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1.  C-Reactive Protein and substance use disorders in adolescence and early adulthood: A Prospective Analysis 
Drug and alcohol dependence  2013;133(2):712-717.
Background
Dysregulated immune function and elevated inflammation markers are seen in adults with chronic diseases, including some psychiatric disorders, but evidence on inflammation in the case of drug abuse is conflicting.
Objective
To test the concurrent and predictive relations between C-reactive protein (CRP) and use and abuse of alcohol, nicotine and cannabis in a longitudinal, population sample of adolescents and young adults, at the period of highest increase in drug use.
Methods
Data from the prospective population-based Great Smoky Mountains Study (N = 1,420) were used, covering children in the community assessed at ages 9–16, 19, and 21. Structured interviews were used to assess substance abuse symptoms and DSM-IV substance use disorders. Bloodspots were collected at each assessment and assayed for CRP.
Results
CRP levels were higher in the presence of nicotine, alcohol, and cannabis use and nicotine dependence. In prospective analyses, higher CRP levels predicted cannabis use and nicotine dependence, and nicotine use predicted higher CRP levels, once covariates were included in the models. Significant covariates were age, race (American Indian), and obesity.
Conclusions
The inter-relationship of CRP and substance abuse has implications for the later health risks associated with early drug and alcohol use and abuse.
doi:10.1016/j.drugalcdep.2013.08.027
PMCID: PMC4106409  PMID: 24099969
Inflammation; CRP; Substance use disorders; Epidemiology; Adolescence
2.  Children with Both Asthma and Depression Are at Risk for Heightened Inflammation 
The Journal of pediatrics  2013;163(5):1443-1447.
Objective
To test whether children and adolescents with co-occurring asthma and depression are at risk for elevated inflammation—concurrently and at the next assessment.
Study design
Up to 6 yearly assessments per person from the prospective, population-based Great Smoky Mountains Study (N = 1420) were used, covering children in the community aged 10–16 years old. High-sensitivity C-reactive protein (CRP) was assayed from annual bloodspot collections and provided indicators of elevated inflammation at CRP > 1, CRP > 2, and CRP > 3 mg/L. Depression was assessed with the Child and Adolescent Psychiatric Assessment. Asthma was assessed using a form adapted from the Centers for Disease Control and Prevention National Health Interview Survey.
Results
Controlling common covariates of CRP, the co-occurrence of asthma and depression predicted heightened CRP—concurrently and at the next assessment. In turn, elevated CRP was relatively stable from one assessment to the next.
Conclusions
The co-occurrence of asthma and depression in childhood poses a risk for substantially elevated inflammation concurrently and over time, which could contribute to pathophysiological processes involved in the development of additional chronic diseases and also to asthma-related morbidity and mortality.
doi:10.1016/j.jpeds.2013.06.046
PMCID: PMC3967500  PMID: 23919906
3.  A Cluster Randomised Controlled Effectiveness Trial Evaluating Perinatal Home Visiting among South African Mothers/Infants 
PLoS ONE  2014;9(10):e105934.
Background
Interventions are needed to reduce poor perinatal health. We trained community health workers (CHWs) as home visitors to address maternal/infant risks.
Methods
In a cluster randomised controlled trial in Cape Town townships, neighbourhoods were randomised within matched pairs to 1) the control, healthcare at clinics (n = 12 neighbourhoods; n = 594 women), or 2) a home visiting intervention by CBW trained in cognitive-behavioural strategies to address health risks (by the Philani Maternal, Child Health and Nutrition Programme), in addition to clinic care (n = 12 neighbourhoods; n = 644 women). Participants were assessed during pregnancy (2% refusal) and 92% were reassessed at two weeks post-birth, 88% at six months and 84% at 18 months later. We analysed 32 measures of maternal/infant well-being over the 18 month follow-up period using longitudinal random effects regressions. A binomial test for correlated outcomes evaluated overall effectiveness over time. The 18 month post-birth assessment outcomes also were examined alone and as a function of the number of home visits received.
