Effects of macronutrient intake in obesity: a meta-analysis of low-carbohydrate and low-fat diets on markers of the metabolic syndrome.

The metabolic syndrome (MetS) comprises cardiometabolic risk factors frequently found in individuals with obesity. Guidelines to prevent or reverse MetS suggest limiting fat intake, however, lowering carbohydrate intake has gained attention too. The aim for this review was to determine to what extent either weight loss, reduction in caloric intake, or changes in macronutrient intake contribute to improvement in markers of MetS in persons with obesity without cardiometabolic disease. A meta-analysis was performed across a spectrum of studies applying low-carbohydrate (LC) and low-fat (LF) diets. PubMed searches yielded 17 articles describing 12 separate intervention studies assessing changes in MetS markers of persons with obesity assigned to LC (<40% energy from carbohydrates) or LF (<30% energy from fat) diets. Both diets could lead to weight loss and improve markers of MetS. Meta-regression revealed that weight loss most efficaciously reduced fasting glucose levels independent of macronutrient intake at the end of the study. Actual carbohydrate intake and actual fat intake at the end of the study, but not the percent changes in intake of these macronutrients, improved diastolic blood pressure and circulating triglyceride levels, without an effect of weight loss. The homeostatic model assessment of insulin resistance improved with both diets, whereas high-density lipoprotein cholesterol only improved in the LC diet, both irrespective of aforementioned factors. Remarkably, changes in caloric intake did not play a primary role in altering MetS markers. Taken together, these data suggest that, beyond the general effects of the LC and LF diet categories to improve MetS markers, there are also specific roles for weight loss, LC and HF intake, but not reduced caloric intake, that improve markers of MetS irrespective of diet categorization. On the basis of the results from this meta-analysis, guidelines to prevent MetS may need to be re-evaluated.

The greener the better? Does neighborhood greenness buffer the effects of stressful life events on externalizing behavior in late adolescence?

We tested whether neighborhood greenness is a promotive and/or a protective factor in the development of adolescent externalizing behavior problems and explored a possible mechanism of its effects via respiratory sinus arrhythmia (RSA) recovery after stress. Data from a longitudinal multi-method study on adolescents (N = 715) was used. Result showed that neighborhood greenness was neither a promotive nor a protective factor. However, adolescents who reported more stressful life events showed more externalizing behavior and -contrary to our expectation- this effect was stronger for adolescents who grew up in greener neighborhoods (vs. less green neighborhoods).

Correction: I Just Ran a Thousand Analyses: Benefits of Multiple Testing in Understanding Equivocal Evidence on Gene-Environment Interactions.

[This corrects the article DOI: 10.1371/journal.pone.0125383.].

Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence. The trails study.

The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during adolescence (N=141). HPA-axis functioning (basal cortisol, cortisol awakening response, anticipation of, reaction to and recovery after a stress task) was measured twice, at age 16 and 19. Adversity (i.e., social defeat and loss/illness) since age 16 was measured extensively with the Life Stress Interview at age 19. Adolescents who reported being exposed to social defeat showed increases in basal cortisol (ɳ2=0.029) and decreases in reaction to the stress task (ɳ2=0.030) from age 16-19, compared to their peers in the loss/illness and no stress group. The current study provides unique longitudinal data on the role of adversity in HPA-axis functioning. Evidence is provided that adversity can affect the body's neuroendocrine response to stress, dependent on the nature of both the HPA-measures and adverse events under study.

The adaptive calibration model of stress responsivity: An empirical test in the Tracking Adolescents' Individual Lives Survey study.

The adaptive calibration model (ACM) is a theory of developmental programing focusing on calibration of stress response systems and associated life history strategies to local environmental conditions. In this article, we tested some key predictions of the ACM in a longitudinal study of Dutch adolescent males (11-16 years old; N = 351). Measures of sympathetic, parasympathetic, and adrenocortical activation, reactivity to, and recovery from social-evaluative stress validated the four-pattern taxonomy of the ACM via latent profile analysis, though with some deviations from expected patterns. The physiological profiles generally showed predicted associations with antecedent measures of familial and ecological conditions and life stress; as expected, high- and low-responsivity patterns were found under both low-stress and high-stress family conditions. The four patterns were also differentially associated with aggressive/rule-breaking behavior and withdrawn/depressed behavior. This study provides measured support for key predictions of the ACM and highlights important empirical issues and methodological challenges for future research.

