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1.
Psychol Med ; : 1-11, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38494928

ABSTRACT

BACKGROUND: Emotional problems, especially anxiety, have become increasingly common in recent generations. Few population-based studies have examined trajectories of emotional problems from early childhood to late adolescence or investigated differences in psychiatric and functional outcomes. METHODS: Using the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 8286, 50.4% male), we modeled latent class growth trajectories of emotional problems, using the parent-reported Strength and Difficulties Questionnaire emotional scale (SDQ-E) on seven occasions (4-17 years). Psychiatric outcomes in young adulthood (21-25 years) were major depressive disorder (MDD), generalized anxiety disorder (GAD), and self-harm. Functional outcomes were exam attainment, educational/occupational status, and social relationship quality. RESULTS: We identified four classes of emotional problems: low (67.0%), decreasing (18.4%), increasing (8.9%), and persistent (5.7%) problems. Compared to those in the low class, individuals with decreasing emotional problems were not at elevated risk of any poor adult outcome. Individuals in the increasing and persistent classes had a greater risk of adult MDD (RR: 1.59 95% CI 1.13-2.26 and RR: 2.25 95% CI 1.49-3.41) and self-harm (RR: 2.37 95% CI 1.91-2.94 and RR: 1.87 95% CI 1.41-2.48), and of impairment in functional domains. Childhood sleep difficulties, irritability, conduct and neurodevelopmental problems, and family adversity were associated with a persistent course of emotional problems. CONCLUSIONS: Childhood emotional problems were common, but those whose symptoms improved over time were not at increased risk for adverse adult outcomes. In contrast, individuals with persistent or adolescent-increasing emotional problems had a higher risk of mental ill-health and social impairment in young adulthood which was especially pronounced for those with persistent emotional problems.

2.
J Affect Disord ; 274: 1004-1012, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32663926

ABSTRACT

BACKGROUND: Well-established evidence exists of an association between depressive symptoms and alterations in the stress and inflammatory response systems; however, the picture is far less coherent during the perinatal period. This study combines the assessment of multiple stress and inflammatory biomarkers in late pregnancy and after delivery in order to investigate cross-sectional and prospective associations with perinatal depressive symptoms. METHODS: One-hundred-ten healthy women were assessed in late pregnancy (mean gestational age=34.76; SD=1.12) and 89 were re-evaluated after delivery (mean hours after delivery=52.36; SD=19.70) for depressive and anxiety symptoms through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. Serum Interleukin-6 (IL-6), C-Reactive Protein (CRP) and diurnal salivary cortisol levels were measured on both occasions, while diurnal salivary alpha amylase (sAA) levels were assessed in late pregnancy. RESULTS: Using Hierarchical Linear Models, higher depressive symptoms were found to be associated with higher IL-6 levels, lower morning cortisol levels and a flatter cortisol diurnal slope during pregnancy, while adjusting for potential confounders. No significant associations were found after delivery or with change in biomarker levels from pre- to post-partum. Furthermore, preliminary evidence of a positive association between inflammation and stress markers in women with higher antenatal depressive symptoms was found. LIMITATIONS: The sample was relatively small and highly selected, thus limiting generalizability of the findings. CONCLUSIONS: Results emphasize the need for an integrated multi-systems approach to the understanding of the biological underpinnings of perinatal depression and suggest that the stress-immune interactions represent a promising avenue for future endeavor.


Subject(s)
Depression, Postpartum , Pregnancy Complications , Cross-Sectional Studies , Depression , Female , Humans , Pregnancy , Prospective Studies , Systems Analysis
3.
Psychoneuroendocrinology ; 101: 253-262, 2019 03.
Article in English | MEDLINE | ID: mdl-30497017