Results
Benefits were found on 7 of 32 measures of outcomes, resulting in significant overall benefits for the intervention compared to the control when using the binomial test (p = 0.008); nevertheless, no effects were observed when only the 18 month outcomes were analyzed. Benefits on individual outcomes were related to the number of home visits received. Among women living with HIV, intervention mothers were more likely to implement the PMTCT regimens, use condoms during all sexual episodes (OR = 1.25; p = 0.014), have infants with healthy weight-for-age measurements (OR = 1.42; p = 0.045), height-for-age measurements (OR = 1.13, p<0.001), breastfeed exclusively for six months (OR = 3.59; p<0.001), and breastfeed longer (OR = 3.08; p<0.001). Number of visits was positively associated with infant birth weight ≥2500 grams (OR = 1.07; p = 0.012), healthy head-circumference-for-age measurements at 6 months (OR = 1.09, p = 0.017), and improved cognitive development at 18 months (OR = 1.02, p = 0.048).
Conclusions
Home visits to neighbourhood mothers by CHWs may be a feasible strategy for enhancing maternal/child outcomes. However, visits likely must extend over several years for persistent benefits.
Trial Registration
ClinicalTrials.gov NCT00996528
doi:10.1371/journal.pone.0105934
PMCID: PMC4207699  PMID: 25340337
4.  Sleep budgets in a globalizing world: biocultural interactions influence sleep sufficiency among Egyptian families 
Declines in self-reported sleep quotas with globalizing lifestyle changes have focused attention on their possible role in rising global health problems such as obesity or depression. Cultural factors that act across the life course and support sleep sufficiency have received scant attention, nor have the potential interactions of cultural and biological factors in age-related changes in sleep behavior been systematically investigated. This study examines the effects of cultural norms for napping and sleeping arrangements along with sleep schedules, age, and gender on sleep budgets among Egyptian households. Data were collected in 2000 from 16 households with 78 members aged 3–56 years at two sites in Egypt (Cairo and an agrarian village). Each participant provided one week of continuous activity records and details of each sleep event. Records showed that nighttime sleep onsets were late and highly variable. Napping was common and, along with wake time flexibility, played a key role in maintaining sleep sufficiency throughout the life course into later middle age. Cosleeping was prevalent and exhibited contrasting associations with reduced duration and sufficiency of both nocturnal and total sleep, and with earlier, more regular, and less disrupted sleep. Daily sleep quotas met published guidelines and showed age-related changes similar to existing reports, but differed in how they were achieved. Cultural norms organizing sleep practices by age and gender appear to tap their intrinsic biological properties as well. Moreover, flexibility in how sleep was achieved contributed to sleep sufficiency. The findings suggest how biocultural dynamics can play key roles in sleep patterns that sustain favorable sleep quotas from infancy onwards in populations pursuing globalizing contemporary lifestyles.
doi:10.1016/j.socscimed.2012.03.048
PMCID: PMC3775587  PMID: 22651897
Egypt; Time use diary; Adolescence; Pediatric sleep; Child development; Insomnia; Sleep ecology; Aging
5.  Companionable sleep: Social regulation of sleep and co-sleeping in Egyptian families 
This exploratory study examines family sleep patterns and quality in a setting of normative napping and co-sleeping. Participants comprised 78 members of 16 families from two locales in Egypt, Cairo and village. Each family member provided a history of sleeping arrangements, one week of continuous activity records, and details of each sleep event. Sleep records documented late-onset and dispersed sleep patterns with extensive co-sleeping. Of recorded sleep events, 69% involved co-sleeping, 24% included more than one co-sleeper, and only 21% were solitary. Mid-late afternoon napping occurred on 31% of days and night sleep onsets averaged after midnight. Age and gender structured sleep arrangements and together with locale, extensively explained sleep behavior (onset, duration, total) and quality. Co-sleepers had fewer night arousals, shorter and less variable night sleep duration, and less total sleep. Increased solitary sleep in adolescents and young adults was associated with increased sleep dysregulation, including exaggerated phase shifts in males and more nighttime arousals in females. Where normative, co-sleeping may provide psychosensory stimuli that moderate arousal and stabilize sleep. Such moderating features may address important self-regulatory developmental needs during adolescence.
