Infant hedonic/anhedonic processing index (HAPI-Infant): Assessing infant anhedonia and its prospective association with adolescent depressive symptoms.

BACKGROUND: Anhedonia, an impairment in the motivation for or experience of pleasure, is a well-established transdiagnostic harbinger and core symptom of mental illness. Given increasing recognition of early life origins of mental illness, we posit that anhedonia should, and could, be recognized earlier if appropriate tools were available. However, reliable diagnostic instruments prior to childhood do not currently exist. METHODS: We developed an assessment instrument for anhedonia/reward processing in infancy, the Infant Hedonic/Anhedonic Processing Index (HAPI-Infant). Exploratory factor and psychometric analyses were conducted using data from 6- and 12-month-old infants from two cohorts (N = 188, N = 212). Then, associations were assessed between infant anhedonia and adolescent self-report of depressive symptoms. RESULTS: The HAPI-Infant (47-items), exhibited excellent psychometric properties. Higher anhedonia scores at 6 (r = 0.23, p < .01) and 12 months (r = 0.19, p < .05) predicted elevated adolescent depressive symptoms, and these associations were stronger than for established infant risk indicators such as negative affectivity. Subsequent analyses supported the validity of short (27-item) and very short (12-item) versions of this measure. LIMITATIONS: The primary limitations of this study are that the HAPI-Infant awaits additional tests of generalizability and of its ability to predict clinical diagnosis of depression. CONCLUSIONS: The HAPI-Infant is a novel, psychometrically strong diagnostic tool suitable for recognizing anhedonia during the first year of life with strong predictive value for later depressive symptoms. In view of the emerging recognition of increasing prevalence of affective disorders in children and adolescents, the importance of the HAPI-Infant in diagnosing anhedonia is encouraging. Early recognition of anhedonia could target high-risk individuals for intervention and perhaps prevention of mental health disorders.

Across ages and places: Unpredictability of maternal sensory signals and child internalizing behaviors.

BACKGROUND: Patterns of sensory inputs early in life play an integral role in shaping the maturation of neural circuits, including those implicated in emotion and cognition. In both experimental animal models and observational human research, unpredictable sensory signals have been linked to aberrant developmental outcomes, including poor memory and effortful control. These findings suggest that sensitivity to unpredictable sensory signals is conserved across species and sculpts the developing brain. The current study provides a novel investigation of unpredictable maternal sensory signals in early life and child internalizing behaviors. We tested these associations in three independent cohorts to probe the generalizability of associations across continents and cultures. METHOD: The three prospective longitudinal cohorts were based in Orange, USA (n = 163, 47.2 % female, Mage = 1 year); Turku, Finland (n = 239, 44.8 % female, Mage = 5 years); and Irvine, USA (n = 129, 43.4 % female, Mage = 9.6 years). Unpredictability of maternal sensory signals was quantified during free-play interactions. Child internalizing behaviors were measured via parent report (Orange & Turku) and child self-report (Irvine). RESULTS: Early life exposure to unpredictable maternal sensory signals was associated with greater child fearfulness/anxiety in all three cohorts, above and beyond maternal sensitivity and sociodemographic factors. The association between unpredictable maternal sensory signals and child sadness/depression was relatively weaker and did not reach traditional thresholds for statistical significance. LIMITATIONS: The correlational design limits our ability to make causal inferences. CONCLUSIONS: Findings across the three diverse cohorts suggest that unpredictable maternal signals early in life shape the development of internalizing behaviors, particularly fearfulness and anxiety.

Reliability of ordinal outcomes in forensic black-box studies.

Forensic science disciplines such as latent print examination, bullet and cartridge case comparisons, and shoeprint analysis, involve subjective decisions by forensic experts throughout the examination process. Most of the decisions involve ordinal categories. Examples include a three-category outcome for latent print comparisons (exclusion, inconclusive, identification) and a seven-category outcome for footwear comparisons (exclusion, indications of non-association, inconclusive, limited association of class characteristics, association of class characteristics, high degree of association, identification). As the results of the forensic examinations of evidence can heavily influence the outcomes of court proceedings, it is important to assess the reliability and accuracy of the underlying decisions. "Black box" studies are the most common approach for assessing the reliability and accuracy of subjective decisions. In these studies, researchers produce evidence samples consisting of a sample of questioned source and a sample of known source where the ground truth (same source or different source) is known. Examiners provide assessments for selected samples using the same approach they would use in actual casework. These studies often have two phases; the first phase comprises of decisions on samples of varying complexities by different examiners, and the second phase involves repeated decisions by the same examiner on a (usually) small subset of samples that were encountered by examiners in the first phase. We provide a statistical method to analyze ordinal decisions from black-box trials with the objective of obtaining inferences for the reliability of these decisions and quantifying the variation in decisions attributable to the examiners, the samples, and statistical interaction effects between examiners and samples. We present simulation studies to judge the performance of the model on data with known parameter values and apply the model to data from a handwritten signature complexity study, a latent fingerprint examination black-box study, and a handwriting comparisons black-box study.

