Damion J. Grasso

Brain-Derived Neurotrophic Factor-5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children

BACKGROUND Child abuse and genotype interact to contribute to risk for depression in children. This study examined gene-by-gene and gene-by-environment interactions. METHODS The study included 196 children: 109 maltreated and 87 nonmaltreated comparison subjects. Measures of psychiatric symptomatology and social supports were obtained using standard research instruments, and serotonin transporter (5-HTTLPR) (locus SLC6A4) and brain-derived neurotrophic factor (BDNF) (variant val66met) genotypes were obtained from saliva-derived DNA specimens. Population structure was controlled by means of ancestral proportion scores computed based on genotypes of ancestry informative markers in the entire sample. RESULTS There was a significant three-way interaction between BDNF genotype, 5-HTTLPR, and maltreatment history in predicting depression. Children with the met allele of the BDNF gene and two short alleles of 5-HTTLPR had the highest depression scores, but the vulnerability associated with these two genotypes was only evident in the maltreated children. A significant four-way interaction also emerged, with social supports found to further moderate risk for depression. CONCLUSIONS To the best of our knowledge, this is the first investigation to demonstrate a gene-by-gene interaction conveying vulnerability to depression. The current data also show a protective effect of social supports in ameliorating genetic and environmental risk for psychopathology.

Poly-victimization among juvenile justice-involved youths

OBJECTIVES This study replicates and extends the research literature on poly-victimization with a vulnerable and under-served population, juvenile justice-involved youths. METHODS N=1959, 10-16 year old youths (76% male; 74% youth of color) consecutively newly admitted to juvenile detention facilities completed psychometric measures of trauma history, posttraumatic stress, affect regulation, alcohol/drug use, suicide risk, and somatic complaints. RESULTS Using latent class analysis derived from 19 types of adversity, three unique classes best fit the data. A poly-victim class (49% female, 51% youth of color) accounted for 5% of the sample and reported a mean of 11.4 (SD=1.1) types. A relatively moderate adversity class (31% female, 70% youth of color) accounted for 36% of the sample and reported a mean of 8.9 (SD=0.3) types of adversity and 2.65 (SD=1.1) types of traumatic adversity. A low adversity class (59% of the sample; 17% female, 78% youth of color) reported a mean of 7.4 (SD=0.4) adversity types but only 0.3 (SD=0.45) types of traumatic adversity. The relatively moderate adversity class was comparable to poly-victims in endorsing extensive non-victimization traumatic adversity (e.g., accidental and loss trauma), but poly-victims were distinct from both moderate and low adversity class members in the likelihood of reporting all but one type of traumatic victimization, multiple types of traumatic victimization, and severe emotional and behavioral problems. Girls were at particularly high risk of poly-victimization, and African American and White youths also were at risk for poly-victimization. CONCLUSIONS Although youth involved in the juvenile justice system typically have experienced substantial victimization, a poly-victimized sub-group, especially (but not exclusively) girls, warrants particular scientific, clinical, and rehabilitative attention in order to address the most severe behavioral and mental health problems and risks faced by this vulnerable population.

An Open-Label Study of Guanfacine Extended Release for Traumatic Stress Related Symptoms in Children and Adolescents

OBJECTIVE The purpose of this open-label pilot study was to investigate the effectiveness and tolerability of guanfacine extended release (GXR) 1-4 mg given in the evening, on the symptoms of traumatic stress (reexperiencing, avoidance, overarousal), generalized anxiety, and functional impairment in children and adolescents with a history of traumatic stress with or without posttraumatic stress disorder (PTSD). As many of our sample had associated attention-deficit/hyperactivity disorder (ADHD) symptoms, we also assessed whether the presence of traumatic stress symptoms impaired the effectiveness of GXR in the treatment of comorbid ADHD symptoms. METHODS Participants were 19 children and adolescents 6-18 years of age, with current traumatic stress symptoms. In an 8 week open-label design, each patients scores on parent-, child-, and clinician-reported symptom rating scales assessing traumatic stress symptoms, generalized anxiety, ADHD symptoms, functional impairment, and global symptom severity and improvement (n=17) were evaluated off and on GXR using χ(2) goodness-of-fit tests, paired t tests, and repeated measures analyses of variance (ANOVAs). To examine patterns of change in outcome measures across treatment, MPlus software was used to conduct linear growth curves modeled with individual-varying times of observation (i.e., random slopes). RESULTS Using an average GXR daily dose of 1.19 mg±0.35 mg and an average weight-adjusted daily dose of 0.03 mg/kg±0.01 mg/kg, significant differences were found on all symptom severity measures. Parent reported UCLA Reaction Index scores assessing cluster B (reexperiencing), C (avoidant), and D (overarousal) symptoms significantly improved. In the presence of PTSD symptoms, children with ADHD experienced significantly improved ADHD symptom scores, suggesting that comorbidity does not attenuate an ADHD symptom response to GXR therapy. Medication was generally well tolerated. CONCLUSIONS Within the limits of an open-label, hypothesis-generating pilot study, our results suggest that the α2A-adrenoceptor agonist GXR may have therapeutic effects in the treatment of PTSD symptoms in traumatically stressed children and adolescents. The effective dose may be lower than that found for ADHD. Our pilot study supports the need for further controlled research on the effects of GXR and other α2A-adrenoceptor agonists in pediatric disorders of traumatic stress.

