Faculty Bibliography

This article summarizes current research related to autism spectrum disorders. Current epidemiological trends, theories about aetiology, and relevant issues in assessment and diagnosis of autism spectrum disorders are discussed

Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) alleviates both anxiety symptoms and associated physiologic disturbances in anxious patients. However, limited research considers the degree to which chronic SSRI treatment influences anxiety in healthy individuals. This study examined the effect of 2-week citalopram treatment on two threat responses: short- and long-duration-potentiated startle. Prior work suggests that these two responses provide neurally and functionally distinct models of fear and anxiety, respectively, in rodents. Healthy volunteers (n=53) received either placebo or citalopram (20 mg per day) for 2 weeks under double-blind conditions. They were each tested twice, before and after treatment. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Aversive states were indexed by acoustic startle. Phasic fear-potentiated startle to the threat cue, as well as sustained startle potentiation to the experimental context in the predictable and unpredictable conditions, were investigated. Citalopram affected neither baseline startle nor short-duration fear-potentiated startle to discrete threat cues. However, citalopram reduced long-duration startle potentiation in the predictable conditions. These results are consistent with the hypothesis that short- and long-duration aversive states are mediated by distinct neural systems. They suggest that citalopram alleviates symptoms of anticipatory anxiety, not fear, by acting on mechanisms underlying long-duration aversive states.

BACKGROUND: Associations between a functional polymorphism in the serotonin transporter gene and amygdala activation have been found in healthy, depressed, and anxious adults. This study explored these gene-brain associations in adolescents by examining predictive effects of serotonin transporter gene variants (S and L(G) allele carriers vs. L(A) allele homozygotes) and their interaction with diagnosis (healthy vs. patients) on amygdala responses to emotional faces. METHODS: Functional magnetic resonance data were collected from 33 healthy adolescents (mean age: 13.71, 55% female) and 31 medication-free adolescents with current anxiety or depressive disorders (or both; mean age: 13.58, 56% female) while viewing fearful, angry, happy, and neutral facial expressions under varying attention states. RESULTS: A significant three-way genotype-by-diagnosis-by-face-emotion interaction characterized right amygdala activity while subjects monitored internal fear levels. This interaction was decomposed to map differential gene-brain associations in healthy and affected adolescents. First, consistent with healthy adult data, healthy adolescents with at least one copy of the S or L(G) allele showed stronger amygdala responses to fearful faces than healthy adolescents without these alleles. Second, patients with two copies of the L(A) allele exhibited greater amygdala responses to fearful faces relative to patients with S or L(G) alleles. Third, although weaker, genotype differences on amygdala responses in patients extended to happy faces. All effects were restricted to the fear-monitoring attention state. CONCLUSIONS: S/L(G) alleles in healthy adolescents, as in healthy adults, predict enhanced amygdala activation to fearful faces. Contrary findings of increased activation in patients with L(A)L(A) relative to the S or L(G) alleles require further exploration.

BACKGROUND:Panic disorder (PD) is hypothesized to be associated with altered function of the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Previous proton magnetic resonance spectroscopy (MRS) studies found lower GABA concentrations in the occipital cortex of subjects with PD relative to healthy control subjects. The current study is the first MRS study to compare GABA concentrations between unmedicated PD subjects and control subjects in the prefrontal cortex (PFC). METHODS:Unmedicated subjects with PD (n = 17) and age- and sex-matched healthy control subjects (n = 17) were scanned on a 3 Tesla scanner using a transmit-receive head coil that provided a sufficiently homogenous radiofrequency field to obtain spectroscopic measurements in the dorsomedial/dorsal anterolateral and ventromedial areas of the PFC. RESULTS:The prefrontal cortical GABA concentrations did not differ significantly between PD subjects and control subjects. There also was no statistically significant difference in glutamate/glutamine (Glx), choline, or N-acetyl aspartate concentrations. CONCLUSIONS:The previously reported finding of reduced GABA concentrations in the occipital cortex of PD subjects does not appear to extend to the PFC.