doi:10.1037/0893-3200.21.1.124
PMCID: PMC3771325  PMID: 17371117
co-sleeping; bed sharing; sleep quality; adolescence; cultural differences
6.  Habits of the Heart: Life History and the Developmental Neuroendocrinology of Emotion 
The centrality of emotion in cognition and social intelligence, as well as its impact on health, has intensified investigation into the causes and consequences of individual variation in emotion regulation. Central processing of experience directly informs regulation of endocrine axes, essentially forming a neuro-endocrine continuum integrating information intake, processing, and physiological and behavioral response. Two major elements of life history—resource allocation and niche partitioning—are served by linking cognitive-affective with physiologic and behavioral processes. Scarce cognitive resources (attention, memory, time) are allocated under guidance from affective co-processing. Affective-cognitive processing, in turn, regulates physiologic activity through neuro-endocrine outflow and thereby orchestrates energetic resource allocation and trade-offs, both acutely and through time. Reciprocally, peripheral activity (e.g., immunologic, metabolic or energetic markers) influences affective-cognitive processing. By guiding attention, memory, and behavior, affective-cognitive processing also informs individual stances toward, patterns of activity in, and relationships with the world. As such, it mediates processes of niche partitioning that adaptively exploit social and material resources. Developmental behavioral neurobiology has identified multiple factors that influence the ontogeny of emotion regulation to form affective and behavioral styles. Evidence is reviewed documenting roles for genetic, epigenetic, and experiential factors in the development of emotion regulation, social cognition and behavior with important implications for understanding mechanisms that underlie life history construction and the sources of differential health. Overall, this dynamic arena for research promises to link the biological bases of life history theory with the psychobehavioral phenomena that figure so centrally in quotidian experience and adaptation, particularly for humans.
doi:10.1002/ajhb.20966
PMCID: PMC3772087  PMID: 19621433
epigenetics; personality; temperament; niche partitioning; mental health
7.  Sex-Differentiated Changes in C-Reactive Protein from Ages 9 to 21: The Contributions of BMI and Physical/Sexual Maturation 
Psychoneuroendocrinology  2013;38(10):2209-2217.
Background
Sex differences in levels of C-reactive Protein (CRP) are well established in adulthood, but little is known about when and why they emerge. Here, we tested longitudinal models of CRP levels from ages 9–21, when marked physical and behavioral changes could contribute to growing sex disparities in CRP.
Methods
Data from the community-based prospective-longitudinal Great Smoky Mountains Study (N = 1,420) were used. Participants were 9–13 years old at intake and were followed through age 21. High-sensitivity C-reactive protein (CRP) was assayed from up to nine bloodspot collections per person. BMI, physical/sexual maturation, substance use, and control variables were assessed during yearly interviews to age 16, and at ages 19 and 21.
Results
Multilevel models revealed that the development of CRP in females was best described by a quadratic trend: After slow increases in CRP until age 15, the rate of increase accelerated thereafter. Changes in CRP in males were best described by a smaller, linear increase. After sex-differentiated associations with BMI, physical/sexual maturation, and substance use variables had been accounted for, increases in CRP after age 15 no longer differed by sex.
Conclusion
Physical/sexual maturation and behavioral changes during adolescence could initiate life-long sex disparities in CRP.
doi:10.1016/j.psyneuen.2013.04.010
PMCID: PMC3777291  PMID: 23711900
C-reactive protein; sex differences; BMI; adolescence; young adulthood; puberty; testosterone
8.  Cultural and community determinants of subjective social status among Cherokee and White youth 
Ethnicity & health  2008;13(4):289-303.
Background
Subjective social status (SSS) is associated with physical and mental health in diverse samples. However, community, cultural, and ethnic influences on SSS are poorly understood, especially among rural and American Indian populations.
Objective
We aimed to examine similarities and differences in how community poverty, family context, and life course attainment predict SSS among Cherokee and White youth in Appalachia.
Design
We assessed culturally and developmentally appropriate aspects of life course attainment among 344 Cherokee and White youth (age 19–24) using the Life Trajectory Interview for Youth (Brown et al. 2006. International Journal of Methods in Psychiatric Research, 15, 192–206). Combined with information regarding community context and family history, these data were used to examine common patterns and ethnic differences in community, family, and cultural influences on SSS.
Results
Overall, both Cherokee and White youth rank their families lower in SSS than previously studied US youth. Family poverty during childhood and low parental education negatively influence family SSS, Cherokee youth rank higher on subjective socioeconomic status (SES) than Whites, as do participants in high poverty areas. However, White youth rank higher on peer SSS. Ethnographically generated items perform better than standard demographic markers in predicting SSS. Educational attainment is associated with peer SSS among Cherokee (but not White) youths.