Early Life Trauma Exposure and Stress Sensitivity in Young Children

OBJECTIVE The current study replicates and extends work with adults that highlights the relationship between trauma exposure and distress in response to subsequent, nontraumatic life stressors. METHODS The sample included 213 2-4-year-old children in which 64.3% had a history of potential trauma exposure. Children were categorized into 4 groups based on trauma history and current life stress. RESULTS In a multivariate analysis of variance, trauma-exposed children with current life stressors had elevated internalizing and externalizing problems compared with trauma-exposed children without current stress and nontrauma-exposed children with and without current stressors. The trauma-exposed groups with or without current stressors did not differ on posttraumatic stress disorder symptom severity. Accounting for number of traumatic events did not change these results. CONCLUSIONS These findings suggest that early life trauma exposure may sensitize young children and place them at risk for internalizing or externalizing problems when exposed to subsequent, nontraumatic life stressors.

Olfactory Discrimination and Transient Mood Change in Young Men and Women: Variation by Season, Mood State, and Time of Day

Odor performance varies by clinical state and gender, though little is known about its variation by season or time of day. Many odors, including lavender, induce transient mood changes. This study explored discrimination differences between various lavender oil blends and their effects on transient mood in the morning and evening in depressed and nondepressed adults. We also determined seasonal influences on these measures. A total of 169 subjects, 98 women and 71 men (mean age ± SD, 19.3 ± 1.6 y) participated, with different subjects studied at different times of the year. The Beck Depression Inventory (BDI) classified subjects as depressed (score ≥10; N = 57) or nondepressed (score <10; N = 112). In the discrimination test, subjects compared pairs of two different lavender oil blends or a control. Transient change in mood was assessed by the Profile of Mood States (POMS) after each trial of five lavender blends interspersed by three control odors. Tests were conducted in the morning (08:00–10:00 h) and evening (18:00–20:00 h). In all subjects, discrimination was significantly better for some odor pairs than for others, thus demonstrating test specificity. Discrimination was better overall in the fall than winter/spring and better in depressed than nondepressed subjects for specific odor pairs. No significant gender or time-of-day differences in discriminability were detected. There were, however, significant group differences in transient mood profiles. Current depressed state affected mood response, with lavender increasing anger in depressed subjects only. In addition, depressed subjects and men, whether or not depressed, exhibited diurnal mood variation, with better mood in the evening; the former group also showed more evening energy. All subjects were more confused in the morning than evening. Season also affected transient mood; winter/spring-tested subjects reported more vigor than fall-tested subjects. In addition, summer-tested subjects showed more tension in the morning, whereas fall-tested subjects showed the opposite pattern in the evening. In all subjects, lavender increased fatigue, tension, confusion, and total mood disturbance, and it decreased vigor. The study showed that both chronobiological (seasonal and time-of-day) and clinical factors modify discrimination and mood response to odors. Brief lavender odor presentation may serve as a nonphotic method for altering mood in young depressed and nondepressed adults particularly during the fall, a time of heightened discriminability.