ABSTRACT

Accumulating evidence suggests that antenatal maternal stress is associated with altered behavioral and physiological outcomes in the offspring, however, whether this association is causal and the underlying biological mechanisms remain largely unknown. While the most studied mediator of maternal stress influences on the fetus has generally been cortisol, alternative novel markers of stress or inflammation warrant further consideration. The current investigation explored the influence of variations in self-reported symptoms of distress, stress hormones and inflammatory markers on infant birth outcomes and early stress regulation. The sample consisted of 104 pregnant women (mean gestational age = 34.76; SD = 1.12) and their healthy newborns. Maternal self-reported symptoms of depression and anxiety were evaluated through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory and levels of serum Interleukine-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol and alpha amylase (sAA) were measured in late pregnancy. Newborns' cortisol and behavioral response to the heel-stick was assessed 48-72 hours after birth. The associations between maternal stress measures and infant birth outcomes and stress reactivity, adjusted for potential confounders, were examined through hierarchical linear regressions and hierarchical linear models. Higher maternal IL-6 levels were associated with smaller head circumference at birth, while diurnal sAA levels were positively associated with birthweight. Maternal diurnal cortisol was related to newborn's stress reactivity: a flatter infant cortisol response to the heel-stick was associated with greater maternal cortisol increases after awakening during pregnancy, while greater infant behavioural reactivity was related to a flatter maternal diurnal cortisol profile. The observational nature of these data does not allow for causal inferences but the current findings illustrate that antenatal factors related to alterations in maternal stress and immune response systems are associated with fetal growth and neonatal stress reactivity. This may have implications for later health and psychological outcomes.


Subject(s)
Pregnancy Outcome/psychology , Stress, Physiological/physiology , Stress, Psychological/metabolism , Adult , Biomarkers , Birth Weight , C-Reactive Protein/analysis , Female , Fetal Development , Fetus/metabolism , Gestational Age , Humans , Hydrocortisone/analysis , Hypothalamo-Hypophyseal System/metabolism , Infant, Newborn , Interleukin-6/analysis , Interleukin-6/blood , Maternal Exposure , Mothers/psychology , Pituitary-Adrenal System/metabolism , Pregnancy , Pregnancy Complications/psychology , Pregnant Women/psychology , Prenatal Exposure Delayed Effects/metabolism , Saliva/chemistry , alpha-Amylases/analysis
4.
J Affect Disord ; 243: 175-181, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30243197

ABSTRACT

BACKGROUND: Depression is the leading global cause of disability and often begins in adolescence. The genetic architecture and treatment response profiles for adults and adolescents differ even though identical criteria are used to diagnose depression across different age groups. There is no clear consensus on how these groups differ in their symptom profiles. METHODS: Using data from a two-generation family study, we compared the presentation of DSM-IV depressive symptoms in adolescents and adults with MDD (Major Depressive Disorder). We also compared DSM-IV depressive symptom counts using latent class analysis. RESULTS: Vegetative symptoms (appetite and weight change, loss of energy and insomnia) were more common in adolescent MDD than adult MDD. Anhedonia/loss of interest and concentration problems were more common in adults with MDD. When using latent class analysis to look at depressive symptoms, a vegetative symptom profile was also seen in adolescent depression only. LIMITATIONS: Adults and adolescents were recruited in different ways. Adolescent cases were more likely to be first-onset while adult cases were recurrences. It was not possible to examine how recurrence affected adolescent depression symptom profiles. CONCLUSION: Differences in how depression presents in adolescents and adults may be consistent with different pathophysiological mechanisms. For adolescents, we found that vegetative/physical disturbances were common (loss of energy, changes in weight, appetite and sleep changes). For adults, anhedonia/loss of interest and concentration difficulties were more common.


Subject(s)
Adolescent Behavior/psychology , Depression/diagnosis , Depressive Disorder, Major/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Recurrence
5.
J Adolesc ; 50: 31-43, 2016 07.
Article in English | MEDLINE | ID: mdl-27176785

ABSTRACT

School transition at around 11-years of age can be anxiety-provoking for children, particularly those with special educational needs (SEN). The present study adopted a longitudinal design to consider how existing transition strategies, categorized into cognitive, behavioral or systemic approaches, were associated with post-transition anxiety amongst 532 typically developing children and 89 children with SEN. Multiple regression analysis indicated that amongst typically developing pupils, systemic interventions were associated with lower school anxiety but not generalized anxiety, when controlling for prior anxiety. Results for children with SEN differed significantly, as illustrated by a Group × Intervention type interaction. Specifically, systemic strategies were associated with lower school anxiety amongst typically developing children and higher school anxiety amongst children with SEN. These findings highlight strategies that schools may find useful in supporting typically developing children over the transition period, whilst suggesting that children with SEN might need a more personalized approach.