Study protocol for a randomized controlled trial to explore the effects of personalized lifestyle advices and tandem skydives on pleasure in anhedonic young adults.

BACKGROUND: Anhedonia is generally defined as the inability to feel pleasure in response to experiences that are usually enjoyable. Anhedonia is one of the two core symptoms of depression and is a major public health concern. Anhedonia has proven particularly difficult to counteract and predicts poor treatment response generally. It has often been hypothesized that anhedonia can be deterred by a healthy lifestyle. However, it is quite unlikely that a one-size-fits-all approach will be effective for everyone. In this study the effects of personalized lifestyle advice based on observed individual patterns of lifestyle behaviors and experienced pleasure will be examined. Further, we will explore whether a tandem skydive following the personalized lifestyle advice positively influences anhedonic young adults' abilities to carry out the recommended lifestyle changes, and whether this ultimately improves their self-reported pleasure. METHODS: Our study design is an exploratory intervention study, preceded by a cross-sectional survey as a screening instrument. For the survey, 2000 young adults (18-24 years old) will be selected from the general population. Based on survey outcomes, 72 individuals (36 males and 36 females) with persistent anhedonia (i.e., more than two months) and 60 individuals (30 males and 30 females) without anhedonia (non-anhedonic control group) will be selected for the intervention study. The non-anhedonic control group will fill out momentary assessments of pleasure and lifestyle behaviors three times a day, for one month. The anhedonic individuals will fill out momentary assessments for three consecutive months. After the first month, the anhedonic individuals will be randomly assigned to (1) no intervention, (2) lifestyle advice only, (3) lifestyle advice plus tandem skydive. The personalized lifestyle advice is based on patterns observed in the first month. DISCUSSION: The present study is the first to examine the effects of a personalized lifestyle advice and tandem skydive on pleasure in anhedonic young adults. Results of the present study may improve treatment for anhedonia, if the interventions are found to be effective. TRIAL REGISTRATION: Dutch Trial Register, NTR5498 , registered September 22, 2015 (retrospectively registered).

I just ran a thousand analyses: benefits of multiple testing in understanding equivocal evidence on gene-environment interactions.

BACKGROUND: In psychiatric genetics research, the volume of ambivalent findings on gene-environment interactions (G x E) is growing at an accelerating pace. In response to the surging suspicions of systematic distortion, we challenge the notion of chance capitalization as a possible contributor. Beyond qualifying multiple testing as a mere methodological issue that, if uncorrected, leads to chance capitalization, we advance towards illustrating the potential benefits of multiple tests in understanding equivocal evidence in genetics literature. METHOD: We focused on the interaction between the serotonin-transporter-linked promotor region (5-HTTLPR) and childhood adversities with regard to depression. After testing 2160 interactions with all relevant measures available within the Dutch population study of adolescents TRAILS, we calculated percentages of significant (p < .05) effects for several subsets of regressions. Using chance capitalization (i.e. overall significance rate of 5% alpha and randomly distributed findings) as a competing hypothesis, we expected more significant effects in the subsets of regressions involving: 1) interview-based instead of questionnaire-based measures; 2) abuse instead of milder childhood adversities; and 3) early instead of later adversities. Furthermore, we expected equal significance percentages across 4) male and female subsamples, and 5) various genotypic models of 5-HTTLPR. RESULTS: We found differences in the percentages of significant interactions among the subsets of analyses, including those regarding sex-specific subsamples and genetic modeling, but often in unexpected directions. Overall, the percentage of significant interactions was 7.9% which is only slightly above the 5% that might be expected based on chance. CONCLUSION: Taken together, multiple testing provides a novel approach to better understand equivocal evidence on G x E, showing that methodological differences across studies are a likely reason for heterogeneity in findings - but chance capitalization is at least equally plausible.

The role of Basal cortisol in predicting change in mental health problems across the transition to middle school.