Developmental patterns of adverse childhood experiences and current symptoms and impairment in youth referred for trauma-specific services

By the time children reach adolescence, most have experienced at least one type of severe adversity and many have been exposed to multiple types. However, whether patterns of adverse childhood experiences are consistent or change across developmental epochs in childhood is not known. Retrospective reports of adverse potentially traumatic childhood experiences in 3 distinct developmental epochs (early childhood, 0- to 5-years-old; middle childhood, 6- to 12-years-old; and adolescence, 13- to 18-years-old) were obtained from adolescents (N = 3485) referred to providers in the National Child Traumatic Stress Network (NCTSN) for trauma-focused assessment and treatment. Results from latent class analysis (LCA) revealed increasingly complex patterns of adverse/traumatic experiences in middle childhood and adolescence compared to early childhood. Depending upon the specific developmental epoch assessed, different patterns of adverse/traumatic experiences were associated with gender and with adolescent psychopathology (e.g., internalizing/externalizing behavior problems), and juvenile justice involvement. A multiply exposed subgroup that had severe problems in adolescence was evident in each of the 3 epochs, but their specific types of adverse/traumatic experiences differed depending upon the developmental epoch. Implications for research and clinical practice are identified.

Seeing the silver lining: potential benefits of trauma exposure in college students

Abstract In the current study we compare college students exposed to a potentially traumatic event (PTE) meeting self-report criteria for Posttraumatic Stress Disorder (PTSD), PTE-exposed students not meeting criteria for PTSD, and non-exposed students on measures of perceived social support, self-esteem, and optimism (i.e., personal resources) and report use of specific coping strategies. Results indicate that the PTE-exposed/probable PTSD group reported fewer personal resources, greater use of avoidance-focused coping, and less use of approach-focused coping than the other two groups. The PTE-exposed/no PTSD group reported greater perceived social support and less use of avoidance-focused coping than the non-exposed group. We discuss the findings’ implications for the prevention and treatment of trauma-related psychopathology.

Patterns of multiple victimization among maltreated children in navy families

The current study examined the cumulative risk associated with childrens exposure to multiple types of parent-inflicted victimization. The sample was comprised of 195 children who were 7 to 17 years old (64.1% female and 48.2% non-White) at the time of referral to the United States Navys Family Advocacy Program due to allegations of sexual abuse, physical abuse, or parental intimate partner violence. We conducted an exploratory latent class analysis to identify distinct subgroups of children based on lifetime victimization. We hypothesized that at least 2 classes or subgroups would be identified, with 1 characterized by greater victimization and poorer outcomes. Results indicated that 3 classes of children best fit the data: (a) high victimization across all 3 categories, (b) high rates of physical abuse and witnessing intimate partner violence, and (c) high rates of physical abuse only. Findings indicated that the high victimization class was at greatest risk for alcohol and substance use, delinquent behavior, and meeting criteria for posttraumatic stress disorder (PTSD) and/or depression 1 year later (odds ratio = 4.53). These findings highlight the serious mental health needs of a small but significantly high-risk portion of multiply victimized children entering the child welfare system.

Perceived parental support predicts enhanced late positive event-related brain potentials to parent faces.

This study examined event-related brain potentials in college students viewing facial pictures of their parents, celebrities, and strangers in the context of a guessing task. A temporal principal component analysis of data obtained from midline electrode sites was used to extract a component reflecting the mid- to late-positive deflection observed between 200 and 500ms following stimulus onset. Parent faces elicited enhanced positivity compared to celebrity and stranger faces suggesting greater attention allocation to parent faces. In addition, greater perceived parental support predicted larger factor scores to parent faces relative to non-parent faces. Greater perceived negative interaction with parent, however, attenuated this relationship.

Electrophysiological Responses to Threat in Youth with and without Posttraumatic Stress Disorder

The current study was designed to examine event-related brain potentials and autonomic responses to pictures indicating threat, relative to non-threat, and acoustic startle reflexes in traumatized youth diagnosed with PTSD, relative to non-exposed children, before and after receiving psychotherapy. Children in the control group were individually yoked and demographically matched to the PTSD group. Both groups displayed enhanced late positive potentials and more prolonged heart rate deceleration to pictures indicating threat, relative to non-threat, and larger skin conductance responses to pictures indicating threat, relative to non-threat, at time one. At time two, controls appeared to habituate, as reflected by an overall attenuated skin conductance response, whereas the PTSD group showed little change. Across time points the PTSD group exhibited greater acoustic startle reflexes than the control group. Psychotherapy and symptom reduction was not associated with electrophysiology. Drawing from the adult literature, this study was an attempt to address the scarcity of research examining electrophysiological irregularities in childhood PTSD. The overall results suggest that children and adolescents allocate more attention to threat-related stimuli regardless of PTSD status, and exaggerated startle and a possible failure to habituate skin conductance responses to threat-related stimuli in youth with versus without PTSD.