Persistence of anxiety among Asian Americans: racial and ethnic heterogeneity in the longitudinal trends in mental well-being during the COVID-19 pandemic.

PURPOSE: To examine within-individual time trends in mental well-being and factors influencing heterogeneity of these trends. METHODS: Longitudinal telephone survey of adults over 3 waves from the New York City (NYC) Metropolitan area during the COVID-19 Pandemic. Participants reported depression using the Patient Health Questionnaire (PHQ)-8, anxiety using the Generalized Anxiety Disorder (GAD)-7, and past 30-day increases in tobacco or alcohol use at each wave. Adjusted mixed effects logistic regression models assessed time trends in mental well-being. RESULTS: There were 1227 respondents. Over 3 study waves, there were statistically significant decreasing time trends in the odds of each outcome (adjusted OR (95% CI) 0.47 (0.37, 0.60); p < 0.001 for depression; aOR (95% CI) 0.55 (0.45, 0.66); p < 0.001 for anxiety; aOR (95% CI) 0.50 (0.35, 0.71); p < 0.001 for past 30-day increased tobacco use; aOR (95% CI) 0.31 (0.24, 0.40); p < 0.001 for past 30-day increased alcohol use). Time trends for anxiety varied by race and ethnicity (p value for interaction = 0.05, 4 df); anxiety declined over time among white, Black, Hispanic, and Other race and ethnicity but not among Asian participants. CONCLUSIONS: In a demographically varied population from the NYC Metropolitan area, depression, anxiety and increased substance use were common during the first months of the pandemic, but decreased over the following year. While this was consistently the case across most demographic groups, the odds of anxiety among Asian participants did not decrease over time.

Psychometric Properties and Diagnostic Associations of the Short-Form Community Assessment of Psychic Experiences in a Population-Based Sample of 29 021 Adult Men.

BACKGROUND AND HYPOTHESIS: Around 5%-7% of the adult population are estimated to have lifetime psychotic experiences (PEs), which are associated with psychosis risk. PEs assessed with Community Assessment of Psychic Experiences (CAPE) are associated with psychosis but also non-psychotic disorders, which could be partly explained by CAPE indirectly capturing emotional symptoms. We investigated the psychometric properties of a shorter version, CAPE-9, and whether CAPE-9 scores are associated with lifetime psychotic or non-psychotic mental disorders after controlling for current anxiety and depressive symptoms. DESIGN: CAPE-9 questionnaire data were obtained from 29 021 men (42.4 ± 5.6 yrs.) from the Norwegian Mother, Father, and Child Cohort Study. We investigated CAPE-9 reliability and factor structure. Logistic regression was used to test effects of current anxiety and depressive symptoms (SCL-12) on associations between CAPE-9 scores and psychiatric diagnoses. RESULTS: CAPE-9 fit a previously reported 3-factor structure and showed good reliability. Twenty-six percent reported at least one lifetime PE. CAPE-9 scores were significantly associated with most psychiatric disorders (schizophrenia, depression, bipolar disorder, substance abuse, anxiety, trauma-related disorders, and ADHD). After controlling for concurrent emotional symptoms, only associations with schizophrenia (OR = 1.29; 95% CI = 1.18-1.38) and trauma-related disorders (OR = 1.09; CI = 1.02-1.15) remained significant. CONCLUSIONS: CAPE-9 showed good psychometric properties in this large population-based adult male sample, and PEs were more clearly associated with psychotic disorders after controlling for current emotional symptoms. These results support the use of the short CAPE-9 as a cost-effective tool for informing public health initiatives and advancing our understanding of the dimensionality of psychosis.

Religiosity, Mental Health and Substance Use among Black and Hispanic Adults during the First Six Months of the COVID-19 Pandemic in New York City.

