Faculty Bibliography

There is a robust association between prenatal smoking and disruptive behavior disorders, but little is known about the emergence of such behaviors in early development. The association of prenatal smoking and hypothesized behavioral precursors to disruptive behavior in toddlers (N=93) was tested. Exposed toddlers demonstrated atypical behavioral patterns, including (1) escalating externalizing problems from 18 to 24 months and (2) observed difficulty modulating behavior in response to social cues. Specification of exposure-related behaviors is a first step toward generating testable hypotheses about putative mechanisms of effect. While it remains unclear whether prenatal exposure plays an etiologic role in the emergence of disruptive behavior, atypical exposure-related behavioral patterns are evident in the first years of life and demonstrate developmental coherence

CONTEXT: Autism represents an unusual pattern of development beginning in the infant and toddler years. OBJECTIVES: To examine the stability of autism spectrum diagnoses made at ages 2 through 9 years and identify features that predicted later diagnosis. DESIGN: Prospective study of diagnostic classifications from standardized instruments including a parent interview (Autism Diagnostic Interview-Revised [ADI-R]), an observational scale (Pre-Linguistic Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule [ADOS]), and independent clinical diagnoses made at ages 2 and 9 years compared with a clinical research team's criterion standard diagnoses. SETTING: Three inception cohorts: consecutive referrals for autism assessment to (1) state-funded community autism centers, (2) a private university autism clinic, and (3) case controls with developmental delay from community clinics. PARTICIPANTS: At 2 years of age, 192 autism referrals and 22 developmentally delayed case controls; 172 children seen at 9 years of age. MAIN OUTCOME MEASURES: Consensus best-estimate diagnoses at 9 years of age. RESULTS: Percentage agreement between best-estimate diagnoses at 2 and 9 years of age was 67, with a weighted kappa of 0.72. Diagnostic change was primarily accounted for by movement from pervasive developmental disorder not otherwise specified to autism. Each measure at age 2 years was strongly prognostic for autism at age 9 years, with odds ratios of 6.6 for parent interview, 6.8 for observation, and 12.8 for clinical judgment. Once verbal IQ (P = .001) was taken into account at age 2 years, the ADI-R repetitive domain (P = .02) and the ADOS social (P = .05) and repetitive domains (P = .005) significantly predicted autism at age 9 years. CONCLUSIONS: Diagnostic stability at age 9 years was very high for autism at age 2 years and less strong for pervasive developmental disorder not otherwise specified. Judgment of experienced clinicians, trained on standard instruments, consistently added to information available from parent interview and standardized observation

OBJECTIVE: Symptoms of posttraumatic stress disorder (PTSD) are a focus of much research with older children, but little research has been conducted with young children, who account for about 40% of all pediatric burn injuries. This is a longitudinal study of 72 acutely burned children (12-48 months old) that assessed the course of acute posttraumatic symptoms and physiological reactivity. METHOD: Parents were interviewed shortly after their child was admitted to the hospital and 1 month after discharge. PTSD symptoms were measured with the Diagnostic Interview for Children and Adolescents (DICA) module. Nurses recorded the child's physiological data throughout the hospital stay. The child's physical and behavioral responses were assessed in a laboratory at about 1 month after discharge. RESULTS: Reduced social smiling in the children was related to PTSD symptoms, as measured by the DICA, and heart rate at 24 hours and 7 days. Reduced vocalization was related to the child's rating of pain at 24 hours. Smiling and vocalizations were also related to some DICA cluster scores but not avoidance. CONCLUSIONS: Preschool children admitted to a burn unit demonstrated PTSD symptoms and physiological reactivity. There was a relation to the frequency of smiles and vocalizations

ABSTRACT: BACKGROUND: Molecular genetic studies suggest the dopamine D1 receptor (D1R) may be implicated in attention-deficit/hyperactivity disorder (ADHD). As little is known about the potential motor role of D1R in ADHD, animal models may provide important insights into this issue. Methods: We investigated the effects of a full and selective D1R agonist, SKF-81297 (0.3, 3 and 10 mg/kg), on motor behaviour and expression of the plasticity-associated gene, c-fos, in habituated young adult male Spontaneously Hypertensive Rats (SHR), the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived). Results: SHR rats were more behaviourally active than WKY rats after injection with vehicle. The 0.3 mg/kg dose of SKF-81297 increased motor behaviour (locomotion, sifting, rearing, and sniffing) in both SHR and WKY rats. Total grooming was also stimulated, but only in WKY rats. The same dose increased c-fos mRNA expression in the piriform cortex of both strains. The 3 mg/kg dose increased sifting and sniffing in both strains. Locomotion was also stimulated towards the end of the testing period. The intermediate dose decreased total rearing in both strains, and produced a significant increase in c-fos mRNA in the striatum, nucleus accumbens, olfactory tuberculum, and in the cingulate, agranular insular and piriform cortices. The 10 mg/kg dose of SKF-81297 produced a biphasic effect on locomotion, which was characterized by an initial decrease followed by later stimulation. The latter stimulatory effect was more pronounced in SHR than in WKY rats when compared to their respective vehicle-injected groups. The 10 mg/kg dose also stimulated sifting and sniffing in both strains. Both the 3 and 10 mg/kg doses had no effect on total grooming. The 10 mg/kg dose induced significantly higher levels of c-fos mRNA expression in the nucleus accumbens and adjacent cortical regions (but not striatum) of SHR when compared to WKY rats. CONCLUSION: The present results suggest a potential alteration in D1R neurotransmission within the frontal-striatal circuitry of SHR involved in motor control. These findings extend our understanding of the molecular alterations in SHR, a heuristically useful model of ADHD

