Intellectual functioning in survivors of extremely low birthweight: Cognitive outcomes in childhood and adolescence.

BACKGROUND: Infants born at extremely low birthweight (ELBW: ≤1000 g) are vulnerable to intellectual disabilities, but the factors that may distinguish between ELBW survivors with and without these impairments are not well understood. In this study, prospective associations between neonatal factors and functional outcomes in childhood and adolescence were compared in ELBW survivors with and without borderline intellectual functioning (BIF). METHODS: Borderline intellectual functioning was defined by IQ < 85, assessed at 8 years. Among 146 ELBW survivors, 48 (33%) had IQ scores under 85, and 98 (67%) had scores equal to or over 85. Group differences in demographic and risk factors were assessed via t-test, chi-squared analysis or non-parametric tests. Neonatal factors that differed between ELBW groups were tested for association with adaptive behaviour assessed at age 5 years, and reading and arithmetic skills assessed at ages 8 and 15 years, using hierarchical regression models. RESULTS: Extremely low birthweight survivors with BIF had significantly lower birthweights than ELBW survivors without BIF (790 vs. 855 g, P < 0.01) and were more likely to be born to mothers with lower socioeconomic status (SES) (78% vs. 48%, P < 0.01). These ELBW survivors also were more likely to be diagnosed with significant neurosensory impairment (NSI; 35% vs. 19%, P < 0.04), experienced more bronchopulmonary dysplasia (56% vs. 38%, P < 0.04), received more days of respiratory support (median 33 vs. 14 days, P < 0.01) and remained in hospital for longer periods (median 81 vs. 63 days, P < 0.03). Birthweight, familial SES, NSI and duration of respiratory support were significant predictors for one or more outcomes. Across groups, lower familial SES was associated with lower academic scores (Ps < 0.05), and NSI predicted lower adaptive functioning (Ps < 0.001). Other associations were moderated by group: among ELBW survivors with BIF, heavier birthweights predicted better arithmetic skills, the presence of NSI was associated with poorer arithmetic skills and more ventilation days predicted poorer reading skills. CONCLUSIONS: At birth, ELBW survivors with BIF faced more physiological and social disadvantages and required more medical intervention than their ELBW peers without BIF. Smaller birth size, NSI burden and prolonged neonatal ventilatory support displayed gradients of risk for childhood and adolescent academic outcomes across groups. Whereas academic performance in ELBW survivors with BIF was sensitive to variation in birth size, NSI or ventilation days, ELBW survivors without BIF attained thresholds of intellectual ability that were sufficient to support higher levels of academic performance at both ages, regardless of their status on these factors. The findings are discussed in relation to Zigler's developmental theory of intellectual disability.

Mental-Physical Multimorbidity in Youth: Associations with Individual, Family, and Health Service Use Outcomes.

Prevalence, correlates, and outcomes of youth with comorbid mental and physical conditions (i.e., multimorbidity) were examined in this cross-sectional study. Participants were 92 youth (14.5 years [SD 2.7]; 69.6% female) and their parents. Mental disorder was assessed using structured interviews and physical health using a standardized questionnaire. Twenty-five percent of youth had multimorbidity and no child or parent demographic or health characteristics were correlated with multimorbidity. Youth with multimorbidity reported similar quality of life and better family functioning [B = - 4.80 (- 8.77, - 0.83)] compared to youth with mental disorder only (i.e., non-multimorbid). Youth with multimorbidity had lower odds of receiving inpatient services [OR = 0.20 (0.05, 0.85)] and shorter stays in hospital for their mental health [OR = 0.74 (0.57, 0.91)] over the past year. Family functioning was found to mediate the association between youth multimorbidity and length of stay [αß = 0.14 (0.01, 0.27)]. Findings reinforce the need for family-centered youth mental health care.

The Menopause Visual Analogue Scale: a new tool for measuring the severity and response to treatment of symptoms throughout the menopausal transition.