The purpose of this study was to investigate the association between personal religiosity, mental health, and substance use outcomes among Black and Hispanic adults during the first six months of the COVID-19 outbreak in New York City (NYC). Phone interviews were conducted with 441 adults to obtain information on all variables. Participants self-reported race/ethnicity as Black/African American (n = 108) or Hispanic (n = 333). Logistic regression were used to examine associations between religiosity, mental health, and substance use. There was a significant inverse association of religiosity and substance use. Religious people had a lower prevalence of drinking alcohol (49.0%) compared to non-religious people (67.1%). Religious people also had substantially lower prevalence of cannabis or other drug use (9.1%) in comparison to non-religious people (31%). After adjusting for age, sex, race/ethnicity, and household income, the association of religiosity with alcohol use and with cannabis/other drug use remained statistically significant. Despite restricted access to in-person religious activities and congregational supports, the findings suggest that religiosity itself may be helpful from a public health perspective, independent of serving as a conduit for other social services.

Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders.

The discovery of prenatal and neonatal molecular biomarkers has the potential to yield insights into autism spectrum disorder (ASD) and facilitate early diagnosis. We characterized metabolomic profiles in ASD using plasma samples collected in the Norwegian Autism Birth Cohort from mothers at weeks 17-21 gestation (maternal mid-gestation, MMG, n = 408) and from children on the day of birth (cord blood, CB, n = 418). We analyzed associations using sex-stratified adjusted logistic regression models with Bayesian analyses. Chemical enrichment analyses (ChemRICH) were performed to determine altered chemical clusters. We also employed machine learning algorithms to assess the utility of metabolomics as ASD biomarkers. We identified ASD associations with a variety of chemical compounds including arachidonic acid, glutamate, and glutamine, and metabolite clusters including hydroxy eicospentaenoic acids, phosphatidylcholines, and ceramides in MMG and CB plasma that are consistent with inflammation, disruption of membrane integrity, and impaired neurotransmission and neurotoxicity. Girls with ASD have disruption of ether/non-ether phospholipid balance in the MMG plasma that is similar to that found in other neurodevelopmental disorders. ASD boys in the CB analyses had the highest number of dysregulated chemical clusters. Machine learning classifiers distinguished ASD cases from controls with area under the receiver operating characteristic (AUROC) values ranging from 0.710 to 0.853. Predictive performance was better in CB analyses than in MMG. These findings may provide new insights into the sex-specific differences in ASD and have implications for discovery of biomarkers that may enable early detection and intervention.

Cohort-guided insights into gene-environment interactions in autism spectrum disorders.

Prospective birth cohorts offer unprecedented opportunities to investigate the pathogenesis of complex disorders such as autism, in which gene-environment interactions must be appreciated in a temporal context. This Perspective article considers the history of autism research, including missteps that reflected an incomplete understanding of the epidemiology of autistic spectrum disorders, the effects of advocacy and philanthropy on the trajectory of scientific inquiry, and the current and future roles of prospective birth cohort research in illuminating the pathology of these and other complex disorders wherein exposures during gestation might not manifest until later in life.

Occupational Conditions Associated With Negative Mental Health Outcomes in New York State Health Professionals During the COVID-19 Pandemic.

OBJECTIVE: The aim of this study was to assess occupational circumstances associated with adverse mental health among health care workers during the COVID-19 pandemic. METHODS: A cross-sectional study examined responses to an on-line survey conducted among 2076 licensed health care workers during the first pandemic peak. Mental health (depression, anxiety, stress, and anger) was examined as a multivariate outcome for association with COVID-related occupational experiences. RESULTS: Odds of negative mental health were increased among those who worked directly with patients while sick themselves (adjusted odds ratio, 2.29; 95% confidence interval, 1.71-3.08) and were independently associated with working more hours than usual in the past 2 weeks, having family/friends who died due to COVID-19, having COVID-19 symptoms, and facing insufficiencies in personal protective equipment/other shortages. CONCLUSIONS: Occupational circumstances were associated with adverse mental health outcomes among health care workers during the COVID-19 pandemic, and some are potentially modifiable.