Conclusions
Cultural identity, community context, and local reference groups are crucial determinants of SSS. Both White and Cherokee youth in Appalachia exhibit SSS rankings consistent with socioeconomic and cultural marginalization. On a local scale, however, living in high poverty areas or minority communities may buffer individuals from some negative social comparisons regarding subjectively perceived SES. Meanwhile, social monitoring in small minority communities may constrain optimistic bias in assessments of peer popularity and status. Social ecology, family context, and individual attainment appear to exert distinctive influences on SSS across different cultural and ethnic groups.
doi:10.1080/13557850701837302
PMCID: PMC4075651  PMID: 18701990
Native American; Appalachia; culture; socioeconomic status; social hierarchy; poverty
9.  Outcomes of Home Visits for Pregnant Mothers and their Infants: a Cluster Randomised Controlled Trial 
AIDS (London, England)  2013;27(9):1461-1471.
Objective
To evaluate the effect of home visits by Community Health Workers (CHW) on maternal and infant well-being from pregnancy through the first six months of life for women living with HIV (WLH) and all neighbourhood mothers.
Design and Methods
In a cluster randomised controlled trial in Cape Town townships, neighbourhoods were randomised within matched pairs to either: 1) Standard Care, comprehensive healthcare at clinics (SC; n=12 neighbourhoods; n=169 WLH; n=594 total mothers), or 2) Philani Intervention Program, home visits by CHW in addition to SC (PIP; n=12 neighbourhoods; n=185 WLH; n=644 total mothers). Participants were assessed during pregnancy (2% refusal) and reassessed at one week (92%) and six months (88%) post-birth. We analysed PIP’s effect on 28 measures of maternal and infant well-being among WLH and among all mothers using random effects regression models. For each group, PIP’s overall effectiveness was evaluated using a binomial test for correlated outcomes.
Results
Significant overall benefits were found in PIP compared to SC among WLH and among all participants. Secondarily, compared to SC, PIP WLH were more likely to complete tasks to prevent vertical transmission, use one feeding method for 6 months, avoid birth-related medical complications, and have infants with healthy height-for-age measurements. Among all mothers, compared to SC, PIP mothers were more likely to use condoms consistently, breastfeed exclusively for 6 months, and have infants with healthy height-for-age measurements.
Conclusions
PIP is a model for countries facing significant reductions in HIV funding whose families face multiple health risks.
doi:10.1097/QAD.0b013e3283601b53
PMCID: PMC3904359  PMID: 23435303
HIV; maternal health; perinatal health
10.  Culture in Psychiatric Epidemiology: Using Ethnography and Multiple Mediator Models to Assess the Relationship of Caste with Depression and Anxiety in Nepal 
Annals of human biology  2009;36(3):261-280.
Background
The causes of ethnic and caste-based disparities in mental health are poorly understood.
Aim
To identify mediators underlying caste-based disparities in mental health in Nepal.
Subjects and methods
A mixed methods ethnographic and epidemiological study of 307 adults (Dalit/Nepali, n=75; high caste Brahman and Chhetri, n=232) assessed with Nepali versions of Beck Depression (BDI) and Anxiety (BAI) Inventories.
Results
One third (33.7%) of participants were classified as depressed: Dalit/Nepali 50.0%, high caste 28.4%. One quarter (27.7%) of participants were classified as anxious: Dalit/Nepali 50.7%, high caste 20.3%. Ethnographic research identified four potential mediators: stressful life events, owning few livestock, no household income, and lack of social support. The direct effect of caste was 1.08 (95% CI -1.10—3.27) on depression score and 4.76 (95% CI 2.33—7.19) on anxiety score. All four variables had significant indirect (mediation) effects on anxiety, and all but social support had significant indirect effects on depression.
Conclusion
Caste-based disparities in mental health in rural Nepal are statistically mediated by poverty, lack of social support, and stressful life events. Interventions should target these areas to alleviate the excess mental health burden born by Dalit/Nepali women and men.