Experiences of COVID-19-Related Racism and Impact on Depression Trajectories Among Racially/Ethnically Minoritized Adolescents.

PURPOSE: In 2020, racially/ethnically minoritized (REMD) youth faced the "dual pandemics" of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic). METHODS: A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%). RESULTS: REMD adolescents' depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date. DISCUSSION: REMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth.

Within-subject changes in methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome.

Background: Adverse early-life experiences (ELA), including poverty, trauma and neglect, affect a majority of the world's children. Whereas the impact of ELA on cognitive and emotional health throughout the lifespan is well-established, it is not clear how distinct types of ELA influence child development, and there are no tools to predict for an individual child their vulnerability or resilience to the consequences of ELAs. Epigenetic markers including DNA-methylation profiles of peripheral cells may encode ELA and provide a predictive outcome marker. However, the rapid dynamic changes in DNA methylation in childhood and the inter-individual variance of the human genome pose barriers to identifying profiles predicting outcomes of ELA exposure. Here, we examined the relation of several dimensions of ELA to changes of DNA methylation, using a longitudinal within-subject design and a high threshold for methylation changes in the hope of mitigating the above challenges. Methods: We analyzed DNA methylation in buccal swab samples collected twice for each of 110 infants: neonatally and at 12 months. We identified CpGs differentially methylated across time, calculated methylation changes for each child, and determined whether several indicators of ELA associated with changes of DNA methylation for individual infants. We then correlated select dimensions of ELA with methylation changes as well as with measures of executive function at age 5 years. We examined for sex differences, and derived a sex-dependent 'impact score' based on sites that most contributed to the methylation changes. Findings: Setting a high threshold for methylation changes, we discovered that changes in methylation between two samples of an individual child reflected age-related trends towards augmented methylation, and also correlated with executive function years later. Among the tested factors and ELA dimensions, including income to needs ratios, maternal sensitivity, body mass index and sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, an interaction was observed between a measure of high early-life unpredictability and methylation changes, in presaging executive function. Interpretation: These findings establish longitudinal, within-subject changes in methylation profiles as a signature of some types of ELA in an individual child. Notably, such changes are detectable beyond the age-associated DNA methylation dynamics. Future studies are required to determine if the methylation profile changes identified here provide a predictive marker of vulnerabilities to poorer cognitive and emotional outcomes.

Exposure to unpredictability and mental health: Validation of the brief version of the Questionnaire of Unpredictability in Childhood (QUIC-5) in English and Spanish.

Unpredictability is increasingly recognized as a primary dimension of early life adversity affecting lifespan mental health trajectories; screening for these experiences is therefore vital. The Questionnaire of Unpredictability in Childhood (QUIC) is a 38-item tool that measures unpredictability in childhood in social, emotional and physical domains. The available evidence indicates that exposure to unpredictable experiences measured with the QUIC predicts internalizing symptoms including depression and anxiety. The purpose of the present study was to validate English and Spanish brief versions (QUIC-5) suitable for administration in time-limited settings (e.g., clinical care settings, large-scale epidemiological studies). Five representative items were identified from the QUIC and their psychometric properties examined. The predictive validity of the QUIC-5 was then compared to the QUIC by examining mental health in four cohorts: (1) English-speaking adult women assessed at 6-months postpartum (N = 116), (2) English-speaking male veterans (N = 95), (3) English-speaking male and female adolescents (N = 155), and (4) Spanish-speaking male and female adults (N = 285). The QUIC-5 demonstrated substantial variance in distributions in each of the cohorts and is correlated on average 0.84 (r's = 0.81-0.87) with the full 38-item version. Furthermore, the QUIC-5 predicted internalizing symptoms (anxiety and depression) in all cohorts with similar effect sizes (r's = 0.16-0.39; all p's < 0.05) to the full versions (r's = 0.19-0.42; all p's < 0.05). In sum, the QUIC-5 exhibits good psychometric properties and is a valid alternative to the full QUIC. These findings support the future use of the QUIC-5 in clinical and research settings as a concise way to measure unpredictability, identify risk of psychopathology, and intervene accordingly.