Adverse Childhood Experiences and Insufficient Sleep Among U.S. Children and Adolescents.

OBJECTIVE: To examine associations between adverse childhood experiences (ACEs) and age-specific insufficient sleep duration (ISD) in American youth. METHODS: Data from the 2016-2017 National Survey of Children's Health, a sample of 46,209 youth ages 6 to 17 were analyzed. The main outcome was sleep duration that did not meet the recent recommendations of the American Academy of Sleep Medicine. Nine types of ACEs, as well as a cumulative count of ACEs, were examined as independent variables in unadjusted and adjusted logistic regression models. RESULTS: Approximately half of U.S. children and adolescents (ages 6-17) experienced at least one ACE and a third did not get sufficient sleep. Among those exposed to any ACE, 40.3% had ISD. Seven of the 9 ACEs examined were significantly associated with a 20% to 60% increase in odds of not getting sufficient sleep (adjusted ORs between 1.2 and 1.6). Children exposed to 2 or more ACEs were nearly twice as likely as those exposed to no ACE to have ISD (adjusted OR = 1.7, 95% CI: 1.5-1.9). Moreover, each individual ACE, except parental death was significantly associated with more than 1 hour less sleep than recommended. CONCLUSIONS: This study reports the association of specific and cumulative ACEs with ISD in a nationally representative sample of American youth. The study findings underscore the importance of screening for both ACEs and insufficient sleep during primary care encounters and addressing potential sleep problems in those exposed to ACEs.

Arrest history, stigma, and self-esteem: a modified labeling theory approach to understanding how arrests impact lives.

PURPOSE: Modified labeling theory theorizes that when people acquire a label, personally held views about that label gain relevance and exert negative effects. We assessed whether being arrested reduces self-esteem to different extents based on the degree to which individuals hold stigmatizing beliefs about people with arrest records. METHODS: Adults living in the South Bronx, New York City (N = 532, 56% of whom had ever been arrested) indicated their level of agreement with statements about people with arrest records. We used exploratory factor analysis to identify categories of stigmatizing views, and calculated scores for the two following categories: "stereotype awareness" and "stereotype agreement." Self-esteem was assessed with the Rosenberg self-esteem scale. Using fitted linear regression models, we assessed interaction between arrest history and each stigma score, and calculated mean differences representing the association between arrest history and self-esteem score, for those with stigma scores one standard deviation (SD) below and above the mean. RESULTS: For each type of stigma, participants with stigma scores one SD below the mean had similar self-esteem scores, regardless of arrest history. However, among participants with stigma scores one SD above the mean, those who had experienced an arrest had lower self-esteem scores than those who had not (mean difference = - 2.07, 95% CI - 3.16, - 0.99 for "stereotype awareness"; mean difference = - 2.92, 95% CI - 4.05, - 1.79 for "stereotype agreement"). CONCLUSION: Being arrested affects self-esteem to a greater degree among persons who hold stigmatizing views about people with arrest records. These findings support a modified labeling theory of arrest-related stigma.

Maternal mid-gestational and child cord blood immune signatures are strongly associated with offspring risk of ASD.

Epidemiological studies and work in animal models indicate that immune activation may be a risk factor for autism spectrum disorders (ASDs). We measured levels of 60 cytokines and growth factors in 869 maternal mid-gestational (MMG) and 807 child cord blood (CB) plasma samples from 457 ASD (385 boys, 72 girls) and 497 control children (418 boys, 79 girls) from the Norwegian Autism Birth Cohort. We analyzed associations first using sex-stratified unadjusted and adjusted logistic regression models, and then employed machine learning strategies (LASSO + interactions, Random Forests, XGBoost classifiers) with cross-validation and randomly sampled test set evaluation to assess the utility of immune signatures as ASD biomarkers. We found prominent case-control differences in both boys and girls with alterations in a wide range of analytes in MMG and CB plasma including but not limited to IL1RA, TNFα, Serpin E1, VCAM1, VEGFD, EGF, CSF1, and CSF2. MMG findings were most striking, with particularly strong effect sizes in girls. Models did not change appreciably upon adjustment for maternal conditions, medication use, or emotional distress ratings. Findings were corroborated using machine learning approaches, with area under the receiver operating characteristic curve values in the test sets ranging from 0.771 to 0.965. Our results are consistent with gestational immunopathology in ASD, may provide insights into sex-specific differences, and have the potential to lead to biomarkers for early diagnosis.

