Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia.

As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity. This protection was diminished by depletion of CD4+ cells prior to the final infection. The resolution of previous pneumococcal infections seeded the lungs with CD4+ resident memory T (TRM) cells, which responded to heterotypic pneumococcus stimulation by producing multiple effector cytokines, particularly interleukin (IL)-17A. Following lobar pneumonias, IL-17-producing CD4+ TRM cells were confined to the previously infected lobe, rather than dispersed throughout the lower respiratory tract. Importantly, pneumonia protection also was confined to that immunologically experienced lobe. Thus regionally localized memory cells provide superior local tissue protection to that mediated by systemic or central memory immune defenses. We conclude that respiratory bacterial infections elicit CD4+ TRM cells that fill a local niche to optimize heterotypic protection of the affected tissue, preventing pneumonia.

An Exploration of Family and Juvenile Justice Systems to Reduce Youth HIV/STI Risk.

Using in-depth interviews with 20 probation youth (60% female; 35% white; 30% Hispanic; mean age 15years, range=13-17), their caregivers (100% female; mean age 44years, range=34-71) and 12 female probation officers (100% white; mean age 46years, range=34-57), we explored how family and probation systems exacerbate or mitigate sexual risk. We conducted thematic analyses of interviews, comparing narratives of families of sexually risky (n=9) versus non-sexually risky (n=11) youth. Family functioning differed by youth sexual risk behavior around quality of relationships, communication, and limit-setting and monitoring. The involvement of families of sexually risky youth in probation positively influenced family functioning. Data suggest these families are amenable to intervention and may benefit from family-based HIV/STI interventions delivered in tandem with probation.

Contribution of maternal smoking during pregnancy and lead exposure to early child behavior problems.

Maternal smoking during pregnancy elevates risk for later child behavior problems. Because prior studies considered only Western settings, where smoking co-occurs with social disadvantage, we examined this association in Yugoslavia, a different cultural setting. Mothers enrolled in pregnancy as the low-exposure group in a prospective study of lead exposure were interviewed about health, including smoking history. A total of 199 children were assessed on the Child Behavior Checklist (CBCL) at ages 4, 4 1/2, and 5 years. Average cumulative blood lead (BPb) was determined from serial samples taken biannually since delivery. Longitudinal analyses were derived from 191 children with available data on behavior and covariates. Smoking was unrelated to social adversity. Controlling for age, gender, birthweight, ethnicity, maternal education, and Home Observation for Measurement of the Environment (HOME) Acceptance, smoking was associated with worse scores on almost all subscales; BPb concentration was related to small increases in the Delinquency subscale. Daughters of smokers received significantly higher scores on Somatic Complaints compared to daughters of nonsmokers, consistent with other work relating biological factors and internalizing problems in young girls. Because the present smoking/child behavior associations persist after control for individual and social factors also related to behavior problems, possible biological mediators are considered.

Methodology, inference and causation: environmental lead exposure and childhood intelligence.

Kaufman's critique of the literature on the associations between lead exposure and child intelligence raises important methodological and inferential points. We address the concerns he raises regarding measuring known and unknown confounders, statistical modeling, reverse causality and quality control. Mismeasurement of potential confounders of the lead-IQ relationship, such as parenting skills, parental intelligence, maternal smoking during pregnancy, or otitis media can either strengthen or weaken the estimated association between exposure and child intelligence. Despite some variability in design and measurement, a series of comprehensive prospective investigations in varied populations, by different sets of investigators, provided consistent replication; taken together these studies point to the conclusion that lead exposure has adverse consequences for child development, and that the deficits are likely to be small in comparison to the contribution of measured social factors.

The Yugoslavia Prospective Lead Study: contributions of prenatal and postnatal lead exposure to early intelligence.

