Individual longitudinal changes in DNA-methylome identify signatures of early-life adversity and correlate with later outcome.

Adverse early-life experiences (ELA) affect a majority of the world's children. Whereas the enduring impact of ELA on cognitive and emotional health is established, there are no tools to predict vulnerability to ELA consequences in an individual child. Epigenetic markers including peripheral-cell DNA-methylation profiles may encode ELA and provide predictive outcome markers, yet the interindividual variance of the human genome and rapid changes in DNA methylation in childhood pose significant challenges. Hoping to mitigate these challenges we examined the relation of several ELA dimensions to DNA methylation changes and outcome using a within-subject longitudinal design and a high methylation-change threshold. DNA methylation was analyzed in buccal swab/saliva samples collected twice (neonatally and at 12 months) in 110 infants. We identified CpGs differentially methylated across time for each child and determined whether they associated with ELA indicators and executive function at age 5. We assessed sex differences and derived a sex-dependent 'impact score' based on sites that most contributed to methylation changes. Changes in methylation between two samples of an individual child reflected age-related trends and correlated with executive function years later. Among tested ELA dimensions and life factors including income to needs ratios, maternal sensitivity, body mass index and infant sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, high early-life unpredictability interacted with methylation changes to presage executive function. Thus, longitudinal, within-subject changes in methylation profiles may provide a signature of ELA and a potential predictive marker of individual outcome.

Single-Cell Transcriptional Changes in Hypothalamic Corticotropin-Releasing Factor-Expressing Neurons After Early-Life Adversity Inform Enduring Alterations in Vulnerabilities to Stress.

Background: Mental health and vulnerabilities to neuropsychiatric disorders involve the interplay of genes and environment, particularly during sensitive developmental periods. Early-life adversity (ELA) and stress promote vulnerabilities to stress-related affective disorders, yet it is unknown how transient ELA dictates lifelong neuroendocrine and behavioral reactions to stress. The population of hypothalamic corticotropin-releasing factor (CRF)-expressing neurons that regulate stress responses is a promising candidate to mediate the long-lasting influences of ELA on stress-related behavioral and hormonal responses via enduring transcriptional and epigenetic mechanisms. Methods: Capitalizing on a well-characterized model of ELA, we examined ELA-induced changes in gene expression profiles of CRF-expressing neurons in the hypothalamic paraventricular nucleus of developing male mice. We used single-cell RNA sequencing on isolated CRF-expressing neurons. We determined the enduring functional consequences of transcriptional changes on stress reactivity in adult ELA mice, including hormonal responses to acute stress, adrenal weights as a measure of chronic stress, and behaviors in the looming shadow threat task. Results: Single-cell transcriptomics identified distinct and novel CRF-expressing neuronal populations, characterized by both their gene expression repertoire and their neurotransmitter profiles. ELA-provoked expression changes were selective to specific subpopulations and affected genes involved in neuronal differentiation, synapse formation, energy metabolism, and cellular responses to stress and injury. Importantly, these expression changes were impactful, apparent from adrenal hypertrophy and augmented behavioral responses to stress in adulthood. Conclusions: We uncover a novel repertoire of stress-regulating CRF cell types differentially affected by ELA and resulting in augmented stress vulnerability, with relevance to the origins of stress-related affective disorders.

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.

Therapist-assisted online treatment for child conduct problems in rural and urban families: Two randomized controlled trials.

OBJECTIVE: We examined the relative efficacy of an online versus face-to-face (FTF) parenting intervention for reducing the severity of child conduct problems and related parent and child outcomes in 2 randomized controlled trials. METHOD: In Study 1, rural families (n = 133) with a child 3-9 years of age with a full or subclinical primary diagnosis of oppositional defiant or conduct disorder traveled to Sydney, Australia for a comprehensive assessment and randomization to receive either AccessEI, a 6-10 week online therapist-assisted parenting program, or FTF treatment, whereby they received the same program presented FTF during a 1-week treatment. To control for unavoidable treatment dosage differences in the first study, Study 2 was conducted in which urban families (n = 73) with a child aged 3 to 14 years meeting similar criteria as Study 1 were randomized to receive AccessEI versus FTF treatment. RESULTS: In both studies, improvements in severity of child diagnoses and maternal measures of child behavior showed very large effect sizes for both treatments at posttreatment and 3-month follow-up and did not differ across treatment conditions. There were moderate effect sizes for improvements in parent mental health and no differences across treatment conditions. CONCLUSIONS: It is concluded that the effects of the therapist-assisted online parenting interventions for the treatment of child conduct problems were similar to a FTF intervention, providing evidence for the effectiveness of an accessible treatment for rural and remote families. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Practice recommendations for addressing racism: A content analysis of the counseling psychology literature.

Although racism persists as a significant public health issue that adversely impacts the mental health of people of color (U.S. Department of Health and Human Service, 2001), there has been very little systematic guidance for mental health professionals to address racism through practice (S. Harrell, 2000). Therefore, we conducted a content analysis of the peer reviewed counseling psychology literature-the first of its kind-to provide a summary and critique of the extant practice recommendations and facilitate the development and enhancement of practice efforts aimed at addressing racism. We reviewed racism-related articles published in the Journal of Counseling Psychology, The Counseling Psychologist, and Counseling Psychology Quarterly and identified 73 relevant articles, of which 51 provided practice recommendations. Based on our review of this literature, we identified eight general categories of recommendations for addressing racism: psychoeducation, validation, self-awareness and critical consciousness, critical examination of privilege and racial attitudes, culturally responsive social support, developing positive identity, externalize/minimize self-blame, and outreach and advocacy. We found that most recommendations within each category were at the individual level with far fewer at the group and systemic level. A critique of recommendations is provided along with suggestions for developing and bolstering practice, research, and consultation efforts aimed at addressing racism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Gendered Racial Microaggressions Scale for Asian American Women: Development and initial validation.

Asian American women's (AAW's) mental health issues have received growing public attention; recent statistics suggest alarmingly high suicide rates among AAW. Yet, little research has examined the nuanced oppression that AAW face and the daily effects of compounded racism and sexism contributing to their mental health issues. Applying the intersectionality and microaggressions framework, we developed the Gendered Racial Microaggressions Scale for Asian American Women (GRMSAAW) using data collected from 564 AAW. Items were developed via literature review, focus group, and expert review. Exploratory (N = 304) and confirmatory (N = 260) factor analyses suggested a 4-factor structure and produced 22-item scales of frequency and stress appraisal with the following subscales: (a) Ascription of Submissiveness, (b) Assumption of Universal Appearance, (c) Asian Fetishism, and (d) Media Invalidation. Internal consistency estimates were .80 and above for frequency and stress appraisal scales, and the scales accounted for 52% and 60% of variance, respectively. Examination of a bifactor model containing one general factor and four group factors suggested that GRMSAAW could be represented unidimensionally (total scale score) for the purpose of applied measurement. Initial construct validity was established as GRMSAAW scores were associated with sexism, racial microaggressions, depressive symptoms, and internalized racism in ways consistent with theory. Implications for research and practice are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).