Early life exposure to unpredictable parental sensory signals shapes cognitive development across three species.

Exposure to early life adversity has long term consequences on cognitive function. Most research has focused on understanding components of early life adversities that contribute to later risk, including poverty, trauma, maltreatment, and neglect. Whereas these factors, in the aggregate, explain a significant proportion of emotional and cognitive problems, there are serious gaps in our ability to identify potential mechanisms by which early life adversities might promote vulnerability or resilience. Here we discuss early life exposure to unpredictable signals from the caretaker as an understudied type of adversity that is amenable to prevention and intervention. We employ a translational approach to discover underlying neurobiological mechanisms by which early life exposure to unpredictable signals sculpts the developing brain. First, we review evidence that exposure to unpredictable signals from the parent during sensitive periods impacts development of neural circuits. Second, we describe a method for characterizing early life patterns of sensory signals across species. Third, we present published and original data illustrating that patterns of maternal care predict memory function in humans, non-human primates, and rodents. Finally, implications are discussed for identifying individuals at risk so that early preventive-intervention can be provided.

Towards a likelihood ratio approach for bloodstain pattern analysis.

In this work, we explore the application of likelihood ratio as a forensic evidence assessment tool to evaluate the causal mechanism of a bloodstain pattern. It is assumed that there are two competing hypotheses regarding the cause of a bloodstain pattern. The bloodstain patterns are represented as a collection of ellipses with each ellipse characterized by its location, size and orientation. Quantitative measures and features are derived to summarize key aspects of the patterns. A bivariate Gaussian model is chosen to estimate the distribution of features under a given hypothesis and thus approximate the likelihood of a pattern. Published data with 59 impact patterns and 55 gunshot patterns is used to train and evaluate the model. Results demonstrate the feasibility of the likelihood ratio approach for bloodstain pattern analysis. The results also hint at some of the challenges that need to be addressed for future use of the likelihood ratio approach for bloodstain pattern analysis.

A cross-species assay demonstrates that reward responsiveness is enduringly impacted by adverse, unpredictable early-life experiences.

Exposure to early-life adversity (ELA) is associated with several neuropsychiatric conditions, including major depressive disorder, yet causality is difficult to establish in humans. Recent work in rodents has implicated impaired reward circuit signaling in anhedonic-like behavior after ELA exposure. Anhedonia, the lack of reactivity to previously rewarding stimuli, is a transdiagnostic construct common to mental illnesses associated with ELA. Here, we employed an assay of reward responsiveness validated across species, the Probabilistic Reward Task (PRT). In the PRT, healthy participants reliably develop a response bias toward the more richly rewarded stimulus, whereas participants with anhedonia exhibit a blunted response bias that correlates with current and future anhedonia. In a well-established model of ELA that generates a stressful, chaotic, and unpredictable early-life environment, ELA led to blunted response biases in the PRT in two separate cohorts, recapitulating findings in humans with anhedonia. The same ELA rats had blunted sucrose preference, further supporting their anhedonic-like phenotypes. Probing the aspects of ELA that might provoke these deficits, we quantified the unpredictability of dam/pup interactions using entropy measures and found that the unpredictability of maternal care was significantly higher in the ELA groups in which PRT and sucrose preference reward deficits were present later in life. Taken together, these data position the PRT, established in clinical patient populations, as a potent instrument to assess the impact of ELA on the reward circuit across species. These findings also implicate the unpredictability of maternal signals during early life as an important driver of reward sensitivity deficits.

Prenatal maternal mood entropy is associated with child neurodevelopment.

