Faculty Bibliography

Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety. Avoidance was initially conceived of as a two-factor learning process in which fear is first acquired through Pavlovian aversive conditioning (so-called fear conditioning), and then behaviors that reduce the fear aroused by the Pavlovian conditioned stimulus are reinforced through instrumental conditioning. Over the years, criticisms of both the avoidance paradigm and the two-factor fear theory arose. By the mid-1980s, avoidance had fallen out of favor as an experimental model relevant to fear and anxiety. However, recent progress in understanding the neural basis of Pavlovian conditioning has stimulated a new wave of research on avoidance. This new work has fostered new insights into contributions of not only Pavlovian and instrumental learning but also habit learning, to avoidance, and has suggested that the reinforcing event underlying the instrumental phase should be conceived in terms of cellular and molecular events in specific circuits rather than in terms of vague notions of fear reduction. In our approach, defensive reactions (freezing), actions (avoidance) and habits (habitual avoidance) are viewed as being controlled by unique circuits that operate nonconsciously in the control of behavior, and that are distinct from the circuits that give rise to conscious feelings of fear and anxiety. These refinements, we suggest, overcome older criticisms, justifying the value of the new wave of research on avoidance, and offering a fresh perspective on the clinical implications of this work.

BACKGROUND: The Multimodal Treatment Study (MTA) began as a 14-month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7-10 years of age) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type. It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as a local normative comparison group (LNCG), with assessments 2-16 years after baseline. METHODS: Primary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow-up, hypothesis-generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication. RESULTS: For ratings of symptom severity, the ADHD-LNCG comparison was statistically significant for the parent/self-report average (0.51 +/- 0.04, p < .0001, d = 1.11), documenting symptom persistence, and for the parent/self-report difference (0.21 +/- 0.04, p < .0001, d = .60), documenting source discrepancy, but the comparisons of naturalistic subgroups reflecting medication effects were not significant. For adult height, the ADHD group was 1.29 +/- 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 +/- 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 +/- 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38). CONCLUSIONS: In the MTA follow-up into adulthood, the ADHD group showed symptom persistence compared to local norms from the LNCG. Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity.

Caregivers of psychiatrically impaired children experience considerable parenting stress. However, no research has evaluated parenting stress within the context of pediatric bipolar spectrum disorders (BPSD). Thus, the aim of this investigation was to identify predictors and moderators of stress among caregivers in the Longitudinal Assessment of Manic Symptoms study. Participants included 640 children and their caregivers in the Longitudinal Assessment of Manic Symptoms cohort. Children had a mean age of 9.4 +/- 1.9 years (68% male, 23% BPSD); parents had a mean age of 36.5 +/- 8.3 years (84% mothers). Children with BPSD had more service utilization, psychiatric diagnoses, mood and anxiety symptoms, and functional impairment but fewer disruptive behavior disorders. Caregivers of children with BPSD were more likely than caregivers of children without BPSD to have a partner, elevated depressive symptoms, antisocial tendencies, and parenting stress (Cohen's d = .49). For the whole sample, higher child IQ, mania, anxiety, disruptive behavior, and caregiver depression predicted increased parenting stress; maternal conduct disorder predicted lower stress. Child anxiety and disruptive behavior were associated with elevated caregiver stress only for non-BPSD children. Caregivers of children with BPSD experience significant burden and thus require specialized, family-focused interventions. As stress was also elevated, to a lesser degree, among depressed caregivers of children with higher IQ, mania, anxiety, and disruptive behavior, these families may need additional supports as well. Although parents with conduct/antisocial problems evidenced lower stress, these difficulties should be monitored. Thus, parenting stress should be evaluated and addressed in the treatment of childhood mental health problems, especially BPSD.

OBJECTIVE: Given the prevalence of mental health (MH) conditions (MHC) in children, pediatricians should initiate treatment alone or in collaboration with a specialist for children with MHC. However, the majority of pediatricians do not manage or comanage common MHC even with an on-site MH provider. We examined which physician, practice, and training characteristics are associated with pediatricians' comanaging at least half of their patients with MHC. METHODS: We analyzed responses of general pediatricians (n = 305) from the American Academy of Pediatrics 2013 Periodic Survey. Practice characteristics include presence of an on-site MH provider and perceived access to services. Independent variables included sociodemographics, training experiences, and interest in further training. The outcome was comanagement of >/=50% of patients with MHC. Weighted univariate, bivariate, and multivariable analyses were performed. RESULTS: Of the pediatricians who reported comanaging >/=50% of their patients with MHC, logistic regression analysis showed that pediatricians who completed >/=4 weeks of developmental behavioral pediatrics training had 1.8 increased odds (95% confidence interval 1.06, 3.08, P = .03) of comanagement, those very interested in further education in managing/treating MHC had 2.75 increased odds (95% confidence interval 1.63, 3.08, P < .001), and those with more training in MH treatment with medications had 1.4 increased odds (95% confidence interval 1.12, 1.75, P = .004) of comanaging children with MHC. CONCLUSIONS: Specific educational experiences and interest in further education in managing or treating MHC were significantly associated with comanaging >/=50% of patients, suggesting that enhanced MH training among pediatricians could increase the comanagement of children with MHC.

OBJECTIVES: We examined whether the cut-point 10 for the Patient Health Questionnaire-9 (PHQ9) depression screen used in primary care populations is equally valid for Mexicans (M), Ecuadorians (E), Puerto Ricans (PR) and non-Hispanic whites (W) from inner-city hospital-based primary care clinics; and whether stressful life events elevate scores and the probability of major depressive disorder (MDD). METHODS: Over 18-months, a sample of persons from hospital clinics with a positive initial PHQ2 and a subsequent PHQ9 were administered a stressful life event questionnaire and a Structured Clinical Interview to establish an MDD diagnosis, with oversampling of those between 8 and 12: (n=261: 75 E, 71 M, 51 PR, 64 W). For analysis, the sample was weighted using chart review (n=368) to represent a typical clinic population. Receiver Operating Characteristics analysis selected cut-points maximizing sensitivity (Sn) plus specificity (Sp). RESULTS: The optimal cut-point for all groups was 13 with the corresponding Sn and Sp estimates for E=(Sn 73%, Sp 71%), M=(76%, 81%), PR=(81%, 63%) and W=(80%, 74%). Stressful life events impacted screen scores and MDD diagnosis. CONCLUSIONS: Elevating the PHQ9 cut-point for inner-city Latinos as well as whites is suggested to avoid high false positive rates leading to improper treatment with clinical and economic consequences.

Animals, including humans, require a highly coordinated and flexible system of social behavior and threat evaluation. However, trauma can disrupt this system, with the amygdala implicated as a mediator of these impairments in behavior. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences, with trauma experienced from an attachment figure, such as occurs in cases of caregiver-child maltreatment, as particularly detrimental. This review focuses on the unique role of caregiver presence during early-life trauma in programming deficits in social behavior and threat processing. Using data primarily from rodent models, we describe the interaction between trauma and attachment during a sensitive period in early life, which highlights the role of the caregiver's presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. These data suggest that trauma experienced directly from an abusive caregiver and trauma experienced in the presence of caregiver cues produce similar neurobehavioral deficits, which are unique from those resulting from trauma alone. We go on to integrate this information into social experience throughout the lifespan, including consequences for complex scenarios, such as dominance hierarchy formation and maintenance.