Faculty Bibliography

LAY ABSTRACT/UNASSIGNED:Youth suicide is a major problem in the United States and globally, but little is known about suicide risk in autistic youth and youth with intellectual disability specifically. Using data from the National Emergency Department Sample, which is the largest database of emergency department visits in the United States, we found that emergency department visits with a suicidal ideation or intentional self-inflicted injury diagnosis were more common in autistic youth and youth with intellectual disability than in youth without these diagnoses (i.e. the comparison group). This was true when examining both suicidal ideation diagnoses and intentional self-inflicted injury diagnoses at emergency department visits. In addition, the number of emergency department visits with a suicidal ideation or intentional self-inflicted injury diagnosis increased more from 2006 to 2014 in autistic youth and youth with intellectual disability compared with the comparison group. We also found both similarities and differences when examining factors, such as age, sex, and co-occurring mental health conditions, related to emergency department visits with a suicidal ideation or intentional self-inflicted injury diagnosis across groups that may be helpful for understanding suicide risk. It is urgent that we improve our understanding, assessment, and treatment of suicidality and self-harm in these groups through more research and clinical efforts.

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.

In the United States, racial/ethnic minoritized groups experience worse sleep than non-Hispanic Whites (nHW), but less is known about pregnant people. This is a key consideration since poor sleep during pregnancy is common and associated with increased risk of adverse perinatal outcomes. This study reports the prevalence of subjective sleep measures in a multi-racial/ethnic pregnant population from the Environmental influences on Child Health Outcomes (ECHO) program. Participants' self-reported race and ethnicity were grouped into: nHW, non-Hispanic Black/African American (nHB/AA), Hispanic, non-Hispanic Asian (nHA). Analyses examined trimester-specific (first (T1), second (T2), third (T3)) nocturnal sleep duration, quality, and disturbances (Pittsburgh Sleep Quality Index and ECHO maternal sleep health questionnaire). Linear or multinomial regressions estimated the associations between race/ethnicity and each sleep domain by trimester, controlling for body mass index and age, with nHW as reference group. We repeated analyses within maternal education strata. nHB/AA participants reported shorter sleep duration (T2: β = -0.55 [-0.80,-0.31]; T3: β = -0.65 [-0.99,-0.31]) and more sleep disturbances (T2: β = 1.92 [1.09,2.75]; T3: β = 1.41 [0.09,2.74]). Hispanic participants reported longer sleep duration (T1: β = 0.22 [0.00004,0.44]; T2: β = 0.61 [0.47,0.76]; T3: β = 0.46 [0.22,0.70]), better sleep quality (Reference group: Very good. Fairly good T1: OR = 0.48 [0.32,0.73], T2: OR = 0.36 [0.26,0.48], T3: OR = 0.31 [0.18,0.52]. Fairly bad T1: OR = 0.27 [0.16,0.44], T2: OR = 0.46 [0.31, 0.67], T3: OR = 0.31 [0.17,0.55]), and fewer sleep disturbances (T2: β = -0.5 [-1.0,-0.12]; T3: β = -1.21 [-2.07,-0.35]). Differences persisted within the high-SES subsample. Given the stark racial/ethnic disparities in perinatal outcomes and their associations with sleep health, further research is warranted to investigate the determinants of these disparities.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

The internet has become an indispensable tool in people´s daily lives during the COVID-19 pandemic. Internet and video game use are experiencing rapid growth in the youth and adult populations as a major source of entertainment. However, excessive gaming may cause addiction and negatively impact mental health, entailing low psychosocial well-being, poor social skills, and decreased academic achievement. We report the case of a 16-year-old student with a "typical" pattern of internet gaming disorder (IGD) developed during the pandemic, which improved after weeks of treatment with pharmacotherapy and psychosocial interventions. This case highlights that it is essential for the mental health professionals to know the psychopathology of IGD and multimodal approaches to treat it.

