life: A population-based cross-sectional study.

J Allergy Clin Immunol 2016 08 28;138(2):509-16. Epub 2016 Apr 28.

Children's Allergies Department, Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom; St John's Institute of Dermatology, Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom. Electronic address:

Background: Domestic water hardness and chlorine have been suggested as important risk factors for atopic dermatitis (AD).

Objective: We sought to examine the link between domestic water calcium carbonate (CaCO3) and chlorine concentrations, skin barrier dysfunction (increased transepidermal water loss), and AD in infancy.

Methods: We recruited 1303 three-month-old infants from the general population and gathered data on domestic water CaCO3 (in milligrams per liter) and chlorine (Cl2; in milligrams per liter) concentrations from local water suppliers. At enrollment, infants were examined for AD and screened for filaggrin (FLG) skin barrier gene mutation status. Transepidermal water loss was measured on unaffected forearm skin.

Results: CaCO3 and chlorine levels were strongly correlated. A hybrid variable of greater than and less than median levels of CaCO3 and total chlorine was constructed: a baseline group of low CaCO3/low total chlorine (CaL/ClL), high CaCO3/low total chlorine (CaH/ClL), low CaCO3/high total chlorine (CaL/ClH) and high CaCO3/high total chlorine (CaH/ClH). Visible AD was more common in all 3 groups versus the baseline group: adjusted odds ratio (AOR) of 1.87 (95% CI, 1.25-2.80; P = .002) for the CaH/ClL group, AOR of 1.46 (95% CI, 0.97-2.21; P = .07) for the CaL/ClH, and AOR of 1.61 (95% CI, 1.09-2.38; P = .02) for the CaH/ClH group. The effect estimates were greater in children carrying FLG mutations, but formal interaction testing between water quality groups and filaggrin status was not statistically significant.

Conclusions: High domestic water CaCO3 levels are associated with an increased risk of AD in infancy. The influence of increased total chlorine levels remains uncertain. An intervention trial is required to see whether installation of a domestic device to decrease CaCO3 levels around the time of birth can reduce this risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2016.03.031DOI Listing
August 2016

Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells.

J Allergy Clin Immunol 2016 08 2;138(2):482-490.e7. Epub 2016 Mar 2.

Department of Dermatology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom; MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom. Electronic address:

Background: Mutations in the gene encoding filaggrin (FLG), an epidermal structural protein, are the strongest risk factor identified for the development of atopic dermatitis (AD). Up to 50% of patients with moderate-to-severe AD in European populations have FLG-null alleles compared with a general population frequency of 7% to 10%.

Objective: This study aimed to investigate the relationship between FLG-null mutations and epidermal antigen-presenting cell (APC) maturation in subjects with and without AD. Additionally, we investigated whether the cis isomer of urocanic acid (UCA), a filaggrin breakdown product, exerts immunomodulatory effects on dendritic cells.

Methods: Epidermal APCs from nonlesional skin were assessed by using flow cytometry (n = 27) and confocal microscopy (n = 16). Monocyte-derived dendritic cells from healthy volunteers were used to assess the effects of cis- and trans-UCA on dendritic cell phenotype by using flow cytometry (n = 11).

Results: Epidermal APCs from FLG-null subjects had increased CD11c expression. Confocal microscopy confirmed this and additionally revealed an increased number of epidermal CD83(+) Langerhans cells in FLG-null subjects. In vitro differentiation in the presence of cis-UCA significantly reduced costimulatory molecule expression on monocyte-derived dendritic cells from healthy volunteers and increased their ability to induce a regulatory T-cell phenotype in mixed lymphocyte reactions.

Conclusions: We show that subjects with FLG-null mutations have more mature Langerhans cells in nonlesional skin irrespective of whether they have AD. We also demonstrate that cis-UCA reduces maturation of dendritic cells and increases their capacity to induce regulatory T cells, suggesting a novel link between filaggrin deficiency and immune dysregulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2015.11.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422581PMC
August 2016

Filaggrin genotype does not determine the skin's threshold to UV-induced erythema.

