A longitudinal study of pain sensitivity and blood pressure in adolescent boys: results from a 5-year follow-up.

A growing literature has observed a significant reduction in pain sensitivity among hypertensive animals and humans. It is uncertain whether a reduced sensitivity to pain can be observed in nonnotensive individuals who go on to develop high blood pressure. Blood pressure (BP) was reassessed in one hundred fifteen 19-year-old boys initially tested at age 14, when they were also presented with a pain stimulus (mechanical finger pressure). Hierarchical regression analyses indicated that information regarding pain tolerance improved prediction of changes in systolic and diastolic blood pressure beyond that afforded by differences in BP at age 14, parental history of hypertension, and body mass index. These analyses suggest that pain sensitivity may be associated with physiological processes involved in the development of sustained high blood pressure.     

Effects of Acute Stress or Centrally Injected Interleukin-1beta on Neuropeptide Expression in the Immune System

Acute stress stimulates the expression and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and the pro-opiomelanocortin products beta-endorphin and ACTH from the anterior pituitary. These neuropeptides are also expressed in immune tissues, and it has been proposed that they may modulate immune responses to stress through paracrine mechanisms. We subjected rats to restraint stress or central injection of interleukin (IL)-1beta to determine whether these acute stimuli can alter the expression of neuropeptides in the spleen and thymus. Restraint stress significantly increased the contents of all these neuropeptides in thymic, but not splenic, extracts. A single icv injection of IL-1beta increased contents of CRH, AVP, ACTH and beta-endorphin in the spleens of both sham-operated and adrenalectomised (ADX) rats. IL-1beta increased thymic contents of CRH and ACTH in sham-operated rats but these increases were not observed in ADX rats. These results suggest that the effects of IL-1beta on neuropeptide expression in the spleen are independent of glucocorticoids, whereas IL-1beta stimulation of neuropeptide expression in the thymus is dependent on circulating glucocorticoids. There were significant correlations between increases in CRH, ACTH and beta-endorphin in the spleen, and between CRH and ACTH in the thymus, consistent with the suggestion that IL-1beta-induced increases in ACTH and beta-endorphin may be mediated through CRH. These results provide evidence that stressors can directly influence neuropeptide expression in immune tissues. Thus stress may influence immune functions through paracrine mechanisms involving locally synthesised neuropeptides as well as through activation of the hypothalamo-pituitary-adrenal axis.     

Trajectories leading to school-age conduct problems

The present study applied a semiparametric mixture model to a sample of 284 low-income boys to model developmental trajectories of overt conduct problems from ages 2 to 8. As in research on older children, 4 developmental trajectories were identified: a persistent problem trajectory, a high-level desister trajectory, a moderate-level desister trajectory, and a persistent low trajectory. Follow-up analyses indicated that initially high and low groups were differentiated in early childhood by high child fearlessness and elevated maternal depressive symptomatology. Persistent problem and high desister trajectories were differentiated by high child fearlessness and maternal rejecting parenting. The implications of the results for early intervention research are discussed, with an emphasis on the identification of at-risk parent-child dyads.     

The Development of Physical Aggression from Toddlerhood to Pre-Adolescence: A Nation Wide Longitudinal Study of Canadian Children

The objectives of the study were to model the developmental trajectories of physical aggression (PA) from toddlerhood to pre-adolescence and to identify risk factors that distinguish typical (normative) from atypical developmental patterns. Ten cohorts of approximately 1,000 children (n = 10,658) drawn form a nationally representative (Canadian) sample were followed over 6 years. Using a group based trajectory approach, we identified three groups of children with distinct developmental trajectories between 2 and 11 years of age. One third of the children (31.1%) followed a low desisting trajectory, reflected in infrequent use of PA in toddlerhood and virtually no PA by pre-adolescence. The majority of children (52.2%) followed a moderate desisting trajectory, reflected in occasional use of PA in toddlerhood and infrequent use by pre-adolescence. One sixth of the children (16.6%) followed a high stable trajectory of PA. Multivariate logistic regression indicated that children in the high PA trajectory group were more likely to be boys (OR: 1.67; CI: 1.5–1.87), from low income families (OR: 1.4; CI; 1.27–1.67), from families where the mother had not completed high school (OR: 1.20; CI: 1.05–1.38) and who reported using hostile/ineffective parenting strategies (OR: 1.16; CI: 1.14–1.18). In sum, the results indicate that the typical developmental pattern of PA was one of occasional and declining use over time. However, about one sixth of children, mostly boys from disadvantaged families, exhibited an atypical developmental pattern reflected in more frequent and stable use of PA. The results suggest that most children learned relatively well to inhibit PA by the end of childhood and that a minority failed to do so. Family risks traditionally found to be associated with antisocial behaviors during adolescence appear to interfere with the socialization of PA during early and middle childhood.     