PURPOSE: The period in which the transition to middle school occurs is marked by major changes in social context, social rules, and scholastic responsibilities. Some adolescents thrive during this period whereas others are overwhelmed and fail to cope adequately with their changing environment. We investigated basal cortisol upon waking as a predictor of change in mental health problems across the transition to middle school. By taking into account the transition experience, we extend prior findings that high basal cortisol predicts deteriorated mental health after the transition. In individuals with high awakening cortisol, we expected mental health problems to increase after negative transition experiences and to decrease after positive transition experiences, reflecting differential susceptibility. Evidence for the former but not the latter would suggest diathesis-stress. METHODS: Data from 1,664 subjects were obtained from two measurement waves (mean ages, 11 and 13.5 years) of the TRacking Adolescents' Individual Lives Survey. Using linear regression, we investigated effects of awakening cortisol level, school transition experience, and their hypothesized interaction on change in mental health problems. RESULTS: We found that a negative but not a positive experience was predictive of change in mental health. Importantly, our results showed that a negative experience predicts deteriorated mental health only in adolescents with high awakening cortisol but not in adolescents with low awakening cortisol. This finding was robust across informants. The converse, high awakening cortisol predicting decreasing mental health problems after a positive transition was not found. CONCLUSIONS: These results support the diathesis-stress model but not the differential susceptibility hypothesis.

Emotion recognition specialization and context-dependent risk of anxiety and depression in adolescents.

BACKGROUND: Some adolescents function poorly in apparently benign environments, while others thrive despite hassles and difficulties. The aim of this study was to examine if adolescents with specialized skills in the recognition of either positive or negative emotions have a context-dependent risk of developing an anxiety or depressive disorder during adolescence, depending on exposure to positive or harsh parenting. METHODS: Data came from a large prospective Dutch population study (N = 1539). At age 11, perceived parental rejection and emotional warmth were measured by questionnaire, and emotion recognition skills by means of a reaction-time task. Lifetime diagnoses of anxiety and depressive disorders were assessed at about age 19, using a standardized diagnostic interview. RESULTS: Adolescents who were specialized in the recognition of positive emotions had a relatively high probability to develop an anxiety disorder when exposed to parental rejection (Bspecialization*rejection = 0.23, P < 0.01) and a relatively low probability in response to parental emotional warmth (Bspecialization*warmth = -0.24, P = 0.01), while the opposite pattern was found for specialists in negative emotions. The effect of parental emotional warmth on depression onset was likewise modified by emotion recognition specialization (B = -0.13, P = 0.03), but the effect of parental rejection was not (B = 0.02, P = 0.72). In general, the relative advantage of specialists in negative emotions was restricted to fairly uncommon negative conditions. CONCLUSIONS: Our results suggest that there is no unequivocal relation between parenting behaviors and the probability to develop an anxiety or depressive disorder in adolescence, and that emotion recognition specialization may be a promising way to distinguish between various types of context-dependent reaction patterns.

Chronic Stress and Adolescents' Mental Health: Modifying Effects of Basal Cortisol and Parental Psychiatric History. The TRAILS Study.

Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to indicate high context sensitivity, would show relatively high problem levels following chronic stress, especially in the presence of parental psychiatric history. With Linear Mixed Models, we investigated the hypotheses in 1917 Dutch adolescents (53.2% boys), assessed at ages 11, 13.5, and 16. Low basal cortisol combined with the absence of a parental psychiatric history increased the risk of externalizing but not internalizing problems following chronic stress. Conversely, low basal cortisol combined with a substantial parental psychiatric history increased the risk of internalizing but not externalizing problems following chronic stress. Thus, parental psychiatric history moderated stress- cortisol interactions in predicting psychopathology, but in a different direction than hypothesized. We conclude that the premise that basal cortisol indicates context sensitivity may be too crude. Context sensitivity may not be a general trait but may depend on the nature of the context (e.g., type or duration of stress exposure) and on the outcome of interest (e.g., internalizing vs. externalizing problems). Although consistent across informants, our findings need replication.

Autonomic and Adrenocortical Interactions Predict Mental Health in Late Adolescence: The TRAILS Study.

The present study is informed by the theory of allostatic load to examine how multiple stress responsive biomarkers are related to mental health outcomes. Data are from the TRAILS study, a large prospective population study of 715 Dutch adolescents (50.9 % girls), assessed at 16.3 and 19.1 years. Reactivity measures of the hypothalamic pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) biomarkers (heart rate, HR; respiratory sinus arrhythmia, RSA; and pre-ejection period, PEP) to a social stress task were used to predict concurrent and longitudinal changes in internalizing and externalizing symptoms. Hierarchical linear modeling revealed relatively few single effects for each biomarker with the exception that high HR reactivity predicted concurrent internalizing problems in boys. More interestingly, interactions were found between HPA-axis reactivity and sympathetic and parasympathetic reactivity. Boys with high HPA reactivity and low RSA reactivity had the largest increases in internalizing problems from 16 to 19 years. Youth with low HPA reactivity along with increased ANS activation characterized by both decreases in RSA and decreases in PEP had the most concurrent externalizing problems, consistent with broad theories of hypo-arousal. Youth with high HPA reactivity along with increases in RSA but decreases in PEP also had elevated concurrent externalizing problems, which increased over time, especially within boys. This profile illustrates the utility of examining the parasympathetic and sympathetic components of the ANS which can act in opposition to one another to achieve, overall, stress responsivity. The framework of allostasis and allostatic load is supported in that examination of multiple biomarkers working together in concert was of value in understanding mental health problems concurrently and longitudinally. Findings argue against an additive panel of risk and instead illustrate the dynamic interplay of stress physiology systems.