Subject(s)
Adaptation, Psychological , Anxiety/etiology , Anxiety/therapy , Social Adjustment , Anxiety/prevention & control , Child , Educational Status , England , Female , Humans , Longitudinal Studies , Male , Models, Psychological , School Health Services , Schools
6.
Psychol Med ; 43(1): 27-38, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22617461

ABSTRACT

BACKGROUND: Alterations in reward processing may represent an early vulnerability factor for the development of depressive disorder. Depression in adults is associated with reward hyposensitivity and diminished reward seeking may also be a feature of depression in children and adolescents. We examined the role of reward responding in predicting depressive symptoms, functional impairment and new-onset depressive disorder over time in the adolescent offspring of depressed parents. In addition, we examined group differences in reward responding between currently depressed adolescents, psychiatric and healthy controls, and also cross-sectional associations between reward responding and measures of positive social/environmental functioning. Method We conducted a 1-year longitudinal study of adolescents at familial risk for depression (n = 197; age range 10-18 years). Reward responding and self-reported social/environmental functioning were assessed at baseline. Clinical interviews determined diagnostic status at baseline and at follow-up. Reports of depressive symptoms and functional impairment were also obtained. RESULTS: Low reward seeking predicted depressive symptoms and new-onset depressive disorder at the 1-year follow-up in individuals free from depressive disorder at baseline, independently of baseline depressive symptoms. Reduced reward seeking also predicted functional impairment. Adolescents with current depressive disorder were less reward seeking (i.e. bet less at favourable odds) than adolescents free from psychopathology and those with externalizing disorders. Reward seeking showed positive associations with social and environmental functioning (extra-curricular activities, humour, friendships) and was negatively associated with anhedonia. There were no group differences in impulsivity, decision making or psychomotor slowing. CONCLUSIONS: Reward seeking predicts depression severity and onset in adolescents at elevated risk of depression. Adaptive reward responses may be amenable to change through modification of existing preventive psychological interventions.


Subject(s)
Adolescent Behavior/psychology , Child of Impaired Parents/psychology , Depressive Disorder/physiopathology , Reward , Adolescent , Adult , Child , Cross-Sectional Studies , Depressive Disorder/etiology , Humans , Longitudinal Studies , Predictive Value of Tests , Prospective Studies , Risk Factors , Time Factors
7.
Eur J Pain ; 16(10): 1414-25, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22556099

ABSTRACT

BACKGROUND: Neuropathy can lead not only to impaired function but also to sensory sensitization. We aimed to link reduced skin nerve fibre density in different levels to layer-specific functional impairment in neuropathic pain patients and tried to identify pain-specific functional and structural markers. METHODS: In 12 healthy controls and 36 patients with neuropathic pain, we assessed clinical characteristics, thermal thresholds (quantitative sensory testing) and electrically induced pain and axon reflex erythema. At the most painful sites and at intra-individual control sites, skin biopsies were taken and innervation densities in the different skin layers were assessed. Moreover, neuronal calcitonin gene-related peptide staining was quantified. RESULTS: Perception of warm, cold and heat pain and nerve fibre density were reduced in the painful areas compared with the control sites and with healthy controls. Warm and cold detection thresholds correlated best with epidermal innervation density, whereas heat and cold pain thresholds and axon reflex flare correlated best with dermal innervation density. Clinical pain ratings correlated only with epidermal nerve fibre density (r = 0.38, p < 0.05) and better preserved cold detection thresholds (r = 0.39, p < 0.05), but not with other assessed functional and structural parameters. CONCLUSIONS: Thermal thresholds, axon reflex measurements and assessment of skin innervation density are valuable tools to characterize and quantify peripheral neuropathy and link neuronal function to different layers of the skin. The severity of small fibre neuropathy, however, did not correspond to clinical pain intensity and a specific parameter or pattern that would predict pain intensity in peripheral neuropathy could not be identified.


