Narrative Ability in Autism and First-Degree Relatives.

Narrative is an important communication skill for sharing personal experiences and connecting with others. Narrative skills are often impacted in autism spectrum disorder (ASD) and have important consequences for social interactions and relationships. Subtle differences in narrative have also been reported among first-degree relatives of autistic individuals, suggesting that narrative may also be an etiologically important language-related skill that is influenced by genes associated with ASD. This study examined narrative ability and related visual attention during narration in ASD and first-degree relatives of individuals with ASD (siblings and parents) to understand how narrative and related attentional styles may be variably impacted across the spectrum of ASD genetic influence. Participants included 56 autistic individuals, 42 siblings of autistic individuals, 49 controls, 161 parents of autistic individuals, and 61 parent controls. Narratives were elicited using a wordless picture book presented on an eye tracker to record concurrent gaze. Findings revealed parallel patterns of narrative differences among ASD and sibling groups in the use of causal language to connect story elements and the use of cognitive and affective language. More subtle differences within the domain of causal language were evident in ASD parents. Parallel patterns in the ASD and sibling groups were also found for gaze during narration. Findings implicate causal language as a critical narrative skill that is impacted in ASD and may be reflective of ASD genetic influence in relatives. Gaze patterns during narration suggest similar attentional mechanisms associated with narrative among ASD families.

Differentiating Performance on the Connors Continuous Performance Test (CPT-3) as a Function of Comorbid Internalizing Psychopathology.

OBJECTIVE: Internalizing psychopathology commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD). Attention concerns are present in both ADHD and internalizing disorders, yet the neuropsychological functioning of those with comorbid ADHD and internalizing psychopathology is underexamined. METHOD: This study compared Conners' Continuous Performance Test-Third Edition (CPT-3) profiles across ADHD (n = 141), internalizing psychopathology (n = 78), and comorbid (ADHD/internalizing psychopathology; n = 240) groups. RESULTS: Compared to the internalizing psychopathology group, the comorbid group had higher mean T-scores on CPT-3 indices indicative of inattentiveness and impulsivity and more clinically elevated T-scores (T>60) on indices measuring inattentiveness and impaired sustained attention. Patients in the comorbid group were also more likely to have abnormal overall CPT-3 profiles (>2 elevated T-scores) than the ADHD and psychopathology only groups. CONCLUSION: Patients with comorbid ADHD/internalizing psychopathology may evidence a more impaired attentional performance on the CPT-3, which could aid in more tailored treatment planning.

The Effect of Adverse Childhood Experiences on ADHD Symptom Reporting, Psychological Symptoms, and Cognitive Performance Among Adult Neuropsychological Referrals.

OBJECTIVE: Adverse childhood experiences (ACEs) are early life experiences that influence mental health outcomes, though there are mixed findings reported in relation to attention deficit hyperactivity disorder (ADHD) symptoms. The current study compared adults who experienced ACEs on measures of ADHD symptom reporting, psychological symptoms, and neurocognitive test performance. METHOD: The sample (n = 115) had mean age of 28.42 (SD = 6.46); educational attainment of 16.47 years (SD = 1.99); and was 35% male/65% female and racially/ethnically diverse. Participants completed measures of ACEs, ADHD symptoms, psychopathology, and perceived stress, as well as neuropsychological tests. RESULTS: The high ACEs group endorsed higher levels of childhood/adulthood inattentive, impulsive, and hyperactive symptoms, and overall childhood symptoms when compared to the low ACEs group. CONCLUSIONS: This study provides a more comprehensive understanding of the association between ACEs and cognitive/mental health outcomes. Greater ACEs resulted in higher ADHD symptom reporting but not significantly greater psychological symptoms or worse neurocognitive performance.

Exploring Subfactors of Adult Cognitive Disengagement Syndrome and Impact on Neuropsychological Performance.

OBJECTIVE: This study investigated subfactors of cognitive disengagement syndrome (CDS; previously referred as sluggish cognitive tempo) among adults referred for neuropsychological evaluation of attentiondeficit/hyperactivity disorder (ADHD). METHOD: Retrospective analyses of data from 164 outpatient neuropsychological evaluations examined associations between CDS subfactors and self-reported psychological symptoms and cognitive performance. RESULTS: Factor analysis produced two distinct but positively correlated constructs: "Cognitive Complaints'' and "Lethargy." Both correlated positively with symptom reports (rs = 0.26-0.57). Cognitive Complaints correlated negatively with working memory, processing speed, and executive functioning performance (rs = -0.21 to -0.37), whereas Lethargy correlated negatively only with processing speed and executive functioning performance (rs = -0.26 to -0.42). Both predicted depression symptoms, but only Cognitive Complaints predicted inattention symptoms. Both subfactors demonstrated modest to nonsignificant associations with cognitive performance after accounting for estimated premorbid intelligence and inattention. CONCLUSION: Findings indicate a bidimensional conceptualization of CDS, with differential associations between its constituent subfactors, reported symptoms, and cognitive performance.

