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1.
Pediatr Res ; 93(5): 1399-1409, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34997222

RESUMO

BACKGROUND: This study examined differences in ADHD symptoms and diagnosis between preterm and term-born adults (≥18 years), and tested if ADHD is related to gestational age, birth weight, multiple births, or neonatal complications in preterm borns. METHODS: (1) A systematic review compared ADHD symptom self-reports and diagnosis between preterm and term-born adults published in PubMed, Web of Science, and PROQUEST until April 2021; (2) a one-stage Individual Participant Data(IPD) meta-analysis (n = 1385 preterm, n = 1633 term; born 1978-1995) examined differences in self-reported ADHD symptoms[age 18-36 years]; and (3) a population-based register-linkage study of all live births in Finland (01/01/1987-31/12/1998; n = 37538 preterm, n = 691,616 term) examined ADHD diagnosis risk in adulthood (≥18 years) until 31/12/2016. RESULTS: Systematic review results were conflicting. In the IPD meta-analysis, ADHD symptoms levels were similar across groups (mean z-score difference 0.00;95% confidence interval [95% CI] -0.07, 0.07). Whereas in the register-linkage study, adults born preterm had a higher relative risk (RR) for ADHD diagnosis compared to term controls (RR = 1.26, 95% CI 1.12, 1.41, p < 0.001). Among preterms, as gestation length (RR = 0.93, 95% CI 0.89, 0.97, p < 0.001) and SD birth weight z-score (RR = 0.88, 95% CI 0.80, 0.97, p < 0.001) increased, ADHD risk decreased. CONCLUSIONS: While preterm adults may not report higher levels of ADHD symptoms, their risk of ADHD diagnosis in adulthood is higher. IMPACT: Preterm-born adults do not self-report higher levels of ADHD symptoms, yet are more likely to receive an ADHD diagnosis in adulthood compared to term-borns. Previous evidence has consisted of limited sample sizes of adults and used different methods with inconsistent findings. This study assessed adult self-reported symptoms across 8 harmonized cohorts and contrasted the findings with diagnosed ADHD in a population-based register-linkage study. Preterm-born adults may not self-report increased ADHD symptoms. However, they have a higher risk of ADHD diagnosis, warranting preventive strategies and interventions to reduce the presentation of more severe ADHD symptomatology in adulthood.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Adulto , Adolescente , Adulto Jovem , Peso ao Nascer , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Idade Gestacional , Parto , Gravidez Múltipla , Nascimento Prematuro/prevenção & controle
2.
Aust N Z J Psychiatry ; 57(7): 966-974, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36448198

RESUMO

OBJECTIVE: Long-term studies following disasters are rare. It is important to quantify long-term effects of disasters to determine impacts on populations over time. We therefore aim to report the long-term associations between exposure to the Canterbury earthquakes and common mental disorders, taking into account potential confounding factors. METHODS: The Christchurch Health and Development Study is a 40-year longitudinal study of a birth cohort of New Zealand children (635 males and 630 females). The Christchurch Health and Development Study includes 884 participants with data on earthquake exposure and mental health outcomes at ages 34 and 40 years. Rates of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) disorders were measured categorically and using an expanded definition that included sub-syndromal symptoms. The current impact of the earthquakes is reported using 12-month prevalence data 7 years after the earthquakes. The cumulative impact of the earthquakes over the 7 years since onset is also reported. RESULTS: There was a linear trend towards increasing rates of disorder with increasing exposure to the earthquakes. After adjusting for covariates, the 12-month prevalence of anxiety disorder symptoms was significantly increased (p = 0.003). The earthquakes were also associated with cumulative increases in symptoms of post-traumatic stress disorder (p < 0.001), anxiety disorder (p = 0.016), nicotine dependence (p = 0.012), and the total number of disorders (p = 0.039). CONCLUSION: The Canterbury earthquakes were associated with persistent increases in Anxiety Disorder symptoms 7 years after their onset. The earthquakes were also associated with cumulative increases in symptoms of common psychiatric disorders. The magnitude of these effects is small, may no longer be clinically significant and has decreased over time.