Subject(s)
Nerve Fibers/pathology , Neuralgia/pathology , Skin , Adult , Case-Control Studies , Cold Temperature , Dermis/innervation , Dermis/pathology , Epidermis/innervation , Epidermis/pathology , Female , Hot Temperature , Humans , Hyperalgesia/pathology , Male , Middle Aged , Pain Threshold , Sensory Thresholds , Skin/innervation , Skin/pathology , Touch
8.
Psychol Med ; 41(6): 1175-85, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20860866

ABSTRACT

BACKGROUND: Genetic and environmental influences on child psychopathology have been studied extensively through twin and adoption designs. We offer a novel methodology to examine genetic and environmental influences on the intergenerational transmission of psychopathology using a sample of parents and children conceived through in vitro fertilization (IVF). METHOD: The sample included families with children born through IVF methods, who varied as to whether the child was genetically related or unrelated to the rearing mother and father (mother genetically related, n=434; mother genetically unrelated, n=127; father genetically related, n=403; father genetically unrelated, n=156). Using standardized questionnaires, mothers and fathers respectively reported on their own psychopathology (depression, aggression), their parenting behavior toward their child (warmth, hostility) and their child's psychopathology (depression, aggression). A cross-rater approach was used, where opposite parents reported on child symptoms (i.e. fathers reported on symptoms for the mother-child dyad, and vice versa). RESULTS: For mother-child dyads, a direct association between mother depression and child depression was observed among genetically unrelated dyads, whereas a fully mediated path was observed among genetically related dyads through mother-to-child hostility and warmth. For father-child dyads, direct and mediated pathways were observed for genetically related father-child dyads. For aggression, the direct association between parent aggression and child aggression was fully mediated by parent-to-child hostility for both groups, indicating the role of parent-to-child hostility as a risk mechanism for transmission. CONCLUSIONS: A differential pattern of genetic and environmental mediation underlying the intergenerational transmission of psychopathology was observed among genetically related and genetically unrelated father-child and mother-child dyads.


Subject(s)
Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Gene-Environment Interaction , Parenting/psychology , Social Environment , Adult , Aged , Aggression/psychology , Antisocial Personality Disorder/diagnosis , Antisocial Personality Disorder/genetics , Antisocial Personality Disorder/psychology , Child , Child, Preschool , Depressive Disorder, Major/psychology , Father-Child Relations , Female , Fertilization in Vitro/psychology , Hostility , Humans , Male , Middle Aged , Mother-Child Relations , Risk Factors , Statistics as Topic , Young Adult
9.
Psychol Med ; 40(2): 335-45, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19476689

ABSTRACT

BACKGROUND: Exposure to prenatal stress is associated with later adverse health and adjustment outcomes. This is generally presumed to arise through early environmentally mediated programming effects on the foetus. However, associations could arise through factors that influence mothers' characteristics and behaviour during pregnancy which are inherited by offspring. METHOD: A 'prenatal cross-fostering' design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences. If links between prenatal stress and offspring outcome are environmental, association should be observed in unrelated as well as related mother-child pairs. Offspring birth weight and gestational age as well as mental health were the outcomes assessed. RESULTS: Associations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother-offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother-offspring pairs and therefore was attributable to inherited factors. CONCLUSIONS: Genetically informative designs can be helpful in testing whether inherited factors contribute to the association between environmental risk factors and health outcomes. These results suggest that associations between prenatal stress and offspring outcomes could arise from inherited factors and post-natal environmental factors in addition to causal prenatal risk effects.


Subject(s)
Child Development/physiology , Mental Disorders/epidemiology , Mental Disorders/genetics , Perinatology , Social Environment , Antisocial Personality Disorder/diagnosis , Antisocial Personality Disorder/epidemiology , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/epidemiology , Birth Weight , Child , Child, Preschool , Female , Gestational Age , Humans , Infant , Infant, Newborn , Male , Mental Disorders/diagnosis , Mother-Child Relations , Pregnancy , Pregnancy Complications/epidemiology , Prospective Studies
10.
Brain Res Rev ; 60(1): 24-35, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19171165

