Dysfunctional oscillatory bursting patterns underlie working memory deficits in adolescents with ADHD.

Identifying neural markers of clinical symptom fluctuations is prerequisite to developing more precise brain-targeted treatments in psychiatry. We have recently shown that working memory (WM) in healthy adults is dependent on the rise and fall interplay between alpha/beta and gamma bursts within frontoparietal regions, and that deviations in these patterns lead to WM performance errors. However, it is not known whether such bursting deviations underlie clinically relevant WM-related symptoms or clinical status in individuals with WM deficits.

Developmental phenotype and quality of life in SLC13A5 citrate transporter disorder.

Aim: To describe the neurodevelopment and quality of life in SLC13A5 (solute carrier family 13 member 5) citrate transporter disorder (developmental and epileptic encephalopathy 25, DEE25), a rare genetic early infantile epileptic encephalopathy caused by deficiency of a sodium-citrate transporter, characterized by heavy seizure burden in the neonatal period.

Method: We analyzed longitudinal neurodevelopmental outcomes from a prospective natural history study of DEE25, using standardized assessments of Mullen Scales of Early Learning, Peabody Developmental Motor Scales, and Vineland Adaptive Behavior Scales.

Results: There was significant global impairment across the cohort, with variable quality of life and limited genotype-phenotype correlation.

Transdiagnostic Attentional Deficits Are Associated with Depressive and Externalizing Symptoms in Children and Adolescents with Neuropsychiatric Disorders.

Objective: Although inattention, impulsivity, and impairments to vigilance are most associated with attention-deficit/hyperactivity disorder (ADHD), transdiagnostic attentional deficits are prevalent across all psychiatric disorders. To further elucidate this relationship, the present study investigated parent-reported neuropsychiatric symptom correlates of attention deficits using the factor structure of the Conners' Continuous Performance Test (CPT-II), a neuropsychological test of attention.

Method: Two-hundred and eighteen children and adolescents (7-21 years old) completed the CPT-II as part of standard clinical protocol during outpatient pediatric neuropsychology visits.

Sleep Abnormalities in SLC13A5 Citrate Transporter Disorder.

Background: SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder. Patients have epilepsy, developmental disability, and impaired mobility. While sleep disorders are common in children with neurodevelopmental disorders, sleep abnormalities have not been reported in SLC13A5 patients.

Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults.

Objectives: Mutations in the X-linked endosomal Na+/H+ exchanger 6 (NHE6) cause Christianson syndrome (CS). Here, in the largest study to date, we examine genetic diversity and clinical progression in CS into adulthood.

Method: Data were collected as part of the International Christianson Syndrome and () Gene Network Study.

The Tower of London task in children and adolescents with neuropsychiatric disorders.

The Tower of London, Drexel Version, Second Edition (TOL-DX) is purported to measure multiple aspects of executive functions, although it also possesses inherent non-executive demands. Such complexity makes it useful in detecting impairment but difficult in interpreting the neurocognitive cause of impairment, particularly in children. This study investigated the developmental, neurocognitive, and symptom correlates of the TOL-DX in children and adolescents with neuropsychiatric disorders.

Early childhood trauma exposure and neurocognitive and emotional processes: Associations in young children in a partial hospital program.

Early childhood trauma has been linked to neurocognitive and emotional processing deficits in older children, yet much less is known about these associations in young children. Early childhood is an important developmental period in which to examine relations between trauma and executive functioning/emotion reactivity, given that these capacities are rapidly developing and are potential transdiagnostic factors implicated in the development of psychopathology. This cross-sectional study examined associations between cumulative trauma, interpersonal trauma, and components of executive functioning, episodic memory, and emotion reactivity, conceptualized using the RDoC framework and assessed with observational and performance-based measures, in a sample of 90 children (ages 4-7) admitted to a partial hospital program.

Frontoparietal beta event characteristics are associated with early life stress and psychiatric symptoms in adults.

