Faculty Bibliography

OBJECTIVE: Posttraumatic stress disorder (PTSD) related to childhood abuse is associated with features of affect regulation and interpersonal disturbances that substantially contribute to impairment. Existing treatments do not address these problems or the difficulties they may pose in the exploration of trauma memories, an efficacious and frequently recommended approach to resolving PTSD. The authors evaluated the benefits and risks of a treatment combining an initial preparatory phase of skills training in affect and interpersonal regulation (STAIR) followed by exposure by comparing it against two control conditions: Supportive Counseling followed by Exposure (Support/Exposure) and skills training followed by Supportive Counseling (STAIR/Support). METHOD: Participants were women with PTSD related to childhood abuse (N=104) who were randomly assigned to the STAIR/Exposure condition, Support/Exposure condition (exposure comparator), or STAIR/Support condition (skills comparator) and assessed at posttreatment, 3 months, and 6 months. RESULTS: The STAIR/Exposure group was more likely to achieve sustained and full PTSD remission relative to the exposure comparator, while the skills comparator condition fell in the middle (27% versus 13% versus 0%). STAIR/Exposure produced greater improvements in emotion regulation than the exposure comparator and greater improvements in interpersonal problems than both conditions. The STAIR/Exposure dropout rate was lower than the rate for the exposure comparator and similar to the rate for the skills comparator. There were significantly lower session-to-session PTSD symptoms during the exposure phase in the STAIR/Exposure condition than in the Support/Exposure condition. STAIR/Exposure was associated with fewer cases of PTSD worsening relative to both of the other two conditions. CONCLUSIONS: For a PTSD population with chronic and early-life trauma, a phase-based skills-to-exposure treatment was associated with greater benefits and fewer adverse effects than treatments that excluded either skills training or exposure

OBJECTIVE: The current paper reviews recent findings regarding how to conceptualize engagement and factors influencing engagement, treatment attendance rates, and interventions that work. METHOD: Research related to the definition of engagement, predictors of engagement and treatment termination, attendance rates, and engaging interventions are summarized as an update to the McKay and Bannon (2004) review. RESULTS: Despite ongoing advances in evidence-based treatments and dissemination strategies, engaging families into mental health treatment remains a serious challenge. Within the last several years, a number of technological advances and interventions have emerged to address this problem. Families with children who present disruptive behavior challenges and symptoms of trauma are considered in terms of the unique barriers they experience regarding engagement in treatment. CONCLUSIONS: Potential solutions to increase treatment utilization and further research in this area are discussed.

Twin studies have found that global brain volumes, including total intracranial volume (ICV), total gray matter, and total white matter volumes are highly heritable in adults and older children. Very little is known about genetic and environmental contributions to brain structure in very young children and whether these contributions change over the course of development. We performed structural imaging on a 3T MR scanner of 217 neonatal twins, 41 same-sex monozygotic, 50 same-sex dizygotic pairs, and 35 "single" twins-neonates with brain scans unavailable for their co-twins. Tissue segmentation and parcellation was performed, and structural equation modeling was used to estimate additive genetic, common environmental, and unique environmental effects on brain structure. Heritability of ICV (0.73) and total white matter volume (0.85) was high and similar to that described in older children and adults; the heritability of total gray matter (0.56) was somewhat lower. Heritability of lateral ventricle volume was high (0.71), whereas the heritability of cerebellar volume was low (0.17). Comparison with previous twin studies in older children and adults reveal that three general patterns of how heritability can change during postnatal brain development: (1) for global white matter volumes, heritability is comparable to reported heritability in adults, (2) for global gray matter volume and cerebellar volume, heritability increases with age, and (3) for lateral ventricle volume, heritability decreases with age. More detailed studies of the changes in the relative genetic and environmental effects on brain structure throughout early childhood development are needed.

BACKGROUND: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. METHODS: Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be >or= 6 weeks and Children's Depression Rating Scale-Revised (CDRS-R) scores were >or= 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher's protected least significant difference was used for multiple comparisons. RESULTS: As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R. CONCLUSIONS: Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome

Using a means-means-ends problem-solving task, this study examined whether 16-month-old walking infants (N = 28) took into account the width of a bridge as a means for crossing a precipice and the location of a handrail as a means for augmenting balance on a narrow bridge. Infants were encouraged to cross from one platform to another over narrow and wide bridges located at various distances from a wooden handrail. Infants attempted to walk over the wide bridge more often than the narrow one and when the handrail was within reach. Infants demonstrated parallel problem solving by modifying exploratory behaviors and bridge-crossing strategies that simultaneously accounted for the spatial and functional relations between body and bridge, body and handrail, and bridge and handrail.