ABSTRACT

Sensory neurons that innervate the skin provide critical information about physical contact between the organism and the environment, including information about potentially-damaging stimuli that give rise to the sensation of pain. These afferents also contribute to the maintenance of tissue homeostasis, inflammation and wound healing, while sensitization of sensory afferents after injury results in painful hypersensitivity and protective behavior. In contrast to the traditional view of primary afferent terminals as the sole site of sensory transduction, recent reports have lead to the intriguing idea that cells of the skin play an active role in the transduction of sensory stimuli. The search for molecules that transduce different types of sensory stimuli (mechanical, heat, chemical) at the axon terminal has yielded a wide range of potential effectors, many of which are expressed by keratinocytes as well as neurons. Emerging evidence underscores the importance of nucleotide signaling through P2X ionotropic and P2Y metabotropic receptors in pain processing, and implicates nucleotide signaling as a critical form of communication between cells of the skin, immune cells and sensory neurons. It is of great interest to determine whether pathological changes in these mechanisms contribute to chronic pain in human disease states such as complex regional pain syndrome (CRPS). This review discusses recent advances in our understanding of communication mechanisms between cells of the skin and sensory axons in the transduction of sensory input leading to pain.


Subject(s)
Nociceptors/metabolism , Nucleotides/metabolism , Pain/metabolism , Sensory Receptor Cells/metabolism , Skin Physiological Phenomena , Skin/innervation , Adenosine Triphosphate/metabolism , Animals , Humans , Pain/physiopathology , Receptors, G-Protein-Coupled/metabolism , Receptors, Purinergic/metabolism , Signal Transduction/physiology , Skin/physiopathology
11.
Am J Med Genet B Neuropsychiatr Genet ; 147B(1): 49-53, 2008 Jan 05.
Article in English | MEDLINE | ID: mdl-17579368

ABSTRACT

Gene x environment (G x E) interactions are increasingly thought to have substantial influence on the aetiology and clinical manifestations of complex disorders. In ADHD, although main effects of specific genetic variants and pre- or peri-natal variables have been reported and replicated using pooled analyses, few studies have looked at possible interactions. In a clinical sample of 266 children with ADHD, we tested for interaction between gene variants (in DRD4, DAT1, DRD5, and 5HTT) found to be associated with ADHD in pooled analyses and maternal smoking, alcohol use during pregnancy and birth weight. First, G x E effects on a diagnosis of ADHD were tested using conditional logistic regression analyses. Second, possible modifying effects of G x E on symptoms of associated conduct disorder and oppositional defiant disorder (ODD) were investigated using linear regression analysis. The sample size associated with each of the analyses differed as not each variant had been genotyped for each individual. No effects of G x E on ADHD diagnosis were observed. The results suggest that lower birth weight and maternal smoking during pregnancy may interact with DRD5 and DAT1 (birth weight only) in influencing associated antisocial behavior symptoms (ODD and conduct disorder). These preliminary findings showed no evidence of interaction between previously implicated variants in ADHD and specific environmental risk factors, on diagnosis of the disorder. There may be evidence of G x E on associated antisocial behavior in ADHD, but further investigation is needed.


Subject(s)
Antisocial Personality Disorder/etiology , Attention Deficit Disorder with Hyperactivity/etiology , Alcohol Drinking/adverse effects , Antisocial Personality Disorder/genetics , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/genetics , Birth Weight , Child , Female , Genotype , Humans , Linkage Disequilibrium , Maternal Exposure , Pregnancy , Smoking/adverse effects
12.
J Psychiatr Ment Health Nurs ; 14(5): 516-21, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17635261

ABSTRACT

Nurses work in a constantly challenging and changing environment. Within this context, there is a continuing need for support. Such support will help increase morale, decrease strain and burnout, and encourage self-awareness and self-expression. Clinical supervision address all these issues and enhances the quality of care for patients. While clinical supervision is a policy imperative in Northern Ireland, it was clear that there were problems in its implementation in mental health nursing. The aim of this project was to explore ways to make clinical supervision available to all mental health nurses and to improve and evaluate their contribution to patient care. The research team undertook a comprehensive literature review and a baseline survey of relevant stakeholders. Results represent the outcome of the group work. They will assist healthcare providers to develop local policies and procedures on clinical supervision for practising mental health nurses.