OBJECTIVES: This study aimed to assess the reliability and validity of the Menopause Visual Analogue Scale (MVAS) in measuring symptoms throughout the menopausal transition. METHODS: Two independent samples of women undergoing the menopausal transition completed both the MVAS and the Greene Climacteric Scale (GCS) at a women's mental health clinic between 2008 and 2016. Data for the first sample were obtained using a retrospective chart review of patients seen between 2008 and 2012 (N1 = 75) and data for the second sample came from a prospective study conducted between 2013 and 2016 (N2 = 86). Internal consistency was assessed using Cronbach's α and Pearson's correlation coefficient was used to evaluate concurrent validity. Bland-Altman plots were developed to assess the degree of agreement between the scales. RESULTS: Internal consistency for the physical and psychological domains of the MVAS was 0.80-0.81 and 0.92-0.94, respectively. Pearson's correlations between the MVAS and the GCS were high for both physical (rphys = 0.74-0.76, p < 0.01) and psychological (rpsych = 0.70-0.72, p < 0.01) components in both samples. Changes in MVAS physical and psychological scores in response to treatment were correlated with changes in GCS physical and psychological scores (rphys = 0.69, p < 0.01; rpsych = 0.49, p < 0.01) in the second sample. Bland-Altman plots indicate low to moderate levels of agreement between most portions of the MVAS and the GCS. CONCLUSIONS: These findings suggest that the MVAS has potential for assessing both severity and change in symptoms throughout the menopausal transition, subject to exploring limitations identified in the analysis and application to other populations.

Exposure to overprotective parenting and psychopathology in extremely low birth weight survivors.

BACKGROUND: Extremely low birth weight (ELBW; <1,000 g) infants are the most vulnerable babies and are at higher risk for experiencing overprotective (i.e., controlling and intrusive) parenting, which is hypothesized to contribute to the risk for mental disorders. Despite the increased risk for anxiety disorders and decreased risk for alcohol or substance use disorders seen in ELBW survivors, no research has examined the impact of parenting. This study investigated if overprotective parenting mediates links between ELBW birth status and psychiatric disorders in adulthood. STUDY DESIGN: Participants included ELBW survivors born in 1977-1982 and matched normal birth weight (≥2,500 g) control participants (ELBW n = 81; normal birth weight n = 87) prospectively followed in Ontario, Canada. These individuals retrospectively reported on whether either of their parents was overprotective using the Parental Bonding Instrument. Presence of a current anxiety disorder and of current alcohol or substance use disorders was assessed using the Mini International Neuropsychiatric Interview at age 29-36 years. RESULTS: Path analysis showed that overprotective parenting was a significant mediator of the association between ELBW status and risk for an anxiety disorder in adulthood and the risk for an alcohol or substance use disorder in adulthood in ELBW survivors. Overprotective parenting accounted for 53% of the association between ELBW status and the risk for an anxiety disorder in adulthood and 26% of the association between ELBW status and alcohol or substance use disorders. CONCLUSIONS: Overprotective parenting accounted for a substantial proportion of the increased risk for anxiety and alcohol or substance use disorders in adulthood in ELBW survivors. Despite their perceived vulnerabilities, it is important that the parents of ELBW survivors be supported in their attempts to facilitate their children's pursuit of independence during childhood and beyond.

Is plasminogen activator inhibitor-1 a physiological bottleneck bridging major depressive disorder and cardiovascular disease?