doi:10.1080/03014460902839194
PMCID: PMC3907946  PMID: 19381985
Mental health; ethnicity; multiple mediator models; mixed methods; Nepal
11.  Philani Plus (+): A Mentor Mother Community Health Worker Home Visiting Program to Improve Maternal and Infants’ Outcomes 
Pregnant mothers in South African townships face multiple health risks for themselves and their babies. Existing clinic-based services face barriers to access, utilization, and human resource capacities. Home visiting by community health workers (CHW) can mitigate such barriers. The Philani Plus (+) Intervention Program builds upon the original Philani CHW home-visiting intervention program for maternal and child nutrition by integrating content and activities to address HIV, alcohol, and mental health. Pregnant Mothers at Risk (MAR) for HIV, alcohol, and/or nutrition problems in 24 neighborhoods in townships in Cape Town, South Africa (n=1,239) were randomly assigned by neighborhood to an intervention (Philani Plus (+), N=12 neighborhoods; n=645 MAR) or a standard-care control condition of neighborhood clinic-based services (N=12 neighborhoods; n=594 MAR). Positive peer deviant “Mentor Mother” CHWs are recruited from the township neighborhoods and trained to deliver four antenatal and four postnatal home visits that address HIV, alcohol, nutrition, depression, health care regimens for the family, caretaking and bonding, and securing government-provided child grants. The MAR and their babies are being monitored during pregnancy, 1 week post-birth, and 6 and 18 months later. Among the 1,239 MAR recruited: 26% were HIV-positive; 27% used alcohol during pregnancy; 17% previously had low-birthweight babies; 23% had at least one chronic condition (10% hypertension, 5% asthma, 2% diabetes); 93% had recent sexual partners with 10% known to be HIV+; and 17% had clinically significant prenatal depression and 42% had borderline depression. This paper presents the intervention protocol and baseline sample characteristics for the “Philani Plus (+)” CHW home-visiting intervention trial.
doi:10.1007/s11121-011-0238-1
PMCID: PMC3907085  PMID: 21850488
HIV; Maternal & child health; Alcohol; Nutrition; Home visiting; South Africa; Community health workers (CHW); Paraprofessionals
12.  Lifecourse Priorities Among Appalachian Emerging Adults: Revisiting Wallace’s Organization of Diversity 
Ethos (Berkeley, Calif.)  2009;37(2):10.1111/j.1548-1352.2009.01040.x.
We examine how social demographics (gender, age, or race–ethnicity), census tract characteristics, and family environment during childhood relate to variability in the lifecourse priorities of 344 Cherokee and white youth during emerging adulthood (age 19–24). Analyses were performed using recursive partitioning and random forest methods to examine determinants of prioritizing education, family formation, economic establishment, self characteristics and close relationships, youth independence, conspicuous consumption, and community reliance. Overall, characteristics of census tracts were the most common and influential predictors of lifecourse priorities. Childhood family poverty, parental relationship problems, parental crime, and stressful life events were also important predictors. Race–ethnicity or cultural group (Cherokee vs. white), age, and gender were relatively unimportant. At this developmental stage and in this population, community characteristics and childhood family experiences may be better proxies for developmental settings (and resulting enculturated values and preferences) than social demographic variables (e.g., ethnicity or gender).
doi:10.1111/j.1548-1352.2009.01040.x
PMCID: PMC3882117  PMID: 24403647
lifecourse; emerging adulthood; recursive partitioning; American Indian; Appalachia
13.  Comparison of mental health between former child soldiers and children never conscripted by armed groups in Nepal 
JAMA : the journal of the American Medical Association  2008;300(6):10.1001/jama.300.6.691.
Context:
Despite child soldiers being considered in need of special mental health interventions, there is a lack of studies investigating the mental health of child soldiers compared with civilian children in armed conflicts.
Objective:
To compare the mental health status of former child soldiers with children who have never been conscripts of armed groups.
Design, Setting, and Participants:
A matched-pair cohort study conducted from March through April 2007 in Nepal compared the mental health of 141 former child soldiers to 141 never conscripted children matched on age, sex, education, and ethnicity.
Outcome Measures:
Depression symptoms were assessed via the Depression Self Rating Scale (DSRS), anxiety symptoms via the Screen for Child Anxiety Related Emotional Disorders (SCARED-5), symptoms of posttraumatic stress disorder (PTSD) via the Child PTSD Symptom Scale (CPSS), general psychological difficulties via the Strength and Difficulties Questionnaire (SDQ), daily functioning via the Function Impairment (FI) tool, and exposure to traumatic events via Kiddie-Schedule of Affective Disorders and Schizophrenia (KIDDIE-SADS) PTSD Traumatic Event Checklist.
Results:
Participants were a mean of 15.75 years at the time of this study and child soldiers ranged in age from 5 to 16 years at the time of conscription. All participants experienced at least 1 type of trauma. Number (%) of child soldiers meeting cutoff scores were 75 (53.2%) for depression, 65 (46.1%) for anxiety, 78 (55.3%) for PTSD, 55 (39.0%) for psychological difficulties, and 88 (62.4%) for function impairment. Child soldiers had greater odds of meeting cutoff for depression (OR=3.56, 95% CI 2.33—5.43), PTSD (for which we employed stratified analyses because of sex interaction: boys’ OR=3.85, 95% CI 1.77—8.39; girls’ OR=6.33, 95% CI 2.64—15.17), psychological difficulties (OR=2.91, 95% CI=1.53—5.51), and function impairment (OR=2.04, 95% CI 1.41—2.96), but no difference for anxiety (OR=1.46, 95% CI 0.72—2.68). After adjusting for traumatic exposures, soldier status was no longer associated with psychological difficulties or function impairment but remained significantly associated with depression (OR=2.69, 95% CI 1.48—4.89) and PTSD among girls (OR=5.98, 95% CI 1.86—19.27), but not PTSD among boys (OR=2.38, 95% CI 0.87—6.50).
Conclusions:
In Nepal, former child soldiers display greater severity of mental health problems compared with children never conscripted by armed groups, and this difference remains for depression and PTSD (the latter especially among girls) even after controlling for trauma exposure.
doi:10.1001/jama.300.6.691
PMCID: PMC3842355  PMID: 18698067
14.  Political violence and mental health in Nepal: prospective study*† 
The British Journal of Psychiatry  2012;201(4):268-275.
Background
Post-conflict mental health studies in low-income countries have lacked pre-conflict data to evaluate changes in psychiatric morbidity resulting from political violence.
Aims
This prospective study compares mental health before and after exposure to direct political violence during the People’s War in Nepal.
Method
An adult cohort completed the Beck Depression Inventory and Beck Anxiety Inventory in 2000 prior to conflict violence in their community and in 2007 after the war.
Results
Of the original 316 participants, 298 (94%) participated in the post-conflict assessment. Depression increased from 30.9 to 40.6%. Anxiety increased from 26.2 to 47.7%. Post-conflict post-traumatic stress disorder (PTSD) was 14.1%. Controlling for ageing, the depression increase was not significant. The anxiety increase showed a dose–response association with conflict exposure when controlling for ageing and daily stressors. No demographic group displayed unique vulnerability or resilience to the effects of conflict exposure.
Conclusions
Conflict exposure should be considered in the context of other types of psychiatric risk factors. Conflict exposure predicted increases in anxiety whereas socioeconomic factors and non-conflict stressful life events were the major predictors of depression. Research and interventions in post-conflict settings therefore should consider differential trajectories for depression v. anxiety and the importance of addressing chronic social problems ranging from poverty to gender and ethnic/caste discrimination.
doi:10.1192/bjp.bp.111.096222
PMCID: PMC3461445  PMID: 22878131
15.  Seasonal and Circadian Variation in Salivary Testosterone in Rural Bolivian Men 
Testosterone (T) plays a key role in the increase and maintenance of muscle mass and bone density in adult men. Life history theory predicts that environmental stress may prompt a reallocation of such investments to those functions critical to survival. We tested this hypothesis in two studies of rural Bolivian adult men by comparing free T levels and circadian rhythms during late winter, which is especially severe, to those in less arduous seasons. For each pair of salivary TAM/TPM samples (collected in a ~12-hour period), circadian rhythm was considered classic (CCLASSIC) if TAM>110%TPM, reverse (CREVERSE) if TPM>110%TAM, and flat (CFLAT) otherwise. We tested the hypotheses that mean TAM>mean TPM and that mean TLWTOTHER-PM (A: p=0.035, B: p=0.0005) and TOTHER-AM>TLW-AM (A: p=0.054, B: p=0.007); TPM did not vary seasonally, and T diurnality was not significant during late winter. T diurnality varied substantially between days within an individual, between individuals and between seasons, but neither T levels nor diurnality varied with age. These patterns may reflect the seasonally varying but unscheduled, life-long, strenuous physical labor that typifies many non-industrialized economies. These results also suggest that single morning samples may substantially underestimate peak circulating T for an individual and, most importantly, that exogenous signals may moderate diurnality and the trajectory of age-related change in the male gonadal axis.
doi:10.1002/ajhb.20927
PMCID: PMC3771338  PMID: 19367574
andrology; testosterone; seasonality; circadian rhythms; aging; Bolivia
16.  Sex Differences in the Association Between Cortisol Concentrations and Laboratory Pain Responses in Healthy Children 
Gender medicine  2009;6(Suppl 2):193-207.
Background
Research in adult populations has highlighted sex differences in cortisol concentrations and laboratory pain responses, with men exhibiting higher cortisol concentrations and reduced pain responses compared with women. Yet, less is known about the relationship of cortisol concentrations to pain in children.
Objective
This study examined associations between sex, cortisol, and pain responses to laboratory pain tasks in children.