Three experiments investigated whether 14- and 15-month-old infants use information for both friction and slant for prospective control of locomotion down slopes. In Experiment 1, high- and low-friction conditions were interleaved on a range of shallow and steep slopes. In Experiment 2, friction conditions were blocked. In Experiment 3, the low-friction surface was visually distinct from the surrounding high-friction surface. In all three experiments, infants could walk down steeper slopes in the high-friction condition than they could in the low-friction condition. Infants detected affordances for walking down slopes in the high-friction condition, but in the low-friction condition, they attempted impossibly slippery slopes and fell repeatedly. In both friction conditions, when infants paused to explore slopes, they were less likely to attempt slopes beyond their ability. Exploration was elicited by visual information for slant (Experiments 1 and 2) or by a visually distinct surface that marked the change in friction (Experiment 3).

Although temporo-parietal cortices mediate spatial navigation in animals and humans, the neural correlates of reward-based spatial learning are less well known. Twenty-five healthy adults performed a virtual reality fMRI task that required learning to use extra-maze cues to navigate an 8-arm radial maze and find hidden rewards. Searching the maze in the spatial learning condition compared to the control conditions was associated with activation of temporo-parietal regions, albeit not including the hippocampus. The receipt of rewards was associated with activation of the hippocampus in a control condition when using the extra-maze cues for navigation was rendered impossible by randomizing the spatial location of cues. Our novel experimental design allowed us to assess the differential contributions of the hippocampus and other temporo-parietal areas to searching and reward processing during reward-based spatial learning. This translational research will permit parallel studies in animals and humans to establish the functional similarity of learning systems across species; cellular and molecular studies in animals may then inform the effects of manipulations on these systems in humans, and fMRI studies in humans may inform the interpretation and relevance of findings in animals.

Emerging research supports the contribution of executive function (EF) to reading comprehension; however, a unique pattern has not been established for children who demonstrate comprehension difficulties despite average word recognition ability (specific reading comprehension deficit; S-RCD). To identify particular EF components on which children with S-RCD struggle, a range of EF skills was compared among 86 children, ages 10 to 14, grouped by word reading and comprehension abilities: 24 average readers, 44 with word recognition deficits (WRD), and 18 S-RCD. An exploratory principal components analysis of EF tests identified three latent factors, used in subsequent group comparisons: Planning/ Spatial Working Memory, Verbal Working Memory, and Response Inhibition. The WRD group exhibited deficits (relative to controls) on Verbal Working Memory and Inhibition factors; S-RCD children performed more poorly than controls on the Planning factor. Further analyses suggested the WRD group's poor performance on EF factors was a by-product of core deficits linked to WRD (after controlling for phonological processing, this group no longer showed EF deficits). In contrast, the S-RCD group's poor performance on the planning component remained significant after controlling for phonological processing. Findings suggest reading comprehension difficulties are linked to executive dysfunction; in particular, poor strategic planning/organizing may lead to reading comprehension problems.

OBJECTIVE: To place imaging-genetics research in the context of child psychiatry. METHOD: A conceptual overview is provided, followed by discussion of specific research examples. RESULTS: Imaging-genetics research is described linking brain function to two specific genes, for the serotonin-reuptake-transporter protein and a monoamine oxidase enzyme. Work is then described on phenotype selection in imaging genetics. CONCLUSIONS: Child psychiatry applications of imaging genetics are only beginning to emerge. The approach holds promise for advancing understandings of pathophysiology and therapeutics.

OBJECTIVE: The goal of our study was to investigate the impact of dysthymic disorder (DD), a form of chronic depression, on naturalistic outcome in individuals with personality disorders (PDs). METHOD: The Collaborative Longitudinal Personality Disorders Study is a cohort initially including 573 subjects with 4 targeted PDs (borderline, avoidant, schizotypal, and obsessive-compulsive) and 95 subjects with major depression but no PD. At baseline, 115 subjects were diagnosed with coexisting DD, of whom 109 (94.8%) were PD subjects. Regression analyses were performed to predict 3 classes of broad clinical outcome after 2 years of prospective follow-up. We hypothesized that DD diagnosis at baseline would be associated with worse outcome on (1) persistence of a PD diagnosis, (2) impairment in psychosocial functioning (as measured by the Longitudinal Interval Follow-up Evaluation), and (3) crisis-related treatment utilization. RESULTS: Baseline DD diagnosis was associated with persistence of PD diagnosis at 2 years, particularly for borderline and avoidant PDs. It was associated with worse outcome on global social adjustment, life satisfaction, recreation, and friendships, but not employment or relationship with spouse. Contrary to expectation, DD did not increase suicide attempts, emergency room visits, or psychiatric hospitalizations. CONCLUSIONS: Comorbidity of DD is associated with persistence of PD diagnosis and with worse outcome on many, but not all, measures of psychosocial functioning