Risk of attention-deficit hyperactivity disorder in offspring of mothers with infections during pregnancy.

Background: Maternal infections during pregnancy are common events that have been suggested to be risk factors for Attention-deficit hyperactivity disorder (ADHD) in offspring. Only a few studies have been conducted to date and results are conflicting. The current study investigates the associations between specific groups of prenatal maternal infections and offspring ADHD, considering timing of exposure and the role of fever. Methods: We used data from the prospective Norwegian Mother, Father and Child Cohort Study (MoBa), including more than 112,000 pregnancies, linked with data from the Medical Birth Registry of Norway and the Norwegian Patient Registry to estimate odds ratios for the likelihood that children develop ADHD after being exposed to maternal infections during gestation. Results: Children exposed to any maternal infection during pregnancy showed increased risk of receiving an ADHD diagnosis (OR = 1.15, CI = 1.03-1.27). Specifically, increased ADHD risk was observed after exposure to genitourinary infections in second (OR = 1.42, CI = 1.06-1.90) or third trimester (OR = 2.04, CI = 1.19-3.49), and to respiratory infections in second trimester (OR = 1.31, CI = 1.12-1.54), provided these infections were accompanied by episodes of fever. Increased ADHD risk was also observed after exposure to diarrhea without fever in the third trimester (OR = 1.25, CI = 1.07-1.46). Conclusions: Overall, our results suggest that prenatal exposure to maternal infections, particularly with co-occurring episodes of fever, are risk factors for ADHD. Fever (or severity of the infection) appears to be more important in mid-pregnancy associations. Our results indicate that type of infection and timing of exposure might influence the associations, but small effect sizes require careful interpretations. The association between infection and ADHD should be estimated using discordant siblings or other negative control designs that give better adjustment for unmeasured familial confounding.

Mental Health of High-Risk Urban Youth: The Housing Subsidies Paradox.

Housing subsidies, including public housing and Section 8 vouchers, are key components of the social safety net, intended to promote family and child welfare. Studies evaluating the impact of housing subsidies on child and adolescent mental health, however, are generally inconclusive. This may reflect variation in the influence by type of subsidies to income, improved physical environment, increased access to resources, and improved perception of neighborhood safety. Further, most prior research focused on housing subsidies failed to simultaneously formally assess child psychopathology. In the present study, we examine, among adolescents (ages 9-17) from a low-income, urban minority area, the association of housing with psychiatric symptoms and disorders, as well as with their social functioning. The data were obtained from the Stress & Justice Study (S&J) baseline survey, an investigation designed to examine impact of parental criminal justice system involvement (CJSI) on their children's mental health. Housing type during the past year was categorized from parental report as public housing, section 8, both, or neither. Child mental health was assessed with the Diagnostic Interview Schedule for Children (DISC). Additionally, family resources and physical quality of the housing environment by housing type was assessed, and we tested whether these dimensions mediated associations of housing type with the adolescent's current mental health outcomes. We found that while internalizing and externalizing disorders and impairment were attenuated by individual characteristics (e.g., SES, CJSI), internalizing and externalizing symptom counts were significantly more prevalent among children in subsidized housing, compared to those in non-subsidized housing, after controlling for individual characteristics. These findings have the potential to inform whether, and through which mechanisms, housing subsidies are associated with adolescent mental health.

Neighborhood characteristics and psychiatric disorders in the aftermath of mass trauma: A representative study of New York City public school 4th-12th graders after 9/11.