Major depressive disorder (MDD) is estimated to affect one in twenty people worldwide. MDD is highly comorbid with cardiovascular disease (CVD), itself one of the single largest causes of mortality worldwide. A number of pathological changes observed in MDD are believed to contribute to the development of cardiovascular disease, although no single mechanism has been identified. There are also no biological markers capable of predicting the future risk of developing heart disease in depressed individuals. Plasminogen activator inhibitor-1 (PAI-1) is a prothrombotic plasma protein secreted by endothelial tissue and has long been implicated in CVD. An expanding body of literature has recently implicated it in the pathogenesis of major depressive disorder as well. In this study, we review candidate pathways implicating MDD in CVD and consider how PAI-1 might act as a mediator by which MDD induces CVD development: chiefly through sleep disruption, adiposity, brain-derived neurotrophic factor (BDNF) metabolism, systemic inflammation and hypothalamic-pituitary-adrenal (HPA)-axis dysregulation. As both MDD and CVD are more prevalent in women than in men, and incidence of either condition is dramatically increased during reproductive milestones, we also explore hormonal and sex-specific associations between MDD, PAI-1 and CVD. Of special interest is the role PAI-1 plays in perinatal depression and in cardiovascular complications of pregnancy. Finally, we propose a theoretical model whereby PAI-1 might serve as a useful biomarker for CVD risk in those with depression, and as a potential target for future treatments.

Adult social outcomes of extremely low birth weight survivors of childhood sexual abuse.

Preterm birth and exposure to childhood sexual abuse (CSA) are early physiological and psychological adversities that have been linked to reduced social functioning across the lifespan. However, the joint effects of being born preterm and being exposed to CSA on adult social outcomes remains unclear. We sought to determine the impact of exposure to both preterm birth and CSA on adult social functioning in a group of 179 extremely low birth weight (ELBW; 2500 g) participants in the fourth decade of life. Social outcome data from a prospective, longitudinal, population-based Canadian birth cohort initiated between the years of 1977 and 1982 were examined. At age 29-36 years, ELBW survivors who experienced CSA reported poorer relationships with their partner, worse family functioning, greater loneliness, lower self-esteem and had higher rates of avoidant personality problems than those who had not experienced CSA. Birth weight status was also found to moderate associations between CSA and self-esteem (P=0.032), loneliness (P=0.021) and family functioning (P=0.060), such that the adverse effects of CSA were amplified in ELBW survivors. Exposure to CSA appears to augment the adult social risks associated with perinatal adversity. Individuals born preterm and exposed to CSA appear to be a group at particularly high risk for adverse social outcomes in adulthood.

Just DO(HaD) It! Testing the clinical potential of the DOHaD hypothesis to prevent mental disorders using experimental study designs.

Optimal early cognitive and emotional development are vital to reaching one's full potential and represent our best chance to improve the mental health of the population. The developmental origins of health and disease (DOHaD) hypothesis posits that adverse perinatal exposures can alter physiology and increase disease risk. As physiological plasticity decreases with age, interventions applied during gestation may hold the most promise for reducing the impact of mental disorders across the lifespan. However, this vast clinical potential remains largely unrealized as the majority of human DOHaD research is observational in nature. The application of more rigorous experimental designs [e.g. Randomized Controlled Trials (RCTs)] not only represents a major step toward unlocking this potential, but are required to fully test the scientific validity of the DOHaD hypothesis as it pertains to mental illness. Here, we argue that the optimization of maternal diet and exercise during pregnancy represents our best chance to improve offspring neurodevelopment and reduce the burden of mental disorders. Follow-up studies of the offspring of pregnant women enrolled in new and existing RCTs of maternal gestational nutrition+exercise interventions are required to determine if acting during pregnancy can prevent and/or meaningfully reduce the prevalence and severity of mental disorders in the population.

Childhood cognition and lifetime risk of major depressive disorder in extremely low birth weight and normal birth weight adults.