Childhood Academic Performance: A Potential Marker of Genetic Liability to Autism.

Autism spectrum disorder (ASD), a heritable neurodevelopmental disorder, confers genetic liability that is often expressed among relatives through subclinical, genetically-meaningful traits, or endophenotypes. For instance, relative to controls, parents of individuals with ASD differ in language-related skills, with differences emerging in childhood. To examine ASD-related endophenotypes, this study investigated developmental academic profiles among clinically unaffected siblings of individuals with ASD (n = 29). Lower performance in language-related skills among siblings mirrored previously-reported patterns among parents, which were also associated with greater subclinical ASD-related traits in themselves and their parents, and with greater symptom severity in their sibling with ASD. Findings demonstrated specific phenotypes, derived from standardized academic testing, that may represent childhood indicators of genetic liability to ASD in first-degree relatives.

Neural Processing of Speech Sounds in ASD and First-Degree Relatives.

Efficient neural encoding of sound plays a critical role in speech and language, and when impaired, may have reverberating effects on communication skills. This study investigated disruptions to neural processing of temporal and spectral properties of speech in individuals with ASD and their parents and found evidence of inefficient temporal encoding of speech sounds in both groups. The ASD group further demonstrated less robust neural representation of spectral properties of speech sounds. Associations between neural processing of speech sounds and language-related abilities were evident in both groups. Parent-child associations were also detected in neural pitch processing. Together, results suggest that atypical neural processing of speech sounds is a heritable ingredient contributing to the ASD language phenotype.

The Phenotypic Profile Associated With the FMR1 Premutation in Women: An Investigation of Clinical-Behavioral, Social-Cognitive, and Executive Abilities.

The FMR1 gene in its premutation (PM) state has been linked to a range of clinical and subclinical phenotypes among FMR1 PM carriers, including some subclinical traits associated with autism spectrum disorder (ASD). This study attempted to further characterize the phenotypic profile associated with the FMR1 PM by studying a battery of assessments examining clinical-behavioral traits, social-cognitive, and executive abilities in women carrying the FMR1 PM, and associations with FMR1-related variability. Participants included 152 female FMR1 PM carriers and 75 female controls who were similar in age and IQ, and screened for neuromotor impairments or signs of fragile X-associated tremor/ataxia syndrome. The phenotypic battery included assessments of ASD-related personality and language (i.e., pragmatic) traits, symptoms of anxiety and depression, four different social-cognitive tasks that tapped the ability to read internal states and emotions based on different cues (e.g., facial expressions, biological motion, and complex social scenes), and a measure of executive function. Results revealed a complex phenotypic profile among the PM carrier group, where subtle differences were observed in pragmatic language, executive function, and social-cognitive tasks that involved evaluating basic emotions and trustworthiness. The PM carrier group also showed elevated rates of ASD-related personality traits. In contrast, PM carriers performed similarly to controls on social-cognitive tasks that involved reliance on faces and biological motion. The PM group did not differ from controls on self-reported depression or anxiety symptoms. Using latent profile analysis, we observed three distinct subgroups of PM carriers who varied considerably in their performance across tasks. Among PM carriers, CGG repeat length was a significant predictor of pragmatic language violations. Results suggest a nuanced phenotypic profile characterized by subtle differences in select clinical-behavioral, social-cognitive, and executive abilities associated with the FMR1 PM in women.

Author Correction: Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

The original and corrected Acknowledgements are shown in the accompanying Author Correction.

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome.

Eye gaze and pupillary response in Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurological disorder characterized by severe developmental disability, communication impairment, elevated seizure risk, and motor system abnormalities. AIMS: The aims of this study were to determine the feasibility of social scene eye tracking and pupillometry measures in individuals with AS and to compare the performance of AS participants to individuals with idiopathic Autism Spectrum Disorder (ASD) and typically developing controls (TDC). METHODS AND PROCEDURES: Individuals with AS and age- and gender- matched controls completed a social eye tracking paradigm. Neurobehavioral characterization of AS participants was completed via a battery of psychological testing and caregiver behavioral evaluations. OUTCOMES AND RESULTS: Eight of seventeen recruited AS participants completed the eye tracking paradigm. Compared to TDC, AS subjects demonstrated significantly less preference for social scenes than geometric shapes. Additionally, AS subjects showed less pupil dilation, compared to TDC, when viewing social scenes versus geometric shapes. There was no statistically significant difference found between AS and ASD subjects in either social eye tracking or pupillometry. CONCLUSIONS AND IMPLICATIONS: The use of eye tracking and pupillometry may represent an innovative measure for quantifying AS-associated impairments in social salience.