Subject(s)
Benchmarking/organization & administration , Clinical Competence , Nurse Administrators/psychology , Nursing, Supervisory/standards , Practice Guidelines as Topic , Psychiatric Nursing/standards , Attitude of Health Personnel , Burnout, Professional/prevention & control , Burnout, Professional/psychology , Curriculum , Education, Nursing, Continuing , Health Knowledge, Attitudes, Practice , Health Planning Guidelines , Humans , Models, Nursing , Morale , Needs Assessment , Northern Ireland , Nurse Administrators/education , Nurse Administrators/organization & administration , Nurse's Role , Nursing Education Research , Nursing Methodology Research , Nursing Staff/education , Nursing Staff/organization & administration , Nursing Staff/psychology , Psychiatric Nursing/education , Social Support
13.
Acta Psychiatr Scand ; 115(3): 171-83, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17302617

ABSTRACT

OBJECTIVE: Events occurring very early in life, even prenatally, may have long-term effects on future health and behaviour. The influence of poor foetal growth and gestational stress in the mother on the risk of emotional problems in offspring was reviewed. METHOD: A selective review of the literature was undertaken. RESULTS: Studies of preterm infants and infants born small for gestational age have shown increased levels of emotional problems across the lifespan. In general, studies examining maternal depression/anxiety during pregnancy and other indices of gestational stress have shown significant associations with emotional problems in children. The results of several studies also point to the importance of psychosocial and genetic factors in moderating associations. CONCLUSION: Future research that focuses on identifying the mechanisms underlying these associations is needed. The moderating role of psychosocial and genetic risk factors is an important area in which future research should be directed. These findings have clinical implications for the provision of antenatal care.


Subject(s)
Fetal Development/physiology , Mood Disorders/epidemiology , Mothers/psychology , Pregnancy/psychology , Stress, Physiological/psychology , Female , Humans , Psychology
14.
Minerva Pediatr ; 57(6): 359-71, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16402008

ABSTRACT

Attention deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder which affects between 3% and 5% of school aged children. Despite much research, little is known regarding the aetiology of the disorder. Maternal cigarette smoking during pregnancy has been linked to a number of negative effects in offspring in infancy, childhood and even into adulthood and has been proposed as a possible risk factor for ADHD. The aim of this review was to discuss the evidence associating maternal smoking during pregnancy and ADHD as well as methodological issues concerning this association. A literature search using PubMed was employed using relevant keywords. The relevant reference sections of articles found were also searched. All English language studies published before June 2005 were assessed. A pooled odds ratio derived from case-control studies was also obtained. Despite methodological limitations, the majority of studies identify maternal smoking during pregnancy as a risk factor for ADHD behaviours. A pooled odds ratio indicates more than a two-fold increase in risk for a diagnosis of ADHD in those individuals whose mothers smoked during pregnancy (odds ratio 2.39, 95% confidence intervals 1.61, 3.52 P<0.001). Maternal smoking during pregnancy is a risk factor for ADHD behaviour and diagnoses, although the mechanisms through which such risks work is unknown.


Subject(s)
Attention Deficit Disorder with Hyperactivity/etiology , Environmental Exposure/adverse effects , Maternal Behavior/psychology , Mothers/statistics & numerical data , Nicotine/adverse effects , Prenatal Exposure Delayed Effects/epidemiology , Child , Female , Humans , Pregnancy , Prospective Studies , Risk Factors
15.
Occup Environ Med ; 60(2): 122-9, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12554840

ABSTRACT

BACKGROUND: Although crystalline silica exposure is associated with silicosis, lung cancer, pulmonary tuberculosis, and chronic obstructive pulmonary disease (COPD), there is less support for an association with autoimmune disease, and renal disease. METHODS: Using data from the US National Occupational Mortality Surveillance (NOMS) system, a matched case-control design was employed to examine each of several diseases (including silicosis, lung cancer, stomach cancer, oesophageal cancer, COPD, pulmonary tuberculosis, sarcoidosis, systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and various types of renal disease). Cases were subjects whose death certificate mentioned the disease of interest. A separate control group for each of the diseases of interest was selected from among subjects whose death certificate did not mention the disease of interest or any of several diseases reported to be associated with crystalline silica exposure. Subjects were assigned into a qualitative crystalline silica exposure category based on the industry/occupation pairing found on their death certificate. We also investigated whether silicotics had a higher risk of disease compared to those without silicosis. RESULTS: Those postulated to have had detectable crystalline silica exposure had a significantly increased risk for silicosis, COPD, pulmonary tuberculosis, and rheumatoid arthritis. In addition, a significant trend of increasing risk with increasing silica exposure was observed for these same conditions and for lung cancer. Those postulated to have had the greatest crystalline silica exposure had a significantly increased risk for silicosis, lung cancer, COPD, and pulmonary tuberculosis only. Finally, those with silicosis had a significantly increased risk for COPD, pulmonary tuberculosis, and rheumatoid arthritis. CONCLUSIONS: This study corroborates the association between crystalline silica exposure and silicosis, lung cancer, COPD, and pulmonary tuberculosis. In addition, support is provided for an association between crystalline silica exposure and rheumatoid arthritis.


