Sex and pubertal variation in reward-related behavior and neural activation in early adolescents.

This study aimed to characterize the role of sex and pubertal markers in reward motivation behavior and neural processing in early adolescence. We used baseline and two-year follow-up data from the Adolescent Brain and Cognitive DevelopmentSM study (15844 observations; 52% from boys; age 9-13). Pubertal development was measured with parent-reported Pubertal Development Scale, and DHEA, testosterone, and estradiol levels. Reward motivation behavior and neural processing at anticipation and feedback stages were assessed with the Monetary Incentive Delay task. Boys had higher reward motivation than girls, demonstrating greater accuracy difference between reward and neutral trials and higher task earnings. Girls had lower neural activation during reward feedback than boys in the nucleus accumbens, caudate, rostral anterior cingulate, medial orbitofrontal cortex, superior frontal gyrus and posterior cingulate. Pubertal stage and testosterone levels were positively associated with reward motivation behavior, although these associations changed when controlling for age. There were no significant associations between pubertal development and neural activation during reward anticipation and feedback. Sex differences in reward-related processing exist in early adolescence, signaling the need to understand their impact on typical and atypical functioning as it unfolds into adulthood.

Within-person associations of cortisol, dehydroepiandrosterone, and testosterone hair hormone concentrations and psychological distress in pregnant and non-pregnant women.

Prenatal hair cortisol concentration is inconsistently associated with maternal psychological distress. However, prior studies have not often measured hair cortisol and maternal psychological distress prospectively over time, examined within-person associations, nor concurrently considered the complex hormonal milieu in which cortisol operates during pregnancy. We addressed these limitations and tested associations against a similar non-pregnant comparison group. Participants included 68 women (34 pregnant and 34 non-pregnant; Mage = 29.14 and 83 % White) from the Midwestern United States. Pregnant women were assessed each trimester, at 12, 26, and 38 weeks and non-pregnant women were assessed three times on the same schedule. At each assessment, participants completed measures of psychological distress and provided hair samples. The first 3 cm (from the scalp) of hair was assayed using enzyme immune-assay kits to reflect cumulative levels within the given trimester/3-month time period of cortisol, dehydroepiandrosterone (DHEA) and testosterone. Within-person associations of hair cortisol and ratio of hair cortisol-to-DHEA and cortisol-to-testosterone with psychological distress were assessed using multilevel models. There were positive within-person associations of hair cortisol with cumulative psychological distress (γ = 0.01, s.e. = 0.003, p = .049), anxiety (γ = 0.09, s.e. = 0.04, p = .046), and pregnancy-related anxiety symptoms (γ = 0.10, s.e. = 0.05, p = .041) in the pregnant sample such that on occasions when hair cortisol was higher than average so were psychological distress symptoms. No within-person associations of hair cortisol were supported in non-pregnant women although there was a negative within-person association, such that on occasions of having lower testosterone level than typical, depression symptoms were higher. There were no within-person associations of psychological distress and cortisol-to-DHEA ratio or cortisol-to-testosterone ratio in either the pregnant or non-pregnant sample. At the between person-level for pregnant women, lower cortisol levels were associated with higher perceived stress (γ = -0.28, s.e. = 0.09, p = .003) and depression symptoms (γ = -0.11, s.e. = 0.06, p = .039), whereas higher cortisol levels were associated with higher psychological distress (γ = 0.03, s.e. = 0.01, p = .010), state anxiety (γ = 0.33, s.e. = 0.13, p = .010), and depression symptoms (γ = 0.23, s.e. = 0.09, p = .017) in non-pregnant women. Modeling hair cortisol at the within-person and between-person level revealed differential findings in pregnant and non-pregnant women. Hair cortisol concentration, psychological distress, pregnancy, hormone coupling, within-person associations.

Sex and pubertal influences on the neurodevelopmental underpinnings of schizophrenia: A case for longitudinal research on adolescents.

