Faculty Bibliography

BACKGROUND: Many chromosomal regions for susceptibility to autism spectrum disorders (ASDs) have been identified, but few have reached genomewide significance. In response, researchers have attempted to increase the power of their analyses by stratifying samples to increase phenotypic homogeneity. Although homogeneity has typically been defined by a single variable, resultant groups often differ in other dimensions that may be directly pertinent. Group differences in age, gender, IQ, and measures of autism severity are examined as related to Autism Diagnostic Interview-Revised (ADI-R) domains previously used for subsetting or Quantitative Trait Analysis (QTL). METHODS: Participants were research participants and clinic referrals for assessment of possible autism. Assessments included the ADI-R, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, and a developmental or cognitive test. Data were collected for 983 individuals, ages 4 to 52 years, with diagnoses of autism and ASDs. RESULTS: Findings suggest that, of several potential grouping variables, only restricted and repetitive behaviors associated with Insistence on Sameness were independent of age, IQ, and autism severity. CONCLUSIONS: Results emphasize the potential unintended effects of stratification and the importance of understanding such interrelationships between phenotypic characteristics when defining subgroups or performing QTL

Despite a remarkably precise spatial representation of odorant stimuli in the early stages of olfactory processing, the projections to the olfactory (piriform) cortex are more diffuse and show characteristics of a combinatorial array, with extensive overlap of afferent inputs and widespread intracortical association connections. Furthermore, although there is increasing evidence for the importance of temporal structure in olfactory bulb odorant-evoked output, little is known about how this temporal patterning is translated within cortical neural ensembles. The present study used multichannel electrode arrays and paired single-unit recordings in rat anterior piriform cortex to test several predictions regarding ensemble coding in this system. The results indicate that odorants evoke activity in a spatially scattered ensemble of anterior piriform cortex neurons, and the ensemble activity includes a rich temporal structure. The most pronounced discrimination between different odorants by cortical ensembles occurs during the first inhalation of a 2 s stimulus. The distributed spatial and temporal structure of cortical activity is present at both global and local scales, with neighboring single units contributing to coding of different odorants and active at different phases of the respiratory cycle. Finally, cross-correlogram analyses suggest that cortical unit activity reflects not only afferent input from the olfactory bulb but also intrinsic activity within the intracortical association fiber system. These results provide direct evidence for predictions stemming from anatomical- and theoretical-based models of piriform cortex

Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.

Attention deficit hyperactivity disorder (ADHD) is the most frequent psychiatric disorder in children, yet data are sparse on its pathophysiology. Particularly relevant are the dopamine transporters since these are the main targets of stimulant medications used for ADHD treatment. Though some imaging studies have shown increases in dopamine transporters in ADHD others have not and their role in the neurobiology of ADHD remains unclear. Here we investigate dopamine transporters in ADHD subjects with control of potentially confounding factors (previous medication and/or drug histories, comorbidity) and their association with clinical symptoms. Positron emission tomography and [11C]cocaine were used to measure dopamine transporters in 20 never medicated adults with ADHD and 25 controls. Dopamine transporters were lower in left caudate (13%, p < 0.05) and in left nucleus accumbens (p < 0.005) in ADHD subjects than in controls. In putamen dopamine transporters did not differ between groups but were associated with scores of inattention (Conners Adult Attention Rating Scale) both in ADHD subjects (p < 0.005) and in controls (p < 0.005). Thus, for a given transporter level the scores for inattention were on average five times greater in ADHD subjects than in controls. These results do not corroborate increases in dopamine transporters in ADHD subjects and show that in some they are reduced. It also provides evidence that dopamine transporter levels modulate attention but suggest that additional pathology (e.g., prefrontal or cingulostriatal pathways, noradrenergic neurotransmission) is necessary to account for the large differences in inattention observed between controls and ADHD subjects