J Allergy Clin Immunol 2016 Apr 29;137(4):1280-1282.e3. Epub 2016 Jan 29.

Dermatology and Genetic Medicine, Medical Research Institute, College of Medicine, Dentistry and Nursing, Ninewells Hospital and Medical School, Dundee, United Kingdom. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2015.11.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819769PMC
April 2016

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

Nat Genet 2015 Dec 19;47(12):1449-1456. Epub 2015 Oct 19.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753676PMC
December 2015

Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis.

J Allergy Clin Immunol 2015 Dec 11;136(6):1573-1580.e2. Epub 2015 Jun 11.

Coronel Institute of Occupational Health, Academic Medical Center, Amsterdam, The Netherlands. Electronic address:

Background: Loss-of-function (LOF) mutations in the filaggrin gene (FLG) are a well-replicated risk factor for atopic dermatitis (AD) and are known to cause an epidermal barrier defect. The nature of this barrier defect is not fully understood. Patients with AD with FLG LOF mutations are known to have more persistent disease, more severe disease, and greater risk of food allergies and eczema herpeticum. Abnormalities in corneocyte morphology have been observed in patients with AD, including prominent villus-like projections (VP); however, these ultrastructural features have not been systematically studied in patients with AD in relation to FLG genotype and acute and convalescent status.

Objective: We sought to quantitatively explore the relationship between FLG genotype, filaggrin breakdown products (natural moisturizing factor [NMF]), and corneocyte morphology in patients with AD.

Methods: We studied 15 children at first presentation of AD and after 6 weeks of standard therapy. We applied atomic force microscopy to study corneocyte conformation in patients with AD stratified by FLG status and NMF level. By using a new quantitative methodology, the number of VPs per investigated corneocyte area was assessed and expressed as the Dermal Texture Index score. Corneocytes were also labeled with an anti-corneodesmosin antibody and visualized with scanning electron microscopy.

Results: We found a strong correlation between NMF levels and Dermal Texture Index scores in both acute and convalescent states (respective r = -0.80 and -0.75, P < .001 and P = .002). Most, but not all, VPs showed the presence of corneodesmosin abundantly all over the cell surface in homozygous/compound heterozygous FLG patients and, to a lesser extent, in heterozygous and wild-type patients.

Conclusions: NMF levels are highly correlated with corneocyte morphology in patients with AD. These corneocyte conformational changes shed further insight into the filaggrin-deficient phenotype and help explain the barrier defect in patients with AD with FLG LOF mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2015.04.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669308PMC
December 2015

An fMRI study of facial emotion processing in children and adolescents with 22q11.2 deletion syndrome.

J Neurodev Disord 2015 2;7(1). Epub 2015 Jan 2.

Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King's College London, London, UK.

Background: 22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood.

Methods: We used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9-17 years) and healthy controls (aged 8-17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls.

Results: Within groups, contrasts showed that individuals significantly activated 'face responsive' areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between-group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment-social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum.

Conclusions: Regions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1866-1955-7-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429366PMC
May 2015

Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.

J Allergy Clin Immunol 2015 Apr 22;135(4):930-935.e1. Epub 2015 Jan 22.

National Children's Research Centre, Dublin, Ireland; Paediatric Dermatology, Our Lady's Children's Hospital, Dublin, Ireland; Clinical Medicine, Trinity College Dublin, Dublin, Ireland. Electronic address:

Background: Loss-of-function mutations in the skin barrier protein filaggrin (FLG) are a major risk for atopic dermatitis (AD). The pathogenic sequence of disturbances in skin barrier function before or during the early development of AD is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, noninvasive test to identify babies at high risk of AD would be important in planning early intervention and/or prevention studies.

Objectives: To ascertain whether a noninvasive measurement of skin barrier function at day 2 after birth and at 2 months predicts the development of AD at 1 year. Furthermore, to determine whether increases in transepidermal water loss (TEWL) predate the development of clinical AD.