Assuntos
Desastres , Terremotos , Transtornos de Estresse Pós-Traumáticos , Masculino , Criança , Feminino , Humanos , Saúde Mental , Estudos Longitudinais , Transtornos de Ansiedade/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Nova Zelândia/epidemiologia
3.
Pediatr Res ; 91(6): 1436-1444, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34923577

RESUMO

BACKGROUND: This paper examines the visuospatial working memory (WM) performance of children and adults born very preterm (VPT) and/or very low birth weight (VLBW) relative to their full-term (FT)-born peers. Of interest was the nature and severity of observed impairments, as well associations with educational/occupational functioning at each age point. METHODS: Participants were drawn from two prospective cohort studies: (1) a regional cohort of 110 VPT (<32 weeks' gestation and <1500 g) and 113 FT born children assessed at age 12 years; (2) a national cohort of 229 VLBW (<1500 g) and 100 FT born adults assessed at age 28 years. Visuospatial WM was assessed using a four-span/difficulty-level computerized task. RESULTS: Both children and adults born VPT/VLBW had poorer visuospatial WM than FT controls, with their performance less accurate, slower (correct trials), and less efficient with increasing task difficulty (Cohen's d = 0.27-0.51; p < 0.05). Adults had better visuospatial WM than children, but between-group differences were highly similar across ages, before and after adjustment for confounding social background and individual factors. Poorer WM was associated with lower levels of educational and occupational/socioeconomic achievement. CONCLUSIONS: Visuospatial WM difficulties persist into adulthood raising concerns for the longer-term cognitive and adaptive functioning of VPT survivors. IMPACT: Both children and adults born very preterm have poorer visuospatial working memory than their term-born peers. They are less accurate, take longer to respond correctly and are less efficient, with test performance declining with increasing cognitive demand. Similar differences in visuospatial working memory are observed between VPT/VLBW and full-term individuals during both childhood and adulthood, with these differences remaining even after covariate adjustment. Individuals with poorer visuospatial working memory have lower levels of educational achievement and occupational/socioeconomic success. Visuospatial working memory difficulties persist into adulthood and appear to continue to impact everyday functioning and life-course opportunities.


Assuntos
Lactente Extremamente Prematuro , Memória de Curto Prazo , Adulto , Criança , Cognição , Humanos , Lactente Extremamente Prematuro/psicologia , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Estudos Prospectivos
4.
Paediatr Perinat Epidemiol ; 36(5): 631-639, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35570644

RESUMO

BACKGROUND: Antenatal corticosteroids (ACS) given to mothers with anticipated very preterm delivery are widely used and improve infant outcomes. Follow-up studies of the first trials of ACS have shown no adverse effects, but recently there have been concerns about possible longer-term harms. OBJECTIVES: We aimed to assess the relationship of ACS therapy to a range of physical health and welfare measures in a cohort of very low birthweight (VLBW; <1500 g) young adults. METHODS: Population-based cohort follow-up study. All VLBW infants born in New Zealand in 1986 were included in a prospective audit of retinopathy of prematurity. Perinatal data collection included information on ACS. At 26-30 years, 250 of 323 (77%) survivors participated, 58% having received ACS, with 229 assessed in one centre, including cardiovascular, metabolic, respiratory and neurocognitive measures. Differences in outcome between those receiving/not receiving ACS were summarised by the mean difference for continuous outcomes supplemented by Cohen's d as a standardised measure of effect size (ES), and risk ratios (RRI) for dichotomous outcomes, adjusted for relevant covariates using generalised linear regression methods. RESULTS: There were no or minimal adverse effects of receipt of ACS versus no receipt across a range of health and welfare outcomes, both for the full cohort (adjusted ES range d = 0.01-0.23; adjusted RR range 0.78-2.03) and for individuals with gestation <28 weeks (extremely preterm; EP), except for a small increase in rates of major depression. In EP adults, receipt of ACS was associated with a higher incidence of hypertension, but might have a small benefit for IQ. CONCLUSIONS: In this population-based VLBW cohort, we detected minimal adverse outcomes associated with exposure to ACS by the third decade of life, a similar result to the 30-year follow-up of participants in the first ACS trial. However, further follow-up is warranted.


Assuntos
Corticosteroides , Doenças do Prematuro , Corticosteroides/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Parto , Gravidez , Adulto Jovem
5.
Paediatr Perinat Epidemiol ; 36(5): 643-653, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35604649

