Faculty Bibliography

OBJECTIVE: Different cultural norms for paranoia that exist among African Americans may be misconstrued and fuel the overdiagnosis of schizophrenia. The present study examined whether the frequency of psychotic psychiatric diagnoses differs by race/ethnicity, particularly with regard to paranoid schizophrenia. We examined the frequency upon admission and at discharge and further explored the pattern of diagnostic changes that occurred by racial/ethnic group. METHOD: The present study is a secondary analysis of diagnostic data obtained on inpatients admitted to a research unit from 1990 to 2003 with a typical length of stay from 3 to 6 months. Admission and discharge diagnoses were obtained from each chart on the sample of 238 patients, 55% (N = 130) of whom were white; 24% (N = 58), African American; and 21% (N = 50), Latino. Inpatients were grouped into 4 diagnostic categories: schizoaffective disorder, paranoid schizophrenia, schizophrenia-undifferentiated or -disorganized type, and other psychotic disorder. RESULTS: Upon admission, African American patients were more likely to receive a less-defined diagnosis, such as psychosis not otherwise specified, in part because they tended on average to be younger. Over the course of hospitalization, diagnoses for white patients were more likely to move toward schizoaffective at discharge (OR = 6.85, 95% CI = 1.53 to 30.66). African American patients were more likely to experience a diagnostic change to paranoid schizophrenia (OR = 4.58, 95% CI = 1.70 to 13.36). Interestingly, Latino patients were the least likely group to experience diagnostic changes during their hospitalization stay. CONCLUSIONS: The present preliminary findings reveal an interesting pattern of diagnostic changes that occurred over the course of hospitalization that should be followed up in a comprehensive study

ABSTRACT: BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent, complex disorder which is characterized by symptoms of inattention, hyperactivity, and impulsivity. Convergent evidence from neurobiological studies of ADHD identifies dysfunction in fronto-striatal-cerebellar circuitry as the source of behavioural deficits. Recent studies have shown that regions governing basic sensory processing, such as the somatosensory cortex, show abnormalities in those with ADHD suggesting that these processes may also be compromised. METHODS: We used event-related magnetoencephalography (MEG) to examine patterns of cortical rhythms in the primary (SI) and secondary (SII) somatosensory cortices in response to median nerve stimulation, in 9 adults with ADHD and 10 healthy controls. Stimuli were brief (0.2 ms) non-painful electrical pulses presented to the median nerve in two counterbalanced conditions: unpredictable and predictable stimulus presentation. We measured changes in strength, synchronicity, and frequency of cortical rhythms. RESULTS: Healthy comparison group showed strong event-related desynchrony and synchrony in SI and SII. By contrast, those with ADHD showed significantly weaker event-related desynchrony and event-related synchrony in the alpha (8-12 Hz) and beta (15-30 Hz) bands, respectively. This was most striking during random presentation of median nerve stimulation. Adults with ADHD showed significantly shorter duration of beta rebound in both SI and SII except for when the onset of the stimulus event could be predicted. In this case, the rhythmicity of SI (but not SII) in the ADHD group did not differ from that of controls. CONCLUSION: Our findings suggest that somatosensory processing is altered in individuals with ADHD. MEG constitutes a promising approach to profiling patterns of neural activity during the processing of sensory input (e.g., detection of a tactile stimulus, stimulus predictability) and facilitating our understanding of how basic sensory processing may underlie and/or be influenced by more complex neural networks involved in higher order processing

BACKGROUND: Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed 'default-mode' network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD. METHODS: Resting-state blood oxygen level-dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers. RESULTS: Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p < .0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex (p < 3 x 10(-11), corrected) and portions of posterior cingulate (p < .02, corrected). CONCLUSIONS: Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD

Event-related potentials (ERPs) were used to assess arousal (low, high), valence (negative, positive), and stimulus repetition effects for normal and distorted images from the International Affective Pictures System (IAPS). Distorted stimuli were constructed by dividing each image into small squares and rearranging the segments randomly to produce a "scrambled" picture. Event-related potentials (ERPs) were elicited by presenting the normal and scrambled images as target stimuli, with a repeated visual pattern used as the standard stimulus. Participants (N=32) were instructed to press a button to the targets and ignore the standard. Stimulus repetition effects were assessed by presenting each stimulus twice in the normal and scrambled condition. High-arousal stimuli yielded larger late positive components for both the normal and scrambled pictures. No overall valence effects were obtained, but arousal and valence influenced component amplitudes for middle-latency ERPs from the scrambled stimuli. For the normal pictures, stimulus repetition was associated with increased component amplitudes for all potentials and decreased RTs of all affective categories. For the scrambled pictures, no repetition changes were obtained. The findings suggest that stimulus arousal level contributes more than valence to affective ERP measures for normal as well as perceptually distorted pictures. Stimulus repetition engages memory for previous normal picture items but is not influenced by affective category. Theoretical implications are discussed.

This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.

Many studies show that early and active parent involvement reduces discipline problems in school, increases academic success, and leads to better outcomes in adult life. The best outcomes are seen when both parents are highly involved. The February issue of our Parent Letter discusses some of the things that fathers and other male role models can do to increase their impact on children’s academic success and overall well-being.

Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effects of these hormones on the neural networks underlying memory. Using Congenital adrenal hyperplasia (CAH) as a naturalistic model of early steroid abnormalities, this study examines the consequences of CAH on memory and its neural correlates for emotionally arousing and neutral material in children. Seventeen patients with CAH and 17 age- and sex-matched healthy children (ages 12-14 years) completed the study. Subjects were presented positive, negative and neutral pictures. Memory recall occurred about 30min after viewing the pictures. Children with CAH showed memory deficits for negative pictures compared to healthy children (p<0.01). There were no group differences on memory performance for either positive or neutral pictures (p>0.1). In patients, 24h urinary-free cortisol levels (reflecting glucocorticoid replacement therapy) and testosterone levels were not associated with memory performance. These findings suggest that early steroid imbalances affect memory for negative material in children with CAH. Such memory impairments may result from abnormal brain organization and function following hormonal dysfunction during critical periods of development.

Identification and validation of novel drug targets continues to be a major bottleneck in drug development, particularly for polygenic complex diseases such as type 2 diabetes. Here, the authors describe an approach that allows researchers to rapidly identify and validate potential drug targets by combining chemical tools and RNA interference technology. As a proof-of-concept study, the known mechanism Sigma LOPAC library was used to screen for glucose-dependent insulin secretion (GDIS) in INS-1 832/13 cells. In addition to several mechanisms that are known to regulate GDIS (such as cyclic adenosine monophosphate-specific phosphodiesterases, adrenoceptors, and Ca(2+) channels), the authors find that several of the dopamine receptor (DRD) antagonists significantly enhance GDIS, whereas DRD agonists profoundly inhibit GDIS. Subsequent siRNA studies in the same cell line indicate that knockdown of DRD2 enhanced GDIS. Furthermore, selective DRD2 antagonists and agonists also enhance or suppress, respectively, GDIS in isolated rat islets. The data support that the approach described here offers a rapid and effective way for target identification and validation.