A Comparative Analysis of the ADOS-G and ADOS-2 Algorithms: Preliminary Findings.

The Autism Diagnostic Observation Schedule (ADOS) is a widely utilized observational assessment tool for diagnosis of autism spectrum disorders. The original ADOS was succeeded by the ADOS-G with noted improvements. More recently, the ADOS-2 was introduced to further increase its diagnostic accuracy. Studies examining the validity of the ADOS have produced mixed findings, and pooled relationship trends between the algorithm versions are yet to be analyzed. The current review seeks to compare the relative merits of the ADOS-G and ADOS-2 algorithms, Modules 1-3. Eight studies met inclusion criteria for the review, and six were selected for paired comparisons of the sensitivity and specificity of the ADOS. Results indicate several contradictory findings, underscoring the importance of further study.

Aberrant development of post-movement beta rebound in adolescents and young adults with fetal alcohol spectrum disorders.

Dependent on maternal (e.g. genetic, age) and exposure (frequency, quantity, and timing) variables, the effects of prenatal alcohol exposure on the developing fetus are known to vary widely, producing a broad range of morphological anomalies and neurocognitive deficits in offspring, referred to as fetal alcohol spectrum disorders (FASD). Maternal drinking during pregnancy remains a leading risk factor for the development of intellectual disabilities in the US. While few functional findings exist today that shed light on the mechanisms responsible for the observed impairments in individuals with FASD, animal models consistently report deleterious effects of early alcohol exposure on GABA-ergic inhibitory pathways. The post-motor beta rebound (PMBR), a transient increase of 15-30 Hz beta power in the motor cortex that follows the termination of movement, has been implicated as a neural signature of GABA-ergic inhibitory activity. Further, PMBR has been shown to be a reliable predictor of age in adolescents. The present study sought to investigate any differences in the development of PMBR between FASD and control groups. Beta event-related de-synchronization (ERD) and movement-related gamma synchronization (MRGS), although not clearly linked to brain maturation, were also examined. Twenty-two participants with FASD and 22 age and sex-matched controls (12-22 years old) underwent magnetoencephalography scans while performing an auditory oddball task, which required a button press in response to select target stimuli. The data surrounding the button presses were localized to the participants' motor cortices, and the time courses from the locations of the maximally evoked PMBR were subjected to wavelet analyses. The subsequent analysis of PMBR, ERD, and MRGS revealed a significant interaction between group and age in their effects on PMBR. While age had a significant effect on PMBR in the controls, no simple effects of age were detected in the FASD group. The FASD group additionally displayed decreased overall ERD levels. No group or age effects on MRGS were detected. The described findings provide further evidence for broad impairments in inhibitory processes in adolescents with FASD, possibly related to aberrant development of GABA-ergic pathways.

Sex-related differences in auditory processing in adolescents with fetal alcohol spectrum disorder: A magnetoencephalographic study.

Children exposed to substantial amounts of alcohol in utero display a broad range of morphological and behavioral outcomes, which are collectively referred to as fetal alcohol spectrum disorders (FASDs). Common to all children on the spectrum are cognitive and behavioral problems that reflect central nervous system dysfunction. Little is known, however, about the potential effects of variables such as sex on alcohol-induced brain damage. The goal of the current research was to utilize magnetoencephalography (MEG) to examine the effect of sex on brain dynamics in adolescents and young adults with FASD during the performance of an auditory oddball task. The stimuli were short trains of 1 kHz "standard" tone bursts (80%) randomly interleaved with 1.5 kHz "target" tone bursts (10%) and "novel" digital sounds (10%). Participants made motor responses to the target tones. Results are reported for 44 individuals (18 males and 26 females) ages 12 through 22 years. Nine males and 13 females had a diagnosis of FASD and the remainder were typically-developing age- and sex-matched controls. The main finding was widespread sex-specific differential activation of the frontal, medial and temporal cortex in adolescents with FASD compared to typically developing controls. Significant differences in evoked-response and time-frequency measures of brain dynamics were observed for all stimulus types in the auditory cortex, inferior frontal sulcus and hippocampus. These results underscore the importance of considering the influence of sex when analyzing neurophysiological data in children with FASD.

