Faculty Bibliography

BACKGROUND/UNASSIGNED:Pragmatic language, or the use of language in social contexts, is a critical skill in daily life, supporting social interactions and the development of meaningful social relationships. Pragmatic language is universally impacted in autism spectrum disorder (ASD) and pragmatic deficits are also common in other neurodevelopmental conditions, particularly those related to ASD, such as fragile X syndrome (FXS). This study used a multi-method, longitudinal approach to characterize potentially unique pragmatic profiles across different neurodevelopmental disabilities, and across contexts that varied in degree of social demand. The utility of computational linguistic analyses, as an efficient tool for capturing pragmatic abilities, was also explored. METHODS/UNASSIGNED: = 24) were compared using variables obtained from a standardized measure, narrative, and semi-naturalistic conversation at up to three time points. RESULTS/UNASSIGNED:Pragmatic language was most significantly impacted among males with ASD-O and FXS-ASD across all three contexts, with more difficulties in the least structured context (conversation), and also some differences based on FXS comorbidity. Patterns of group differences were more nuanced for boys with FXS-O and DS, with context having less of an impact. Clinical groups demonstrated minimal changes in pragmatic skills with age, with some exceptions. Computational language measurement tools showed some utility for measuring pragmatic skills, but were not as successful as traditional methods at capturing differences between clinical groups. CONCLUSION/UNASSIGNED:Overlap and differences between ASD and other forms of neurodevelopmental disability in general, and between idiopathic and syndromic ASD in particular, have important implications for developing precisely tailored assessment and intervention approaches, consistent with a personalized medicine approach to clinical study and care in ASD.

BACKGROUND/UNASSIGNED:Increasing reports of manic episodes in patients during acute infection with COVID-19 have been documented since the pandemic began, including individuals without a previous personal or family history of bipolar disorder. As infections and autoimmunity have putative roles in bipolar disorder, we aimed to document the clinical presentations, associated stressors, family aggregation patterns, and brain imaging and electroencephalographic correlates with a series of patients with episodes of mania that emerged shortly after COVID-19 infections. METHODS/UNASSIGNED:We obtained all relevant clinical information from 12 patients whose first manic episode started within a month of COVID-19 infection and were treated at Rasool-e-Akram hospital and Iran psychiatric hospital, two tertiary medical centers in Tehran, Iran, in 2021. RESULTS/UNASSIGNED:Patients had a mean age of 44. The interval between the onset of symptoms of COVID and mania ranged between 0 and 28 days (mean: 16.25, median: 14 days); it was observed to be shorter in patients with a family history of mood disorders but not in those receiving corticosteroids. Alongside a descriptive overview of our sample, we provide detailed narrative descriptions of two of the cases for illustrative purposes and discuss our observations in the context of other cases reported elsewhere and the state-of-the-art regarding infectious diseases, COVID-19, and bipolar disorder as reported in previous literature. CONCLUSION/UNASSIGNED:Our case series documents observational and naturalistic evidence from a dozen of cases of mania in the context of acute COVID-19, which, while limited, calls for analytical research of the phenomenon, and points at a family history of bipolar disorder and the use of corticosteroids as factors for particular focus.

IMPORTANCE/OBJECTIVE:Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS:RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION/CONCLUSIONS:RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER/BACKGROUND:Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Emotion regulation and executive function are associated: adaptive regulatory strategies are linked to better executive functioning while maladaptive strategies correspond with worse executive functioning. However, if - and how - these two processes affect one another has not previously been explored; most studies have employed a correlational approach, leaving the direction of influence unknown. We aim to address this gap by using an experimental design to explore the impact of emotion regulation on executive functioning. Adult participants (N=31) completed an executive functioning task (Computerized Task-Switching Test) under four induced emotion regulation conditions (1) neutral/baseline, (2) positive mood-maintain, (3) negative mood-maintain, (4) negative mood-reduce (conditions 2-4 were randomized). Relative to baseline, participants demonstrated better set-shifting performance across regulation conditions. In contrast, inhibitory control performance was slower, despite anticipated improvement due to practice effects. This suggests that inhibitory control may be more involved in the emotion regulation process than set-shifting when participants have a specific emotion regulation goal to achieve. The present study provides preliminary evidence that individuals' ability to perform executive function tasks may be affected by concurrent emotion regulation demands; additional experiments are necessary to further probe the complexity of the association between these two processes.

INTRODUCTION:There is a striking knowledge gap on ADHD in older adults, and the diagnosis as well as treatment for ADHD in this age group. AREAS COVERED:The authors first review the literature on the prevalence, functional impairment, and health comorbidities of ADHD across the lifespan. Next, they address the diagnostic criteria for ADHD in adults according to the DSM/ICD, available screening/diagnostic tools, differential diagnosis, and the validity of diagnostic criteria for ADHD in older adults. Finally, the authors focus on empirical evidence on the prevalence rates, medication response, and safety of pharmacological treatment of ADHD in older adults, and national and international clinical guidelines on the treatment of ADHD in this age group. EXPERT OPINION:It is expected that future editions of the DSM and ICD will provide specifiers to the standard ADHD criteria, to better inform the diagnosis of ADHD in older adults. It is also expected that the increasing number of epidemiological studies will provide rigorous estimates on the prevalence, incidence, and burden of ADHD in older adults. One may expect an increasing number of RCTs assessing the efficacy/effectiveness and tolerability/safety of pharmacological as well as non-pharmacological interventions which will inform future guidelines on ADHD in older adults.

