Faculty Bibliography

BACKGROUND: Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging. METHOD: A total of 61 youth (9-17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy. RESULTS: There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n=22) and low and decreasing (LowD; n=39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p<0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's<0.001, corrected). CONCLUSIONS: Patterns of function in lateral prefrontal cortical-amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.

Many techniques of functional data analysis require choosing a measure of distance between functions, with the most common choice being L2 distance. In this article we show that using a weighted L2 distance, with a judiciously chosen weight function, can improve the performance of various statistical methods for functional data, including k-medoids clustering, nonparametric classification, and permutation testing. Assuming a quadratically penalized (e.g., spline) basis representation for the functional data, we consider three nontrivial weight functions: design density weights, inverse-variance weights, and a new weight function that minimizes the coefficient of variation of the resulting squared distance by means of an efficient iterative procedure. The benefits of weighting, in particular with the proposed weight function, are demonstrated both in simulation studies and in applications to the Berkeley growth data and a functional magnetic resonance imaging data set.

This article reviews the clinical features and neurochemical hypotheses of obsessive-compulsive disorder (OCD) with a focus on the serotonin system. In DSM-5, OCD was moved from the anxiety disorders to a new category of Obsessive-Compulsive and Related Disorders. OCD is a common, typically persistent disorder marked by intrusive and disturbing thoughts (obsessions) and repetitive behaviors (compulsions) that the person feels driven to perform. The preferential efficacy of serotonin reuptake inhibitors (SRIs) in OCD led to the so-called serotonin hypothesis. However, direct support for a role of serotonin in the pathophysiology (e.g., biomarkers in pharmacological challenge studies) of OCD remains elusive. A role of the glutamatergic system in OCD has been gaining traction based on imaging data, genomic studies and animal models of aberrant grooming behavior. These findings have spurred interest in testing the efficacy of medications that modulate glutamate function. A role of glutamate is compatible with circuit-based theories of OCD.

Tourette syndrome is a childhood onset neurodevelopmental disorder characterized by multiple motor and vocal tics. Although many youth experience attenuation or even remission of tics in adolescence and young adulthood, some individuals experience persistent tics, which can be debilitating or disabling. Most patients also have 1 or more psychiatric comorbid disorders, such as attention-deficit/hyperactivity disorder or obsessive-compulsive disorder. Treatment is multimodal, including both pharmacotherapy and cognitive-behavioral treatment, and requires disentanglement of tics and the comorbid symptoms.

How does the brain's response to speech change over the first months of life? Although behavioral findings indicate that neonates' listening biases are sharpened over the first months of life, with a species-specific preference for speech emerging by 3 months, the neural substrates underlying this developmental change are unknown. We examined neural responses to speech compared with biological non-speech sounds in 1- to 4-month-old infants using fMRI. Infants heard speech and biological non-speech sounds, including heterospecific vocalizations and human non-speech. We observed a left-lateralized response in temporal cortex for speech compared to biological non-speech sounds, indicating that this region is highly selective for speech by the first month of life. Specifically, this brain region becomes increasingly selective for speech over the next 3 months as neural substrates become less responsive to non-speech sounds. These results reveal specific changes in neural responses during a developmental period characterized by rapid behavioral changes.

The aim of this study was to investigate the temporal abilities of children treated by surgery for a malignant tumor in the cerebellum, both in the perception and the production of rhythm. Children with a diagnosed medulloblastoma and age-matched control children were tested in a rhythm discrimination task and a sensorimotor synchronization task. Their motor and cognitive capabilities were also assessed through a battery of age-adapted neuropsychological tests. The results did not show any significant difference in performance between groups for the discrimination task. On the contrary, children with cerebellar lesions produced longer and more variable inter-tap intervals (ITI) in their spontaneous motor tempo (SMT) than did the control children. However, the length and, to a lesser extent, the variability of their SMT decreased after a synchronization phase, when they had been instructed to tap in synchrony with a beep. During the synchronization task, the children with medulloblastoma succeeded to modify the length of their ITI in response to an auditory rhythm, although with better success when the inter-stimuli intervals (ISI) were shorter than when they were longer than the ITIs of their own SMT. Correlational analyses revealed that children's poorer synchronization performance was related to lower scores in neuropsychological tests assessing motor dexterity and processing speed.