Studies of the relationship between neighborhood characteristics and childhood/adolescent psychopathology in large samples examined one outcome only, and/or general (e.g., 'psychological distress') or aggregate (e.g., 'any anxiety disorder') measures of psychopathology. Thus, in the only representative sample of New York City public school 4th-12th graders (N = 8202) surveyed after the attacks of 9/11/2001, this study examined whether (1) indices of neighborhood Socioeconomic Status, Quality, and Safety and (2) neighborhood disadvantage (defined as multidimensional combinations of SES, Quality and Safety indicators) are associated with eight psychiatric disorders: posttraumatic stress disorder, separation anxiety disorder (SAD), agoraphobia, generalized anxiety disorder (GAD), panic disorder, major depression, conduct disorder, and alcohol use disorder (AUD). (1) The odds ratios (OR) of psychiatric disorders were between 0.55 (AUD) and 1.55 (agoraphobia), in low and intermediate-low SES neighborhoods, respectively, between 0.50 (AUD) and 2.54 (agoraphobia) in low Quality neighborhoods, and between 0.52 (agoraphobia) and 0.65 (SAD) in low Safety neighborhoods. (2) In neighborhoods characterized by high disadvantage, the OR were between 0.42 (AUD) and 1.36 (SAD). This study suggests that neighborhood factors are important social determinants of childhood/adolescent psychopathology, even in the aftermath of mass trauma. At the community level, interventions on modifiable neighborhood characteristics and targeted resources allocation to high-risk contexts could have a cost-effective broad impact on children's mental health. At the individual-level, increased knowledge of the living environment during psychiatric assessment and treatment could improve mental health outcomes; for example, specific questions about neighborhood factors could be incorporated in DSM-5's Cultural Formulation Interview.

Exposure to mass disaster and probable panic disorder among children in New York City.

While both direct and indirect exposure to mass trauma are increasing in the United States, relatively little is known about the potential link between mass trauma and risk of panic disorder early in life. It is also unclear whether history of prior individual trauma increases risk of panic disorder even further among those with exposure to mass trauma. The current study investigated the association between exposure to a mass trauma event (the World Trade Center (WTC) attack) and risk of panic disorder among children, how panic disorder varies by exposure severity and sociodemographic characteristics, and whether there is an interaction between individual and mass trauma exposure in the risk of panic disorder. Data were from an epidemiologic study of probable mental disorders among New York City schoolchildren exposed to the WTC terrorist attack. Severe (adjusted odds ratio [AOR] = 2.0 (1.1, 3.7)) exposure to the WTC disaster was associated with increased odds of probable panic disorder, relative to mild exposure. The prevalence of panic disorder increased with higher level of WTC exposure among all sociodemographic strata. Prior individual trauma exposure was associated with increased odds of panic disorder (AOR = 2.4 (1.6, 3.5)), but there was no evidence of interaction between prior individual trauma exposure and exposure to the WTC disaster. Preventive measures to address the widespread nature of mass disaster exposure at increasingly earlier ages and via media could mitigate the potential impact on mental health.

Acetaminophen use during pregnancy and offspring attention deficit hyperactivity disorder - a longitudinal sibling control study.