Emerging evidence indicates that the predictability of signals early in life may influence the developing brain. This study examines links between a novel indicator of maternal mood dysregulation, mood entropy, and child neurodevelopmental outcomes. Associations between prenatal maternal mood entropy and child neurodevelopment were assessed in 2 longitudinal cohorts. Maternal mood was measured several times over pregnancy beginning as early as 15 weeks' gestation. Shannon's mood entropy was applied to distributions of mothers' responses on mood questionnaires. Child cognitive and language development were evaluated at 2 and 6-9 years of age. Higher prenatal maternal mood entropy was associated with lower cognitive development scores at 2 years of age and lower expressive language scores at 6-9 years of age. These associations persisted after adjusting for maternal pre and postnatal mood levels and for other relevant sociodemographic factors. Our findings identify maternal mood entropy as a novel predictor of child neurodevelopment. Characterizing components of maternal mood in addition to level of severity or valence may further our understanding of specific processes by which maternal mood shapes child development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Development and initial validation of self-report measures of general health, preoperative anxiety, and postoperative pain in young children using computer-administered animation.

BACKGROUND: For young children, existing measures of children's health-related quality of life must be parent-reported or interviewer-administered for those who cannot read or complete measures independently. Parents' and childrens' reports about the child's health have been shown to disagree. AIMS: (a) To test the reliability and validity of an animated, computer-administered Child Health Rating Inventories (CHRIS2.0) among children aged 4-12 undergoing surgery; and (b) to develop and test two CHRIS measures of preoperative anxiety and postoperative pain management. METHODS: We conducted a longitudinal cohort study of a diverse group of 542 children aged 4-12 undergoing surgery. We compared the CHRIS measures to Pediatric Quality of Life Inventory (PedsQL), the Functional Disabilities Inventory (FDI), State-Trait Anxiety Inventory for children (STAI-CH), and the Parent Postoperative Pain Measure (PPPM). RESULTS: Factor analyses supported the construct validity of the 12-item general physical health and the 8-item mental health CHRIS scales, as well as a composite 20-item scale, and the CHRIS preoperative anxiety and postoperative pain scales. Internal consistency reliability for all CHRIS scales exceeded the standard for group comparisons (Cronbach's α ≥0.70). The CHRIS general health composite was significantly correlated with composite PedsQL and FDI (r = 0.28, P < .001 and r = 0.43, P < .001, respectively). The CHRIS peri-operative anxiety measure was significantly correlated with the STAI-CH (r = 0.44, P < .001), as was the CHRIS postoperative pain scale with the PPPM (r = 0.52, P < .001). CONCLUSIONS: The CHRIS measures were reliable and valid in this diverse sample of young children (4-12). Because CHRIS measures are self-administered, scored in real time, and run on multiple different platforms, this approach provides a feasible method for the collection of health-related quality of life in young children and those with limited literacy. Our data indicate that this approach is psychometrically sound and has the potential for adding the child's voice to pediatric outcomes.

Why Temporal Persistence of Biometric Features, as Assessed by the Intraclass Correlation Coefficient, Is So Valuable for Classification Performance.

It is generally accepted that relatively more permanent (i.e., more temporally persistent) traits are more valuable for biometric performance than less permanent traits. Although this finding is intuitive, there is no current work identifying exactly where in the biometric analysis temporal persistence makes a difference. In this paper, we answer this question. In a recent report, we introduced the intraclass correlation coefficient (ICC) as an index of temporal persistence for such features. Here, we present a novel approach using synthetic features to study which aspects of a biometric identification study are influenced by the temporal persistence of features. What we show is that using more temporally persistent features produces effects on the similarity score distributions that explain why this quality is so key to biometric performance. The results identified with the synthetic data are largely reinforced by an analysis of two datasets, one based on eye-movements and one based on gait. There was one difference between the synthetic and real data, related to the intercorrelation of features in real data. Removing these intercorrelations for real datasets with a decorrelation step produced results which were very similar to that obtained with synthetic features.

Unpredictable maternal behavior is associated with a blunted infant cortisol response.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with poor physical and mental health. Early-life adversity may dysregulate cortisol response to subsequent stress. This study examines the association between patterns of maternal behavior and infant stress response to a challenge. Specifically, we test whether infant exposure to unpredictable maternal sensory signals is related to the cortisol response to a painful stressor. METHOD: Participants were 102 mothers and their children enrolled in a longitudinal study. Patterns of maternal sensory signals were evaluated at 6 and 12 months during a 10-min mother-infant play episode. Entropy rate was calculated as a quantitative measure of the degree of unpredictability of maternal sensory signals (visual, auditory, and tactile) exhibited during the play episode. Infant saliva samples were collected for cortisol analysis before and after inoculation at 12 months. RESULTS: Unpredictable patterns of maternal sensory signals were associated with a blunted infant cortisol response to a painful stressor. This relation persisted after evaluation of covariates including maternal sensitivity and maternal psychological distress. CONCLUSIONS: This study provides evidence that unpredictable patterns of maternal sensory signals are one process through which caregiving affects the function of infant stress response systems.