Delays in auditory processing identified in preschool children with FASD.

BACKGROUND: Both sensory and cognitive deficits have been associated with prenatal exposure to alcohol; however, very few studies have focused on sensory deficits in preschool-aged children. As sensory skills develop early, characterization of sensory deficits using novel imaging methods may reveal important neural markers of prenatal alcohol exposure. METHODS: Participants in this study were 10 children with a fetal alcohol spectrum disorder (FASD) and 15 healthy control (HC) children aged 3 to 6 years. All participants had normal hearing as determined by clinical screens. We measured their neurophysiological responses to auditory stimuli (1,000 Hz, 72 dB tone) using magnetoencephalography (MEG). We used a multidipole spatio-temporal modeling technique to identify the location and timecourse of cortical activity in response to the auditory tones. The timing and amplitude of the left and right superior temporal gyrus sources associated with activation of left and right primary/secondary auditory cortices were compared across groups. RESULTS: There was a significant delay in M100 and M200 latencies for the FASD children relative to the HC children (p = 0.01), when including age as a covariate. The within-subjects effect of hemisphere was not significant. A comparable delay in M100 and M200 latencies was observed in children across the FASD subtypes. CONCLUSIONS: Auditory delay revealed by MEG in children with FASDs may prove to be a useful neural marker of information processing difficulties in young children with prenatal alcohol exposure. The fact that delayed auditory responses were observed across the FASD spectrum suggests that it may be a sensitive measure of alcohol-induced brain damage. Therefore, this measure in conjunction with other clinical tools may prove useful for early identification of alcohol affected children, particularly those without dysmorphia.

From research to practice: an integrative framework for the development of interventions for children with fetal alcohol spectrum disorders.

Since fetal alcohol syndrome was first described over 35 years ago, considerable progress has been made in the delineation of the neurocognitive profile in children with prenatal alcohol exposure. Preclinical investigators have made impressive strides in elucidating the mechanisms of alcohol teratogenesis and in testing the effectiveness of pharmacological agents and dietary supplementation in the amelioration of alcohol-induced deficits. Despite these advances, only limited progress has been made in the development of evidence-based comprehensive interventions for functional impairment in alcohol-exposed children. Having performed a search in PubMed and PsycINFO using key words, interventions, treatment, fetal alcohol syndrome, prenatal alcohol exposure, and fetal alcohol spectrum disorders, we found only 12 papers on empirically-based interventions. Only two of these interventions had been replicated and none met the criteria of "well-established," as defined by Chambless and Hollon (Journal of Consulting and Clinical Psychology 66(1):7-18, 1998). There has been only limited cross-fertilization of ideas between preclinical and clinical research with regard to the development of interventions. Therefore, we propose a framework that allows integrating data from preclinical and clinical investigations to develop comprehensive intervention programs for children with fetal alcohol spectrum disorders. This framework underscores the importance of multi-level evaluations and interventions.

A neurodevelopmental framework for the development of interventions for children with fetal alcohol spectrum disorders.

Despite considerable data published on cognitive and behavioral disabilities in children with fetal alcohol spectrum disorders (FASD), relatively little information is available on behavioral or pharmacological interventions for alcohol-affected children. The main goals of this article, therefore, are to summarize published intervention studies of FASD and to present a neurodevelopmental framework, based on recent findings from a number of disciplines, for designing new therapies for alcohol-affected children. This framework assumes a neuroconstructionist view, which posits that reciprocal interactions between neural activity and the brain's hardware lead to the progressive formation of intra- and interregional neural connections. In this view, behavioral interventions can be conceptualized as a series of guided experiences that are designed to produce neural activation. Based on evidence from cognitive neuroscience, it is hypothesized that specific interventions targeting executive attention and self-regulation may produce greater generalizable results than those aimed at domain-specific skills in children with FASD. In view of reciprocal interactions between environmental effects and neural structures, the proposed framework suggests that the maximum effects of interventions can eventually be achieved by optimally combining behavioral methods and cognition-enhancing drugs.

Neurocognitive profile in children with fetal alcohol spectrum disorders.

