Faculty Bibliography

OBJECTIVE: There has been limited research on anxiety in pediatric bipolar disorder (BPD). Adult BPD studies suggest comorbid anxiety disorders are common and impact treatment outcome. We explored the association of comorbid anxiety with two phenotypes of pediatric BPD. METHODS: We studied two groups of children. The first group (BPD; N = 31) represents the "narrow phenotype" of pediatric BPD, meeting stringent DSM-IV criteria for mania, including duration and elevated/expansive mood. The second group (ED; N = 32) exhibited chronic, non-episodic irritability without elation or grandiosity ("broad phenotype"). RESULTS: Both samples demonstrate high prevalence of anxiety (BPD 77.4%; ED 46.9%). In the BPD sample, anxiety predates BPD onset, and those with comorbid anxiety have earlier age of onset of BPD than those without. Children with BPD plus anxiety have more hospitalizations than those without anxiety. ED subjects with and without comorbid anxiety did not differ with respect to onset of ED symptoms or number of hospitalizations. CONCLUSIONS: Narrow and broad phenotype BPD children have high rates of comorbid anxiety, although only in the narrow phenotype group is comorbid anxiety associated with greater functional impairment BPD plus comorbid anxiety may represent a particularly severe phenotype of pediatric BPD.

The aim of the study was to clarify the developmental risk for interpersonal relationship problems and ineffective coping strategies associated with hyperactive behaviour in girls in a longitudinal epidemiological design. This was investigated in a follow-up study of girls who were identified by parent and teacher ratings in a large community survey of 6- and 7-year-olds as showing pervasive hyperactivity or conduct problems or the comorbid mixture of both problems or neither problem. They were later investigated, at the age of 14-16 years, in a detailed interview. Childhood hyperactivity was a risk for disrupted relationships in adolescence with peers and the opposite sex, but not parents. Findings were independent of the existence of conduct problems. Hyperactivity was a risk for the use of a wide variety of ineffective coping strategies. On the other hand, conduct problem girls reported applying specific coping strategies, but rated these to be ineffective. It is concluded that early therapeutic interventions targeting the development of social skills and problem-solving skills are required in order to help overcome these problems in later life

This study reports a one-year prospective investigation of the relations between overt and relational victimization and social anxiety and phobia in a sample of adolescents. The Social Experience Questionnaire-Self Report Form (SEQ-S), Social Anxiety Scale for Adolescents (SAS-A), and Social Phobia and Anxiety Inventory for Children (SPAI-C) were administered to 144 ninth grade adolescents. A follow-up assessment with the SEQ-S, SAS-A, and SPAI-C was conducted one year later. Results indicated that relational victimization predicted symptoms of social phobia but not general social anxiety and avoidance one year later. Overt victimization was not a significant predictor of social anxiety and phobia one year later. Social anxiety and phobia did not predict peer victimization one year later. However, increases in social anxiety and social phobia symptoms (for boys) over time were positively associated with increases in relational victimization over time. Implications of these findings for peer victimization and social anxiety in the development of social phobia and negative peer experiences are discussed

Children with Attention Deficit/Hyperactivity Disorder (ADHD) often perform poorly on tasks requiring sustained and systematic attention to stimuli for extended periods of time. The current paper tested the hypothesis that such deficits are the result of observable abnormalities in search behaviour (e.g., attention-onset, -duration and -sequencing), and therefore can be explained without reference to deficits in non-observable (i.e., cognitive) processes. Forty boys (20 ADHD and 20 controls) performed a computer-based complex discrimination task adapted from the Matching Familiar Figures Task with four different fixed search interval lengths (5-, 10-, 15- and 20-s). Children with ADHD identified fewer targets than controls (p < 0.001), initiated searches later, spent less time attending to stimuli, and searched in a less intensive and less systematic way (p's < 0.05). There were significant univariate associations between ADHD, task performance and search behaviour. However, there was no support for the hypothesis that abnormalities in search carried the effect of ADHD on performance. The pattern of results in fact suggested that abnormal attending during testing is a statistical marker, rather than a mediator, of ADHD performance deficits. The results confirm the importance of examining covert processes, as well as behavioural abnormalities when trying to understand the psychopathophyiology of ADHD