RESUMO

BACKGROUND: Executive function difficulties are common among children born very preterm and/or very low birthweight (<1500 g; VLBW), but little is known about whether they persist into adulthood. OBJECTIVES: Examine the nature and pattern of self-reported executive functioning at 23 and 28 years of age using data from a national cohort study of adults born VLBW and a comparison group of same-age full-term (FT) born adults. Also examined were associations between executive function difficulties and socio-economic outcomes. METHODS: All infants born VLBW in New Zealand during 1986 were prospectively included in an audit of retinopathy of prematurity (n = 413), with 250 (77% of survivors) followed to median age 28 years. A comparison group of FT adults was also recruited at age 23 and followed to 28 years (n = 100). Across both adult assessments, executive functioning was assessed using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) and analysed with semi-parametric models to examine the effects of age and group on executive function. RESULTS: At 23 and 28 years, VLBW adults had increased risk of executive function impairment compared with FT adults in behaviour regulation (relative risk [CI] 2.37, 95% confidence interval (CI)1.27, 4.45), meta-cognition (RR 6.03, 95% CI 2.18, 16.78) and global functioning (RR 3.20, 95% CI 1.40, 7.28). Impaired global executive functioning was associated with lower socio-economic status (regression estimate [b] = -0.43, 95% CI -0.59, -0.27) and a reduced likelihood of home ownership by age 28 years (RR 0.98, 95% CI 0.96, 1.00), even after controlling for sex, ethnicity and parental socio-economic backgrounds for both groups. CONCLUSION(S): VLBW-born adults continue to experience more executive function difficulties in their everyday life relative to term controls at age 28 years. These difficulties were negatively associated with their socio-economic opportunities as young adults.


Assuntos
Função Executiva , Recém-Nascido de muito Baixo Peso , Adulto , Criança , Estudos de Coortes , Função Executiva/fisiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso/fisiologia , Pais , Autorrelato , Adulto Jovem
6.
Reprod Fertil Dev ; 34(7): 540-548, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35412968

RESUMO

Maternal tobacco smoking during pregnancy is a large driver of health inequalities and a higher prevalence of conduct problem (CP) has been observed in exposed offspring. Further, maternal tobacco use during pregnancy can also alter offspring DNA methylation. However, currently, limited molecular evidence has been found to support this observation. Thus we aim to examine the association between maternal tobacco use in pregnancy and offspring CP, to determine whether offspring CP is mediated by tobacco exposure-induced DNA methylation differences. Understanding the etiology of the association between maternal tobacco use and offspring CP will be crucial in the early identification and treatment of CP in children and adolescents. Here, a sub group of N =96 individuals was sourced from the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years in New Zealand. Whole blood samples underwent bisulphite-based amplicon sequencing at 10 loci known to play a role in neurodevelopment, or which had associations with CP phenotypes. We identified significant (P CYP1A1 , ASH2L and MEF2C in individuals with CP who were exposed to tobacco in utero . We conclude that environmentally-induced DNA methylation differences could play a role in the observed link between maternal tobacco use during pregnancy and childhood/adolescent CP. However, larger sample sizes are needed to produce an adequate amount of power to investigate this interaction further.


Assuntos
Metilação de DNA , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Sulfitos , Uso de Tabaco
7.
Nicotine Tob Res ; 22(11): 2006-2013, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31408171

RESUMO

INTRODUCTION: Unemployment has been related to smoking, yet the causal nature of the association is subject to continued debate. Social causation argues that unemployment triggers changes in smoking, whereas the social selection hypothesis proposes that pre-existing smoking behavior lowers the probability of maintaining employment. The present study tested these competing explanations while accounting for another alternative explanation-common liability. METHODS: Data were from the Christchurch Health and Development Study, a longitudinal cohort followed from birth to age 35. Odds were generated for having nicotine dependence in models for social causation and being unemployed in models for social selection. These models were extended to include possible common liability factors during childhood (eg, novelty seeking) and young adulthood (eg, major depression). RESULTS: In the model testing social causation, coefficients representing the impacts of unemployment on nicotine dependence remained statistically significant and robust (odds ratio [OR] = 1.55; 95% confidence interval [CI] = 1.20, 2.00), even after accounting for common determinant measures. In contrast, a reverse social selection model revealed that coefficients representing the impacts of nicotine dependence on unemployment substantially attenuated and became statistically nonsignificant as childhood factors were added (OR = 1.14; 95% CI = 0.90, 1.45). CONCLUSIONS: Unemployment may serve as inroads to nicotine addiction among young adults, not the other way, even in the context of nicotine dependence, a more impaired form of smoking that may arguably hold higher potential to generate social selection processes. This social causation process cannot be completely attributable to common determinant factors. IMPLICATIONS: It is critical to clarify whether unemployment triggers changes in smoking behaviors (ie, social causation) or vice versa (ie, social selection)-the answers to the question will lead to public health strategies with very different intervention targets to break the linkage. The current study findings favor social causation over social selection, regardless of gender, and support a needed shift in service profiles for unemployed young adults-from a narrow focus on job skills training to a more holistic approach that incorporates knowledge from addiction science in which unemployed young adults can find needed services to cope with job loss.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Características de Residência/estatística & dados numéricos , Meio Social , Fatores Socioeconômicos , Tabagismo/epidemiologia , Tabagismo/psicologia , Desemprego/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Nova Zelândia/epidemiologia , Desemprego/estatística & dados numéricos , Adulto Jovem
8.
Dev Med Child Neurol ; 62(12): 1423-1428, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32767385

