Faculty Bibliography

Children form a strong attachment to their caregiver-even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues-a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.

Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the "reading network." Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same "double hit" of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status.

Children with mental health problems are increasingly being evaluated and treated in pediatric clinical settings. This article focuses on the epidemiology, evaluation, and management of the 2 most common pediatric mental health emergencies, suicidal and homicidal/aggressive patients, as well as the equally challenging population of children with autism or other developmental disabilities.

BACKGROUND: Better and earlier predictive differentiation of bipolar (BD) vs. unipolar major depressive disorder (UD) diagnoses should improve long-term clinical planning. METHODS: We reviewed randomly selected clinical records of 334 adults diagnosed with DSM-IV-TR BD-I (n=109), BD-II (n=106), and UD (n=119) and compared features preceding major affective episodes or diagnoses, using bivariate, multivariate, and Bayesian methods. RESULTS: We identified antecedents selectively associated with later BD vs. UD in 52.6% vs. 31.1% of subjects in childhood, starting at age 7.4 years, and 60.0% vs. 32.8% in adolescence, with far more features in BD than UD cases (10.3 vs. 4.64/100 person-years; p<0.001). In multivariate modeling, BD-selective factors were: younger at first clinical event > male sex > family BD-history > cyclothymic or hyperthymic temperament > antecedents/person-year. Nonaffective (anxiety, eating, or substance-use) disorders preceded BD vs. UD in 41.4% vs. 28.6% of subjects (p=0.02). By ROC analysis, differential prediction of BD vs. UD was optimal with any >/=3 factors/person. LIMITATIONS: The validity and timing of antecedent events and factors identified retrospectively from clinical records could not be verified independently, but information was recorded systematically and consistently by a single mood-disorder expert prior to diagnosis, and extracted by two independent observers. COMMENT: Early clinical features distinguished later BD from UD, often by years. Such prediction should improve treatment-planning and limit risk of mood-switching.

Research indicates that female risk of developing Alzheimer's disease (AD) is greater than that of males. Moderate reduction of calorie intake, known as calorie restriction (CR), reduces pathology in AD mouse models and is a potentially translatable prevention measure for individuals at-risk for AD, as well as an important tool for understanding how the brain endogenously attenuates age-related pathology. Whether sex influences the response to CR remains unknown. In this study, we assessed the effect of CR on beta-amyloid peptide (Abeta) pathology and hippocampal CA1 neuron specific gene expression in the Tg2576 mouse model of cerebral amyloidosis. Relative to ad libitum (AL) feeding, CR feeding significantly reduced hippocampal Abeta burden in 15-month-old female, but not age-matched male, Tg2576 mice. Sustained CR also significantly reduced expression of presenilin enhancer 2 (Psenen) and presenilin 1, components of the gamma-secretase complex, in Tg2576 females. These results indicate that long-term CR significantly reduces age-dependent female Tg2576 Abeta pathology, which is likely to involve CR-mediated reductions in gamma-secretase-dependent amyloid precursor protein (APP) metabolism.

BACKGROUND/PURPOSE: Melatonin, an indoleamine secreted by the pineal gland, plays a key role in regulating circadian rhythm. It has chronobiotic, antioxidant, anti-inflammatory and free radical scavenging properties. METHODS: A conference in Rome in 2014 aimed to establish consensus on the roles of melatonin in children and on treatment guidelines. RESULTS AND CONCLUSION: The best evidence for efficacy is in sleep onset insomnia and delayed sleep phase syndrome. It is most effective when administered 3-5 h before physiological dim light melatonin onset. There is no evidence that extended-release melatonin confers advantage over immediate release. Many children with developmental disorders, such as autism spectrum disorder, attention-deficit/hyperactivity disorder and intellectual disability have sleep disturbance and can benefit from melatonin treatment. Melatonin decreases sleep onset latency and increases total sleep time but does not decrease night awakenings. Decreased CYP 1A2 activity, genetically determined or from concomitant medication, can slow metabolism, with loss of variation in melatonin level and loss of effect. Decreasing the dose can remedy this. Animal work and limited human data suggest that melatonin does not exacerbate seizures and might decrease them. Melatonin has been used successfully in treating headache. Animal work has confirmed a neuroprotective effect of melatonin, suggesting a role in minimising neuronal damage from birth asphyxia; results from human studies are awaited. Melatonin can also be of value in the performance of sleep EEGs and as sedation for brainstem auditory evoked potential assessments. No serious adverse effects of melatonin in humans have been identified.

Objective: The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD). Method: Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudorandomly to experimentally prevent learning. Results: Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy comparison group, exhibited activation in the left posterior hippocampus. Unlike healthy subjects, participants in the OCD group did not show activation in the left ventral putamen and amygdala when anticipating rewards or in the left hippocampus, amygdala, and ventral putamen when receiving unexpected rewards (control condition). Signal in these regions decreased relative to baseline during unexpected reward receipt among those in the OCD group, and the degree of activation was inversely associated with doubt/checking symptoms. Conclusions: Participants in the OCD group displayed abnormal recruitment of mesolimbic and ventral striatal circuitry during reward-based spatial learning. Whereas healthy comparison subjects exhibited activation in this circuitry in response to the violation of reward expectations, unmedicated OCD participants did not and instead over-relied on the posterior hippocampus during learning. Thus, dopaminergic innervation of reward circuitry may be altered, and future study of anterior/posterior hippocampal dysfunction in OCD is warranted.

Objective: This study compared the unique and combined effects of evidence-based treatments for ADHD-stimulant medication and behavior modification-on children's rates of reinforcement for deviant peer behavior (RDPB). Method: Using a within-subjects design, 222 elementary school-age children attending a summer treatment program, including 151 children with ADHD (127 male), with and without comorbid conduct problems, and 71 control children (57 male), received varying combinations of behavior modification (no, low-intensity, and high-intensity) and methylphenidate (placebo, 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg). RDPB was measured through direct observation and compared across all behavior modification and medication conditions. Results: Children with ADHD reinforced the deviant behavior of their peers at a significantly higher rate than control children in the absence of either intervention. However, that difference largely disappeared in the presence of both behavior modification and medication. Both low and high-intensity behavior modification, as well as medium (0.30 mg/kg) and high (0.60 mg/kg) doses of methylphenidate, significantly reduced the rate of ADHD children's RDPB to levels similar to the control group. Conclusions: Results indicate that although untreated children with ADHD do engage in RDPB at a greater rate than their non-ADHD peers, existing evidence-based interventions can substantially decrease the presence of RDPB, thereby limiting potential iatrogenic effects in group-based treatment settings. (PsycINFO Database Record (c) 2014 APA, all rights reserved).