To identify the state-level policies and policy domains that state policymakers and advocates perceive as most important for positively impacting the use of children's mental health services (CMHS). We used a modified Delphi technique (i.e., two rounds of questionnaires and an interview) during Spring 2021 to elicit perceptions among state mental health agency officials and advocates (n = 28) from twelve states on state policies that impact the use of CMHS. Participants rated a list of pre-specified policies on a 7-point Likert scale (1 = not important, 7 = extremely important) in the following policy domains: insurance coverage and limits, mental health services, school and social. Participants added nine policies to the initial list of 24 policies. The "school" policy domain was perceived as the most important, while the "social" policy domain was perceived as the least important after the first questionnaire and the second most important policy domain after the second questionnaire. The individual policies perceived as most important were school-based mental health services, state mental health parity, and Medicaid reimbursement rates. Key stakeholders in CMHS should leverage this group of policies to understand the current policy landscape in their state and to identify gaps in policy domains and potential policy opportunities to create a more comprehensive system to address children's mental health from a holistic, evidence-based policymaking perspective.

BACKGROUND:The COVID-19 pandemic has caused an increase in mental ill health compared with prepandemic levels. Longer-term trajectories of depression in adults during the pandemic remain unclear. OBJECTIVE:We used latent growth curve modelling to examine individual trajectories of depression symptoms, and their predictors, beyond the early stage of the pandemic. METHODS:Data were collected in three waves in May 2020, September/October 2020 and February/March 2021 in four UK cohorts (Millennium Cohort Study, Next Steps cohort, British Cohort and National Child Development Study). We included n=16 978 participants (mean age at baseline: 20, 30, 50 and 62, respectively). Self-reported depressive symptoms were the study outcome. FINDINGS/RESULTS:Symptoms of depression were higher in younger compared with older age groups (d=0.7) across all waves. While depressive symptoms remained stable from May 2020 to Autumn 2020 overall (standardized mean difference (SMD)=0.03, 95% CI 0.02 to 0.04), they increased in all age groups from May 2020 to Spring 2021 (SMD=0.12, 95% CI 0.11 to 0.13). Feelings of loneliness were the strongest predictor and concurrent correlate of increasing depressive symptoms across all cohorts, prepandemic mental health problems and having a long-term illness were also significantly associated with an increase in depression symptoms across all ages. By contrast, compliance with social distancing measures did not predict an increase in depression symptoms. CONCLUSIONS:Feeling lonely and isolated had a large effect on depression trajectories across all generations, while social distancing measures did not. CLINICAL IMPLICATIONS/CONCLUSIONS:These findings highlight the importance of fostering the feeling of connectedness during COVID-19-related distancing measures.

Local protein synthesis at synapses can provide a rapid supply of proteins to support synaptic changes during consolidation of new memories, but its role in the maintenance or updating of established memories is unknown. Consolidation requires new protein synthesis in the period immediately following learning, whereas established memories are resistant to protein synthesis inhibitors. We have previously reported that polyribosomes are up-regulated in the lateral amygdala (LA) during consolidation of aversive-cued Pavlovian conditioning. In this study, we used serial section electron microscopy reconstructions to determine whether the distribution of dendritic polyribosomes returns to baseline during the long-term memory phase. Relative to control groups, long-term memory was associated with up-regulation of polyribosomes throughout dendrites, including in dendritic spines of all sizes. Retrieval of a consolidated memory by presentation of a small number of cues induces a new, transient requirement for protein synthesis to maintain the memory, while presentation of a large number of cues results in extinction learning, forming a new memory. One hour after retrieval or extinction training, the distribution of dendritic polyribosomes was similar except in the smallest spines, which had more polyribosomes in the extinction group. Our results demonstrate that the effects of learning on dendritic polyribosomes are not restricted to the transient translation-dependent phase of memory formation. Cued Pavlovian conditioning induces persistent synapse strengthening in the LA that is not reversed by retrieval or extinction, and dendritic polyribosomes may therefore correlate generally with synapse strength as opposed to recent activity or transient translational processes.