Methods
Salivary cortisol samples from subjects aged 8 to 18 years were obtained at baseline after entering the laboratory (SCb), after the completion of all pain tasks (SC1), and at the end of the session (SC2), 20 minutes later. Blood cortisol samples were also taken after completion of the pain tasks (BC1) and at the end of the session (BC2), 20 minutes later. Subjects completed 3 counterbalanced laboratory pain tasks: pressure, heat, and cold pressor tasks. Pain measures included pain tolerance, and self-reported pain intensity and unpleasantness for all 3 tasks.
Results
The study included 235 healthy children and adolescents (119 boys, 116 girls; mean age, 12.7 years; range, 8–18 years; 109 [46.4%] were in early puberty; 94 [40.0%] white). Salivary and blood cortisol levels were highly correlated with each other. Salivary cortisol levels for the total sample and for boys and girls declined significantly from SCb to SC1 (P < 0.01), although there were no significant changes from SC1 to SC2. No significant sex differences in salivary or blood cortisol levels were evident at any assessment point. Separate examination of the cortisol–laboratory pain response relationships by sex (controlling for age and time of day) suggested different sex-specific patterns. Higher cortisol levels were associated with lower pain reactivity (ie, increased pressure tolerance) among boys compared with girls at SC1, SC2, and BC1 (SC1: r = 0.338, P = 0.003; SC2: r = 0.271, P = 0.020; and BC1: r = 0.261, P = 0.026). However, higher cortisol levels were related to higher pain response (ie, increased cold intensity [BC2: r = 0.229, P = 0.048] and unpleasantness [BC1: r = 0.237, P = 0.041]) in girls compared with boys.
Conclusions
These findings suggest important sex differences in cortisol–pain relationships in children and adolescents. Cortisol levels were positively associated with increased pain tolerance in boys and increased pain sensitivity in girls.
doi:10.1016/j.genm.2009.03.001
PMCID: PMC3486740  PMID: 19406369
pain; children; cortisol; sex differences
17.  Sex Matters during Adolescence: Testosterone-Related Cortical Thickness Maturation Differs between Boys and Girls 
PLoS ONE  2012;7(3):e33850.
Age-related changes in cortical thickness have been observed during adolescence, including thinning in frontal and parietal cortices, and thickening in the lateral temporal lobes. Studies have shown sex differences in hormone-related brain maturation when boys and girls are age-matched, however, because girls mature 1–2 years earlier than boys, these sex differences could be confounded by pubertal maturation. To address puberty effects directly, this study assessed sex differences in testosterone-related cortical maturation by studying 85 boys and girls in a narrow age range and matched on sexual maturity. We expected that testosterone-by-sex interactions on cortical thickness would be observed in brain regions known from the animal literature to be high in androgen receptors. We found sex differences in associations between circulating testosterone and thickness in left inferior parietal lobule, middle temporal gyrus, calcarine sulcus, and right lingual gyrus, all regions known to be high in androgen receptors. Visual areas increased with testosterone in boys, but decreased in girls. All other regions were more impacted by testosterone levels in girls than boys. The regional pattern of sex-by-testosterone interactions may have implications for understanding sex differences in behavior and adolescent-onset neuropsychiatric disorders.
doi:10.1371/journal.pone.0033850
PMCID: PMC3315517  PMID: 22479458
18.  Puberty Influences Medial Temporal Lobe and Cortical Gray Matter Maturation Differently in Boys Than Girls Matched for Sexual Maturity 
Cerebral Cortex (New York, NY)  2010;21(3):636-646.
Sex differences in age- and puberty-related maturation of human brain structure have been observed in typically developing age-matched boys and girls. Because girls mature 1–2 years earlier than boys, the present study aimed at assessing sex differences in brain structure by studying 80 adolescent boys and girls matched on sexual maturity, rather than age. We evaluated pubertal influences on medial temporal lobe (MTL), thalamic, caudate, and cortical gray matter volumes utilizing structural magnetic resonance imaging and 2 measures of pubertal status: physical sexual maturity and circulating testosterone. As predicted, significant interactions between sex and the effect of puberty were observed in regions with high sex steroid hormone receptor densities; sex differences in the right hippocampus, bilateral amygdala, and cortical gray matter were greater in more sexually mature adolescents. Within sex, we found larger volumes in MTL structures in more sexually mature boys, whereas smaller volumes were observed in more sexually mature girls. Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys, which may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.
doi:10.1093/cercor/bhq137
PMCID: PMC3041011  PMID: 20713504
21.  Moving from ethnography to epidemiology: lessons learned in Appalachia 
Annals of human biology  2009;36(3):248-260.