The neurocognition of conduct disorder behaviors: specificity to physical aggression and theft after controlling for ADHD symptoms

There is growing evidence that among the different conduct disorder (CD) behaviors, physical aggression, but not theft, links to low neurocognitive abilities. Specifically, physical aggression has consistently been found to be negatively related to neurocognitive abilities, whereas theft has been shown to be either positively or not related to neurocognition. The specificity of these links needs further examination because attention deficit hyperactivity disorder (ADHD) links to both physical aggression and neurocognitive variation. The development of self-reported physical aggression and theft, from age 11 to 17 years, was studied in a prospective at-risk male cohort via a dual process latent growth curve model. Seven neurocognitive tests at age 20 were regressed on the growth parameters of physical aggression and theft. The links between neurocognition and the growth parameters of physical aggression and theft were adjusted for ADHD symptoms at ages 11 and 15 (parent, child and teacher reports). Results indicated that verbal abilities were negatively related to physical aggression while they were positively associated with theft. However, inductive reasoning was negatively associated with increases in theft across adolescence. Symptoms of ADHD accounted for part of the neurocognitive test links with physical aggression but did not account for the associations with theft. These differences emphasize the importance of examining specific CD behaviors to better understand their neurodevelopmental mechanisms. They also suggest that youth who engage in different levels of physical aggression or theft behaviors may require different preventive and corrective interventions.     

Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats

Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.     

Cognitive-neuropsychological function in chronic physical aggression and hyperactivity

Histories of violence and of hyperactivity are both characterized by poor cognitive-neuropsychological function. However, researchers do not know whether these histories combine in additive or interactive ways. The authors tested 303 male young adults from a community sample whose trajectories of teacher-rated physical aggression and motoric hyperactivity from kindergarten to age 15 were well defined. No significant interaction was found. In a 1st model, both histories of problem behavior were independently associated with cognitive-neuropsychological function in most domains. In a 2nd model controlling for IQ, general memory, and test motivation, the 3 working-memory tests (relevant to executive function) remained associated with physical aggression, and 1 remained associated with hyperactivity. These results support an additive model.     

Causal inferences with group based trajectory models

A central theme of research on human development and psychopathology is whether a therapeutic intervention or a turning-point event, such as a family break-up, alters the trajectory of the behavior under study. This paper lays out and applies a method for using observational longitudinal data to make more confident causal inferences about the impact of such events on developmental trajectories. The method draws upon two distinct lines of research: work on the use of finite mixture modeling to analyze developmental trajectories and work on propensity scores. The essence of the method is to use the posterior probabilities of trajectory group membership from a finite mixture modeling framework, to create balance on lagged outcomes and other covariates established prior to t for the purpose of inferring the impact of first-time treatment at t on the outcome of interest. The approach is demonstrated with an analysis of the impact of gang membership on violent delinquency based on data from a large longitudinal study conducted in Montreal. The research has been supported by the National Science Foundation (NSF) (SES-99113700) and the National Institute of Mental Health (RO1 MH65611-01A2). It also made heavy use of data collected with the support from Québec’s CQRS and FCAR funding agencies, Canada’s NHRDP and SSHRC funding agencies, and the Molson Foundation. We thank Stephen Fienberg, Susan Murphy, Paul Rosenbaum, the editor, Paul De Boeck, and two anonymous reviewers for their insightful suggestions.     

Combining propensity score matching and group-based trajectory analysis in an observational study

In a nonrandomized or observational study, propensity scores may be used to balance observed covariates and trajectory groups may be used to control baseline or pretreatment measures of outcome. The trajectory groups also aid in characterizing classes of subjects for whom no good matches are available and to define substantively interesting groups between which treatment effects may vary. These and related methods are illustrated using data from a Montreal-based study. The effects on subsequent violence of gang joining at age 14 are studied while controlling for measured characteristics of boys prior to age 14. The boys are divided into trajectory groups based on violence from ages 11 to 13. Within trajectory group, joiners are optimally matched to a variable number of controls using propensity scores, Mahalanobis distances, and a combinatorial optimization algorithm. Use of variable ratio matching results in greater efficiency than pair matching and also greater bias reduction than matching at a fixed ratio. The possible impact of failing to adjust for an important but unmeasured covariate is examined using sensitivity analysis.