Recent work has found that the presence of transient, oscillatory burst-like events, particularly within the beta band (15-29 Hz), is more closely tied to disease state and behavior across species than traditional electroencephalography (EEG) power metrics. This study sought to examine whether features of beta events over frontoparietal electrodes were associated with early life stress (ELS) and the related clinical presentation. Eighteen adults with documented ELS (n = 18; ELS + ) and eighteen adults without documented ELS (n = 18; ELS-) completed eyes-closed resting state EEG as part of their participation in a larger childhood stress study.

Childhood stress, gender, and cognitive control: Midline theta power.

The emergence of psychiatric symptoms is a common consequence of childhood stress exposure. However, there are a dearth of reliable clinical hallmarks or physiological biomarkers to predict post-trauma symptom emergence. The objective of this study was to examine if childhood stressors and stress-related symptoms are associated with altered midline theta power (MTP) during cognitive control demands, and how these associations interact with gender and early adversity.

Christianson Syndrome across the Lifespan: An International Longitudinal Study in Children, Adolescents, and Adults.

Mutations in the X-linked endosomal Na+/H+ Exchanger 6 (NHE6) causes Christianson Syndrome (CS). In the largest study to date, we examine genetic diversity and clinical progression, including cerebellar degeneration, in CS into adulthood. Data were collected as part of the International Christianson Syndrome and NHE6 (SLC9A6) Gene Network Study.

Pre-treatment frontal beta events are associated with executive dysfunction improvement after repetitive transcranial magnetic stimulation for depression: A preliminary report.

Repetitive transcranial magnetic stimulation (rTMS) is an established clinical treatment for major depressive disorder (MDD) that has also been found to improve aspects of executive functioning. The objective of this study was to examine whether oscillatory burst-like events within the beta band (15-29 Hz) prior to treatment could predict subsequent change in self-reported executive dysfunction (EDF) across a clinical course of rTMS for MDD. Twenty-eight adults (64% female) with MDD completed the self-report Frontal Systems Behavior Scale (FrSBe) and provided eyes-closed resting-state electroencephalography (EEG) before and after a clinical course of rTMS therapy for primary MDD.

Parental age and autism severity in the Rhode Island Consortium for Autism Research and Treatment (RI-CART) study.

Advanced parental age at offspring birth has been associated with autism spectrum disorder (ASD). The objective of the current study was to investigate associations between parental age at birth and autism severity. The Rhode Island Consortium for Autism Research and Treatment (RI-CART) study represents a community-based sample with a range of autism severity, including participants with and without ASD.

Cognitive Control Deficits in Depression: A Novel Target to Improve Suboptimal Outcomes in Childhood.

Cognitive control deficits are one of three primary endophenotypes in depression, and the enhanced targeting of these deficits in clinical and research work is expected to lead to improved depression outcomes. Cognitive control is a set of self-regulatory processes responsible for goal-oriented behavior that predicts clinical/functional outcomes across the spectrum of brain-based disorders. In depression, cognitive control deficits emerge by the first depressive episode, persist during symptom remission, and worsen over the course of depression.

Psychiatric Outcomes of Childhood Maltreatment: A Retrospective Chart Review from a Children's Psychiatric Inpatient Program.

Childhood maltreatment is linked to deleterious outcomes, whereby post-traumatic stress disorder (PTSD) has been identified as one of the most debilitating. This retrospective chart review examined whether self-reported affective measures (anxiety, depression, trauma), type of maltreatment (sexual, physical, emotional/verbal abuses), and demographics predicted a diagnosis of anxiety or PTSD among 169 children in a psychiatric inpatient hospital. Secondly, this study identified significant predictors of a PTSD diagnosis.

Moderators of Age of Diagnosis in > 20,000 Females with Autism in Two Large US Studies.

The objective of this study was to determine the clinical features that moderate a later age at ASD diagnosis in females in a large sample of females with ASD. Within two large and independent ASD datasets (> 20,000 females), females were first diagnosed with ASD 14-months later relative to males. This later age at diagnosis was moderated by a mild or atypical presentation, wherein repetitive behaviors were limited, IQ and language were broadly intact, and recognized symptoms emerged later in development.

A preliminary investigation of childhood anxiety/depressive symptomatology and working memory across multiple units of analysis.