Phenotypic programming as a distal cause of resilience.

During early childhood, individuals with high sensitivity to early programming adjust their phenotype in a way that is expected to be adaptive in their later environment. These adaptations are hypothesized to result in resilience in environments that match the early environment. As appraisal style is a putative target of adaptive programming, early experiences could be a distal cause of resilience.

Adolescent personality: associations with Basal, awakening, and stress-induced cortisol responses.

The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n = 343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the association between facets of Neuroticism, Extraversion, and Conscientiousness and basal cortisol, the cortisol awakening response (CAR), and four measures of stress-induced HPA-axis activity. Basal cortisol levels were related to facets of all three personality traits. The CAR and stress-induced cortisol were not related to personality. Possibly due to its more trait-like nature, basal cortisol seems more informative than stress-induced cortisol when investigating trait-like characteristics such as personality facets.

Childhood adversities and adolescent depression: a matter of both risk and resilience.

Childhood adversities have been proposed to modify later stress sensitivity and risk of depressive disorder in several ways: by stress sensitization, stress amplification, and stress inoculation. Combining these models, we hypothesized that childhood adversities would increase risk of early, but not later, onsets of depression (Hypothesis 1). In those without an early onset, childhood adversities were hypothesized to predict a relatively low risk of depression in high-stress conditions (Hypothesis 2a) and a relatively high risk of depression in low-stress conditions (Hypothesis 2b), compared to no childhood adversities. These hypotheses were tested in 1,584 participants of the Tracking Adolescents' Individual Lives Survey, a prospective cohort study of adolescents. Childhood adversities were assessed retrospectively at ages 11 and 13.5, using self-reports and parent reports. Lifetime DSM-IV major depressive episodes were assessed at age 19, by means of the Composite International Diagnostic Interview. Stressful life events during adolescence were established using interview-based contextual ratings of personal and network events. The results provided support for all hypotheses, regardless of the informant and timeframe used to assess childhood adversities and regardless of the nature (personal vs. network, dependent vs. independent) of recent stressful events. These findings suggest that age at first onset of depression may be an effective marker to distinguish between various types of reaction patterns.

A test of the vulnerability model: temperament and temperament change as predictors of future mental disorders - the TRAILS study.

BACKGROUND: This study aimed to test the vulnerability model of the relationship between temperament and mental disorders using a large sample of adolescents from the TRacking Adolescents Individual Lives' Survey (TRAILS). The vulnerability model argues that particular temperaments can place individuals at risk for the development of mental health problems. Importantly, the model may imply that not only baseline temperament predicts mental health problems prospectively, but additionally, that changes in temperament predict corresponding changes in risk for mental health problems. METHODS: Data were used from 1195 TRAILS participants. Adolescent temperament was assessed both at age 11 and at age 16. Onset of mental disorders between age 16 and 19 was assessed at age 19, by means of the World Health Organization Composite International Diagnostic Interview (WHO CIDI). RESULTS: Results showed that temperament at age 11 predicted future mental disorders, thereby providing support for the vulnerability model. Moreover, temperament change predicted future mental disorders above and beyond the effect of basal temperament. For example, an increase in frustration increased the risk of mental disorders proportionally. CONCLUSION: This study confirms, and extends, the vulnerability model. Consequences of both temperament and temperament change were general (e.g., changes in frustration predicted both internalizing and externalizing disorders) as well as dimension specific (e.g., changes in fear predicted internalizing but not externalizing disorders). These findings confirm previous studies, which showed that mental disorders have both unique and shared underlying temperamental risk factors.

Mismatch or cumulative stress: the pathway to depression is conditional on attention style.