To investigate associations between the timing of lead (Pb) exposure on early intelligence, we examined the results of psychometric evaluations at ages 3, 4, 5, and 7 years, from 442 children whose mothers were recruited during pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia. We compared the relative contribution of prenatal blood lead (BPb) with that of relative increases in BPb in either the early (0-2 years) or the later (from 2 years on) postnatal period to child intelligence measured longitudinally at ages 3 and 4 (McCarthy GCI), 5 (Wechsler Preschool and Primary Scale of Intelligence-Revised, WPPSI-R IQ), and 7 (Wechsler Intelligence Scale for Children-version III, WISC-III IQ), controlling for: Home Observation for Measurement of the Environment (HOME) quality; maternal age, intelligence, education, and ethnicity; and birthweight and gender. Elevations in both prenatal and postnatal BPb were associated with small decrements in young children's intelligence.

Lead exposure and motor functioning in 4(1/2)-year-old children: the Yugoslavia prospective study.

OBJECTIVE: To investigate associations between lead exposure and early motor development. STUDY DESIGN: We conducted standardized assessments of motor function (Bruininks-Oseretsky Test of Motor Proficiency and Beery Developmental Test of Visual-Motor Integration) at age 54 months in 283 children whose mothers were recruited in pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia and who have been monitored twice yearly since birth. Blood lead concentration (BPb) was summarized in a measure reflecting the average of the child's semiannual serial log BPbs through 54 months. RESULTS: Multiple regression showed that taken together, anthropometric measures (birth weight, body mass index) and markers of a stimulating and organized home life (HOME scale, parental education and intelligence, availability of siblings) explained a significant 10% to 18% of the variance in motor functioning. Beyond these contributions, BPb was significantly associated with poorer fine motor and visual motor function but was unrelated to gross motor coordination. CONCLUSIONS: Modest associations between early lead exposure and fine motor and visual motor functioning appear even after statistical adjustment is done for other contributors to motor development. Associations with BPb are specific to these areas of motor skill; gross motor development was unaffected.

Memory and anxiety in prepubertal boys at risk for delinquency.

OBJECTIVE: To examine the association between memory and anxiety symptoms in young urban-dwelling boys. METHOD: A series of 111 boys, aged 7 to 11 years, at risk for disruptive psychopathology received standardized assessments of psychopathology and neuropsychological abilities, including verbal and design memory ability. While neuropsychological ability was rated at an initial study wave, psychopathology was rated at both an initial and a follow-up study wave, separated by approximately 18 months. RESULTS: Anxiety symptoms were more strongly correlated with poor memory ability than with reduced intelligence. Disruptive symptoms, in contrast, were more strongly correlated with reduced intelligence than with poor memory ability. Finally, boys with an anxiety disorder exhibited reduced memory abilities relative to other boys in the sample. Relationships generally appeared strongest in longitudinal analyses, such that poorer memory ability at study intake predicted increased anxiety at follow-up. CONCLUSIONS: Anxiety is associated with reduced memory ability in young urban boys at risk for disruptive psychopathology.

Dichotic listening deficits and the prediction of substance use in young boys.

OBJECTIVE: Prior studies note relationships among verbal deficits, disruptive psychopathology, and substance use. The current study examines the relationship between verbal deficits, assessed through a dichotic listening test, and children's substance use. METHOD: A series of 87 young boys was prospectively followed over a 1- to 2-year period. A prior study in these boys noted a cross-sectional relationship between disruptive psychopathology and deficits on a dichotic consonant-vowel listening test. The current study examines the predictive relationship between this language-related deficit at one study wave and substance use assessed during a follow-up study wave. RESULTS: Reduced right ear accuracy, reflecting a deficit in left hemisphere processing ability, predicted substance use at follow-up. This association was independent of any other predictors, including cognitive or behavioral indices of substance use risk. CONCLUSIONS: A lateralized deficit in verbal processing on a dichotic listening task predicts change in substance use by follow-up. Findings are consistent with other evidence linking early childhood lateralization abnormalities to development of disruptive psychopathology.

Darryl, a cartoon-based measure of cardinal posttraumatic stress symptoms in school-age children.

OBJECTIVES: This report examines the reliability and validity of Darryl, a cartoon-based measure of the cardinal symptoms of posttraumatic stress disorder (PTSD). METHODS: We measured exposure to community violence through the reports of children and their parents and then administered Darryl to a sample of 110 children aged 7 to 9 residing in urban neighborhoods with high crime rates. RESULTS: Darryl's reliability is excellent overall and is acceptable for the reexperiencing, avoidance, and arousal subscales, considered separately. Child reports of exposure to community violence were significantly associated with child reports of PTSD symptoms. CONCLUSIONS: Darryl possesses acceptable psychometric properties in a sample of children with frequent exposure to community violence.