BACKGROUND: Before 1980, attention-deficit/hyperactivity disorder (ADHD) was called minimal brain dysfunction and included emotional symptoms now listed as 'associated features' in DSM-IV. Data from two multicenter, placebo-controlled studies with 536 patients were reexamined to assess: 1) the pervasiveness of these symptoms in samples of adults with ADHD; 2) the response of these symptoms to atomoxetine; and 3) their association with depressive/anxiety symptoms. METHODS: The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) was used to assess temper, affective lability, and emotional overreactivity, thus identifying patients exhibiting 'emotional dysregulation.' Other DSM-IV Axis I diagnoses were exclusionary. Outcome measures were the Conners' Adult ADHD Rating Scale (CAARS) and the WRAADDS. RESULTS: Thirty-two percent of the sample met post hoc criteria for emotional dysregulation and had higher baseline scores on ADHD measures, a lower response to placebo, and greater response to atomoxetine (p = .048). Symptoms of emotional dysregulation had a treatment effect (p < .001) at least as large as the CAARS (p = .002) and the total WRAADDS (p = .001). Emotional dysregulation was present in the absence of anxiety or depressive diagnosis. CONCLUSIONS: Symptoms of emotional dysregulation were present in many patients with ADHD and showed a treatment response similar to other ADHD symptoms

Laser Doppler imaging (LDI) signal and noise characteristics can vary significantly depending upon the underlying vascular caliber. Further, noise characteristics are not constant over time (non-stationary) and can vary during resting and activated conditions in a typical experiment. Since only a limited number of images can be acquired in a single run, concatenation of data from similar experimental trials becomes necessary which can induce further variation in temporal noise due to instrumental response. In conventional statistical analysis methods such as cross-correlation, a fixed significance threshold is generally used (for the entire image) to detect activation assuming constant noise over time and a normal distribution. As a consequence, statistical significance can become strong or weak due to temporal differences in baseline LD noise, which can possibly deviate from a normal distribution. The main emphasis of this study was the application of bootstrap resampling in conjunction with cross-correlation to estimate the confidence intervals on a pixel-by-pixel basis to avoid distributional specifications on the additive measurement error leading to reliable whisker activation-induced CBF changes. At a 95% confidence level, bootstrap resampling followed by confidence intervals for the correlation coefficient distribution increased the number of active pixels by almost 45% when compared to conventional cross-correlation. These pixels were mostly confined to areas with intermediate and large baseline LD flux with considerable deviation from normality. It is suggested that confidence intervals of the bootstrap estimates can lead to unbiased detection of CBF change in the cerebral cortex, particularly in regions with large temporal variation in noise and low CNR

BACKGROUND: Pre-, peri-, and postnatal obstetric complications (OC) are reported to be more frequent in adult patients with schizophrenia and have been linked to both greater severity and to 'earlier' age of onset (before either age 18 or 22) in studies of adult patients. We hypothesized that by extrapolation, patients with childhood-onset schizophrenia (COS), with very early onset and very severe illness, would have had more numerous or more salient OC compared with their healthy siblings. METHODS: We compared the obstetric records of 60 COS children and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a comprehensive measurement scale consisting of 37 variables having included a separate scale for fetal hypoxia. RESULTS: Patients with COS did not have a higher incidence of OC than the healthy sibling control group with the exception of increased incidence of maternal vomiting. CONCLUSIONS: Obstetric complications, with the possible exception of maternal vomiting, are unlikely to play a major role in the etiopathogenesis of childhood-onset schizophrenia

To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA, the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients comparing the fluent (n=21) and nonfluent (n=26) subjects. We further compared language features with PET/SPECT data available on 39 of these patients. Compared to the nonfluent PPA patients, those with fluent PPA had greater impairment of confrontational naming and loss of single word comprehension. They also exhibited semantic paraphasic errors and loss of single word comprehension. Patients with nonfluent PPA were more likely to be female, were more often dysarthric, and exhibited phonological speech errors in the absence of semantic errors. No significant differences were seen with regard to left hemisphere abnormalities, suggesting that both variants result from mechanisms that overlap frontal, temporal, and parietal regions. Of the language measures, only semantic paraphasias were strongly localized, in this case to the left temporal lobe. Fluent and nonfluent forms of PPA are clinically distinguishable by letter fluency, single word comprehension, object naming, and types of paraphasic errors. Nevertheless, there is a large amount of overlap between dysfunctional anatomic regions associated with these syndromes

CONTEXT: While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD. OBJECTIVE: To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex. DESIGN: Ongoing study of the pathophysiology of pediatric BPD. SETTING: Intramural National Institute of Mental Health; approved by the institutional review board.Patients Pediatric subjects with BPD (n = 20) with at least 1 manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ. MAIN OUTCOME MEASURES: With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry. RESULTS: Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex. CONCLUSIONS: Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD