OBJECTIVES: To compare 2 short-term, community caregiver training interventions for preschool-aged children with Autism Spectrum Disorder who had low resources. Low resource was defined by the US Department of Housing and Urban Development low-income index or 1 “indicator,” (eg, Medicaid eligibility). Child outcomes focused on joint engagement, joint attention, and play. METHODS: Participants included 112 families of a child who had Autism Spectrum Disorder who met criteria for being low-resourced and who were randomly assigned to 1 of 2 3-month interventions, group caregiver education or individualized caregiver-mediated intervention (CMM). Children were assessed for social communication skills pre- and post-treatment, and followed up at 3 months. RESULTS: All children improved in joint engagement and initiating joint attention, with significantly greater improvement by the CMM group. Outcomes on play skills were mixed, with improvement of symbolic play for the CMM group and no change in functional play skills. Joint engagement maintained over time for the CMM group, and initiating joint attention maintained for both groups over time. CONCLUSIONS: This study is among the first randomized trials comparing 2 active interventions with a large sample of low-resourced families. Results suggest improvements in core autism deficits of joint engagement, joint attention, and symbolic play with relatively brief, caregiver-mediated interventions, but additional support is necessary to maintain and generalize these gains over time.

Peak alpha frequency is a neural marker of cognitive function across the autism spectrum. Permalink AbstractCognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants.

Intelligence testing in children with intellectual disabilities (ID) has significant limitations. The normative samples of widely used intelligence tests, such as the Wechsler Intelligence Scales, rarely include an adequate number of subjects with ID needed to provide sensitive measurement in the very low ability range, and they are highly subject to floor effects. The IQ measurement problems in these children prevent characterization of strengths and weaknesses, poorer estimates of cognitive abilities in research applications, and in clinical settings, limited utility for assessment, prognosis estimation, and planning intervention. Here, we examined the sensitivity of the Wechsler Intelligence Scale for Children (WISC-III) in a large sample of children with fragile X syndrome (FXS), the most common cause of inherited ID. The WISC-III was administered to 217 children with FXS (age 6–17 years, 83 girls and 134 boys). Using raw norms data obtained with permission from the Psychological Corporation, we calculated normalized scores representing each participant’s actual deviation from the standardization sample using a z-score transformation. To validate this approach, we compared correlations between the new normalized scores versus the usual standard scores with a measure of adaptive behavior (Vineland Adaptive Behavior Scales) and with a genetic measure specific to FXS (FMR1 protein or FMRP). The distribution of WISC-III standard scores showed significant skewing with floor effects in a high proportion of participants, especially males (64.9%–94.0% across subtests). With the z-score normalization, the flooring problems were eliminated and scores were normally distributed. Furthermore, we found correlations between cognitive performance and adaptive behavior, and between cognition and FMRP that were very much improved when using these normalized scores in contrast to the usual standardized scores. The results of this study show that meaningful variation in intellectual ability in children with FXS, and probably other populations of children with neurodevelopmental disorders, is obscured by the usual translation of raw scores into standardized scores. A method of raw score transformation may improve the characterization of cognitive functioning in ID populations, especially for research applications.

Short-term low intensity parent implemented intervention studies for toddlers with autism spectrum disorder (ASD) have found it difficult to demonstrate significantly improved developmental scores or autism severity compared to community treatment. We conducted a randomized comparative intent-to-treat study of a parent implemented intervention to (1) test the effects of an enhanced version on parent and child learning, and (2) evaluate the sensitivity to change of proximal versus distal measures of child behavior. We randomized 45 children with ASD, 12-30 months of age, into one of two versions of parent-implemented Early Start Denver Model (P-ESDM), the basic model, in which we delivered 1.5 h of clinic-based parent coaching weekly, and an enhanced version that contained three additions: motivational interviewing, multimodal learning tools, and a weekly 1.5-h home visit. We delivered the intervention for 12 weeks and measured child and parent change frequently in multiple settings. We found a time-by-group interaction: parents in the enhanced group demonstrated significantly greater gains in interaction skills than did parents in the non-enhanced group. Both interventions were associated with significant developmental acceleration; however, child outcomes did not differ by group. We found a significant relationship between degree of change in parental interaction skill and rate of children's improvement on our proximal measure. Parents in both groups reported satisfaction with the intervention. These findings suggest that parent skills improved more in the enhanced group than the comparison group. Children in the two groups showed similar improvements. Rate of individual parent learning was associated with greater individual child progress on a measure quite proximal to the treatment, though not on standardized assessments.

Introduction22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins.MethodsHigh-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10–25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed.ResultsRelative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS.ConclusionDifferential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.

Objective We evaluated the potential of methylphenidate to improve antidepressant response to citalopram in elderly depressed patients with respect to clinical and cognitive outcomes. Methods We conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three groups: 1) methylphenidate and placebo (N=48); 2) citalopram and placebo (N=48); 3) methylphenidate and citalopram (N=47). Primary outcome was defined as the change in depression severity. Remission was defined as Hamilton Depression Rating Scale (HDRS-24) score of 6 or below. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition. Results Citalopram daily doses ranged between 20–60 mg (mean 32 mg); methylphenidate daily doses ranged between 5–40 mg (mean 16 mg). All groups showed significant improvement in the severity of depression. However, the improvement in depression severity and the clinical global impression was more prominent in the methylphenidate and citalopram group compared to methylphenidate and placebo and citalopram and placebo (P<0.05). Additionally, the rate of improvement in the methylphenidate and citalopram group was significantly faster than that in the citalopram and placebo in the first 4 weeks of the trial. The groups did not differ on cognitive improvement or the number of side-effects. Conclusions Combined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in the mood and wellbeing, and the rate of response compared to either drug. All treatments led to an improvement in cognitive functioning, without additional benefit from the use of methylphenidate.

The U.S. military deployed in support to Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) show high rates of posttraumatic stress disorder (PTSD) and relationship, partner, and parenting distress. Given the pervasive effect of combat-related PTSD on returning veterans and its effect on their loved ones, the investigators have developed a couples-based treatment, structured approach therapy (SAT), to reduce PTSD while simultaneously decreasing relationship and partner distress. This study presents treatment outcome data measuring PTSD and relationship outcomes from a randomized clinical trial (RCT) comparing SAT, a manualized 12-session novel couples-based PTSD treatment, to a manualized 12-session couples-based educational intervention (PTSD Family Education [PFE]). Data were collected from 57 returning veterans meeting Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text revision; DSM-IV-TR) criteria for PTSD and their cohabiting partners; data collection was scheduled for pretreatment, posttreatment, and 3-month follow-up. Findings from an intent-to-treat analysis revealed that veterans receiving SAT showed significantly greater reductions in self-rated (PTSD Checklist; p < .0006) and Clinician-Administered PTSD Scale (CAPS)-rated PTSD (p < .0001) through the 3-month follow-up compared with veterans receiving PFE; 15 of 29 (52%) veterans receiving SAT and 2 of 28 (7%) receiving PFE no longer met DSM-IV-TR criteria for PTSD. Furthermore, SAT was associated with significant improvements in veteran relationship adjustment, attachment avoidance, and state anxiety. Partners showed significant reductions in attachment anxiety. This couples-based treatment for combat-related PTSD appears to have a strong therapeutic effect on combat-related PTSD in recently returned veterans.

This prospective study characterizes early developmental markers of ASD in infants with TSC. The early delay in visual reception and fine motor ability in the TSC group as a whole, coupled with the decline in nonverbal ability in infants diagnosed with ASD, suggests a domain-specific pathway to ASD that can inform more targeted interventions for these high-risk infants.