Background: Maternal acetaminophen use during pregnancy is associated with increased risk of ADHD in the child. This could reflect causal influence of acetaminophen on fetal neurodevelopment or could be due to confounding factors. The aim of the current study was to examine unmeasured familial confounding factors of this association. Methods: We used data from 26,613 children from 12,902 families participating in the prospective Norwegian Mother, Father, and Child Cohort Study (MoBa). The MoBa was linked to the Norwegian Medical Birth Register and the Norwegian Patient Registry. Siblings discordant for prenatal acetaminophen exposure were compared regarding risk of having an ADHD diagnosis. Results: Children exposed to acetaminophen up to 28 days during pregnancy did not have increased risk of receiving an ADHD diagnosis compared to unexposed children. The adjusted Hazard ratio (aHR) was 0.87 (95% C.I. = 0.70-1.08) for exposure 1 to 7 days, and 1.13 (95% C.I. = 0.82-1.49) for 8-28 days. Long-term exposure (29 days or more) was associated with a two-fold increase in risk of ADHD diagnosis (aHR = 2.02, 95% C.I = 1.17-3.25). In the sibling control model, the association between long-term acetaminophen use and ADHD in the child was aHR = 2.77 (95% C.I. = 1.48-5.05) at the between-family level, and aHR = 1.06 (95% C.I. = 0.51-2.05) at the within-family level. Conclusions: Both the exposed and the unexposed children of mothers with long-term use of acetaminophen in one of the pregnancies had increased risk of receiving an ADHD diagnosis. This indicates that the observed association between long-term acetaminophen use during pregnancy and ADHD in the child may at least partly be confounded by unobserved family factors.

Functional Outcomes of Children Identified Early in the Developmental Period as at Risk for ASD Utilizing the The Norwegian Mother, Father and Child Cohort Study (MoBa).

Early identification of autism spectrum disorder (ASD) is regarded as crucial for swift access to early intervention and, subsequently, better outcomes later in life. However, current instruments miss large proportions of children who later go on to be diagnosed with ASD, raising a question of what these instruments measure. The present study utilized data from the Norwegian Mother, Father, and Child Cohort Study and the Autism Birth Cohort study to explore the subsequent developmental and diagnostic characteristics of children raising developmental concern on the six-critical discriminative item criterion of the M-CHAT (DFA6) at 18 months of age (N = 834). The DFA6 identified 28.8% of children diagnosed with ASD (N = 163), but 4.4% with language disorder (N = 188) and 81.3% with intellectual disability (N = 32) without ASD. Scoring in the «at-risk¼ range was associated with lower IQ, impaired functional language, and greater severity of autism symptoms whether children had ASD or not.

Age of walking and intellectual ability in autism spectrum disorder and other neurodevelopmental disorders: a population-based study.

BACKGROUND: Delayed walking is common in intellectual disability (ID) but may be less common when ID occurs with autism spectrum disorder (ASD). Previous studies examining this were limited by reliance on clinical samples and exclusion of children with severe motor deficits. OBJECTIVE: To examine in a population-based sample if age of walking is differentially related to intellectual ability in children with ASD versus other neurodevelopmental disorders (NDD). METHODS: Participants were from the nested Autism Birth Cohort Study of the Norwegian Mother, Father and Child Cohort Study (MoBa). Cox proportional hazards regression assessed if diagnosis (ASD n = 212 vs. NDD n = 354), continuous nonverbal IQ, and their interaction, were associated with continuous age of walking. RESULTS: The relationship between nonverbal IQ and age of walking was stronger for NDD than for ASD (Group × nonverbal IQ interaction, χ2  = 13.93, p = .0002). This interaction was characterized by a 21% decrease in the likelihood of walking onset at any given time during the observation period per 10-point decrease in nonverbal IQ (hazard ratio = 0.79, 95% CI: 0.78-0.85) in the NDD group compared to 8% (hazard ratio = 0.92, 95% CI: 0.86-0.98) in the ASD group. CONCLUSIONS: The finding that age of walking is less strongly related to low intellectual ability in children with ASD than in children without other NDDs supports the hypothesis that ID in ASD may result from heterogeneous developmental pathways. Late walking may be a useful stratification variable in etiological research focused on ASD and other NDDs.

Parental Occupational Exposure is Associated With Their Children's Psychopathology: A Study of Families of Israeli First Responders.