Optimally Balanced Gaussian Process Propensity Scores for Estimating Treatment Effects.

Propensity scores are commonly employed in observational study settings where the goal is to estimate average treatment effects. This paper introduces a flexible propensity score modeling approach, where the probability of treatment is modeled through a Gaussian process framework. To evaluate the effectiveness of the estimated propensity score, a metric of covariate imbalance is developed that quantifies the discrepancy between the distributions of covariates in the treated and control groups. It is demonstrated that this metric is ultimately a function of the hyperparameters of the covariance matrix of the Gaussian process and therefore it is possible to select the hyperparameters to optimize the metric and minimize overall covariate imbalance. The effectiveness of the GP method is compared in a simulation against other methods of estimating the propensity score and the method is applied to data from Dehejia and Wahba (1999) to demonstrate benchmark performance within a relevant policy application.

Across continents and demographics, unpredictable maternal signals are associated with children's cognitive function.

BACKGROUND: Early life experiences have persisting influence on brain function throughout life. Maternal signals constitute a primary source of early life experiences, and their quantity and quality during sensitive developmental periods exert enduring effects on cognitive function and emotional and social behaviors. Here we examined if, in addition to established qualitative dimensions of maternal behavior during her interactions with her infant and child, patterns of maternal signals may contribute to the maturation of children's executive functions. We focused primarily on effortful control, a potent predictor of mental health outcomes later in life. METHODS: In two independent prospective cohorts in Turku, Finland (N = 135), and Irvine, CA, USA (N = 192) that differed significantly in race/ethnicity and sociodemographic parameters, we assessed whether infant exposure to unpredictable patterns of maternal-derived sensory signals portended poor effortful control. OUTCOMES: In both the Irvine and Turku cohorts, unpredictable sequences of maternal behavior during infancy were associated with worse effortful control at one year of age. Longitudinal analyses demonstrated that this association persisted for as long as each cohort was assessed-until two years of age in the Turku cohort and to 9.5 years in the Irvine cohort. The relation of unpredictable maternal signals during infancy and the measures of executive function persisted after adjusting for covariates. INTERPRETATIONS: The consistency of our findings across two cohorts from different demographic backgrounds substantiated the finding that patterns, and specifically unpredictable sequences, of maternal behaviors may influence the development of executive functions which may be associated with vulnerability to subsequent psychopathology. FUND: This research was supported by the National Institutes of Health (NIH) awards P50MH096889, HD051852, NS041298, HD02413, HD050662, HD065823, and by the FinnBrain funders: Academy of Finland (129839, 134950, 253270, 286829, 287908, 308176, 308252), Jane and Aatos Erkko Foundation, Signe and Ane Gyllenberg Foundation, Yrjö Jahnsson Foundation, and State Research Grants (P3498, P3654).

Intra-individual methylomics detects the impact of early-life adversity.

Genetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an "epigenetic signature" of early-life experiences. Here, we used a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular metabolic enzymes, ion channels, and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate-related transcription factors, indicating their potential up-regulation. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth, and function.

Data and methods for studying commercial motor vehicle driver fatigue, highway safety and long-term driver health.

This article summarizes the recommendations on data and methodology issues for studying commercial motor vehicle driver fatigue of a National Academies of Sciences, Engineering, and Medicine study. A framework is provided that identifies the various factors affecting driver fatigue and relating driver fatigue to crash risk and long-term driver health. The relevant factors include characteristics of the driver, vehicle, carrier and environment. Limitations of existing data are considered and potential sources of additional data described. Statistical methods that can be used to improve understanding of the relevant relationships from observational data are also described. The recommendations for enhanced data collection and the use of modern statistical methods for causal inference have the potential to enhance our understanding of the relationship of fatigue to highway safety and to long-term driver health.

Measuring novel antecedents of mental illness: the Questionnaire of Unpredictability in Childhood.