In general population samples, better childhood cognitive functioning is associated with decreased risk of depression in adulthood. However, this link has not been examined in extremely low birth weight survivors (ELBW, <1000 g), a group known to have poorer cognition and greater depression risk. This study assessed associations between cognition at age 8 and lifetime risk of major depressive disorder in 84 ELBW survivors and 90 normal birth weight (NBW, ⩾2500 g) individuals up to 29-36 years of age. The Wechsler Intelligence Scale for Children, Revised (WISC-R), Raven's Coloured Progressive Matrices and the Token Test assessed general, fluid, and verbal intelligence, respectively, at 8 years of age. Lifetime major depressive disorder was assessed using the Mini International Neuropsychiatric Interview at age 29-36 years. Associations were examined using logistic regression adjusted for childhood socioeconomic status, educational attainment, age, sex, and marital status. Neither overall intelligence quotient (IQ) [WISC-R Full-Scale IQ, odds ratios (OR)=0.87, 95% confidence interval (CI)=0.43-1.77], fluid intelligence (WISC-R Performance IQ, OR=0.98, 95% CI=0.48-2.00), nor verbal intelligence (WISC-R Verbal IQ, OR=0.81, 95% CI=0.40-1.63) predicted lifetime major depression in ELBW survivors. However, every standard deviation increase in WISC-R Full-Scale IQ (OR=0.43, 95% CI=0.20-0.92) and Performance IQ (OR=0.46, 95% CI=0.21-0.97), and each one point increase on the Token Test (OR=0.80, 95% CI=0.67-0.94) at age 8 was associated with a reduced risk of lifetime depression in NBW participants. Higher childhood IQ, better fluid intelligence, and greater verbal comprehension in childhood predicted reduced depression risk in NBW adults. Our findings suggest that ELBW survivors may be less protected by superior cognition than NBW individuals.

Emotional and behavioral problems in adolescents and young adults with food allergy.

BACKGROUND: Adolescents with food allergy have poorer psychosocial outcomes compared with their nonallergic counterparts; however, few studies have prospectively examined the mental health of adolescents and young adults in this vulnerable population. Our objectives were to estimate the prevalence of emotional and behavioral problems in an epidemiological sample of adolescents and young adults with food allergy; determine whether food allergy is associated with adolescent and maternal reports of such problems; and examine the patterns of change in emotional and behavioral problems from adolescence to young adulthood among individuals with and without food allergy. METHODS: Data came from 1303 participants at 14 and 21 years of age in the Mater University Study of Pregnancy. Emotional and behavioral problems were measured using self- and maternal-reported symptoms of depression, anxiety, attention/deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder. RESULTS: Maternal, but not self-reports suggested that emotional and behavioral problems were higher among adolescents with food allergy. Food allergy was associated with increased odds of elevated levels of maternal-reported symptoms of depression [OR = 4.50 (1.83, 11.07)], anxiety [OR = 2.68 (1.12, 6.44)], and ADHD [OR = 3.14 (1.07, 9.19)] in adolescence. Food allergy was also associated with depressive symptoms that persisted from adolescence to young adulthood [OR = 2.05 (1.04, 4.03)]. CONCLUSIONS: Emotional and behavioral problems, particularly symptoms of depression, anxiety, and ADHD, are common among adolescents with food allergy in the general population and, in the case of elevated levels of depressive symptoms, persist into young adulthood. Healthcare professionals should seek adolescent and parental perspectives when assessing emotional and behavioral problems and monitor mental health during the transition to adulthood.

Pre-pregnancy maternal overweight and obesity increase the risk for affective disorders in offspring.

Maternal pre-pregnancy obesity has been linked with an increased risk for negative emotionality and inattentiveness in offspring in early childhood. The aim of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and the development of affective problems (dysthymic disorder, major depressive disorder) throughout childhood and adolescence. In the Western Australian Pregnancy Cohort (Raine) Study, 2900 women provided data on their pre-pregnancy weight, and height measurements were taken at 18 weeks of gestation. BMI was calculated and categorized using standardized methods. Live-born children (n = 2868) were followed up at ages 5, 8, 10, 14 and 17 years using the Diagnostic and Statistical Manual of Mental Disorders-oriented scales of the Child Behavior Checklist (CBCL/4-18). Longitudinal models were applied to assess the relationships between maternal pre-pregnancy BMI and affective problems from age 5 through 17. There was a higher risk of affective problems between the ages of 5 and 17 years among children of women who were overweight and obese compared with the offspring of women in the healthy pre-pregnancy weight range (BMI 18.5-24.99) after adjustment for confounders, including paternal BMI. Maternal pre-pregnancy overweight and obesity may be implicated in the development of affective problems, including depression, in their offspring later in life.