Subject(s)
Occupational Diseases/etiology , Occupational Exposure/adverse effects , Silicon Dioxide/adverse effects , Adult , Aged , Autoimmune Diseases/etiology , Autoimmune Diseases/mortality , Case-Control Studies , Chronic Disease , Female , Humans , Inhalation Exposure , Kidney Diseases/etiology , Kidney Diseases/mortality , Logistic Models , Male , Middle Aged , Occupational Diseases/mortality , Odds Ratio , Risk Factors , United States/epidemiology
16.
Occup Environ Med ; 59(1): 36-43, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11836467

ABSTRACT

OBJECTIVES: To estimate excess lifetime risk of (a) mortality from lung disease other than cancer (LDOC), and, (b) onset of radiographic silicosis, arising from occupational exposure to respirable crystalline silica dust. METHODS: Data from a cohort of California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly as cristobalite) were reanalyzed with Poisson regression methods with internal and external adjustments for potential confounding by calendar time, age, smoking, Hispanic ethnicity, and time since first observation. Model fit was evaluated by comparing deviances and fitting cubic spline models. Lifetime risks of death from LDOC and radiographic silicosis were estimated up to age 85 with an actuarial approach accounting for competing causes of death. RESULTS: For deaths due to LDOC, a linear relative rate model gave the best fit in Poisson regression analyses. At the mean cumulative exposure of LDOC cases to silica, after adjustment for smoking, the estimated rate ratio was 4.2 (p<0.0001); at the maximum cumulative exposure of cases, the rate ratio was 18.4. The excess lifetime risk for white men exposed to respirable cristobalite dust for 45 years at the current permissible exposure limit (PEL; about 0.05 mg/m(3)) of the Occupational Safety and Health Administration was 54/1000 (95% confidence interval (95% CI) 17 to 150). For 70 incident cases of radiographic silicosis largely manifest before the end of employment, the best fit was also the linear relative rate model, predicting a rate ratio of 25.6 for silicosis at the mean cumulative exposure of the cases (p<0.0001). The excess lifetime risk for silicosis at the current PEL was 75/1000. CONCLUSION: Current occupational health standards for crystalline silica permit risks of lung disease other than cancer far in excess of what is usually considered acceptable by the Occupational Safety and Health Administration (a lifetime risk of less than one in a thousand deaths).


Subject(s)
Lung Diseases/mortality , Mining , Occupational Diseases/mortality , Occupational Exposure/statistics & numerical data , Adult , Aged , California/epidemiology , Cohort Studies , Dust/adverse effects , Humans , Male , Middle Aged , Models, Statistical , Occupational Exposure/adverse effects , Retrospective Studies , Risk Assessment , Risk Factors , Silicon Dioxide/adverse effects , Silicosis/etiology
17.
J Neurosci ; 21(18): 7236-46, 2001 Sep 15.
Article in English | MEDLINE | ID: mdl-11549734

ABSTRACT

Meissner corpuscles (MCs) in the glabrous skin of monkey digits have at least three types of innervation as revealed by immunofluorescence. The previously well known Aalphabeta-fiber terminals are closely intertwined with endings from peptidergic C-fibers. These intertwined endings are segregated into zones that alternate with zones containing a third type of ending supplied by nonpeptidergic C-fibers. Although MCs are widely regarded as low-threshold mechanoreceptors, all three types of innervation express immunochemical properties associated with nociception. The peptidergic C-fiber endings have readily detectable levels of immunoreactivity (IR) for calcitonin gene-related peptide (CGRP) and substance P (SP). The Aalphabeta endings have relatively lower levels of IR for CGRP and SP as well as the SP neurokinin 1 receptor and vanilloid-like receptor 1. Both the Aalphabeta and peptidergic C-fiber endings were also labeled with antibodies for different combinations of adrenergic, opioid, and purinergic receptors. The nonpeptidergic C-fiber endings express IR for vanilloid receptor 1, which has also been implicated in nociception. Thus, MCs are multiafferented receptor organs that may have nociceptive capabilities in addition to being low-threshold mechanoreceptors.


