John Sideris

Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP

We examined autistic behavior in a cross‐sectional sample of 179 children with fragile X syndrome (FXS) and a longitudinal subset of 116 children using the Childhood Autism Rating Scale (CARS) to (a) determine a prevalence of autistic behavior in FXS, (b) examine the stability of autistic ratings over time, and (c) assess the association between the fragile X mental retardation protein (FMRP) and autistic behavior. Approximately 21% of the sample of 129 children (25.9% of boys) scored at or above the cutoff for autism. CARS scores increased slowly, yet significantly, over time, and low levels of FMRP were associated with higher mean levels of autistic behavior as measured by the CARS.

Mood and anxiety disorders in females with the FMR1 premutation

Fragile X syndrome (FXS) is a model for studying the relative contributions of genetic and environmental factors to psychiatric disorders in mothers of children with disabilities. Here, we examine the frequency and predictors of mood and anxiety disorders in mothers with the FMR1 premutation. Ninety‐three females with the FMR1 premutation were in the study and were compared to 2,159 women from the National Comorbidity Survey Replication (NCS‐R) dataset. Mood and anxiety disorders were assessed using the SCID‐I. Our data reflect elevated lifetime major depressive disorder (MDD), lifetime panic disorder without agoraphobia and current agoraphobia without panic disorder in the FMR1 premutation sample. Also, we found a low frequency of lifetime social phobia, specific phobia, and post‐traumatic stress disorders and current specific phobia in the FMR1 premutation sample. The profile of MDD in the FMR1 premutation sample was not episodic or comorbid with an anxiety disorder, as in the NCS‐R dataset. Never having been married and smaller CGG repeat length were associated with increased likelihood of MDD while increased children with FXS in the family and greater child problem behaviors were associated with increased likelihood of an anxiety disorder in the FMR 1 premutation group. Major depression in females with the FMR1 premutation may not be characterized as an episodically chronic recurrent disorder as it is in community samples and may have a genetic basis given the relationship with CGG repeat length and lack of association with all child and most demographic factors.

Sensory features and repetitive behaviors in children with autism and developmental delays.

This study combined parent and observational measures to examine the association between aberrant sensory features and restricted, repetitive behaviors in children with autism (N=67) and those with developmental delays (N=42). Confirmatory factor analysis was used to empirically validate three sensory constructs of interest: hyperresponsiveness, hyporesponsiveness, and sensory seeking. Examining the association between the three derived sensory factor scores and scores on the Repetitive Behavior Scales—Revised revealed the co‐occurrence of these behaviors in both clinical groups. Specifically, high levels of hyperresponsive behaviors predicted high levels of repetitive behaviors, and the relationship between these variables remained the same controlling for mental age. We primarily found non‐significant associations between hyporesponsiveness or sensory seeking and repetitive behaviors, with the exception that sensory seeking was associated with ritualistic/sameness behaviors. These findings suggest that shared neurobiological mechanisms may underlie hyperresponsive sensory symptoms and repetitive behaviors and have implications for diagnostic classification as well as intervention.

ADHD symptoms in children with FXS.

Parent‐ and teacher‐report of attention‐deficit/hyperactivity disorder (ADHD) symptoms were examined using problem behavior and DSM‐IV symptom inventory questionnaires for 63 children with full mutation fragile X syndrome (FXS) and 56 children without disabilities matched on mental age (MA). Prevalence rates of ADHD symptoms varied depending on type of measure (problem behavior or DSM‐IV criteria), subscale (ADHD‐inattentive or ADHD‐hyperactive), scoring method (continuous T‐scores or categorical scores based on DSM‐IV algorithm), and rater (parent or teacher). Overall, 54–59% of boys with FXS met diagnostic behavioral criteria for either ADHD‐inattentive type only, ADHD‐hyperactive type only, or ADHD‐combined type based on parent or teacher report. Boys with FXS were rated as having clinically high scores or met diagnostic criteria at higher rates than expected for the general population and had higher raw scores than their MA‐matched peers. Parent ratings of boys with FXS resulted in higher ADHD‐inattentive type and ADHD‐hyperactive type T‐scores than teachers. Boys who were rated as meeting DSM‐IV criteria were more likely to be taking psychotropic medication and to have younger mental ages. Parents were substantially more likely than teachers to rate boys as meeting DSM‐IV criteria for ADHD‐inattentive type, while teachers were only slightly more likely than parents to rate boys as meeting DSM‐IV criteria for ADHD‐hyperactive type. Teachers were more likely than parents to rate boys as meeting DSM‐IV criteria for ADHD when boys had lower levels of FMRP.

Executive functions in young males with fragile X syndrome in comparison to mental age-matched controls: baseline findings from a longitudinal study.

The performance of 54 boys with fragile X syndrome (FXS), ages 7 to 13 years, was compared to that of a group of typically developing boys who were matched on mental age (MA) and ethnicity across multiple measures of executive function (EF). Boys with FXS varied in their ability to complete EF measures, with only 25.9% being able to complete a set-shifting task and 94.4% being able to complete a memory for word span task. When compared to the control group, and controlling for MA and maternal education, boys with FXS showed significant deficits in inhibition, working memory, cognitive flexibility/set-shifting, and planning. No group differences were observed in processing speed. Mental age significantly impacted performance on working memory, set-shifting, planning, and processing speed tasks for both groups. In boys with FXS, MA significantly predicted performance on working memory and set-shifting tasks. Our findings suggest that deficits in EF in boys with FXS are not solely attributable to developmental delays but, rather, present as a true array of neurocognitive deficits.

Developmental trajectories and correlates of sensory processing in young boys with fragile X syndrome.