INTRODUCTION:Neurological/neuropsychiatric symptoms are commonly reported by children/young people with long COVID, especially headache, fatigue, cognitive deficits, anosmia and ageusia, dizziness, mood symptoms, and sleep problems. However, reported prevalence estimates are highly variable due to study heterogeneity and often small sample size; most studies only considered short-term follow-ups; and, apart from mood and sleep problems, neuropsychiatric conditions have received less attention. Considering the potential debilitating effects of neurological/neuropsychiatric conditions, a comprehensive review of the topic is timely, and needed to support clinical recognition as well as to set the direction for future research. AREAS COVERED:The authors discuss neurological/neuropsychiatric manifestations of long COVID in pediatric populations, with a focus on prevalence, associated demographic characteristics, and potential pathogenetic mechanisms. EXPERT OPINION:Children/young people may develop persistent neurological/neuropsychiatric symptoms following acute SARS-CoV-2 infection, which may affect daily functioning and well-being. Studies in larger samples with longer follow-ups are needed to clarify prevalence and symptom duration; as well as less investigated risk factors, including genetic predisposition, ethnicity, and comorbidities. Controlled studies may help separate infection-related direct effects from pandemic-related psychosocial stressors. Clarifying pathogenetic mechanisms is paramount to develop more targeted and effective treatments; whilst screening programs and psychoeducation may enhance early recognition.

BACKGROUND:In the short term, parental presence while a human infant is in pain buffers the immediate pain responses, although emerging evidence suggests repeated social buffering of pain may have untoward long-term effects. METHODS/FINDING/UNASSIGNED:To explore the short- and long-term impacts of social buffering of pain, we first measured the infant rat pup's [postnatal day (PN) 8, or 12] response to mild tail shock with the mother present compared to shock alone or no shock. Shock with the mother reduced pain-related behavioral activation and USVs of pups at both ages and reduced Fos expression in the periaqueductal gray, hypothalamic paraventricular nucleus, and the amygdala at PN12 only. At PN12, shock with the mother compared to shock alone differentially regulated expression of several hundred genes related to G-protein-coupled receptors (GPCRs) and neural development, whereas PN8 pups showed a less robust and less coherent expression pattern. In a second set of experiments, pups were exposed to daily repeated Shock-mother pairings (or controls) at PN5-9 or PN10-14 (during and after pain sensitive period, respectively) and long-term outcome assessed in adults. Shock+mother pairing at PN5-9 reduced adult carrageenan-induced thermal hyperalgesia and reduced Fos expression, but PN10-14 pairings had minimal impact. The effect of infant treatment on adult affective behavior showed a complex treatment by age dependent effect. Adult social behavior was decreased following Shock+mother pairings at both PN5-9 and PN10-14, whereas shock alone had no effect. Adult fear responses to a predator odor were decreased only by PN10-14 treatment and the infant Shock alone and Shock+mother did not differ. CONCLUSIONS/SIGNIFICANCE/CONCLUSIONS:Overall, integrating these results into our understanding of long-term programming by repeated infant pain experiences, the data suggest that pain experienced within a social context impacts infant neurobehavioral responses and initiates an altered developmental trajectory of pain and affect processing that diverges from experiencing pain alone.

BACKGROUND:Transcranial direct current stimulation (tDCS) may provide a potential therapy for cognitive deficits caused by traumatic brain injury (TBI), yet its efficacy and mechanisms of action are still uncertain. OBJECTIVE:We hypothesized that anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) would boost the influence of a cognitive training regimen in a mild-to-moderate TBI (mmTBI) sample. Cognitive enhancement was measured by examining event-related potentials (ERPs) during cognitive control tasks from pre- to post-treatment. METHODS:Thirty-four participants with mmTBI underwent ten sessions of cognitive training with active (n = 17) or sham (n = 17) anodal tDCS to the left DLPFC. ERPs were assessed during performance of an auditory oddball (3AOB), N-back, and dot pattern expectancy (DPX) task before and after treatment. RESULTS:P3b amplitudes significantly decreased from baseline to post-treatment testing, regardless of tDCS condition, in the N-back task. The active tDCS group demonstrated a significantly increased P3a amplitude in the DPX task. No statistically significant stimulation effects were seen during the 3AOB and N-back tasks. CONCLUSION/CONCLUSIONS:Active anodal tDCS paired with cognitive training led to increases in P3a amplitudes in the DPX, inferring increased cognitive control. P3b decreased in the N-back task demonstrating the effects of cognitive training. These dissociated P3 findings suggest separate mechanisms invoked by different neuroplasticity-inducing paradigms (stimulation versus training) in brain networks that support executive functioning.