BACKGROUND: Family-based evidence for association at serotonin system genes SLC6A4, HTR1B, HTR2A, and brain-derived neurotrophic factor (BDNF) has been previously reported in obsessive-compulsive disorder (OCD). Early-onset OCD is a more familial form of the disorder. METHODS: We used the transmission-disequilibrium test of association at common polymorphisms in each of these genes in 54 parent-child trios ascertained through probands with early-onset OCD. RESULTS: No evidence for association was detected at any of the polymorphisms in the entire set of subjects. Nominally significant association was found at the HTR2A rs6311 polymorphism in subjects with tic disorder and OCD (p = .05), replicating a previous finding in Tourette syndrome and OCD. Nominally significant association was also found for the SLC6A4 HT transporter gene-linked polymorphic region (5-HTTLPR) polymorphism for female subjects (p = .03). Neither association would remain significant after statistical correction for multiple testing. Despite no individual study reporting replication, a pooled analysis of five replication studies of the SLC6A4 5-HTTLPR polymorphism supports association (p = .02). CONCLUSIONS: Low power across individual association studies in OCD may lead to a false acceptance of the null hypothesis. Accumulation of evidence from multiple studies will be necessary to evaluate the potential role for these genes in contributing to susceptibility to OCD

BACKGROUND: Despite the wealth of information in adult posttraumatic stress disorder (PTSD) literature, few studies have explored the memory and learning performance of trauma-exposed youth. This study examined if memory deficits are associated with PTSD or with trauma exposure in the absence of PTSD. METHODS: Youth exposed to traumatic incidents underwent clinical interviews to diagnose PTSD and exclude major comorbid disorders. Youth with conditions that could impede performance on a memory scale (e.g., limited intellectual functioning, current substance abuse, psychopharmacological treatment) were excluded. Three groups of participants were identified (PTSD positives [n = 29], traumatized PTSD negatives [n = 62], and nontraumatized control subjects [n = 40]). Participants completed the Wide Range Assessment of Memory and Learning (WRAML). RESULTS: Youth with PTSD evidenced significantly lower scores on the WRAML General Memory, Verbal Memory, and Learning indices compared with nontraumatized control subjects. With the exception of Verbal Memory, youth with and without PTSD performed comparably on all other indices. Nonsignificant differences were noted on the Visual Memory Index. CONCLUSIONS: General memory and verbal memory impairments as evidenced in adult populations were observed among this sample of youth. Given the developmental trajectory of memory capabilities, the implications of such early trauma exposure and memory deficits are considered

Seven hundred and thirty-two parents reported when and how their infants learned to climb stairs. Children typically mastered stair ascent (mean age=10.97 months) several months after crawling onset and several weeks prior to descent (mean age=12.53 months). Most infants (94%) crawled upstairs the first time they ascended independently. Most infants (76%) turned around and backed at initial descent. Other descent strategies included scooting down sitting, walking, and sliding down face first. Children with stairs in their home were more likely to learn to ascend stairs at a younger age, devise backing as a descent strategy, and be explicitly taught to descend by their parents than children without stairs in their home. However, all infants learned to descend stairs at the same age, regardless of the presence of stairs in their home. Parents' teaching strategies and infants' access to stairs worked together to constrain development and to influence the acquisition of stair climbing milestones.

INTRODUCTION: Although mental health problems are increasing in the primary care sector, the prevalence of mental health problems in families presenting for nonpsychiatric complaints in the emergency department (ED) setting is generally unknown. As such, we set out to assess the frequency of mental health concerns and associated risk factors in children presenting for care in a pediatric ED. METHODS: A total of 411 mother-child dyads were randomly selected during a 2-year period from the less acute area of a large pediatric ED. Mothers were interviewed for child mental health concerns using structured diagnostic instruments. Mothers were also interviewed for their own mental health symptoms. Risk factor analysis for the outcome of a pediatric mental health concern was performed using bivariate and multivariate techniques. RESULTS: Of all children, 45% met criteria for a mental health concern, with 23% of all children meeting criteria for two or more mental health concerns; 21% of mothers screened positive for a mental health problem themselves. Once adjusted, children whose mothers' screened positive for a mental illness were more likely to have a mental health concern themselves. CONCLUSION: There is a large burden of mental health concerns in children and their mothers presenting to the ED for medical care. Efficiently and accurately identifying mental illness in children presenting to a pediatric ED is the first step in the intervention process for a population that might otherwise slip through the system

Tetrachloroethylene is a solvent used in dry cleaning with reported neurotoxic effects. Using proportional hazard methods, we examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring born in Jerusalem from 1964 through 1976, followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia. We observed an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, 95% CI, 1.3-9.2, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia