Faculty Bibliography

The present study tested outcomes of the Transdiagnostic Sleep and Circadian Intervention (TranS-C) among midlife and older adults with serious mental illness (SMI). Further, we tested predictors-credibility, expectancy, usefulness, and utilization-that may affect TranS-C outcomes. Midlife and older participants from a community setting (>49 years, 62.3% female, 37.7% African American or Black) with sleep and circadian problems and SMI were randomized to receive TranS-C plus usual care (TranS-C+UC, n = 27) or usual care followed by delayed treatment with TranS-C (UC-DT, n = 26). Immediate and delayed TranS-C data were combined to increase power (combined n = 52). Outcomes were assessed at pretreatment, posttreatment, and 6-month follow-up. Credibility and expectancy were assessed during the second session. Usefulness and utilization of TranS-C skills were assessed at posttreatment and 6-month follow-up. TranS-C+UC, relative to UC-DT, was associated with improvements in depression symptoms, sleep disturbance, overall sleep health, and select sleep/wake outcomes, though not all improvements were sustained at 6-month follow-up. Lower usefulness of TranS-C skills predicted more severe sleep disturbance at posttreatment and daytime sleep-related impairment at posttreatment and 6-month follow-up. Lower utilization predicted more severe psychiatric symptoms at posttreatment, sleep disturbance at posttreatment and 6-month follow-up, and overall impairment and daytime sleep-related impairment at 6-month follow-up. Higher credibility and expectancy predicted greater usefulness of TranS-C skills at posttreatment and 6-month follow-up and greater utilization at 6-month follow-up. Together, findings highlight benefits of TranS-C for midlife and older adults with SMI. However, boosting credibility, expectancy, utilization, and usefulness may meaningfully improve TranS-C outcomes.

The electrocardiogram (ECG) is a common source of electrical artifact in electroencephalogram (EEG). Here, we present a novel method for removing ECG artifact that requires neither simultaneous ECG nor transformation of the EEG signals. The approach relies upon processing a subset of EEG channels that contain ECG artifact to identify the times of each R-wave of the ECG. Within selected brief epochs, data in each EEG channel is signal-averaged ± 60 ms around each R-wave to derive an ECG template specific to each channel. This template is subtracted from each EEG channel which are aligned with the R-waves. The methodology was developed using two cohorts of infants: one with 128-lead EEG including an ECG reference and another with 32-lead EEG without ECG reference. The results for the first cohort validated the methodology the ECG reference and the second demonstrated its feasibility when ECG was not recorded. This method does not require independent, simultaneous recording of ECG, nor does it involve creation of an artifact template based on a mixture of EEG channel data as required by other methods such as Independent Component Analysis (ICA). Spectral analysis confirms that the method compares favorably to results using simultaneous recordings of ECG. The method removes ECG artifact on an epoch by epoch level and does not require stationarity of the artifact. Clinical Relevance - This approach facilitates the removal of ECG noise in frequency bands known to play a central role in brain mechanisms underlying cognitive processes.

OBJECTIVE:(1) investigate the associations of attention-deficit/hyperactivity disorder (ADHD) with systolic and diastolic blood pressure, resting heart rate, pulse pressure (PP), physical fitness, and BMI; (2) explore whether cardiovascular risk factors and ADHD share genetic and environmental influences; (3) assess if pharmacological treatment for ADHD influences these associations. METHODS:We identified 395,978 individuals born between 1973 and 1991 who had military conscription examinations at a mean age of 18.3 years (SD = 0.57) and their full-siblings within the same cohort (N = 208,060) by linking population-based registers in Sweden. RESULTS:Significantly increased risk of ADHD was observed in individuals with low systolic blood pressure (SBP) and PP, low physical fitness, and in those who had overweight or obesity after adjustments (adjusted Odds Ratio [OR] ranging from 1.10 to 1.45). Full siblings of individuals with low SBP, low physical fitness, and obesity were more likely to receive an ADHD diagnosis compared to full siblings without those risk factors (OR ranging from 1.17 to 1.31). Additionally, analyses showed robust associations between ADHD and low SBP, low physical fitness, and obesity, even in ADHD medication-naïve individuals. CONCLUSIONS:Individuals with several cardiovascular risk factors are more often diagnosed with ADHD, regardless of psychiatric comorbidity. These association are not explained by ADHD pharmacotherapy, rather, they are in part due to shared familial risk factors.