This exploratory study examined multiple units of working memory (WM) analysis in a transdiagnostic, treatment-seeking, pediatric sample. This included a) an electroencephalography marker of WM (coupling of theta and gamma oscillations [i.e.

Human neurons from Christianson syndrome iPSCs reveal mutation-specific responses to rescue strategies.

Christianson syndrome (CS), an X-linked neurological disorder characterized by postnatal attenuation of brain growth (postnatal microcephaly), is caused by mutations in , the gene encoding endosomal Na/H exchanger 6 (NHE6). To hasten treatment development, we established induced pluripotent stem cell (iPSC) lines from patients with CS representing a mutational spectrum, as well as biologically related and isogenic control lines. We demonstrated that pathogenic mutations lead to loss of protein function by a variety of mechanisms: The majority of mutations caused loss of mRNA due to nonsense-mediated mRNA decay; however, a recurrent, missense mutation (the G383D mutation) had both loss-of-function and dominant-negative activities.

The association between neurocognition and sexual abuse within a children's psychiatric inpatient program.

: The aim of this study was to understand the detrimental effects of sexual abuse on neuropsychological variables including child's intelligence, executive functioning (EF), and learning/memory within a pediatric inpatient population.: This study examined the effect of sexual abuse on children's intelligence, EF, and learning/memory by conducting a retrospective chart review for 144 children (aged 7-12) who completed a neuropsychological assessment during a psychiatric inpatient hospitalization. Of the 144 children, participants were matched two to one by gender and age, with one group (n = 52) categorized by reported sexual abuse and the other group (n = 92) categorized by no reported sexual abuse.

Clinical Genetic Testing in Autism Spectrum Disorder in a Large Community-Based Population Sample.

This study analyzes data from a large, population-based study of people with autism spectrum disorder to evaluate what proportion underwent genetic testing.

Autism Heterogeneity in a Densely Sampled U.S. Population: Results From the First 1,000 Participants in the RI-CART Study.

The objective of this study was to establish a large, densely sampled, U.S. population-based cohort of people with autism spectrum disorder (ASD).

Assessing performance validity with the TOMM and automatized sequences task in a pediatric psychiatric inpatient setting.

This study examined the performance of children consecutively admitted to an inpatient psychiatric unit on the Test of Memory Malingering (TOMM) (aged 5-12; = 96) and Automatized Sequences Task (aged 8-12; = 67). Eighty-three percent of children passed the TOMM Trial 2 ( raw score = 47.7,  = 4.

Measurement of executive functioning with the National Institute of Health Toolbox and the association to anxiety/depressive symptomatology in childhood/adolescence.

Introduction: Despite preliminary research, there remain inconsistent findings with regard to the role of executive functioning (EF) deficits in childhood anxiety and depression. This report examined the association of The National Institute of Health (NIH) Toolbox to clinical neuropsychological measures and to childhood, anxiety/depressive symptomatology. Methods: One-hundred eight children and adolescents completed the three EF measures from the NIH Toolbox (List Sorting Working Memory Test [LSWMT], Dimensional Change Card Sorting Test [DCCST], and Flanker Test of Attention and Inhibition [Flanker]) in an outpatient neuropsychology program.

GPT2 mutations in autosomal recessive developmental disability: extending the clinical phenotype and population prevalence estimates.

The glutamate pyruvate transaminase 2 (GPT2) gene produces a nuclear-encoded mitochondrial enzyme that catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate. Recessive mutations in GPT2 have been recently identified in a new syndrome involving intellectual and developmental disability (IDD), postnatal microcephaly, and spastic paraplegia. We have identified additional families with recessive GPT2 mutations and expanded the phenotype to include small stature.

Longitudinal MRI findings in patient with SLC25A12 pathogenic variants inform disease progression and classification.

Aspartate-glutamate carrier 1 (AGC1) is one of two exchangers within the malate-aspartate shuttle. AGC1 is encoded by the SLC25A12 gene. Three patients with pathogenic variants in SLC25A12 have been reported in the literature.