Pre-pregnancy and pregnancy obesity and neurodevelopmental outcomes in offspring: a systematic review.

Maternal obesity in pregnancy is associated with a number of adverse outcomes for mother and her offspring both perinatally and later in life. This includes recent evidence that suggests that obesity in pregnancy may be associated with central nervous system problems in the foetus and newborn. Here, we systematically review studies that have explored associations between maternal overweight and obesity in pregnancy and cognitive, behavioural and emotional problems in offspring. The 12 studies eligible for this review examined a wide range of outcomes across the lifespan and eight provided evidence of a link. These data suggest that the offspring of obese pregnancies may be at increased risk of cognitive problems and symptoms of attention deficit hyperactivity disorder in childhood, eating disorders in adolescence and psychotic disorders in adulthood. Given the limitations of existing data, these findings warrant further study, particularly in light of the current worldwide obesity epidemic.

Is bigger better? Macrosomia and psychopathology later in life.

Evidence suggests that a curvilinear relationship may exist between birth weight and later psychopathology. Increases in the prevalence of macrosomia and of two of its risk factors (maternal pre-pregnancy obesity and diabetes mellitus) and their amenability to intervention argue for a critical review of the association between macrosomia and mental illness. Of the nine studies in adults and six studies in youth that have examined associations between macrosomia and psychiatric disorders, seven have provided evidence suggestive of a link. Significant methodological variability and an inability to adjust for important confounders limit the findings of these studies. As a result, it remains unclear if individuals born macrosomic are at increased risk for psychopathology later in life. Future work should attempt to examine a broader range of psychiatric outcomes, use validated measures, include data on putative confounders and utilize genetically sensitive designs to assess associations between macrosomia, its precursors and later psychological and emotional functioning.

Psychopathology in young adults born at extremely low birth weight.

BACKGROUND: Little is known about the long-term mental health of extremely low birth weight (ELBW) (<1000 g) survivors. We test whether young adults aged 22 to 26 years born at ELBW differ from normal birth weight (NBW) controls in self-reported levels of psychopathology. METHOD: Participants included 142 ELBW survivors (86% response) born between 1977 and 1982 to residents of central-west Ontario, Canada and 133 NBW control subjects (92% response). The Young Adult Self-Report measure was used to create five DSM-IV oriented scales aggregated to form internalizing (depressive problems, anxiety problems, avoidant personality problems) and externalizing (attention deficit-hyperactivity disorder problems and antisocial personality problems) scales. RESULTS: After adjusting for family background characteristics, mean scores for ELBW survivors were 3.02 [95% confidence interval (CI) 0.78-5.26] points higher for internalizing problems and no different, i.e. 0.00 (95% CI -1.17 to 1.17), for externalizing problems. There was a sex × group statistical interaction such that being male muted the risk for externalizing problems among those born at ELBW: -2.11 (95% CI -4.21 to -0.01). Stratifying ELBW adults as born small for gestational age (SGA) versus appropriate weight for gestational age (AGA) revealed a significant gradient of risk for levels of internalizing problems that was largest for SGA, i.e. 4.75 (95% CI 1.24-8.26), and next largest for AGA, 2.49 (95% CI 0.11-4.87), compared with NBW controls. CONCLUSIONS: Depression, anxiety and avoidant personality problems (internalizing problems) are elevated in young adulthood among ELBW survivors. This effect is relatively small overall but noticeably larger among ELBW survivors born SGA.

Three-dimensional flow-through protein platform.