OBJECTIVE:: To evaluate the effects of stimulant medication on organizational, time management, and planning (OTMP) in children with attention-deficit/hyperactivity disorder (ADHD) and ascertain whether OTMP is normalized with medication. METHOD:: Participants included 19 stimulant-naive children with ADHD (aged 8-13 years) and impaired OTMP functioning, defined as greater than 1 SD below norms on the Children's Organizational Skills Scale. A double-blind, placebo-controlled, crossover design, with 4 weeks of each condition, evaluated medication (methylphenidate-osmotic-release oral system [MPH-OROS]) effects on OTMP, based on the parent and teacher versions of the Children's Organizational Skills Scale. The parent and teacher Swanson, Nolan, and Pelham, Version IV, rating scales assessed ADHD symptoms. 'Not impaired' in OTMP was defined as no longer meeting study entry criteria, and 'not impaired' in ADHD symptoms was defined as having mean Swanson, Nolan, and Pelham, Version IV, scores of </=1.0. RESULTS:: MPH-OROS significantly improved children's OTMP behaviors. These improvements were correlated with significant reductions in ADHD symptoms. However, most of the children (61%) continued to show significant OTMP impairments on MPH-OROS. CONCLUSIONS:: The MPH-OROS reduced children's OTMP deficits, and these improvements were associated with improvements in ADHD symptoms. Some children remained impaired in OTMP even after effective stimulant treatment of ADHD symptoms. These youngsters may require other treatments that target OTMP deficits

This randomized, double-blind, placebo-controlled, 6-month trial examined the efficacy and safety of once-daily morning-dosed atomoxetine in adult patients with attention-deficit/hyperactivity disorder (ADHD) and the efficacy of atomoxetine in ameliorating symptoms through the evening hours. Patients received once-daily atomoxetine (n = 250) or placebo (n = 251) in the morning for approximately 6 months. The efficacy measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version, Clinical Global Impressions-ADHD-Severity of Illness, and Adult ADHD Quality of Life Scale. Overall, 94 patients randomized to atomoxetine and 112 patients randomized to placebo completed the study. On the AISRS total score, Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version evening index total score, Clinical Global Impressions-ADHD-Severity of Illness score, and Adult ADHD Quality of Life Scale total score, atomoxetine was statistically superior to placebo at the 10-week and 6-month time points. From the visitwise analysis, the mean (SD) AISRS total scores for atomoxetine decreased from 38.2 (7.5) at baseline to 21.4 (12.3) at the 6-month end point compared with 38.6 (7.0) to 25.8 (13.2) for placebo (P = 0.035). Nausea, dry mouth, fatigue, decreased appetite, urinary hesitation, and erectile dysfunction were the treatment-emergent adverse events reported significantly more often with atomoxetine. Discontinuations due to adverse events were 17.2% and 5.6% for atomoxetine and placebo, respectively (P < 0.001). Once-daily morning-dosed atomoxetine is efficacious for treating ADHD in adults when measured 10 weeks and 6 months after initiating treatment. Atomoxetine demonstrated significant efficacy that continued into the evening. Adverse events were similar to previous trials

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has been widely used to investigate the development of white matter (WM). However, information about this development in healthy children younger than 2 years of age is lacking, and most previous studies have only measured fractional anisotropy (FA). This study used FA and radial and axonal diffusivities in children younger than 2 years of age, aiming to determine the temporal and spatial development of axonal maturation and myelination of WM in healthy children. MATERIALS AND METHODS: A total of 60 healthy pediatric subjects were imaged by using a 3T MR imaging scanner. They were divided into 3 groups: 20 at 3 weeks, 20 at 1 year of age, and 20 at 2 years of age. All subjects were imaged asleep without sedation. FA and axial and radial diffusivities were obtained. Eight regions of interest were defined, including both central and peripheral WM for measuring diffusion parameters. RESULTS: A significant elevation in FA (P < .0001) and a reduction in axial and radial diffusivities (P < .0001) were observed from 22 days to 1 year of age, whereas only radial diffusivity showed significant changes (P = .0014) from 1 to 2 years of age. The region-of-interest analysis revealed that FA alone may not depict the underlying biologic underpinnings of WM development, whereas directional diffusivities provide more insights into the development of WM. Finally, the spatial development of WM begins from the central to the peripheral WM and from the occipital to the frontal lobes. CONCLUSIONS: With both FA and directional diffusivities, our results demonstrate the temporal and spatial development of WM in healthy children younger than 2 years of age.

This study explores relationships among childhood sexual abuse (CSA), age of substance use initiation, additional traumatic events, and posttraumatic stress disorder (PTSD) in a sample of adolescents. A history of CSA that preceded substance use was not related to an earlier age of substance use initiation. Early initiation of substance use predicted exposure to additional traumatic experiences. This relationship was partially mediated by engagement in risky behavior while under the influence of substances. Posttraumatic stress disorder was related to CSA, additional traumatic experiences and engagement in risky behavior while under the influence of substances