RESUMO

AIM: To determine IQ at 26 to 30 years in very-low-birthweight (VLBW) adults compared with term-born controls; and to examine the stability of IQ in VLBW individuals between 7 to 8 years and 26 to 30 years, identify perinatal and social predictors of IQ, and assess the contribution of brain volume to IQ. METHOD: At 26 to 30 years, 229 VLBW adults (71% survivors of prospectively enrolled national cohort) and 100 term-born controls were tested on the Wechsler Abbreviated Scale of Intelligence. For VLBW, IQ at 7 to 8 years, perinatal and social data were extracted from the data set, and 150 adults underwent volumetric cranial magnetic resonance imaging (MRI). RESULTS: At 26 to 30 years, the mean adjusted difference between VLBW and controls for total IQ was 9.4 (95% CI 6.5-12.4) points. In VLBW individuals the correlation between IQ scores at 7 to 8 years and 26 to 30 years was 0.78. On multiple regression analysis, parental education was the strongest predictor of verbal and total IQ at both ages. Birthweight was a strong predictor of perceptual and total IQ. In VLBW individuals with MRI scans, the addition of brain volume as a variable increased the variance explained for perceptual and total IQ. INTERPRETATION: VLBW adults have mean IQ scores 9 to 11 points below controls. Parental education and birthweight are the strongest predictors of IQ.


Assuntos
Peso ao Nascer/fisiologia , Encéfalo/anatomia & histologia , Desenvolvimento Humano/fisiologia , Recém-Nascido de muito Baixo Peso/fisiologia , Inteligência/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Criança , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Escalas de Wechsler
9.
Aust N Z J Psychiatry ; 54(11): 1095-1100, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32900208

RESUMO

OBJECTIVE: The International Classification of Diseases, 11th Revision classification of personality disorder removes all categories of disorder in favour of a single diagnostic spectrum extending from no personality dysfunction to severe personality disorder. Following concerns from some clinicians and Personality Disorder Societies, it was subsequently agreed to include a borderline pattern descriptor as a qualifier of the main diagnosis. We explore the value of this additional descriptor by examining personality data in patients with major depression. METHOD: We examined personality data obtained using the Structured Clinical Interview for Personality Disorder-II in 606 patients enrolled in five randomised controlled trials of depression. The Structured Clinical Interview for Personality Disorder-II uses the Diagnostic and Statistical Manual of Mental Disorders categorical system, which includes borderline personality disorder. The International Classification of Diseases, 11th Revision classification has five domain traits. Each of the Diagnostic and Statistical Manual of Mental Disorders personality disorder symptoms or behaviours from Structured Clinical Interview for Personality Disorder-II was reordered into the five domains independently by two assessors. The relationship between the two systems was examined by tabular and correlational analysis. RESULTS: The findings showed that the symptoms of borderline personality disorder were associated with greater severity of personality disturbance in the International Classification of Diseases, 11th Revision classification (p < 0.0001) and were associated primarily with the Negative Affective, Dissocial and Disinhibited domains. There was only a weak association with the other two domains, Anankastia and Detachment. CONCLUSION: The addition of a borderline pattern descriptor is likely to add little to the International Classification of Diseases, 11th Revision classification of personality disorder. Its features are well represented within the severity/domain structure, which allows for more fine-grained description of the personality features that constitute the borderline concept.


Assuntos
Transtorno da Personalidade Borderline/classificação , Classificação Internacional de Doenças , Transtornos da Personalidade/classificação , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Personalidade
10.
J Pediatr ; 206: 128-133.e5, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30545563