Subject(s)
Mechanoreceptors/cytology , Neurons, Afferent/cytology , Nociceptors/cytology , Skin/innervation , Animals , Antigens, Surface/metabolism , Calcitonin Gene-Related Peptide/metabolism , Fluorescent Antibody Technique , Hand , Immunohistochemistry , Macaca fascicularis , Macaca mulatta , Mechanoreceptors/metabolism , Nerve Fibers/metabolism , Neurons, Afferent/metabolism , Nociceptors/metabolism , Receptors, Drug/metabolism , Receptors, Neurokinin-1/metabolism , Skin/cytology , Substance P/metabolism
18.
Occup Environ Med ; 58(1): 38-45, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11119633

ABSTRACT

OBJECTIVE: To use various exposure-response models to estimate the risk of mortality from lung cancer due to occupational exposure to respirable crystalline silica dust. METHODS: Data from a cohort mortality study of 2342 white male California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly cristobalite) were reanalyzed with Poisson regression and Cox's proportional hazards models. Internal and external adjustments were used to control for potential confounding from the effects of time since first observation, calendar time, age, and Hispanic ethnicity. Cubic smoothing spline models were used to assess the fit of the models. Exposures were lagged by 10 years. Evaluations of the fit of the models were performed by comparing their deviances. Lifetime risks of lung cancer were estimated up to age 85 with an actuarial approach that accounted for competing causes of death. RESULTS: Exposure to respirable crystalline silica dust was a significant predictor (p<0.05) in nearly all of the models evaluated and the linear relative rate model with a 10 year exposure lag seemed to give the best fit in the Poisson regression analysis. For those who died of lung cancer the linear relative rate model predicted rate ratios for mortality from lung cancer of about 1.6 for the mean cumulative exposure to respirable silica compared with no exposure. The excess lifetime risk (to age 85) of mortality from lung cancer for white men exposed for 45 years and with a 10 year lag period at the current Occupational Safety and Health Administration (OSHA) standard of about 0.05 mg/m(3) for respirable cristobalite dust is 19/1000 (95% confidence interval (95% CI) 5/1000 to 46/1000). CONCLUSIONS: There was a significant risk of mortality from lung cancer that increased with cumulative exposure to respirable crystalline silica dust. The predicted number of deaths from lung cancer suggests that current occupational health standards may not be adequately protecting workers from the risk of lung cancer.


Subject(s)
Diatomaceous Earth/adverse effects , Dust/adverse effects , Lung Neoplasms/etiology , Mining , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Adult , Aged , Aged, 80 and over , California/epidemiology , Cohort Studies , Data Interpretation, Statistical , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Occupational Diseases/mortality , Regression Analysis , Risk Assessment , Risk Factors
19.
Science ; 290(5500): 2304-5, 2000 Dec 22.
Article in English | MEDLINE | ID: mdl-11125144

ABSTRACT

The apolipoprotein E (APOE) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of APOE genotype.


Subject(s)
Alzheimer Disease/genetics , Chromosomes, Human, Pair 10/genetics , Genetic Predisposition to Disease , Age of Onset , Aged , Alleles , Apolipoprotein E4 , Apolipoproteins E/genetics , Genetic Linkage , Genetic Markers , Genotype , Humans , Lod Score , Nuclear Family , Odds Ratio
20.
J Comp Neurol ; 417(4): 467-90, 2000 Feb 21.
Article in English | MEDLINE | ID: mdl-10701867

ABSTRACT

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffini-like endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic.


Subject(s)
Forelimb/innervation , Raccoons/anatomy & histology , Animals , Blood Vessels/innervation , Coloring Agents , Fluorescent Antibody Technique , Hair , Hoof and Claw/innervation , Immunohistochemistry , In Vitro Techniques , Nervous System/anatomy & histology , Nervous System/chemistry , Sebaceous Glands/innervation , Skin/innervation , Sweat Glands/innervation , p-Dimethylaminoazobenzene
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