The spatial pattern of activation in response to multiple whisker stimulation was studied using high-resolution laser Doppler (LD) imaging in urethane-anesthetized rats. LD flux change representing cerebral blood flow (CBF) responses were analyzed from a single trial or after averaging a number of similar trials. CBF change in a single trial was observed predominantly over pixels having low baseline flux values (microvessels), which included diffuse circular patterns of activation 400-800 microm in diameter similar to the histological dimensions of individual barrels established in the layer IV of the rat somatosensory cortex. The overall activation pattern varied considerably between each trial (only about 9-10% overlap); however, the diffuse circular pattern of activation was reproducible in every single trial within and across all rats. With trial averaging, no significant increase was observed in the outer boundary of activation, but the number of activated pixels increased within the diffuse circular patterns of activation. Emergence of further active pixels primarily within the diffuse circular regions of activity with trial averaging indicates distinct CBF responses in the septal and barrel regions, with a lesser LD signal to noise ratio in the barrel core

BACKGROUND: Neurocognitive deficits are considered to be central to the pathophysiology of schizophrenia, and the neurodevelopmental model suggests that such deficits precede full-blown psychosis. The present study examined performance on a broad neuropsychological battery of young subjects considered to be at clinical high risk for schizophrenia, who were subsequently followed to determine clinical outcome. METHODS: Subjects were 38 clinical high-risk patients (58% male patients; mean age = 16.5) and 39 sex- and age-matched healthy control subjects. At baseline, all high-risk patients had attenuated (subpsychotic) schizophrenialike positive symptoms. Clinical follow-up data of at least 6 months duration was available on 33 patients, of whom 12 developed nonaffective psychotic disorders. RESULTS: At baseline, clinical high-risk patients had significantly impaired global cognitive performance relative to control subjects and to estimates of their own prior intellectual functioning. Measures of verbal memory and executive functioning/working memory showed significantly greater impairments; visuospatial functioning was relatively spared. Prodromal patients who later developed psychosis had significantly lower verbal memory scores at baseline compared with patients who remained nonpsychotic. CONCLUSIONS: Verbal memory deficits may be an important risk marker for the development of schizophrenia-spectrum psychotic disorders, possibly indicating the presence of a prefrontal-hippocampal neurodevelopmental abnormality. Generalized neurocognitive impairment may be a nonspecific vulnerability marker.

This study examined the associations between physical and psychological proximity to terrorist attacks and post-traumatic symptoms (PTS), depressive symptoms, and alcohol use among Israeli youth. Self-administered questionnaires were completed under anonymous conditions by 1,150 high and junior high school students (51.3% boys and 48.7% girls) in a town in the Tel Aviv metropolitan area. Standardized, validated scales were used to measure psychological symptoms and alcohol use. High levels of exposure to terrorism were reported. Physical and psychological proximity to terrorist attacks were associated with more PTS symptoms and alcohol consumption. Physical proximity was also associated with symptoms of depression. The implications of terror-associated early drinking for later alcohol problems should be explored.

OBJECTIVE: Since the 1980s, there has been an increase in the frequency with which children and adolescents with psychiatric symptoms present to emergency departments (ED). Recent trend data from the National Hospital Ambulatory Medical Care Survey database suggest that the increase in ED use for mental health concerns is not driven by a rise in the frequency of medically serious suicide attempts but, rather, nonurgent diagnoses. The current paper is a systematic review of the existing research literature on child and adolescent psychiatric emergencies among nonsuicidal samples to assess the type and quality of the data reported. This is a first step in developing a profile of which children, in the absence of medically serious suicide attempt, seek psychiatric care in EDs. METHODS: Literature searches were conducted through PsycINFO, MEDLINE, and PubMed databases for the years 1990 through 2004. Twelve studies were identified as meeting inclusion criteria and were reviewed for general study information (ie, bibliography); quality indicators; study characteristics (ie, data source, location of study, method of subject recruitment, and study inclusion/exclusion criteria); subject characteristics, and outcome measures and results (specific outcome assessed, types of data analyses). RESULTS: Most of the studies were cross-sectional, retrospective chart reviews, with one data source. Only one study reported on all variables of interest, and there was no consistency in data collection or reporting across studies. CONCLUSIONS: Although there has been a documented increase in children and adolescents seeking care for psychiatric emergencies in EDs, a clear and basic understanding of who these patients are cannot be determined from existing published research reports. Significant inconsistencies in data collection and reporting make recommendations for treatment planning and service delivery challenging. A research agenda in the field of child and adolescent psychiatric emergencies is proposed.

Autistic disorder and the group of related conditions defined as pervasive developmental disorders are chronic neurodevelopmental disorders starting in early childhood and affecting a significant number of children and families. Although the causes and much of the pathophysiology of the disorder remain unknown, in recent years a number of available medication treatments have been identified as holding promise in alleviating some of the most disabling maladaptive behaviors, associated with pervasive developmental disorders. However these treatments do not address the core symptoms of the disease and oftentimes their side effects outweigh their benefits. Therefore there is substantial need for new medications that are safer and more effective in addressing the behavior symptoms of autism. The aim of this review is to highlight the available current pharmacotherapies and those emerging treatments with potential to enhance the treatment options of patients with pervasive developmental disorders