Prepubertal boys' sexual behavior and behavior problems.

The increasingly early initiation of penetrative sexual practices and the implication for prevention of HIV and sexually transmitted diseases requires the study of childhood sexual behavior and its determinants. In adolescence, early sexual initiation is associated with other "problem behaviors" (Jessor & Jessor, 1977). To explore an analogous association for the middle childhood years, we studied 126 boys aged 5 to 11 years at increased risk for the development of conduct-disorder-related behavior with the Child Behavior Checklist (CBCL)/4-18 (Achenbach, 1991) and reevaluated 112 of them 15 months later. At both time points, the boys scored higher on the Sex Problems scale as well as on the nonsexual CBCL scales than Achenbach's nonclinical norm sample. Within the at-risk sample, the Sex Problems scale was significantly related to externalizing problem behaviors, but also to the other CBCL scales of behavioral/emotional problems. These data point to childhood precursors of the association observed by Jessor and Jessor (1977) in adolescence.

Witnessed community violence and antisocial behavior in high-risk, urban boys.

Examined the longitudinal relation between children's self-report of witnessing community violence, family environment, and parent report of child antisocial behavior in a sample of 6- to 10-year-old urban American boys (N = 97) at familial risk for antisocial behavior. Boys reported high rates of lifetime exposure to community violence. Boys' reports of witnessing community violence were significantly positively related to changes over 15 months in child antisocial behavior, even after controlling for the possible effects of 3 aspects of parent-child interactions shown previously to be related to problematic child behavior. Furthermore, family environment, particularly the degree to which parents engaged in conflict with their sons, moderated the effect of witnessed violence on changes in antisocial behavior. In families with low conflict, higher levels of witnessed violence predicted increases in antisocial behavior over time. In contrast, in families with relatively high levels of parent-child conflict, high-witnessed violence had no additional influence on antisocial outcome. This is the first prospective longitudinal study to document an association between witnessed community violence and changes in antisocial behavior in young, urban boys at familial risk for antisocial behavior.

Heart period variability and psychopathology in urban boys at risk for delinquency.

To examine associations between heart period variability (HPV) and psychopathology in young urban boys at risk for delinquency, a series of 697-11-year-old younger brothers of adjudicated delinquents received a standardized psychiatric evaluation and an assessment of heart period variability (HPV). Psychiatric symptoms were rated in two domains: externalizing and internalizing psychopathology. Continuous measures of both externalizing and internalizing psychopathology were associated with reductions in HPV components related to parasympathetic activity. These associations could not be explained by a number of potentially confounding variables, such as age, ethnicity, social class, body size, or family history of hypertension. Although familial hypertension predicted reduced HPV and externalizing psychopathology, associations between externalizing psychopathology and HPV were independent of familial hypertension. Psychiatric symptoms are associated with reduced HPV in young urban boys at risk for delinquency.

Prenatal cocaine exposure and school-age intelligence.

Assessments of the possible consequences of prenatal exposure to cocaine have been limited by lack of control for socio-demographic confounders and lack of follow-up into the school years. We evaluated intelligence at ages 6-9 years in 88 children from a cohort of 280 born between September 1, 1985 and August 31, 1986 and identified at birth as cocaine-exposed, and in a group of unexposed (n = 96) births of comparable gender and birthweight. IQ scores did not differ between children with and without prenatal exposure to cocaine (mean 82.9 vs. 82.4, difference = 0.5 points, 95% CI-3.1, 4.1); results were unchanged with adjustment for child height, head circumference and prior residence in a shelter or on the street, and for caregiver IQ and home environment (mean difference = 2.2 points, 95% CI-1.5, 5.8).

The effect of lead exposure on behavior problems in preschool children.