Sex is a significant source of heterogeneity in schizophrenia, with more negative symptoms in males and more affective symptoms and internalizing comorbidity in females. In this narrative review, we argue that there are likely sex differences in the pathophysiological mechanisms of schizophrenia-spectrum disorders (SZ) that originate during puberty and relate to the sex-specific impacts of pubertal maturation on brain development. Pubertal maturation might also trigger underlying (genetic or other) vulnerabilities in at-risk individuals, influencing brain development trajectories that contribute to the emergence of SZ. This review is the first to integrate links between pubertal development and neural development with cognitive neuroscience research in SZ to form and evaluate these hypotheses, with a focus on the frontal-striatal and frontal-limbic networks and their hypothesized contribution to negative and mood symptoms respectively. To test these hypotheses, longitudinal research with human adolescents is needed that examines the role of sex and pubertal development using large cohorts or high risk samples. We provide recommendations for such studies, which will integrate the fields of psychiatry, developmental cognitive neuroscience, and developmental endocrinology towards a more nuanced understanding of the role of pubertal factors in the hypothesized sex-specific pathophysiological mechanisms of schizophrenia.

Measurement of gonadal hormones in dried blood spots versus serum: verification of menstrual cycle phase.

In the present study, we show that blood spot assays for estradiol, progesterone, and testosterone are a reliable, accurate, and sensitive means for measuring circulating gonadal hormones. The lower limit of sensitivity of each blood spot assay is sufficient to determine gonadal hormone levels in adult females. Correspondence of serum to blood spot measures is high, with blood spot hormone levels explaining an average of 88.60% of the variance in serum gonadal hormones in females, but only 46.20% in males. We provide formulas for converting hormone levels in blood to hormone levels in serum (which traditional endocrinology studies report). Finally, we show that careful attempts to estimate hormone status by day-count methods are unreliable when compared to hormone assay in blood spots.

Use of salivary biomarkers in biobehavioral research: cotton-based sample collection methods can interfere with salivary immunoassay results.

In a series of studies, we evaluated the susceptibility of immunoassays for saliva biomarkers to interference effects caused by cotton materials used to absorb saliva during sample collection. Salivary assay results for testosterone, DHEA, progesterone, and estradiol are artificially high, and for sIgA artificially low, when samples are collected using cotton absorbent materials. In contrast, results for salivary cortisol, DHEA-S, and cotinine are not affected by the use of cotton collection methods. The order of individual results from samples collected using cotton versus no-cotton methods for certain markers is not conserved, suggesting that for some biomarkers this collection method can be a significant source of unsystematic error. It was shown, using DHEA as an example, that the cotton interference effect is of sufficient magnitude to attenuate the association between serum and saliva levels. Awareness of this issue is critical to ensure measurement validity in future studies and analyses of archived samples collected using cotton materials.

Assessing estradiol in biobehavioral studies using saliva and blood spots: simple radioimmunoassay protocols, reliability, and comparative validity.

We developed simple, reliable, and highly sensitive assay modifications of commercially available radioimmunoassay kits to measure estradiol in saliva and blood spot specimens. The saliva assay has average intra- and interassay coefficients of variation (CV) of 6.45 and 9.01%, with average analytical and serial dilution recoveries 100.65 and 89.25%. The blood spot assay has average intra- and interassay CVs of 7.57 and 8.22%, with analytical and serial dilution recoveries of 80.50 and 108.50%. The analytical sensitivity ranges of the saliva (0.25-7.50 pg/ml) and blood spot (2. 00-375 pg/ml) assays are sufficient to determine levels in the majority of pre- and postpubertal males and females. Blood spot assay results are correlated with serum estradiol levels for adult males, r (17) = 0.73, and females, r (18) = 0.96. In contrast, the serum-saliva correlation is only modest for adult females, r (14) = 0.60, and not significant for adult males. Substitution of blood spot assay results for serum values underestimates the known serum estradiol-behavior correlation by only 3.45%, whereas substitution of saliva assay results for serum values underestimates the association by 37.55%. The findings have important implications for the use and potential misuse of noninvasive measures of estradiol in studies of health and human development.