Background
Anthropologists are beginning to translate insights from ethnography into tools for population studies that assess the role of culture in human behavior, biology, and health.
Aim
We describe several lessons learned in the creation and administration of an ethnographically-based instrument to assess the life course perspectives of Appalachian youth, the Life Trajectory Interview for Youth (LTI-Y). Then, we explore the utility of the LTI-Y in predicting depressive affect, controlling for prior depressed mood and severe negative life events throughout the life course.
Subjects and methods
In a sample of 319 youth (190 White, 129 Cherokee), we tested the association between depressive affect and two domains of the LTI-Y - life course barriers and milestones. Longitudinal data on previous depressed mood and negative life events were included in the model.
Results
The ethnographically-based scales of life course barriers and milestones were associated with unique variance in depressed mood, together accounting for 11% of the variance in this outcome.
Conclusion
When creating ethnographically-based instruments, it is important to strike a balance between detailed, participant-driven procedures and the analytic needs of hypothesis testing. Ethnographically-based instruments have utility for predicting health outcomes in longitudinal studies.
doi:10.1080/03014460902832942
PMCID: PMC2868371  PMID: 19353406
Appalachia; depression; population health; life course; American Indian
22.  Healthy Adolescents' Neural Response to Reward: Associations with Puberty, Positive Affect, and Depressive Symptoms 
Objective
Changes in reward-related behavior are an important component of normal adolescent affective development. Understanding the neural underpinnings of these normative changes creates a foundation for investigating adolescence as a period of vulnerability to affective disorders, substance use disorders, and health problems. Studies of reward-related brain function have revealed conflicting findings regarding developmental change in the reactivity of the striatum and medial prefrontal cortex (mPFC) and have not considered puberty. The current study focused on puberty-specific changes in brain function and their association with mood.
Method
A sample of 77 healthy adolescents (26 pre/early pubertal, 51 mid/late pubertal) recruited in a narrow age range (M=11.94 years, SD=.75) were assessed for sexual maturation and circulating testosterone, completed an fMRI guessing task with monetary reward, and underwent experience sampling of mood in natural environments. For comparison, 19 healthy adults completed the fMRI assessment.
Results
Adolescents with more advanced pubertal maturation exhibited less striatal and more mPFC reactivity during reward outcome than similarly aged adolescents with less advanced maturation. Testosterone was positively correlated with striatal reactivity in boys during reward anticipation and negatively correlated with striatal reactivity in girls and boys during reward outcome. Striatal reactivity was positively correlated with real-world subjective positive affect and negatively correlated with depressive symptoms. mPFC reactivity was positively correlated with depressive symptoms.
Conclusions
Reward-related brain function changes with puberty and is associated with adolescents' positive affect and depressive symptoms. Increased reward-seeking behavior at this developmental point could serve to compensate for these changes.
PMCID: PMC2837556  PMID: 20215938
reward; brain function; development; depression
23.  Tracking Biocultural Pathways to Health Disparities: The Value of Biomarkers 
Annals of human biology  2009;36(3):281-297.
Background
Cultural factors and biomarkers are emerging emphases in social epidemiology that readily ally with human biology and anthropology. Persistent health challenges and disparities have established biocultural roots, and environment plays an integral role in physical development and function that form the bases of population health. Biomarkers have proven to be valuable tools for investigating biocultural bases of health disparities.
Aims
We apply recent insights from biology to consider how culture gets under the skin and evaluate the construct of embodiment. We analyze contrasting biomarker models and applications, and propose an integrated model for biomarkers. Three examples from the Great Smoky Mountains Study (GSMS) illustrate these points.
Subjects and methods
The longitudinal developmental epidemiological GSMS comprises a population-based sample of 1420 children with repeated measures including mental and physical health, life events, household conditions, and biomarkers for pubertal development and allostatic load.
Results
Analyses using biomarkers resolved competing explanations for links between puberty and depression, identified gender differences in stress at puberty, and revealed interactive effects of birthweight and postnatal adversity on risk for depression at puberty in girls.
Conclusion
An integrated biomarker model can both enrich epidemiology and illuminate biocultural pathways in population health.
doi:10.1080/03014460902832934
PMCID: PMC2761016  PMID: 19381986
biomarkers; embodiment; culture; epidemiology

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