Faculty Bibliography

OBJECTIVE: To test the hypothesis that patients with pediatric bipolar disorder (PBPD) would demonstrate impairment relative to diagnosis-free controls of comparable age, gender, and IQ on measures of memory functioning. METHOD: The authors administered a battery of verbal and visuospatial memory tests to 35 outpatients with PBPD and 20 healthy controls who participated as volunteers in this study. Groups did not differ on age, gender, or IQ. RESULTS: Consistent with findings in adults with BPD, patients with PBPD performed more poorly than controls on measures of verbal learning/memory and delayed facial recognition memory. Impaired memory was particularly evident in patients with comorbid PBPD/attention-deficit/hyperactivity disorder or acute mood symptoms. CONCLUSIONS: These findings suggest that deficits in verbal learning and memory, as well as some aspects of visuospatial memory, characterize patients with narrow phenotype PBPD. Further research is needed, however, to clarify the roles of comorbid attention-deficit/hyperactivity disorder and acute mood state in the emergence of these deficits. Given the apparent continuity in memory dysfunction between adult BPD and narrow phenotype PBPD, research aimed at elucidating underlying neural mechanisms for this set of deficits is warranted.

CONTEXT: Children exposed to a traumatic event may be at higher risk for developing mental disorders. The prevalence of child psychopathology, however, has not been assessed in a population-based sample exposed to different levels of mass trauma or across a range of disorders. OBJECTIVE: To determine prevalence and correlates of probable mental disorders among New York City, NY, public school students 6 months following the September 11, 2001, World Trade Center attack. DESIGN: Survey. SETTING: New York City public schools. PARTICIPANTS: A citywide, random, representative sample of 8236 students in grades 4 through 12, including oversampling in closest proximity to the World Trade Center site (ground zero) and other high-risk areas. MAIN OUTCOME MEASURE: Children were screened for probable mental disorders with the Diagnostic Interview Schedule for Children Predictive Scales. RESULTS: One or more of 6 probable anxiety/depressive disorders were identified in 28.6% of all children. The most prevalent were probable agoraphobia (14.8%), probable separation anxiety (12.3%), and probable posttraumatic stress disorder (10.6%). Higher levels of exposure correspond to higher prevalence for all probable anxiety/depressive disorders. Girls and children in grades 4 and 5 were the most affected. In logistic regression analyses, child's exposure (adjusted odds ratio, 1.62), exposure of a child's family member (adjusted odds ratio, 1.80), and the child's prior trauma (adjusted odds ratio, 2.01) were related to increased likelihood of probable anxiety/depressive disorders. Results were adjusted for different types of exposure, sociodemographic characteristics, and child mental health service use. CONCLUSIONS: A high proportion of New York City public school children had a probable mental disorder 6 months after September 11, 2001. The data suggest that there is a relationship between level of exposure to trauma and likelihood of child anxiety/depressive disorders in the community. The results support the need to apply wide-area epidemiological approaches to mental health assessment after any large-scale disaster

BACKGROUND: Boys with attention deficit/hyperactivity disorder (AD/HD) demonstrate disruptive behaviour at significantly higher rates compared to girls. Disruptive behaviour often develops as a result of negative interaction patterns within the caregiving relationship. Given the importance of parental cognitions as mediators of parental behaviour, the consideration of parent and child sex in the investigation of causal attributions regarding AD/HD may, at least partially, explain sex differences in the prevalence of disruptive behaviour among children with AD/HD. AIM: To examine the effect of parent and child sex on parental causal attributions and reactions about AD/HD and to investigate the interrelationships between these variables. SAMPLE: Three hundred and seventeen mothers and 317 fathers of boys and girls aged 4-6 years and enrolled in kindergartens in Athens. METHOD: A Greek version of the Parental Account of the Causes of Childhood Problems Questionnaire was used, which followed a vignette about a hypothetical child displaying symptoms of AD/HD. Half of the participants received a male and another half received a female version of the vignette. RESULTS: The child's sex greatly influenced parents' causal attributions about AD/HD. Higher ratings of intentionality were conferred to boys with AD/HD than girls and these attributions were related to stricter responses towards boys. In contrast, parents who considered biological dysfunction as underlying AD/HD, they mostly did so in the case of girls. Minimal effect of parent sex on causal attributions was found. CONCLUSIONS: Because causal attributions of intentionality relate to the response of more strictness and such attributions are more prevalent for boys than girls, then these perceptions about the aetiology of AD/HD in boys may be at the basis of negative interaction patterns. The increase of such interaction patterns may place boys at a more vulnerable position towards the development of secondary behaviour problems

The authors examined inhibitory control processes in 8 adolescents diagnosed with attention-deficit/ hyperactivity disorder (ADHD) during childhood and in 8 adolescent control participants using functional MRI with the Stimulus and Response Conflict Tasks (K. W. Nassauer & J. M. Halperin, 2003). No group differences in performance were evident on measures of interference control and/or response competition created by location and direction stimuli. However, the ADHD group demonstrated significantly greater activation of the left ventrolateral prefrontal cortex during interference control as well as greater activation of the left anterior cingulate cortex, right ventrolateral prefrontal cortex, and left basal ganglia during the dual task of interference control and response competition. The magnitude of the prefrontal and basal ganglia activation was positively correlated with severity of ADHD. Response competition alone did not yield group differences in activation.