OBJECTIVES: Interpreting associations between lead exposure and child behavior problems is difficult because studies have not controlled for sociodemographic confounders or have used shed teeth to mark exposure. This study explored associations between blood lead and preschool behavior. METHODS: Children from a smelter town and a non-lead-exposed town in Yugoslavia were followed up prospectively from pregnancy through age 3. The Child Behavior Checklist was used to assess behavior problems in 379 3-year-olds, controlling for sociodemographic factors and difficult infant temperament. RESULTS: Multiple regression revealed the expected significant associations between checklist subscales and sociodemographic factors, which explained 7% to 18% of the variance on the subscales. Concurrent blood lead explained a significant 1% to 4% of the variance on the Destructive and Withdrawn subscales. Earlier difficult temperament explained an additional 2% to 5% of the checklist variance. Scores on the Destructive subscale were consistently associated with blood lead. As blood lead increased from 10 to 20 micrograms/dL, subscale scores increased by approximately 0.5 points. CONCLUSIONS: Lead/behavior associations are significant but small compared with the effects of social factors.

Neurological soft signs: one-year stability and relationship to psychiatric symptoms in boys.

OBJECTIVE: This study had two main objectives: (1) to examine the 1-year stability of neurological soft signs and (2) to examine the longitudinal relationship between soft signs and psychiatric symptoms in young boys. METHOD: A consecutive series of 56 boys from a high-risk sample received standardized psychiatric and soft sign assessments at study intake. Approximately 1 year later, 48 (86%) of these boys received a reassessment of their psychiatric and soft sign status. RESULTS: Soft signs exhibited marked stability across the 1-year period (intraclass correlation = .70, p < .001). Symptoms of both internalizing and externalizing disorders correlated with poor performance on the soft sign examination. For both internalizing and externalizing symptoms, the association with soft signs occurred primarily among individuals with persistently high scores on symptom scales across the two assessments. CONCLUSIONS: Performance on a standardized neurological soft sign examination is stable over a 1-year period. Soft signs measured with this examination relate to both internalizing and externalizing symptoms in young boys, particularly when symptoms are relatively stable over time. Further research should consider the clinical significance of childhood soft signs.

Lead exposure and intelligence in 7-year-old children: the Yugoslavia Prospective Study.

For a prospective study of lead exposure and early development, we recruited pregnant women from a lead smelter town and from an unexposed town in Yugoslavia and followed their children through 7 years of age. In this paper we consider associations between lifetime lead exposure, estimated by the area under the blood lead (BPb) versus time curve (AUC7), and intelligence, with particular concern for identifying lead's behavioral signature. The Wechsler Intelligence Scales for Children-Version III (WISC-III) was administered to 309 7-year-old children, 261 of whom had complete data on intelligence, blood lead, and relevant sociodemographic covariates (i.e., Home Observation for the Measurement of the Environment (HOME), birth weight, gender, sibship size, and maternal age, ethnicity, intelligence, and education). These showed anticipated associations with 7-year intelligence, explaining 41-4% of the variance in Full Scale, Performance, and Verbal IQ. Before covariate adjustment, AUC7 was unrelated to intelligence; after adjustment, AUC7 explained a significant 2.8%-4.2% of the variance in IQ. After adjustment, a change in lifetime BPb from 10 to 30 micro/dl related to an estimated decrease of 4.3 Full Scale IQ points; estimated decreases for Verbal and Performance IQ were 3.4 and 4.5 points, respectively. AUC7 was significantly and negatively related to three WISC-III factor scores: Freedom from Distractibility, Perceptual Organization, and Verbal Comprehension; the association with Perceptual Organization was the strongest. Consistent with previous studies, the IQ/lead association is small relative to more powerful social factors. Findings offer support for lead's behavioral signature; perceptual-motor skills are significantly more sensitive to lead exposure than are the language-related aspects of intelligence.

Verbal dichotic listening in boys at risk for behavior disorders.