OBJECTIVE: The goal of the present study was to examine whether within-person, episode-specific changes in drinking-to-cope (DTC) motivation from the previous evening were associated with concurrent daily mood and fatigue-related symptoms among college student drinkers (N = 1,421; 54% female). METHOD: We conducted an Internet-based daily diary study in which students reported over 30 days on their previous night's drinking level and motivation and their current mood (i.e., sadness, anxiety, anger/hostility, and positive mood) and fatigue-related symptoms. Hypotheses were tested using hierarchical linear models in which the current day's outcome was predicted by last night's levels of DTC motivation and drinking, controlling for drinking to enhance motivation, sex, current day's physical symptoms and drinking, and yesterday's level of the outcome. Subsequent models also predicted outcomes 2 days following the drinking event. RESULTS: Relative increases in previous night's DTC motivation were associated with higher levels of current day negative mood and fatigue-related symptoms and lower levels of positive mood. Also, the association between episode-specific DTC motivation and negative mood was stronger in the positive direction when individuals reported higher levels of nonsocial drinking from the previous night. Last, episode-specific DTC showed similar associations with sadness and anger/hostility 2 days after the drinking event. CONCLUSIONS: The results are generally consistent with the posited attention allocation and ego-depletion mechanisms. Findings suggest that the deleterious effects of repeated episodes of DTC, over time, could help to explain the increased likelihood of alcohol-related problems seen in prior studies.

Difficulty engaging families in mental health treatment is seen as an underlying reason for the disparity between child mental health need and service use. Interpretation of the literature on how best to engage families is complicated by a diversity of operational definitions of engagement outcomes and related interventions. Thus, we sought to review studies of engagement interventions using a structured methodology allowing for an aggregate summary of the most common practices associated with effective engagement interventions. We identified 344 articles through a combination of database search methods and recommendations from engagement research experts; 38 articles describing 40 studies met our inclusion criteria. Following coding methods described by Chorpita and Daleiden (J Consul Clin Psychol 77(3):566-579, 2009, doi: 10.1037/a0014565 ), we identified 22 engagement practice elements from 89 study groups that examined or implemented family engagement strategies. Most frequently identified engagement practice elements included assessment, accessibility promotion, psychoeducation about services, homework assignment, and appointment reminders. Assessment and accessibility promotion were two practice elements present in at least 50 % of treatment groups that outperformed a control group in a randomized controlled trial. With the exception of appointment reminders, these frequently identified engagement practice elements had a high likelihood of being associated with winning treatments when they were used. This approach offers a novel way of summarizing the engagement literature and provides the foundation for enhancing clinical decision-making around treatment engagement.

BACKGROUND: Due to the devastating late effects associated with cranial irradiation in young children with central nervous system (CNS) tumors, treatment for these patients has evolved to include the use of intensive chemotherapy to either avoid or postpone irradiation. While survival outcomes have improved, late effects data in survivors treated on such regimens are needed. OBJECTIVE: This multi-institutional study comprehensively describes late effects in survivors treated on the Head Start I/II protocols. METHODS: Survivors of CNS tumors treated on Head Start I/II protocols were enrolled. Late effects data were collected using a validated parent-report questionnaire. Social, emotional, and behavioral functioning and quality of life were assessed using parent-report on the BASC-2 and CHQ-PF50 questionnaires. RESULTS: Twenty-one survivors (medulloblastoma = 13, sPNET = 4, ATRT = 1, ependymoma = 3) were enrolled. Ten (48%) were irradiation-free. Late effects (frequency; median time of onset since diagnosis) included >/= grade III hearing loss (67%; 3.9 years), vision (67%; 4.1 years), hypothyroidism (33%; 4 years), growth hormone (GH) deficiency (48%; 4.7 years), dental (52%; 7.1 years), and no cases of secondary leukemia. Irradiation-free (vs. irradiated) survivors reported low rates of hypothyroidism (0/10 vs. 7/11; P = 0.004) and GH deficiency (2/10 vs. 8/11; P = 0.03). The BASC-2 and CHQPF-50 mean composite scores were within average ranges relative to healthy comparison norms. Neither age at diagnosis nor irradiation was associated with these scores. CONCLUSIONS: Irradiation-free Head Start survivors have lower risk of hypothyroidism and GH deficiency. Secondary leukemias are not reported. With extended follow-up, survivors demonstrate quality of life, social, emotional, and behavioral functioning within average ranges.