Elizabeth D. Handley

Developmental cascades: Linking adolescent substance use, affiliation with substance use promoting peers, and academic achievement to adult substance use disorders

Using a high-risk community sample (N = 405), the current study examined developmental cascades among substance use, affiliation with substance use promoting peers, and academic achievement over an 18-year period and tested whether these pathways mediated the influence of parental alcoholism on adult alcohol and drug use disorders. Results showed that the influence of parental alcoholism on adult drug disorders was mediated by developmental cascades across all three domains, whereas the influence of parental alcoholism on adult alcohol disorders was mediated through affiliation with substance use promoting peers and persistence in binge drinking. Adolescent drug use had more implications for adult outcomes than did adolescent alcohol use, which was less likely to spill over into other domains of functioning. Findings indicated that adolescent risk factors had indirect rather than unique effects on adult substance use disorders, suggesting that adolescent risk is not immutable and is largely mediated by later influences.

Parents and families as contexts for the development of substance use and substance use disorders.

Parenting and familial influences on substance use and substance use disorders (SUDs) are important areas of study both for theories of etiology and for the development of preventive and treatment interventions. The articles in this special section illustrate both the value and the challenges of studying parenting and familial influences. Noteworthy issues include the need for mediational and moderational models examining the processes by which familial influences operate in a longitudinal framework to consider outcomes in a developmental context. Future directions include a multidisciplinary expansion of these studies.

Child maltreatment, inflammation, and internalizing symptoms: Investigating the roles of C-reactive protein, gene variation, and neuroendocrine regulation.

Prior research has found inconsistent evidence regarding the association among childhood adversity, inflammation, and internalizing symptoms, perhaps because previous studies have yet to adequately integrate important factors such as the timing of the adversity, genetic variation, and other relevant processes such as neuroendocrine regulation. The aims of the present study were threefold: (a) to determine whether the effect of the timing of child maltreatment on C-reactive protein (CRP), an inflammatory marker, varies by CRP gene variation; (b) to explore whether links between salivary CRP and childhood internalizing symptoms depend on the presence and timing of maltreatment experiences; and (c) to investigate the role of CRP in the relations between child neuroendocrine regulation and internalizing symptoms and examine whether these associations are moderated by the presence and timing of child maltreatment. Participants included a sample of 267 maltreated and 222 nonmaltreated children (M age = 9.72, SD = 0.99; 52.4% male; 66% African American) who attended a summer day camp research program designed for school-aged low-income children. Department of Human Services records were examined to determine the onset and recency of maltreatment for children in the maltreated group. The results indicated that among children with recent onset maltreatment, those with at least one A allele from CRP single nucleotide polymorphism rs1417938 evidenced significantly higher CRP levels compared to recently maltreated children carrying the TT genotype. Moreover, higher levels of CRP were associated with higher levels of internalizing symptoms only for recently maltreated children. Finally, we did not find support for salivary CRP as a mechanism in the relation between neuroendocrine regulation and childhood internalizing symptoms. Our findings highlight the importance of the timing of child maltreatment and have important implications for characterizing variability in inflammation and internalizing symptoms among youth.

Genetic moderation of interpersonal psychotherapy efficacy for low-income mothers with major depressive disorder: Implications for differential susceptibility

Genetic moderation of interpersonal psychotherapy (IPT) efficacy for economically disadvantaged women with major depressive disorder was examined. Specifically, we investigated whether genotypic variation in corticotropin releasing hormone receptor 1 (CRHR1) and the linked polymorphic region of the serotonin transporter gene (5-HTTLPR) moderated effects of IPT on depressive symptoms over time. We also tested genotype moderation of IPT mechanisms on social adjustment and perceived stress. Non-treatment-seeking urban women at or below the poverty level with infants were recruited from the community (N = 126; M age = 25.33 years, SD = 4.99; 54.0% African American, 22.2% Caucasian, and 23.8% Hispanic/biracial) and randomized to individual IPT or Enhanced Community Standard groups. The results revealed that changes in depressive symptoms over time depended on both intervention group and genotypes (5-HTTLPR and CRHR1). Moreover, multiple-group path analysis indicated that IPT improved depressive symptoms, increased social adjustment, and decreased perceived stress at posttreatment among women with the 0 copies of the CRHR1 TAT haplotype only. Finally, improved social adjustment at postintervention significantly mediated the effect of IPT on reduced depressive symptoms at 8 months postintervention for women with 0 copies of the TAT haplotype only. Post hoc analyses of 5-HTTLPR were indicative of differential susceptibility, albeit among African American women only.

