Associations between prenatal and postnatal substance exposure and salivary C-reactive protein in early childhood.

BACKGROUND: Exposure to tobacco and cannabis during developmental periods of enhanced vulnerability (e.g., in utero and early childhood) may have long-lasting effects on child health. One potential mechanism underlying these associations is the alteration of inflammatory pathways. Using data from a longitudinal study of mother/child dyads, we examined the adjusted and combined associations of prenatal and postnatal tobacco and cannabis exposure with inflammation in early childhood. Furthermore, we explored the relations between different measures of exposure, partly reflecting differences in timing, dose, and level of fetal exposure (e.g., self-report vs. biomarker), and inflammation. Finally, we explored child sex as a moderator of prenatal and postnatal tobacco and cannabis exposure and inflammation. METHOD: Women were recruited from a local hospital during their first prenatal appointment. Repeated assessments were conducted at each trimester, at birth, and when children were 2, 9, 16, 24, 36, and 60 months old (N = 215; 112 female children). To evaluate associations with different measurement approaches, prenatal tobacco and cannabis exposure were assessed using: 1) continuous dose-response variables of maternal self-reported tobacco and cannabis use during each trimester to assess associations with timing and severity of exposure, 2) categorization of children into exposure groups based on drugs and metabolites present in infant meconium reflecting later pregnancy fetal exposure, and 3) categorization into exposure groups using a combination of maternal self-report data and biomarker data derived from maternal saliva samples and infant meconium taking advantage of multiple methods of assessment to examine group differences. Postnatal exposure to tobacco (assessed using child salivary cotinine) and cannabis (assessed using maternal self-reported average joints smoked per day) was measured at each infancy/early childhood assessment. Adjusted pre- and postnatal exposure associations with child inflammation were assessed by including both measures as predictor variables in linear regression models predicting child salivary C-reactive protein (CRP) concentrations at 60 months. Interactions between pre- and postnatal exposure variables were then modeled to investigate the combined relations between pre- and postnatal substance exposure with child salivary CRP concentrations at 60 months. RESULTS: Adjusting for postnatal exposure variables, there was a significant interaction between the average daily cigarettes and the average daily cannabis joints smoked during the third trimester predicting salivary CRP concentrations in early childhood. At high tobacco exposure, the effect of cannabis on CRP concentrations was negligible, whereas at low tobacco exposure, the effect of cannabis exposure on CRP concentrations was positive. Adjusting for postnatal tobacco and cannabis exposure, children for whom meconium data indicated co-exposure to tobacco and cannabis showed approximately 43% lower CRP concentrations at age 60 months compared to children with no exposure. However, when mother/child dyads were categorized based on a combination of maternal self-report data and biomarker data from saliva samples and infant meconium, there were no differences in salivary CRP concentrations at age 60 months across the three groups (no prenatal exposure, prenatal tobacco exposure only, prenatal co-exposure to tobacco and cannabis), controlling for postnatal associations. Regardless of the measurement method used to assess prenatal exposures in adjusted analyses, prenatal tobacco exposure alone did not predict CRP concentrations in early childhood, nor did postnatal tobacco exposure. Among boys, postnatal cannabis exposure was associated with higher concentrations of CRP at age 60 months, controlling for prenatal exposure relations. There were no significant combined associations of pre- and postnatal exposure with CRP concentrations. CONCLUSION: This study expands upon known relations between prenatal and postnatal substance exposure and immunological outcomes in early childhood, underscoring the importance of assessing cannabis exposure during gestation and early life in combination with tobacco exposure.

Hypothalamic-pituitary-adrenal and sympathetic nervous system responses to social evaluative stress in chronic cannabis users and non-users.

BACKGROUND: To advance our understanding of the health-related consequences of chronic cannabis use, this study examined hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) reactivity and regulation in response to a well-characterized, acute, social evaluative stress task among cannabis users and non-users. We also explored differences in HPA-SNS coordination across the stress task in cannabis users and non-users. METHOD: Participants were 75 adults (53% female) who reported no use of tobacco/nicotine products. Cannabis use was measured using self-report and salivary/urinary THC levels. Participants were classified as cannabis users (n = 33) if they reported using cannabis at least twice per week in the prior year and had a positive salivary/urinary THC test or as non-users (n = 42) if they reported no use in the prior year and had a negative THC test. During a laboratory visit, participants completed the standard Trier Social Stress Test (TSST) and provided saliva samples before, and 5, 20, and 40 min after the task. Samples were assayed for salivary cortisol and alpha-amylase (sAA) as indices of HPA axis and SNS activity, respectively. RESULTS: Multilevel piecewise growth models revealed that, relative to non-users, cannabis users showed (a) blunted cortisol reactivity and recovery to the TSST, and (b) greater reductions in sAA concentrations following the TSST. Chronic cannabis users may exhibit blunted HPA axis responses and greater SNS recovery to acute psychosocial stress. Implications of individual differences in stress reactivity and regulation for the biobehavioral health of chronic cannabis users are discussed.

Taking context to heart: Momentary emotions, menstrual cycle phase, and cardiac autonomic regulation.

Emotions have long been discussed in conjunction with the autonomic nervous system. Most research on emotion-autonomic linkages does not consider sex differences or an evident underlying mechanism for sex differences: menstrual cycle phase. Further, most research is limited to cross-sectional and laboratory studies. The degree to which emotion-autonomic associations manifest in everyday life may be different and may vary by sex and, for women, by menstrual cycle phase. This study employs the ambulatory monitoring of cardiovascular measures (e.g., heart rate and heart rate variability; HRV) and concurrent emotional states (e.g., sadness, stress, anxiety, anger, and happiness) in everyday life to better characterize emotion-autonomic associations as a function of sex and menstrual cycle phase. Participants (N = 174; 87 female) ages 18 to 46 (31.23 ± 6.49) were monitored over a 5-day observation period (one 2- and one 3-day session), using an ambulatory 24-hour electrocardiogram to monitor heart rate and ecological momentary assessment to record emotions every ~30 min. Women were monitored in both the early to mid-follicular and -luteal phases and men in two comparably distanced sessions. Multilevel models indicated that across sex, negative emotions and happiness were associated with elevated heart rate. Relative to men, women exhibited an elevated heart rate and reduced HRV during reports of anger. For women, during the luteal phase, but not follicular phase, momentary sadness, stress, and anxiety predicted increased heart rate and reduced HRV. These findings demonstrate the importance of considering sex and menstrual cycle phase in research investigating emotion-autonomic linkages.