OBJECTIVE: To examine the association between parental occupational exposure to traumatic events and their children's mental health in families of First Responders (FRs), a neglected area of research. METHODS: In 208 families of Israeli FRs, children's symptoms and comorbidity patterns of seven psychiatric disorders were regressed on parental work-related variables, controlling for relevant covariates. RESULTS: Having a father working as a FR and higher paternal exposure were associated with a greater number of separation anxiety and posttraumatic stress symptoms, respectively. Maternal exposure was associated with a greater number of symptoms of generalized anxiety, panic disorder, depression, and oppositional defiant disorder, and with increased odds of comorbid internalizing symptomatology. CONCLUSIONS: Additional research on children of FRs is encouraged. An adaption to this understudied population of family-centered interventions available for military families could inform targeted prevention efforts.

Sensitivity and specificity of early screening for autism.

BACKGROUND: Early identification and diagnosis is beneficial for children with autism spectrum disorder (ASD). Universal early screening is recommended by many experts, but disputed because evidence is limited, and sensitivity and specificity in general populations are largely unknown. AIMS: To estimate the sensitivity and specificity of early population-based screening for ASDs. METHOD: The study was based on the Norwegian Mother and Child Cohort Study. The 36-month cohort questionnaire included the Social Communication Questionnaire (SCQ), a 40-item screening instrument for ASD. RESULTS: A total of 58 520 mothers (58%) responded to the questionnaire. By the end of follow-up on 31 December 2015, 385 (0.7%) individuals with ASD had been identified among the responders' children. The distributions of SCQ scores in those with ASD and other children had large degrees of overlap. With the cut-off of 15 recommended in the SCQ manual, screening sensitivity was 20% (95% CI 16-24) for ASD overall. For children with ASD who had not developed phrase speech at 36 months, sensitivity was 46% (95% CI 35-57%), whereas it was 13% (95% CI 9-17) for children with ASD with phrase speech. Screening specificity was 99% (95% CI 99-99). With the currently recommended cut-off of 11, sensitivity increased to 42% for ASD overall (95% CI 37-47), 69% (95% CI 58-79) for ASD without phrase speech and 34% (95% CI 29-40) for ASD with phrase speech. Specificity was then reduced to 89% (95% CI 89-90). CONCLUSIONS: Early ASD screening with a parent checklist had low sensitivity. It identified mainly individuals with ASD with significant developmental delay and captured very few children with ASD with cognitive skills in the normal range. Increasing sensitivity was not possible without severely compromising specificity. DECLARATION OF INTEREST: C.L. receives royalty for the Social Communication Questionnaire, which she has co-authored.

Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure.

INTRODUCTION: Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype-decreased fetal growth-previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings. METHODS: Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review. RESULTS: Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring. CONCLUSIONS: Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.

Maternal fever during pregnancy and offspring attention deficit hyperactivity disorder.

Maternal fever during pregnancy is associated with several adverse child outcomes. We investigated associations between maternal fever and ADHD among offspring, as well as the sub-dimensions of ADHD - inattention and hyperactivity/impulsivity. Data came from the Norwegian Mother and Child Cohort Study, including more than 114,000 children. Information about children's ADHD diagnoses was obtained from the Norwegian Patient Register. Mothers reported on inattention and hyperactivity/impulsivity symptoms in questionnaires at 8 years. Logistic regression analysis showed that children exposed to maternal fever in the first trimester received an ADHD diagnosis more often than unexposed children (Odds Ratio (OR) = 1.31, 95% confidence interval (CI) = 1.06-1.61). For children exposed twice or more in the first trimester, the OR was 2.64 (CI = 1.36-5.14). Linear regression analysis showed elevated inattention symptoms among children exposed to fever in the first (Cohen's d = 0.09, CI = 0.03-0.15) and second (Cohen's d = 0.05, CI = 0.01-0.09) trimester. Results were similar whether the mother had taken acetaminophen for their fever or not. Hyperactivity/impulsivity symptoms were not related to maternal fever. The results indicate that maternal fever in early pregnancy may be a risk factor for ADHD, and particularly for inattention problems. This risk is neither mitigated nor inflated by use of acetaminophen.