RESUMO

OBJECTIVE: To assess the physical well-being and components of the metabolic syndrome in a national cohort of very low birth weight (VLBW) young adults and same age controls. STUDY DESIGN: The New Zealand VLBW Study cohort prospectively included all infants with birth weight <1500 g born in 1986, with 338 (82%) surviving to discharge home. Height and weight were measured at age 7-8 years. The VLBW cohort (n = 229; 71% alive) and term-born controls (n = 100) aged 27-29 years were clinically assessed in a single center over 2 days, including assessment for components of the metabolic syndrome. RESULTS: Compared with controls, both male and female VLBW adults were significantly shorter (P < .001), but only females were lighter (P < .001) and had lower mean body mass index (P = .044), fat mass, and body fat percentage. Males, but not females, had significantly higher systolic blood pressure (P = .028), but there were no significant differences in other components of the metabolic syndrome. There was no difference in the prevalence of the metabolic syndrome in VLBW adults compared with controls (males, 22.2% vs 11.1%; P = .15: females, 12.8% vs 13.1%; P = .95). Examining the VLBW cohort with logistic regression, male sex, gestational age <28 weeks, Maori/Pacific Island ethnicity, and body mass index >90th percentile at age 7-8 years were significant predictors for the metabolic syndrome at age 27-29 years, with ORs of 2-4. CONCLUSIONS: Systolic blood pressure in males was the only component of the metabolic syndrome that was significantly elevated in VLBW adults compared with controls. Extreme prematurity (<28 weeks) and body mass index >90th percentile at age 7-8 years were significant predictors of the metabolic syndrome at age 27-29 years. TRIAL REGISTRATION: Registered at the Australian Clinical Trials Registry: ACTRN12612000995875.


Assuntos
Peso ao Nascer , Síndrome Metabólica/epidemiologia , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Modelos Logísticos , Masculino , Nova Zelândia , Prevalência , Adulto Jovem
11.
Br J Psychiatry ; 214(3): 153-158, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30774061

RESUMO

BACKGROUND: The extent to which exposure to childhood sexual and physical abuse increases the risk of psychotic experiences in adulthood is currently unclear.AimsTo examine the relationship between childhood sexual and physical abuse and psychotic experiences in adulthood taking into account potential confounding and time-dynamic covariate factors. METHOD: Data were from a cohort of 1265 participants studied from birth to 35 years. At ages 18 and 21, cohort members were questioned about childhood sexual and physical abuse. At ages 30 and 35, they were questioned about psychotic experiences (symptoms of abnormal thought and perception). Generalised estimating equation models investigated covariation of the association between abuse exposure and psychotic experiences including potential confounding factors in childhood (socioeconomic disadvantage, adverse family functioning) and time-dynamic covariate factors (mental health, substance use and life stress). RESULTS: Data were available for 962 participants; 6.3% had been exposed to severe sexual abuse and 6.4% to severe physical abuse in childhood. After adjustment for confounding and time-dynamic covariate factors, those exposed to severe sexual abuse had rates of abnormal thought and abnormal perception symptoms that were 2.25 and 4.08 times higher, respectively than the 'no exposure' group. There were no significant associations between exposure to severe physical abuse and psychotic experiences. CONCLUSIONS: Findings indicate that exposure to severe childhood sexual (but not physical) abuse is independently associated with an increased risk of psychotic experiences in adulthood (particularly symptoms of abnormal perception) and this association could not be fully accounted for by confounding or time-dynamic covariate factors.Declaration of interestNone.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Transtornos Psicóticos/psicologia , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco , Estresse Psicológico/psicologia , Adulto Jovem
12.
Clin Chem ; 64(2): 363-373, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29097512

RESUMO

BACKGROUND: In community studies, plasma B-type natriuretic peptide (BNP) is positively associated with cardiovascular disorders. Those born with very low birth weight (VLBW) have increased risk of metabolic and vascular disorders in later life, but plasma concentrations of natriuretic peptides have not been studied. The objectives here were to evaluate BNP and C-type natriuretic peptide (CNP)-a putative marker of vascular risk-in young adults born with VLBW. METHODS: In all, 220 VLBW cases and 97 matched controls were studied 28 years after birth during a 2-day period at 1 research center. Aminoterminal (NT) products (NTproBNP, NTproCNP) and a range of conventional vascular risk factors including echocardiographic indices were measured along with genetic polymorphisms known to increase plasma NTproBNP. RESULTS: VLBW individuals were smaller, had smaller hearts, reduced stroke volume and endothelial function, and higher systolic blood pressure and arterial elastance. Of the many humoral vascular and metabolic risk factors measured, including NTproBNP, only plasma NTproCNP (higher in VLBW individuals) differed significantly. Across all individuals, associations of NTproCNP with each of 7 conventional risk factors, as well as with arterial elastance, were positive, whereas associations of NTproBNP with risk were all inverse. In multivariate analysis, the genetic variant rs198358 was independently associated with NTproBNP. CONCLUSIONS: In young adults at increased risk of cardiovascular disease, higher NTproCNP likely reflects a compensatory vascular response to vascular stress, whereas the negative link with NTproBNP likely reflects beneficial genetic mutations. The ratio of NTproBNP to NTproCNP may provide a novel index of ideal cardiovascular health.