Methods: A total of 1903 infants were enrolled in the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study from July 2009 to October 2011. Measurements of TEWL were made at birth (day 2) and at 2 and 6 months. The presence of AD was ascertained at 6 and 12 months, and disease severity was assessed by using the SCORing Atopic Dermatitis clinical tool at 6 months and by using both the SCORing Atopic Dermatitis clinical tool and Nottingham Severity Score at 12 months. A total of 1300 infants were genotyped for FLG mutations.

Results: At 6 months, 18.7% of the children had AD, and at 12 months, 15.53%. In a logistic regression model, day 2 upper quartile TEWL measurement was significantly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.81; P < .05). Lowest quartile day 2 TEWL was protective against AD at 12 months. An upper quartile 2 month TEWL was also strongly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.84; P < .05). At both ages, this effect was independent of parental atopy, FLG status, or report of an itchy flexural rash at 2 months. Associations were increased when parental atopy status or child FLG mutation status was added into the linear regression model.

Conclusions: Impairment of skin barrier function at birth and at 2 months precedes clinical AD. In addition to providing important mechanistic insights into disease pathogenesis, these findings have implications for the optimal timing of interventions for the prevention of AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2014.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382348PMC
April 2015

Parents with serious mental illness: differences in internalised and externalised mental illness stigma and gender stigma between mothers and fathers.

Psychiatry Res 2015 Feb 28;225(3):723-33. Epub 2014 Sep 28.

School of Psychology, Faculty of Science and Information Technology, University of Newcastle, Ourimbah, NSW, Australia; Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia. Electronic address:

Research demonstrates that people living with serious mental illness (SMI) contend with widespread public stigma; however, little is known about the specific experiences of stigma that mothers, and in particular fathers, with SMI encounter as parents. This study aimed to explore and compare the experiences of stigma for mothers and fathers with SMI inferred not only by living with a mental illness but also potential compounding gender effects, and the associated impact of stigma on parenting. Telephone surveys were conducted with 93 participants with SMI who previously identified as parents in the Second Australian National Survey of Psychosis. Results indicated that mothers were more likely than fathers to perceive and internalise stigma associated with their mental illness. Conversely, fathers were more inclined to perceive stigma relating to their gender and to hold stigmatising attitudes towards others. Mental illness and gender stigma predicted poorer self-reported parenting experiences for both mothers and fathers. These findings may assist in tailoring interventions for mothers and fathers with SMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2014.09.010DOI Listing
February 2015

Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome.

Am J Psychiatry 2014 Jun;171(6):627-39

Objective: Chromosome 22q11.2 deletion syndrome is a neurogenetic disorder associated with high rates of schizophrenia and other psychiatric conditions. The authors report what is to their knowledge the first large-scale collaborative study of rates and sex distributions of psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome. The associations among psychopathology, intellect, and functioning were examined in a subgroup of participants.

Method: The 1,402 participants with 22q11.2 deletion syndrome, ages 6–68 years, were assessed for psychiatric disorders with validated diagnostic instruments. Data on intelligence and adaptive functioning were available for 183 participants ages 6 to 24 years.

Results: Attention deficit hyperactivity disorder (ADHD) was the most frequent disorder in children (37.10%) and was overrepresented in males. Anxiety disorders were more prevalent than mood disorders at all ages, but especially in children and adolescents. Anxiety and unipolar mood disorders were overrepresented in females. Psychotic disorders were present in 41% of adults over age 25. Males did not predominate in psychotic or autism spectrum disorders. Hierarchical regressions in the subgroup revealed that daily living skills were predicted by the presence of anxiety disorders. Psychopathology was not associated with communication or socialization skills.

Conclusions: To the authors’ knowledge, this is the largest study of psychiatric morbidity in 22q11.2 deletion syndrome. It validates previous findings that this condition is one of the strongest risk factors for psychosis. Anxiety and developmental disorders were also prevalent. These results highlight the need to monitor and reduce the long-term burden of psychopathology in 22q11.2 deletion syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ajp.2013.13070864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285461PMC
June 2014
-->