Increasing evidence indicates that, in addition to poverty, maternal depression, and other well-established factors, unpredictability of maternal and environmental signals early in life influences trajectories of brain development, determining risk for subsequent mental illness. However, whereas most risk factors for later vulnerability to mental illness are readily measured using existing, clinically available tools, there are no similar measures for assessing early-life unpredictability. Here we validate the Questionnaire of Unpredictability in Childhood (QUIC) and examine its associations with mental health in the context of other indicators of childhood adversity (e.g., traumatic life events, socioeconomic status, and parenting quality). The QUIC was initially validated through administration to a cohort of adult females (N = 116) and then further refined in two additional independent cohorts (male Veterans, N = 95, and male and female adolescents, N = 175). The QUIC demonstrated excellent internal (α = 0.89) and test-retest reliability (r = 92). Scores on the QUIC were positively correlated with other prospective indicators of exposures to unpredictable maternal inputs in infancy and childhood (unpredictable maternal mood and sensory signals), and accuracy of recall also was confirmed with prospective data. Importantly, the QUIC predicted symptoms of anxiety, depression, and anhedonia in the three study cohorts, and these effects persisted after adjusting for other previously established risk factors. The QUIC, a reliable and valid self-report assessment of exposure to unpredictability in the social, emotional, and physical domains during early life, is a brief, comprehensive, and promising instrument for predicting risk for mental illness.

Does Anhedonia Presage Increased Risk of Posttraumatic Stress Disorder? : Adolescent Anhedonia and Posttraumatic Disorders.

Anhedonia, the reduced ability to experience pleasure, is a dimensional entity linked to multiple neuropsychiatric disorders, where it is associated with diminished treatment response, reduced global function, and increased suicidality. It has been suggested that anhedonia and the related disruption in reward processing may be critical precursors to development of psychiatric symptoms later in life. Here, we examine cross-species evidence supporting the hypothesis that early life experiences modulate development of reward processing, which if disrupted, result in anhedonia. Importantly, we find that anhedonia may confer risk for later neuropsychiatric disorders, especially posttraumatic stress disorder (PTSD). Whereas childhood trauma has long been associated with increased anhedonia and increased subsequent risk for trauma-related disorders in adulthood, here we focus on an additional novel, emerging direct contributor to anhedonia in rodents and humans: fragmented, chaotic environmental signals ("FRAG") during critical periods of development. In rodents, recent data suggest that adolescent anhedonia may derive from aberrant pleasure/reward circuit maturation. In humans, recent longitudinal studies support that FRAG is associated with increased anhedonia in adolescence. Both human and rodent FRAG exposure also leads to aberrant hippocampal function. Prospective studies are underway to examine if anhedonia is also a marker of PTSD risk. These preliminary cross-species studies provide a critical construct for future examination of the etiology of trauma-related symptoms in adults and for and development of prophylactic and therapeutic interventions. In addition, longitudinal studies of reward circuit development with and without FRAG will be critical to test the mechanistic hypothesis that early life FRAG modifies reward circuitry with subsequent consequences for adolescent-emergent anhedonia and contributes to risk and resilience to trauma and stress in adulthood.

Prenatal maternal mood patterns predict child temperament and adolescent mental health.

BACKGROUND: This study quantifies the dynamics of maternal mood focusing on unpredictability, and to assess if greater unpredictability of prenatal maternal mood predicts child temperament and internalizing symptoms through early adolescence. METHODS: The association between prenatal mood predictability and child internalizing symptoms were assessed in two longitudinal cohorts (N's = 227 and 180). Maternal mood was assessed repeatedly during pregnancy as early as 15 weeks' gestation. Predictability of maternal mood was calculated by applying Shannon's entropy to the distribution of responses on mood questionnaires. Maternal reports of child negative affectivity (a predictor of later internalizing) were collected at 6, 12, 24 months and 7 years of age. Child self-reports of anxiety symptoms were collected at 10 years and reports of depression symptoms at 13 years. RESULTS: Fetal exposure to more elevated maternal mood entropy predicted higher levels of child negative affectivity at 12 months (r = .36; p < 01), 24 months (r = .31; p < 01) and 7 years (r = .32; p < 01) of age. In addition, children exposed to higher prenatal maternal mood entropy, reported higher levels of anxiety symptoms at 10 years (r = .24; p < 01) and elevated depressive symptoms at 13 years (r = .29; p < .01). These associations persisted after adjusting for maternal pre and postnatal mood valence (e.g. depression levels) and for other relevant demographic characteristics. CONCLUSIONS: Our findings provide strong support for the notion that patterns of maternal mood influence the developing brain. More specifically, they suggest that prenatal maternal mood predictability may be a critical predictor of developmental mental health trajectories and should be considered when assessing early life influences on lifespan mental health.