In the study reported here, the main question we investigated was whether attention style could be a conditional adaptation. We organized participants of the TRacking Adolescents' Individual Lives Survey (TRAILS; N = 2,230) into shifters, sustainers, and two comparison groups, depending on their performance on a shifting- and a sustained-attention task at age 11 years. Compared with sustainers, shifters reported more pre- and perinatal risk factors and more childhood stress, and they adopted a faster life-history strategy. These differences were not found between the comparison groups, who performed well or poorly on both tasks, which suggests that specialization for either sustained or shifting attention is the key to conditional adaptation. In a subsample (n = 860), we found that stress did not increase depression risk in shifters, whereas a mismatch between early and recent stress predicted depression in sustainers. Cumulative stress predicted depression in the comparison group. These results suggest that shifters retain high levels of plasticity throughout life, whereas sustainers' adapted their phenotype early in life to the expected mature environment.

Stressful events and psychological difficulties: testing alternative candidates for sensitivity.

The current study investigated the longitudinal, reciprocal associations between stressful events and psychological difficulties from early childhood to mid-adolescence. Child age, sex, prenatal maternal anxiety, and difficult temperament were tested as sources of sensitivity, that is, factors that may make children more sensitive to stressful life events. Analyses were based on data from 10,417 children from a prospective, longitudinal study of child development. At ages 4, 7, 9, 11, and 16 years, stressful events and psychological difficulties were measured. Prenatal anxiety was measured at 32 weeks of gestation and difficult temperament was measured at 6 months. Children exposed to stressful events showed significantly increased psychological difficulties at ages 7 and 11 years; there was consistent evidence of a reciprocal pattern: psychological difficulties predicted stressful events at each stage. Analyses also indicated that the associations between stressful events and psychological difficulties were stronger in girls than in boys. We found no evidence for the hypothesis that prenatal anxiety or difficult temperament increased stress sensitivity, that is, moderated the link between life events and psychological difficulties. The findings extend prior work on stress exposure and psychological difficulties and highlight the need for additional research to investigate sources of sensitivity and the mechanisms that might underlie differences in sensitivity to stressful events.

Anhedonia and depressed mood in adolescence: course, stability, and reciprocal relation in the TRAILS study.

Adolescence is marked by increases in the incidence of major depression (MDD), a disorder recognized as one of the leading causes of disability. Anhedonia and depressed mood predict both onset and chronicity of major depression (MDD), but have never been studied together longitudinally in the general adolescent population. The present study examined (1) the course and the stability of anhedonia and depressed mood and (2) their cross-sectional and longitudinal relations during adolescence. The study cohort consisted of 2,230 adolescents. Anhedonia and depressed mood were assessed with items of the YSR and ASR self-report forms at four measurement waves between ages 11 and 19. The proportion of adolescents reporting anhedonia decreased between ages 11 and 19, while the proportion of female adolescents reporting depressed mood increased. The stability of anhedonia and the cross-sectional association between anhedonia and depressed mood was larger at age 19 than at age 11. We found a mutual association between anhedonia and depressed mood without a clear temporal sequence. The presence of anhedonia at the end of adolescence might put adolescents at increased risk for MDD given the increasingly stronger stability and association with depressed mood. This suggests that it becomes more difficult to prevent MDD during late adolescence compared with early and middle adolescence.

Effects of family cohesion and heart rate reactivity on aggressive/rule-breaking behavior and prosocial behavior in adolescence: the Tracking Adolescents' Individual Lives Survey study.

The biological sensitivity to context hypothesis posits that high physiological reactivity (i.e., increases in arousal from baseline) constitutes heightened sensitivity to environmental influences, for better or worse. To test this hypothesis, we examined the interactive effects of family cohesion and heart rate reactivity to a public speaking task on aggressive/rule-breaking and prosocial behavior in a large sample of adolescents (N = 679; M age = 16.14). Multivariate analyses revealed small- to medium-sized main effects of lower family cohesion and lower heart rate reactivity on higher levels of aggressive/rule-breaking and lower levels of prosocial behavior. Although there was some evidence of three-way interactions among family cohesion, heart rate reactivity, and sex in predicting these outcome variables, these interactions were not in the direction predicted by the biological sensitivity to context hypothesis. Instead, heightened reactivity appeared to operate as a protective factor against family adversity, rather than as a susceptibility factor. The results of the present study raise the possibility that stress reactivity may no longer operate as a mechanism of differential susceptibility in adolescence.