The question of whether children with fetal alcohol spectrum disorders (FASD) exhibit a unique neurocognitive profile has received considerable attention over the past three decades. The identification of a syndrome-specific neurocognitive profile would aid in diagnosing prenatally exposed children with cognitive deficits who do not exhibit clinically discernable physical anomalies. The current review of the literature, therefore, focuses on the studies of higher-order cognitive skills in children with FASDs with a view towards delineating a pattern of cognitive functioning. Researchers have documented that children with FASDs show diminished intellectual functioning, with average IQ scores falling within the borderline to low average ranges. Slow information processing and disturbances of attention have been observed from infancy through adulthood in individuals with FASDs. Clinical and experimental reports on individuals with FASD have documented marked deficits in executive functioning, particularly in tasks that involve holding and manipulating information in working memory. Studies examining specific domains of cognitive functioning such as language, visual perception, memory and learning, social functioning, and number processing in individuals with FASDs have revealed performance decrements associated with increased task complexity. The above findings converge on the conclusion that children with FASDs have a generalized deficit in the processing and integration of information. We recommend the study of developmental trajectories of both elementary and higher-order functions in future research on FASD to elucidate the development of this cognitive profile.

Epidemiology of FASD in a province in Italy: Prevalence and characteristics of children in a random sample of schools.

BACKGROUND: Accurate estimates of the prevalence and characteristics of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) in a Western European population are lacking and are of particular interest in settings where the usual pattern of alcohol consumption is thought to be daily drinking with meals. To address these issues, an epidemiology study of FAS and other FASD was undertaken in Italian schools. METHODS: Primary schools (n = 25) in 2 health districts of the Lazio region were randomly selected and recruited for the study. Five hundred forty-three children, 50% of those enrolled in first-grade classes, received parental permission to participate in a 2-tiered, active case ascertainment screening process. Detailed evaluation of children selected in a preliminary screening phase was carried out on those who were small for height, weight, and head circumference and/or referred by teachers for suspected learning and behavioral problems. Detailed evaluation was carried out on each child's: (1) physical growth and dysmorphology, (2) psychological development and behavior, and (3) prenatal exposure to alcohol and other risk factors for FASD via maternal interviews. A group of 67 randomly selected children without FASD from the same classes was utilized as a comparison group. RESULTS: Using 2 denominators for prevalence estimation, a conservative one and a strict sample-based estimate, the prevalence of FAS in this province of Italy was 3.7 to 7.4 per 1,000 children. When cases of partial FAS (PFAS) and a case of alcohol-related neurodevelopmental deficits (ARND) were added to FAS cases, the rate of FASD was 20.3 to 40.5 per 1,000 and estimated at 35 per 1,000 overall or between 2.3 and 4.1% of all children. This exceeds previously published estimates of both FAS and FASD for the western world. Detailed data are presented that demonstrate the utility of the guidelines of the revised Institute of Medicine diagnostic criteria for FASD. Children with FASD are significantly more impaired/affected (p < 0.05) than randomly selected comparison children on all measures of growth deficiency, key facial features of FASD, overall dysmorphology scores, language comprehension, nonverbal IQ, and behavior. Maternal reports of current drinking were significantly higher for mothers of FASD children than comparison mothers, but reported rates of overall drinking during pregnancy were not significantly different. In contrast to expectations, daily drinking among mothers of the comparison group was not common. However, dysmorphology scores of the children were significantly correlated with drinking in the second and third trimesters, drinks per current drinking day, and current drinks per month. Finally, children with the physical features of FASD had lower IQs; nonverbal IQ was significantly correlated with head circumference and negatively correlated with overall dysmorphology score, smooth philtrum, and several other facial and physical anomalies characteristic of FAS. CONCLUSIONS: Using careful measures of ascertainment in a primary school setting, these results provide relatively high estimates of the prevalence of FASD and raise the question of whether FASD is more common in the western world than previously estimated.

Letter and category fluency in children with fetal alcohol syndrome from a community in South Africa.