Assuntos
Recém-Nascido de muito Baixo Peso , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Tipo C/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Ecocardiografia , Feminino , Humanos , Recém-Nascido , Masculino , Síndrome Metabólica/sangue , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Peptídeo Natriurético Tipo C/genética , Peptídeo Natriurético Tipo C/metabolismo , Estudos Prospectivos , Fatores de Risco , Transdução de Sinais/genética
13.
Am J Physiol Endocrinol Metab ; 313(2): E183-E194, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28487438

RESUMO

A genome-wide association study (GWAS) reported that common variation in the human Niemann-Pick C1 gene (NPC1) is associated with morbid adult obesity. This study was confirmed using our BALB/cJ Npc1 mouse model, whereby heterozygous mice (Npc1+/- ) with decreased gene dosage were susceptible to weight gain when fed a high-fat diet (HFD) compared with homozygous normal mice (Npc1+/+ ) fed the same diet. The objective for our current study was to validate this Npc1 gene-diet interaction using statistical modeling with fitted growth trajectories, conduct body weight analyses for different measures, and define the physiological basis responsible for weight gain. Metabolic phenotype analysis indicated no significant difference between Npc1+/+ and Npc1+/- mice fed a HFD for food and water intake, oxygen consumption, carbon dioxide production, locomotor activity, adaptive thermogenesis, and intestinal lipid absorption. However, the livers from Npc1+/- mice had significantly increased amounts of mature sterol regulatory element-binding protein-1 (SREBP-1) and increased expression of SREBP-1 target genes that regulate glycolysis and lipogenesis with an accumulation of triacylglycerol and cholesterol. Moreover, white adipose tissue from Npc1+/- mice had significantly decreased amounts of phosphorylated hormone-sensitive lipase with decreased triacylglycerol lipolysis. Consistent with these results, cellular energy metabolism studies indicated that Npc1+/- fibroblasts had significantly increased glycolysis and lipogenesis, in addition to significantly decreased substrate (glucose and endogenous fatty acid) oxidative metabolism with an accumulation of triacylglycerol and cholesterol. In conclusion, these studies demonstrate that the Npc1 gene interacts with a HFD to promote weight gain through differential regulation of central energy metabolism pathways.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/genética , Interação Gene-Ambiente , Redes e Vias Metabólicas/genética , Proteínas/fisiologia , Aumento de Peso/genética , Animais , Células Cultivadas , Regulação da Expressão Gênica/genética , Peptídeos e Proteínas de Sinalização Intracelular , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Proteína C1 de Niemann-Pick , Proteínas/genética
14.
BMC Med Genet ; 18(1): 12, 2017 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-28158988

RESUMO

BACKGROUND: The genetic and environmental influences on human personality and behaviour are a complex matter of ongoing debate. Accumulating evidence indicates that short tandem repeats (STRs) in regulatory regions are good candidates to explain heritability not accessed by genome-wide association studies. METHODS: We tested for associations between the genotypes of four selected repeats and 18 traits relating to personality, behaviour, cognitive ability and mental health in a well-studied longitudinal birth cohort (n = 458-589) using one way analysis of variance. The repeats were a highly conserved poly-AC microsatellite in the upstream promoter region of the T-box brain 1 (TBR1) gene and three previously studied STRs in the activating enhancer-binding protein 2-beta (AP2-ß) and androgen receptor (AR) genes. Where significance was found we used multiple regression to assess the influence of confounding factors. RESULTS: Carriers of the shorter, most common, allele of the AR gene's GGN microsatellite polymorphism had fewer anxiety-related symptoms, which was consistent with previous studies, but in our study this was not significant following Bonferroni correction. No associations with two repeats in the AP2-ß gene withstood this correction. A novel finding was that carriers of the minor allele of the TBR1 AC microsatellite were at higher risk of conduct problems in childhood at age 7-9 (p = 0.0007, which did pass Bonferroni correction). Including maternal smoking during pregnancy (MSDP) in models controlling for potentially confounding influences showed that an interaction between TBR1 genotype and MSDP was a significant predictor of conduct problems in childhood and adolescence (p < 0.001), and of self-reported criminal behaviour up to age 25 years (p ≤ 0.02). This interaction remained significant after controlling for possible confounders including maternal age at birth, socio-economic status and education, and offspring birth weight. CONCLUSIONS: The potential functional importance of the TBR1 gene's promoter microsatellite deserves further investigation. Our results suggest that it participates in a gene-environment interaction with MDSP and antisocial behaviour. However, previous evidence that mothers who smoke during pregnancy carry genes for antisocial behaviour suggests that epistasis may influence the interaction.