There has been little research done in South Africa that investigates how families nested within communities can be strengthened to support the prevention of HIV infection in youth. A focused ethnographic case-study approach was employed to better understand how families in a semi-rural area outside Durban, South Africa, could support youth to make healthy life choices, particularly with respect to HIV risk behaviour. This involved a volunteer convenience sample of parents or caregivers and key community members. A psychodynamic extension of social representational theory was applied to an interpretation of the data. The findings suggest that caregivers of youth feel disempowered and unsupported in a context of fractured and un-containing leadership structures, which works against social cohesion. In the context of social change and relatively new and threatening phenomena such as HIV/AIDS, we argue that strong unified leadership structures are necessary to assist with anchoring the unfamiliar and rendering it manageable, as well as to form the building blocks of social cohesion, a protective social environmental factor for youth. In addition, we suggest that programmes aimed at empowering parents or caregivers with knowledge about HIV/AIDS as well as renegotiating parental practices to promote greater parental authority, would be important interventions at a family level.

The Nova family of neuron-specific RNA-binding proteins were originally identified as targets in an autoimmune neurologic disease characterized by failure of motor inhibition. Nova-1 regulates alternative splicing of pre-mRNAs encoding the inhibitory neurotransmitter receptor subunits GABA(A)Rgamma2 and GlyRalpha2 by directly binding intronic elements, resulting in enhancement of exon inclusion. Here we identify exon E4 in the Nova-1 pre-mRNA itself, encoding a phosphorylated protein domain, as an additional target of Nova-dependent splicing regulation in the mouse spinal cord. Nova binding to E4 is necessary and sufficient for Nova-dependent exon exclusion. E4 harbors five repeats of the known Nova-binding tetranucleotide YCAY and mutation of these elements destroys Nova-dependent regulation. Furthermore, swapping of the sites from Nova-1 and GABA(A)Rgamma2 indicates that the ability of Nova to enhance or repress alternative exon inclusion is dependent on the position of the Nova-binding element within the pre-mRNA. These studies demonstrate that in addition to its previously described role as a splicing activator, Nova autoregulates its own expression by acting as a splicing repressor.

BACKGROUND: While children form an attachment to their abusive caregiver, they are susceptible to mental illness and brain abnormalities. To understand this important clinical issue, we have developed a rat animal model of abusive attachment where odor paired with shock paradoxically produces an odor preference. Here, we extend this model to a seminaturalistic paradigm using a stressed, 'abusive' mother during an odor presentation and assess the underlying learning neural circuit. METHODS: We used a classical conditioning paradigm pairing a novel odor with a stressed mother that predominantly abused pups to assess olfactory learning in a seminaturalistic environment. Additionally, we used Fos protein immunohistochemistry to assess brain areas involved in learning this pain-induced odor preference within a more controlled maltreatment environment (odor-shock conditioning). RESULTS: Odor-maternal maltreatment pairings within a seminatural setting and odor-shock pairings both resulted in paradoxical odor preferences. Learning-induced gene expression was altered in the olfactory bulb and anterior piriform cortex (part of olfactory cortex) but not the amygdala. CONCLUSIONS: Infants appear to use a unique brain circuit that optimizes learned odor preferences necessary for attachment. A fuller understanding of infant brain function may provide insight into why early maltreatment affects psychiatric well-being

Application of fMRI to studies of cognitive development is of growing interest because of its sensitivity and non-invasive nature. However, interpretation of fMRI results in children is presently based on vascular dynamics that have been studied primarily in healthy adults. Comparison of the neurological basis of cognitive development is valid to the extent that the neurovascular responsiveness between children and adults is equal. The present study was designed to detect age-related vascular differences that may contribute to altered BOLD fMRI signal responsiveness. We examined BOLD signal changes in response to breath holding, a global, systemic state change in brain oxygenation. Children exhibited greater percent signal changes than adults in grey and white matter, and this was accompanied by an increase in noise. Consequently, the volume of activation exceeding statistical threshold was reduced in children. The reduced activation in children was well modeled by adding noise to adult data. These findings raise the possibility that developmental differences in fMRI findings between children and adults could, under some circumstances, reflect greater noise in the BOLD response in the brains of children than adults. BOLD responses varied across brain regions, but showed similar regional variation in children and adults.

Attention deficit hyperactivity disorder (ADHD) is a common, multifactorial disorder with significant genetic contribution. Multiple candidate genes have been studied in ADHD, including the norepinephrine transporter (NET1) and dopamine D1 receptor (DRD1). NET1 is implicated in ADHD because of the efficacy of atomoxetine, a selective noradrenergic reuptake inhibitor, in the treatment of ADHD. DRD1 is primarily implicated through mouse models of ADHD. DNA from 163 ADHD probands, 192 parents, and 129 healthy controls was used to investigate possible associations between ADHD and polymorphisms in 12 previously studied candidate genes (5-HT1B, 5-HT2A, 5-HT2C, ADRA2A, CHRNA4, COMT, DAT1, DRD1, DRD4, DRD5, NET1, and SNAP-25). Analyses included case-control and family-based methods, and dimensional measures of behavior, cognition, and anatomic brain magnetic resonance imaging (MRI). Of the 12 genes examined, two showed a significant association with ADHD. Transmission disequilibrium test (TDT) analysis revealed significant association of two NET1 single nucleotide polymorphisms (SNPs) with ADHD (P < or = 0.009); case-control analysis revealed significant association of two DRD1 SNPs with ADHD (P < or = 0.008). No behavioral, cognitive, or brain MRI volume measurement significantly differed across NET1 or DRD1 genotypes at an alpha of 0.01. This study provides support for an association between ADHD and polymorphisms in both NET1 and DRD1; polymorphisms in ten other candidate genes were not associated with ADHD. Because family-based and case-control methods gave divergent results, both should be used in genetic studies of ADHD