Faculty Bibliography

Functional magnetic resonance imaging blood-oxygenation-level-dependent (fMRI-BOLD) signal representing neural activity may be optimized by discriminating MR signal components related to neural activity and those related to intrinsic properties of the cortical vasculature. The objective of this study was to reduce the hemodynamic change independent of neural activity to obtain a scaled fMRI-BOLD response using two factors, namely, low-frequency spectral amplitude (LFSA) and breath-hold amplitude (BHA). Ten subjects (age range, 22-38 years) were scanned during four task conditions: (a) rest while breathing room air, (b) bilateral finger tapping while breathing room air, (c) rest during a partial inspirational breath-hold, and (d) rest during moderate hypercapnia (breathing 5% CO2, 20% O2 and 75% N2). In all subjects who breathed 5% CO2, regions with significant BOLD response during breath-hold correlated significantly with the percent signal increase during 5% CO2 inhalation. Finger-tapping-induced responses in the motor cortex were diminished to a similar extent after scaling using either LFSA or BHA. Inter- and intrasubject variation in the amplitude of the BOLD signal response reduced after hemodynamic scaling using LFSA or BHA. The results validated the hemodynamic amplitude scaling using LFSA with the earlier established BHA. LFSA free from motor-task contamination can be used to calibrate the fMRI-BOLD response in lieu of BHA or hypercapnia to minimize intra- and intersubject variation arising from vascular anatomy and vasodilative capacity

In recent years, there has been a growing interest in sleep problems associated with attention-deficit/hyperactivity disorder (ADHD). The etiology of these sleep problems is multifactorial. In this paper, we review the current literature on the treatment of the most common disorders or factors underlying sleep problems associated with ADHD. In particular, we focus on the management of sleep problems associated with ADHD medications, restless legs syndrome, excessive nocturnal motricity in sleep, sleep disordered breathing, sleep-onset insomnia and psychiatric comorbidities associated with ADHD. Given the paucity of randomized, controlled, double-blinded, placebo-controlled studies, it is hoped that this review will encourage further methodologically sound studies in order to be able to develop treatment guidelines.

OBJECTIVE: Recent evidence suggests an association between obesity and Attention Deficit/Hyperactivity Disorder (ADHD) or ADHD traits. The characteristics of obese subjects with a higher probability of ADHD symptoms are still unclear. We explore the hypothesis that obese adolescents with sleep/alertness problems represent a subgroup at high risk for ADHD traits, independently from associated symptoms of anxiety/depression. The aim of this study was to assess the relationship between parent reports of sleep/alertness problems and ADHD traits in a clinical sample of obese adolescents, controlling for symptoms of anxiety/depression. METHODS: Seventy obese subjects (age range, 10-16 years) were included. The parents filled out the Sleep Disturbance Scale for Children (SDSC), the Conners Parents Rating Scale-Revised (Short Version) (CPRS-R:S), and the Child Behavior Checklist (CBCL). The ADHD Rating Scale (ADHD-RS) was completed by a child psychiatrist. RESULTS: Using multiple regression models controlling for symptoms of anxiety/depression, scores of excessive daytime sleepiness on the SDSC were significantly associated with ADHD traits on the CPRS-R:S as well as on the ADHD-RS. CONCLUSIONS: Obese adolescents described as excessively sleepy by their parents may be at higher risk of ADHD symptoms, independently from symptoms of anxiety/depression. Although the clinician may overlook a potential diagnosis of ADHD in obese adolescents described as sleepy, the results of this study suggest to systematically look for symptoms of ADHD in this subgroup of obese patients. Further studies using objective methods to assess sleep/alertness disturbances are needed to gain insight into the relationship between sleep/alertness disturbances and ADHD in obese individuals.

Systematic research and practice guidelines addressing preschool psychopharmacological treatment in very young children are limited, despite evidence of increasing clinical use of medications in this population. The Preschool Psychopharmacology Working Group (PPWG) was developed to review existing literature relevant to preschool psychopharmacology treatment and to develop treatment recommendations to guide clinicians considering psychopharmacological treatment in very young children. This article reviews the developmental considerations related to preschool psychopharmacological treatment, presents current evidence bases for specific disorders in early childhood, and describes the recommended algorithms for medication use. The purpose of this effort is to promote responsible treatment of young children, recognizing that this will sometimes involve the use of medications.

OBJECTIVES: Previous studies have indicated abnormalities in response flexibility in pediatric bipolar disorder (BD). Dysfunction in response flexibility may contribute to the pattern of behavioral and emotional dysregulation that is characteristic of BD, since depressed and manic patients respond inflexibly to emotional stimuli (i.e., anhedonia in the case of depression or inappropriate positive affect in the case of mania). The present study was undertaken to determine if neuronal responses differed between BD and control subjects on a simple motor response flexibility task. METHODS: To elucidate the neural substrates mediating response flexibility in pediatric BD, we studied 25 youth with BD and 17 age-, gender- and IQ-matched controls (CON) as they performed the change task while undergoing event-related functional magnetic resonance imaging (fMRI). The change task is a new fMRI task that requires subjects to both inhibit and replace a prepotent motor response with another motor response after the initial response has been cued. RESULTS: On correctly performed change trials relative to correctly performed go trials, BD patients generated significantly more activity in the left dorsolateral prefrontal cortex (DLPFC) and in the primary motor cortex than did healthy controls, even though performance levels did not differ across groups. CONCLUSIONS: These results indicate that functional deficits within the left DLPFC may mediate deficits in response flexibility in pediatric BD. This deficit may extend beyond the realm of motor control and also affect emotion regulation.

OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H-MRS) has been increasingly used to examine striatal neurochemistry in adult major depressive disorder. This study extends the use of this modality to pediatric major depression to test the hypothesis that adolescents with major depression have elevated concentrations of striatal choline and creatine and lower concentrations of N-acetylaspartate. METHOD: Fourteen adolescents (ages 12-19 years, eight female) who had major depressive disorder for at least 8 weeks and a severity score of 40 or higher on the Children's Depression Rating Scale-Revised and 10 healthy comparison adolescents (six female) group-matched for gender, age, and handedness were enrolled. All underwent three-dimensional 3-T (1)H-MRS at high spatial resolution (0.75-cm(3) voxels). Relative levels of choline, creatine, and N-acetylaspartate in the left and right caudate, putamen, and thalamus were scaled into concentrations using phantom replacement, and levels were compared for the two cohorts. RESULTS: Relative to comparison subjects, adolescents with major depressive disorder had significantly elevated concentrations of choline (2.11 mM versus 1.56 mM) and creatine (6.65 mM versus 5.26 mM) in the left caudate. No other neurochemical differences were observed between the groups. CONCLUSIONS: These findings most likely reflect accelerated membrane turnover and impaired metabolism in the left caudate. The results are consistent with prior imaging reports of focal and lateralized abnormalities in the caudate in adult major depression