OBJECTIVE: This study investigated whether there were differential effects of substantial prenatal alcohol exposure on letter and category fluency in children. Given that children with prenatal alcohol exposure are often impaired in executive functioning and that letter fluency taxes executive processes more than category fluency, it was expected that children with fetal alcohol syndrome (FAS) would be more impaired in letter than in category fluency. A second objective of the study was to examine the developmental trends in the two types of fluency in children with prenatal alcohol exposure. It was hypothesized that between the ages of 6 and 9 years, these FAS children would show age-related changes in category fluency but not in letter fluency. METHOD: As part of a neuropsychological test battery designed for an international collaborative study of FAS in South Africa, tests of letter and category fluency were administered in Afrikaans. The participants were 62 children with FAS and 61 controls matched with respect to age, gender (58 boys and 65 girls), ethnicity, and socioeconomic status. RESULTS: Results showed that the FAS group had relatively greater difficulty with letter fluency than with category fluency and that the FAS group generated fewer words in both fluency conditions. Contrary to the expectation, however, alcohol-affected children demonstrated age-related linear trends in both letter and category fluency. CONCLUSIONS: This is the first study of verbal fluency involving a large sample of well-diagnosed children with FAS conducted in a nonwestern environment. The results are nonetheless consistent with those obtained in western countries in studies of children with various levels of prenatal alcohol exposure and various levels of fetal alcohol spectrum disorder. This study suggests that at least some aspects of the cognitive profile associated with prenatal alcohol exposure may be generalizable across cultural and ethnic boundaries.

Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder.

BACKGROUND: Reduced hippocampal volumes in posttraumatic stress disorder (PTSD) patients are thought to reflect specific changes of this structure. Previous magnetic resonance imaging (MRI) studies have not consistently examined indices of overall brain atrophy, therefore it cannot be completely ruled out that hippocampal changes are explained by whole-brain atrophy. The purpose of this study was to assess hippocampal and whole-brain volume in civilian PTSD. METHODS: Twelve subjects with PTSD and 10 control subjects underwent brain MRI. Hippocampal volumes were visually quantified using a computerized volumetric program. Whole-brain volumes were obtained with automated k-means-based segmentation. RESULTS: No differences were found in intracranial volumes (ICV). Subjects with PTSD had higher cerebrospinal fluid (CSF)/ICV ratios and lower white matter/ICV ratios, consistent with generalized white matter (WM) atrophy. The effect of age on CSF/ICV was more pronounced in the PTSD group. Subjects with PTSD had smaller absolute and normalized bilateral hippocampal volumes. These differences persisted after adjusting for lifetime weeks of alcohol intoxication. Posttraumatic stress disorder and depression scores correlated negatively with left hippocampal volume, but PTSD scores were a better predictor of hippocampal volumes. CONCLUSIONS: Our results replicate previous findings of reduced hippocampal volume in PTSD but also suggest independent, generalized, white matter atrophy.

Characteristics of mothers of children with fetal alcohol syndrome in the Western Cape Province of South Africa: a case control study.

OBJECTIVE: Factors associated with alcohol consumption during pregnancy and with fetal alcohol syndrome (FAS) births were examined as part of a larger epidemiologic study of FAS in a community in the Western Cape Province of South Africa. METHOD: Using retrospective case-control methodology, 31 mothers who had given birth to FAS children 6 to 9 years previously were compared with 31 matched controls on a variety of demographic, socioeconomic, drinking, family and maternity variables. Descriptive analyses were utilized to determine major differential characteristics between the two groups. RESULTS: In this community with a very high rate of FAS and rather uniform low socioeconomic status, the two groups were found to be comparable with respect to age, annual income, ethnic background, age of initiation of regular drinking, age at birth of the index child, gravidity and parity. However, mothers of FAS children reported initiating drinking at an earlier age, as well as reporting higher rates of heavy alcohol consumption in their extended family, current use of alcohol, drinking before and during pregnancy, and smoking of tobacco (percentage who smoke) during each trimester of the pregnancy. Mothers of FAS children had lower educational attainment and reported lower religiosity than control mothers. CONCLUSIONS: This study in South Africa draws upon the experience of mothers of 31 children with FAS to confirm many of the same high-risk variables identified in maternal risk studies in the United States and Europe. Some factors associated with less maternal alcohol abuse in this high-risk population were also identified, which may be helpful for implementing prevention in this region as well as in other developing countries.