Assuntos
Comportamento , Cognição , Repetições de Microssatélites/genética , Adolescente , Adulto , Alelos , Criança , Comportamento Criminoso , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Desequilíbrio de Ligação , Estudos Longitudinais , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Gravidez , Regiões Promotoras Genéticas , Receptores Androgênicos/genética , Fumar , Proteínas com Domínio T/genética , Fator de Transcrição AP-2/genética , Adulto Jovem
15.
J Head Trauma Rehabil ; 32(6): E24-E28, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28060210

RESUMO

OBJECTIVE: To investigate the concordance between medically documented childhood traumatic brain injury (TBI) and recall of same by adults aged 35 years. PARTICIPANTS: A total of 962 birth cohort members from the Christchurch Health and Development Study available at the 35-year follow-up. MAIN MEASURES: Childhood TBI information prospectively collected yearly over ages 0 to 15 years as part of the Christchurch Health and Development Study. At age 35 years, cohort members were administered the Ohio State University TBI Identification Method (OSU TBI-ID) to elicit recall of TBIs with loss of consciousness (LOC). RESULTS: Ninety-four individuals reported 116 TBI events. Twenty-five TBI events resulting in LOC, 17 (68%) were recalled (true positives) and 8 (32%) were not recalled (false negatives). LOC was incorrectly recalled for 56 events (false positives), but 868 individuals correctly recalled no TBI event (no LOC). A further 35 events were (correctly) recalled for which a TBI had been recorded but no LOC (true negatives; 91.8%). IMPLICATIONS: We evaluated the utility of the OSU TBI-ID to identify adult recall of childhood TBI with LOC occurring 19 to 35 years earlier. Most of the cohort accurately reported whether or not they had experienced a medically attended TBI with LOC, indicating that a positive result from the OSU TBI-ID provides useful screening information.


Assuntos
Lesões Encefálicas Traumáticas/diagnóstico , Rememoração Mental , Autorrelato , Inconsciência/diagnóstico , Adulto , Fatores Etários , Lesões Encefálicas Traumáticas/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Funções Verossimilhança , Masculino , Nova Zelândia , Medidas de Resultados Relatados pelo Paciente , Valor Preditivo dos Testes , Estudos Retrospectivos , Inconsciência/epidemiologia , Adulto Jovem
16.
Aust N Z J Psychiatry ; 51(7): 711-718, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28633571

RESUMO

OBJECTIVE: Few studies have examined the contribution of specific disaster-related experiences to symptoms of depression. The aims of this study were to do this by examining the roles of peri-traumatic stress and distress due to lingering disaster-related disruption in explaining linkages between disaster exposure and major depressive disorder symptoms among a cohort exposed to the 2010-2011 Canterbury (New Zealand) earthquakes. METHODS: Structural equation models were fitted to data obtained from the Christchurch Health and Development Study at age 35 ( n = 495), 20-24 months following the onset of the disaster. Measures included earthquake exposure, peri-traumatic stress, disruption distress and symptoms of major depressive disorder. RESULTS: The associations between earthquake exposure and major depression were explained largely by the experience of peri-traumatic stress during the earthquakes (ß = 0.180, p < 0.01) and not by disruption distress following the earthquakes (ß = 0.048, p = 0.47). CONCLUSION: The results suggest that peri-traumatic stress has been under-recognised as a predictor of major depressive disorder.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Desastres/estatística & dados numéricos , Terremotos/estatística & dados numéricos , Estresse Psicológico/epidemiologia , Ferimentos e Lesões/psicologia , Adulto , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Nova Zelândia/epidemiologia
17.
J Int Neuropsychol Soc ; 22(7): 717-23, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27265159

RESUMO

BACKGROUND: Traumatic brain injury (TBI) occurs frequently during child and early adulthood, and is associated with negative outcomes including increased risk of drug abuse, mental health disorders and criminal offending. Identification of previous TBI for at-risk populations in clinical settings often relies on self-report, despite little information regarding self-report accuracy. This study examines the accuracy of adult self-report of hospitalized TBI events and the factors that enhance recall. METHODS: The Christchurch Health and Development Study is a birth cohort of 1265 children born in Christchurch, New Zealand, in 1977. A history of TBI events was prospectively gathered at each follow-up (yearly intervals 0-16, 18, 21, 25 years) using parental/self-report, verified using hospital records. RESULTS: At 25 years, 1003 cohort members were available, with 59/101 of all hospitalized TBI events being recalled. Recall varied depending on the age at injury and injury severity, with 10/11 of moderate/severe TBI being recalled. Logistic regression analysis indicated that a model using recorded loss of consciousness, age at injury, and injury severity, could accurately classify whether or not TBI would be reported in over 74% of cases. CONCLUSIONS: This research demonstrates that, even when individuals are carefully cued, many instances of TBI will not recalled in adulthood despite the injury having required a period of hospitalization. Therefore, screening for TBI may require a combination of self-report and review of hospital files to ensure that all cases are identified. (JINS, 2016, 22, 717-723).