An investigation of child maltreatment and epigenetic mechanisms of mental and physical health risk.

In the present investigation, differential methylation analyses of the whole genome were conducted among a sample of 548 school-aged low-income children (47.8% female, 67.7% Black, M age = 9.40 years), 54.4% of whom had a history of child maltreatment. In the context of a summer research camp, DNA samples via saliva were obtained. Using GenomeStudio, Methylation Module, and the Illumina Custom Model, differential methylation analyses revealed a pattern of greater methylation at low methylation sites (n = 197 sites) and medium methylation sites (n = 730 sites) and less methylation at high methylation sites (n = 907 sites) among maltreated children. The mean difference in methylation between the maltreated and nonmaltreated children was 6.2%. The relative risk of maltreatment with known disease biomarkers was also investigated using GenoGo MetaCore Software. A large number of network objects previously associated with mental health, cancer, cardiovascular systems, and immune functioning were identified evidencing differential methylation among maltreated and nonmaltreated children. Site-specific analyses were also conducted for aldehyde dehydrogenase 2 (ALDH2), ankyrin repeat and kinase domain containing 1 (ANKK1), and nuclear receptor subfamily 3, group C, member 1 (NR3C1) genes, and the results highlight the importance of considering gender and the developmental timing of maltreatment. For ALDH2, the results indicated that maltreated girls evidenced significantly lower methylation compared to nonmaltreated girls, and maltreated boys evidenced significantly higher methylation compared to nonmaltreated boys. Moreover, early onset-not recently maltreated boys evidenced significantly higher methylation at ALDH2 compared to nonmaltreated boys. Similarly, children with early onset-nonrecent maltreatment evidenced significantly higher methylation compared to nonmaltreated children at ANKK1. The site-specific results were not altered by controlling for genotypic variation of respective genes. The findings demonstrate increased risk for adverse physical and mental health outcomes associated with differences in methylation in maltreated children and indicate differences among maltreated children related to developmental timing of maltreatment and gender in genes involved in mental health functioning.

Neighborhood disadvantage and adolescent substance use disorder: The moderating role of maltreatment

The ecological–transactional model proposes that nested contexts interact to influence development. From this perspective, child maltreatment represents an individual-level risk factor posited to interact with numerous other nested contextual levels, such as the neighborhood environment, to affect development. The aim of this study was to investigate whether adolescents with maltreatment histories represent a vulnerable group for whom disadvantaged neighborhoods confer risk for substance use disorders. Participants were 411 adolescents (age 15–18; mean age = 16.24) from an investigation of the developmental sequelae of childhood maltreatment. Multiple-group structural equation models, controlling for family-level socioeconomic status, indicated that neighborhood disadvantage was associated with more marijuana-dependence symptoms among maltreated but not among non-maltreated adolescents. Moreover, among maltreated adolescents, those who experienced multiple subtypes of maltreatment were at greatest risk for problematic marijuana use in the context of neighborhood disadvantage. Interestingly, the direct effect of neighborhood disadvantage, but not the interaction with maltreatment, was related to adolescent alcohol-dependence symptoms. Results highlight the importance of considering multiple levels of influence when examining risk associated with child maltreatment.

Developmental Trajectories of Substance Use among Sexual Minority Girls: Associations with Sexual Victimization and Sexual Health Risk

PURPOSE To examine mechanisms underlying the development of sexual health risk behaviors in sexual minority girls (SMGs) and its association with sexual victimization. METHODS Data were drawn from the Project on Human Development in Chicago Neighborhoods cohorts, aged 15 and 18 years (N = 391; 54 SMGs). RESULTS Sexual minority girls reported more sexual victimization and steeper positive trajectories of substance misuse over time than heterosexual girls. Growth in alcohol use during adolescence mediated the link between SMG status and past year number of partners, whereas growth in marijuana use mediated the link between SMG status and self-reported sexually transmitted diseases (STDs). Adding unwanted sexual experiences to the models resulted in a reduction of significance in the direct or indirect effects from SMG status on the sexual health outcomes. Unwanted sexual experiences emerged as a robust predictor directly and indirectly related to past-year number of partners via growth in alcohol use. Unwanted sexual experiences also directly predicted STD history. CONCLUSIONS The increased risk of SMGs for alcohol and marijuana during adolescence, higher rates of sexual partners, and STD diagnosis may also be linked to their significant risk for sexual victimization. Findings highlight the importance of preventive interventions targeting victimization of SMGs.