Background and Purpose: No longitudinal study on sensory processing in children with fragile X syndrome (FXS) exists. This study examined developmental trajectories and correlates of sensory processing from infancy through preschool years in 13 boys with FXS. Method: Participants were assessed using observational and parent-report measures 2–6 times between 9 and 54 months of age. Results: Over time, an increasing proportion of boys displayed sensory processing that differed significantly from test norms. Observational measures were more sensitive than parent-reports early in infancy. Age and developmental quotient significantly predicted levels of hyporesponsiveness; there was a trend for hyperresponsiveness to increase with age. Baseline physiological and biological measures were not predictive. Conclusions: Sensory processing problems are observable early and grow increasingly problematic from infancy through the preschool ages. Early identification and intervention may attenuate long-term difficulties for children with FXS.

Emotional expression and the reduction of motivated cognitive bias: Evidence from cognitive dissonance and distancing from victims' paradigms.

Two experiments tested whether expression of emotions from which motivated cognitive biases presumably provide protection would reduce the extent of such biases. In Study I, we hypothesized that expressing any tension produced by writing a counterattitudinal essay would reduce the extent of dissonance-reducing attitude change. To test this hypothesis, Ss were induced to write an essay arguing for higher tuition. High-choice Ss were either encouraged to express their emotions, to suppress them, or to do neither. As expected, high-choice-express Ss exhibited the least attitude change. Study 2 tested the hypothesis that expressing fear of cancer would reduce the extent of defensive distancing from cancer patients, but expressing sympathy would not. Although control Ss clearly distanced from cancer patients, fear-expression Ss did not. Implications for understanding the role of affect in defense are discussed.

Child and genetic variables associated with maternal adaptation to fragile X syndrome: a multidimensional analysis.

One hundred eight carrier mothers (95 premutation, 13 full mutation) of children with the full mutation fragile X syndrome completed seven scales to assess maternal stress, depressive symptoms, anger, anxiety, quality of life, hope, and optimism. A wide range of responses was found on each measure, with most mothers scoring in the non‐clinical range on any individual measure. However, nearly half of the mothers scored in the clinically significant range on at least one measure and 25% on two or more measures. High stress and low quality of life were the most common domains of concern. Mothers with the full mutation generally did not differ from mothers with the premutation. CGG repeat length was not associated with responses on any of the measures completed by mothers with the premutation. Severity of the childs delay was not associated with any of the outcome measures, but child behavior problems accounted for significant variance in stress, depressive symptoms, anxiety, anger, and quality of life. Maternal adaptation appears to be a multidimensional phenomenon experienced in unique ways by each mother. Most mothers experienced positive adaptation, but a subset appear to be more vulnerable, especially those with children who have significant behavior problems. Future research needs to identify family, child, and support factors associated with maternal vulnerability and how adaptation changes over time in response to these factors.

Longitudinal predictors of reading and math trajectories through middle school for African American versus Caucasian students across two samples.

This studys primary purpose was to examine the relative contribution of social-behavioral predictors to reading and math skills. The study expands on Duncan et al.s (2007) work by using longitudinal methodology from the National Institute of Child Health and Human Developments Study of Child Care and Youth Development (SECCYD) and the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K) databases, and by focusing on potential differences in patterns of early predictors of later reading and math trajectories for African American versus Caucasian students. Predictor measures were selected at kindergarten, and the outcomes included standardized reading and math scores obtained from Grades 1, 3, 5, and 9 for the SECCYD sample, and Grades 3, 5, and 8 for the ECLS-K sample. Consistent with Duncan et al.s findings, results reflect the relative contributions of early reading and math skills to later functioning in these respective academic domains for both samples, and there are indications for the importance of early expressive language skills to both reading and math in the SECCYD sample. Findings related to the power of social-behavioral predictors, however, are not consistent across samples. Although the SECCYD sample evidenced no such predictors, several interactions in the ECLS-K sample suggested the moderating effects of early ratings of aggressive behaviors and internalizing behaviors on later reading and math for African American students. The moderating effects of early teacher ratings of attention and internalizing behaviors for African American students as compared with Caucasian students in later math growth also were noted. The importance of early social-behavioral functions as related to later academic skills remains an important area of inquiry.

Resting-State Connectivity Predictors of Response to Psychotherapy in Major Depressive Disorder

Despite the heterogeneous symptom presentation and complex etiology of major depressive disorder (MDD), functional neuroimaging studies have shown with remarkable consistency that dysfunction in mesocorticolimbic brain systems are central to the disorder. Relatively less research has focused on the identification of biological markers of response to antidepressant treatment that would serve to improve the personalized delivery of empirically supported antidepressant interventions. In the present study, we investigated whether resting-state functional brain connectivity (rs-fcMRI) predicted response to Behavioral Activation Treatment for Depression, an empirically validated psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20 matched nondepressed controls completed rs-fcMRI scans after which the MDD group received an average of 12 sessions of psychotherapy. The mean change in Beck Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically meaningful response. Resting-state neuroimaging data were analyzed with a seed-based approach to investigate functional connectivity with four canonical resting-state networks: the default mode network, the dorsal attention network, the executive control network, and the salience network. At baseline, the MDD group was characterized by relative hyperconnectivity of multiple regions with precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity of the precuneus with the left middle temporal gyrus and connectivity of the dACC with the parahippocampal gyrus predicted the magnitude of pretreatment MDD symptoms. Hierarchical linear modeling revealed that response to psychotherapy in the MDD group was predicted by pretreatment connectivity of the right insula with the right middle temporal gyrus and the left intraparietal sulcus with the orbital frontal cortex. These results add to the nascent body of literature investigating pretreatment rs-fcMRI predictors of antidepressant treatment response and is the first study to examine rs-fcMRI predictors of response to psychotherapy.