Assuntos
Lesões Encefálicas Traumáticas/epidemiologia , Hospitalização/estatística & dados numéricos , Autorrelato/normas , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Nova Zelândia/epidemiologia , Adulto Jovem
18.
Hum Genet ; 134(1): 67-75, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25287832

RESUMO

DUF1220 protein domains exhibit the greatest human lineage-specific copy number expansion of any protein-coding sequence in the genome, and variation in DUF1220 copy number has been linked to both brain size in humans and brain evolution among primates. Given these findings, we examined associations between DUF1220 subtypes CON1 and CON2 and cognitive aptitude. We identified a linear association between CON2 copy number and cognitive function in two independent populations of European descent. In North American males, an increase in CON2 copy number corresponded with an increase in WISC IQ (R (2) = 0.13, p = 0.02), which may be driven by males aged 6-11 (R (2) = 0.42, p = 0.003). We utilized ddPCR in a subset as a confirmatory measurement. This group had 26-33 copies of CON2 with a mean of 29, and each copy increase of CON2 was associated with a 3.3-point increase in WISC IQ (R (2) = 0.22, p = 0.045). In individuals from New Zealand, an increase in CON2 copy number was associated with an increase in math aptitude ability (R (2) = 0.10 p = 0.018). These were not confounded by brain size. To our knowledge, this is the first study to report a replicated association between copy number of a gene coding sequence and cognitive aptitude. Remarkably, dosage variations involving DUF1220 sequences have now been linked to human brain expansion, autism severity and cognitive aptitude, suggesting that such processes may be genetically and mechanistically inter-related. The findings presented here warrant expanded investigations in larger, well-characterized cohorts.


Assuntos
Aptidão/fisiologia , Encéfalo/metabolismo , Proteínas de Transporte/genética , Cromossomos Humanos Par 1/genética , Cognição/fisiologia , Variações do Número de Cópias de DNA/genética , Inteligência/fisiologia , Adolescente , Adulto , Encéfalo/patologia , Criança , Hibridização Genômica Comparativa/métodos , Feminino , Seguimentos , Humanos , Masculino , Matemática , Tamanho do Órgão , Reação em Cadeia da Polimerase/métodos , Estrutura Terciária de Proteína , Adulto Jovem
19.
Twin Res Hum Genet ; 18(4): 335-47, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26081443

RESUMO

The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N=2,126, obs=12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR<0.1) and six others met our 'suggestive' criterion (FDR<0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.


Assuntos
Alcoolismo/genética , Proteínas da Membrana Plasmática de Transporte de GABA/genética , GTP Fosfo-Hidrolases/genética , Estudo de Associação Genômica Ampla , Proteínas de Transporte da Membrana Mitocondrial/genética , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/fisiopatologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem
20.
Aust N Z J Psychiatry ; 49(4): 351-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25430912

RESUMO

OBJECTIVES: Research on the impact of natural disasters on health and well-being faces several methodological challenges, including: sampling issues; exposure assessment; and outcome measurement. The present study used a comprehensive measure of disaster exposure to assess relationships between exposure to the Canterbury (New Zealand) Earthquakes of 2010-2011 and both: (a) self-reported distress and (b) positive outcomes; and also investigated gender differences in reports. METHODS: Data were gathered from the Christchurch Health and Development Study, a 35-year longitudinal study. The study examined data from 495 individuals exposed to the Canterbury Earthquakes for who complete data on exposure and reactions to the earthquakes at age 35 were available. RESULTS: Participants with higher levels of exposure to the earthquakes reported significantly (p<0.0001) higher levels of distress due to fear, death and injury, and disruption caused by the earthquakes. Higher levels of exposure to the earthquakes were also associated with significantly (p<0.0001) higher levels of reporting positive consequences following the earthquakes. Women reported significantly (p<0.0001) greater distress than men and significantly (p<0.001) greater positive consequences. CONCLUSIONS: Higher levels of exposure to disaster were associated with higher levels of distress, but also with higher levels of self-reported positive outcomes, with females reporting higher levels of both positive and negative outcomes. The findings highlight the need for comprehensive assessment of disaster exposure, to consider gender and other group differences in reactions to disaster exposure, and for studies of disasters to examine both positive and negative consequences.


Assuntos
Desastres , Terremotos , Qualidade de Vida/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Nova Zelândia , Autorrelato , Fatores Sexuais
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