Self-Criticism as a Mechanism Linking Childhood Maltreatment and Maternal Efficacy Beliefs in Low-Income Mothers With and Without Depression

The primary aim of the current study was to examine self-criticism as a potential mechanism mediating the relation between mothers’ own childhood maltreatment history and changes in subsequent maternal efficacy beliefs in a diverse sample of low-income mothers with and without major depressive disorder. Longitudinal data were drawn from a larger randomized clinical trial evaluating the effectiveness of interpersonal psychotherapy for depression among low-income mothers and their 12-month-old infant. Results indicated that higher levels of maltreatment in childhood led mothers to hold more self-critical judgments in adulthood. Additionally, mothers who had experienced more extensive childhood maltreatment histories perceived themselves as less efficacious in their role as mother. Structural equation modeling indicated that self-criticism mediated the relationship between childhood maltreatment and mothers’ decreased perceived competency in her maternal role from when her child was an infant to the more demanding toddler years. Finally, this relationship held over and above the influence of mothers’ depressive diagnostic status. Directions for future research and the clinical implications of these findings are discussed.

Genome-wide DNA methylation in 1-year-old infants of mothers with major depressive disorder

A genome-wide methylation study was conducted among a sample of 114 infants (M age = 13.2 months, SD = 1.08) of low-income urban women with (n = 73) and without (n = 41) major depressive disorder. The Illumina HumanMethylation450 BeadChip array with a GenomeStudio Methylation Module and Illumina Custom model were used to conduct differential methylation analyses. Using the 5.0 × 10-7 p value, 2,119 loci were found to be significantly different between infants of depressed and nondepressed mothers. Infants of depressed mothers had greater methylation at low methylation sites (0%-29%) compared to infants of nondepressed mothers. At high levels of methylation (70%-100%), the infants of depressed mothers were predominantly hypomethylated. The mean difference in methylation between the infants of depressed and infants of nondepressed mothers was 5.23%. Disease by biomarker analyses were also conducted using GeneGo MetaCore Software. The results indicated significant cancer-related differences in biomarker networks such as prostatic neoplasms, ovarian and breast neoplasms, and colonic neoplasms. The results of a process networks analysis indicated significant differences in process networks associated with neuronal development and central nervous system functioning, as well as cardiac development between infants of depressed and nondepressed mothers. These findings indicate that early in development, infants of mothers with major depressive disorder evince epigenetic differences relative to infants of well mothers that suggest risk for later adverse health outcomes.

Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FK506 binding protein 5 gene ( FKBP5 )

The current study examined the prospective association between child maltreatment and the development of substance use disorder in adolescence with the aim of investigating pathways underlying this relation, as well as genetic moderation of these developmental mechanisms. Specifically, we tested whether youth who experienced maltreatment prior to age 8 were at risk for the development of marijuana dependence in adolescence by way of a childhood externalizing pathway and a childhood internalizing pathway. Moreover, we tested whether variation in FK506 binding protein 5 gene (FKBP5) CATT haplotype moderated these pathways. The participants were 326 children (n =179 maltreated; n = 147 nonmaltreated) assessed across two waves of data collection (childhood: ages 7-9 and adolescence: ages 15-18). Results indicated that higher levels of child externalizing symptoms significantly mediated the effect of child maltreatment on adolescent marijuana dependence symptoms for individuals with one or two copies of the FKBP5 CATT haplotype only. We did not find support for an internalizing pathway from child maltreatment to adolescent marijuana dependence, nor did we find evidence of moderation of the internalizing pathway by FKBP5 haplotype variation. Findings extend previous research by demonstrating that whether a maltreated child will traverse an externalizing pathway toward substance use disorder in adolescence is dependent on FKBP5 genetic variation.