We have developed a new protein microarray (ImmunoFlow Protein Platform, IFPP) that utilizes a porous nitrocellulose (NC) membrane with printed spots of capture probes. The sample is pumped actively through the NC membrane, to enhance binding efficiency and introduce stringency. Compared to protein microarrays assayed with the conventional incubation-shaking method the rate of binding is enhanced on the IFPP by at least a factor of 10, so that the total assay time can be reduced drastically without compromising sensitivity. Similarly, the sensitivity can be improved. We demonstrate the detection of 1 pM of C-reactive protein (CRP) in 70 microL of plasma within a total assay time of 7 min. The small sample and reagent volumes, combined with the speed of the assay, make our IFPP also well-suited for a point-of-care/near-patient setting. The potential clinical application of the IFPP is demonstrated by validating CRP detection both in human plasma and serum samples against standard clinical laboratory methods.

Dysglycemia in a community sample of people treated for schizophrenia: the Diabetes in Schizophrenia in Central-South Ontario (DiSCO) study.

OBJECTIVE: Despite increasing recognition of schizophrenia as a risk factor for diabetes, the prevalence and correlates of dysglycemia in people with schizophrenia have not been adequately studied. Discerning the modifiable risk factors is crucial for developing diabetes prevention strategies in schizophrenia. METHODS: Socio-demographic, clinical and recent laboratory data were compiled from the case records and supplemental sources of 1123 people treated for schizophrenia who were living across five different communities in the region. RESULTS: Screening rates for fasting plasma glucose (FPG) varied between 63-100% across the five communities, while other metabolic indices were monitored less frequently. 39 subjects (3.5%) in the sample had an existing diagnosis of type 2 diabetes. Among the others, 845 (78%) had FPG measured in the preceding 6 months, with the following results: FPG < or = 5.6 mmol/l in 474 (56%), 5.6-6.9 mmol/l in 268 (31%), and > or = 7 mmol/l in 103 (12.2%) subjects. Dysglycemia (FPG > or = 5.6 mmol/l) was significantly associated with older age (odds ratio [OR] 1.031), longer duration of schizophrenia (OR 1.062), self reported family history of diabetes (OR 8.87), body mass index (OR 1.081), excess weight (OR 1.014) and independent living status (OR 1.779), while European ethnicity (OR 0.706) and regular physical activity (OR 0.958) lowered the risk. No statistically significant correlations were noted with gender, level of education or functioning, or the type of antipsychotic drug prescribed. CONCLUSIONS: There was a two-fold increase in the prevalence of dysglycemia, while there was a substantial under-recognition of and intervention for, diabetes and pre-diabetes in this sample of people treated for schizophrenia.

Directiveness in teachers' language input to toddlers and preschoolers in day care.

Five subtypes of directiveness were examined in the interactions of day care teachers with toddler and preschooler groups. The instructional context (book reading, play dough) yielded significant differences across all five subtypes of directiveness, indicating that these two activities elicited different types of teacher-child discourse. Book reading was characterized by significantly more behavior and response control and less conversation control in comparison with the play-dough activity. Correlations between teachers' directiveness and child language productivity indicated that behavior control and turn-taking control were associated with low levels of productivity, whereas conversation control was associated with the highest levels of productivity. The results of this study confirm that instructional context is an important mediator of teachers' directiveness and suggest that subtypes of directiveness have differential effects on child language output.

Teaching mentally retarded children to use an experimental device for telling time and meeting appointments.

This study evaluated a program for teaching mentally retarded children to use an experimental clock-agenda combination (CAC). The CAC was designed to serve as a prosthetic device for children with minimal numerical skills and time concepts to (a) tell time to the nearest 5-minute interval, and (b) meet scheduled appointments. The target skills were trained in two phases, each of which consisted of two or more steps and substeps. A modified multiple-probe technique was used for each phase. Three mildly mentally retarded children and one moderately retarded child served as subjects. The data indicated that all subjects acquired both skills in 5 to 10 hours.