OBJECTIVE: The association between deficits in verbal processing skills and disruptive psychopathology remains one of the most frequently replicated findings in all of child psychiatry. This study uses a dichotic consonant-vowel listening test to examine the potential neural basis for this association. METHOD: A series of 87 young boys recruited from a sample at risk for disruptive disorders received standardized psychiatric, neuropsychological, and language skills assessments. Approximately 1 year later, these boys received a reassessment of their psychiatric status and a test that assesses the neural basis of language-processing ability, a dichotic consonant-vowel listening test. RESULTS: Disruptive psychopathology predicted reduced right ear accuracy for dichotic syllables, indicative of a deficit in left hemisphere processing ability. Deficits in reading and language ability also correlated with right ear accuracy for dichotic syllables. CONCLUSIONS: Boys with disruptive behavior disorders, relative to at-risk but nondisruptive boys, exhibit a deficit in verbal processing abilities on dichotic listening tasks. This deficit in verbal processing ability is also manifested as low scores on standardized tests of reading achievement and language comprehension.

Neuroendocrine response to fenfluramine challenge in boys. Associations with aggressive behavior and adverse rearing.

BACKGROUND: There is evidence of relationships among serotonin, aggressive behavior, and a childhood history of socially adverse-rearing conditions. This study examines the prolactin response to fenfluramine hydrochloride challenge in young boys who show clinically significant aggressive behavior or who are raised in a social environment that is conducive to the development of chronic aggression. METHODS: A series of 34 younger brothers of convicted delinquents underwent standardized psychiatric and observation-based assessments of their social-rearing environments that were conducted during home visits. Approximately 2 years later, these boys underwent a reassessment of psychiatric status and an assessment of central serotonergic activity using the fenfluramine challenge procedure. RESULTS: Increasing degrees of aggressive behavior at either assessment were positively correlated with the prolactin response to fenfluramine challenge. Furthermore, adverse-rearing circumstances that were conducive to the development of aggressive behavior also exhibited positive correlations with the prolactin response. This association between adverse rearing and the prolactin response was statistically independent of that between aggression and the prolactin response. CONCLUSION: In young boys, aggressive behavior and social circumstances that are conducive to the development of aggressive behavior are positively correlated with a marker of central serotonergic activity.

Parenting predictors of early conduct problems in urban, high-risk boys.

OBJECTIVE: As part of a larger, prospective study, the authors examined concurrent and prospective relations among parenting and child antisocial behavior in inner-city boys at high risk for delinquent behavior. METHOD: One hundred twenty-six younger brothers (aged 6 to 10 years) of convicted delinquents in New York City and their parents were assessed; 15 months later 112 boys were reassessed. Demographics, parenting, and child diagnosis were examined as they relate to child externalizing behavior problems. Hierarchical multiple regression analyses predicted changes in Externalizing scores from year I parenting. RESULTS: At years I and II, 22% and 27% of boys, respectively, scored above the clinical cutoff for Externalizing. Controlling for earlier Externalizing, each of three domains of parenting still made significant independent contributions to later Externalizing scores, explaining 17% of the variance. Altogether this model explained 51% of the variance in year II Externalizing scores. CONCLUSIONS: Data support a cumulative risk model, whereby each of several adverse parenting factors further compounds the likelihood of child conduct problems.

Platelet serotonin 2A (5-HT2A) receptor characteristics and parenting factors for boys at risk for delinquency: a preliminary report.

OBJECTIVE: This study examined the cross-sectional association between platelet membrane serotonin 2A (5-HT2A) receptor variables in children and characteristics of their parents that place these children at risk for antisocial behavior. METHOD: As part of a larger prospective study investigating predictors of antisocial behavior, 38 younger brothers of convicted delinquents provided platelet samples; samples from 34 boys (mean age=8.3 years) were usable. The authors determined the density (Bmax) and affinity (Kd) of platelet membrane 5-HT2A receptors by using [3H]lysergic acid diethylamide. They also measured parental characteristics related to serotonergic dysfunction in prior studies, the quality of parent-child interactions, and psychiatric profiles of the boys who provided platelets. RESULTS: Bmax was significantly lower in boys whose parents had histories of substance abuse or incarceration. Bmax was also inversely related to harsh parenting; boys raised in environments characterized by frequent parental physical punishment and anger had a significantly lower Bmax. Bmax was not related to boys' disruptive behavior. CONCLUSIONS: In boys at risk for antisocial behavior, the density of 5-HT2A receptors on platelets is inversely related to parental factors known to place youth at risk for antisocial behavior.