Neural plasticity in subareas of the rodent amygdala is widely known to be essential for Pavlovian threat conditioning and safety learning. However, less consistent results have been observed in human neuroimaging studies. Here, we identify and test three important factors that may contribute to these discrepancies: the temporal profile of amygdala response in threat conditioning, the anatomical specificity of amygdala responses during threat conditioning and safety learning, and insufficient power to identify these responses. We combined data across multiple studies using a well-validated human threat conditioning paradigm to examine amygdala involvement during threat conditioning and safety learning. In 601 humans, we show that two amygdala subregions tracked the conditioned stimulus with aversive shock during early conditioning while only one demonstrated delayed responding to a stimulus not paired with shock. Our findings identify cross-species similarities in temporal- and anatomical-specific amygdala contributions to threat and safety learning, affirm human amygdala involvement in associative learning and highlight important factors for future associative learning research in humans.

Maternal stress can shape long-term child neurodevelopment beginning in utero. One mechanism by which stress is transmitted from mothers to their offspring is via alterations in maternal cortisol, which can cross the placenta and bind to glucocorticoid receptor-rich regions in the fetal brain, such as the hippocampus. Although prior studies have demonstrated associations between maternal prenatal stress and cortisol levels with child brain development, we lack information about the extent to which these associations originate prior to birth and prior to confounding postnatal influences. Pregnant mothers (n = 77) completed questionnaires about current perceived stress, depressive symptoms, and anxiety symptoms, provided three to four salivary cortisol samples, and completed a fetal resting-state functional MRI scan during their second or third trimester of pregnancy (mean gestational age = 32.8 weeks). Voxelwise seed-based connectivity analyses revealed that higher prenatal self-reported distress and higher maternal cortisol levels corresponded to dissociable differences in fetal hippocampal functional connectivity. Specifically, self-reported distress was correlated with increased positive functional coupling between the hippocampus and right posterior parietal association cortex, while higher maternal cortisol was associated with stronger positive hippocampal coupling with the dorsal anterior cingulate cortex and left medial prefrontal cortex. Moreover, the association between maternal distress, but not maternal cortisol, on fetal hippocampal connectivity was moderated by fetal sex. These results suggest that prenatal stress and peripheral cortisol levels may shape fetal hippocampal development through unique mechanisms.

BACKGROUND:The mechanisms underlying placebo effects of psychotropic drugs remain poorly understood. We carried out the first systematic review of functional neuroimaging correlates of placebo response in adults with anxiety/depressive disorders. METHODS:We systematically searched a large set of databases up to February 2021 based on a pre-registered protocol (PROSPERO CRD42019156911). We extracted neuroimaging data related to clinical improvement following placebo or related to placebo mechanisms. We did not perform a meta-analysis due to the small number of included studies and significant heterogeneity in study design and outcome measures. RESULTS:We found 12 relevant studies for depressive disorders and four for anxiety disorders. Activity in the ventral striatum, rostral anterior cingulate cortex and other default mode network regions, orbitofrontal cortex, and dorsolateral prefrontal cortex correlated with placebo antidepressant responses. Activity in regions of the default mode network, including posterior cingulate cortex, was associated with placebo anxiolysis. There was also evidence for possible involvement of the endogenous opioid, dopamine and serotonin systems in placebo antidepressant and anxiolytic effects. CONCLUSIONS:Several brain regions and molecular systems may be involved in these placebo effects. Further adequately powered studies exploring causality and controlling for confounders are required.

Inattention to faces in clinical assessments is a robust marker for autism. However, a new study distinguishes diagnostic marker from behavioral mechanism, showing that face looking in everyday activity is equally rare in autistic and neurotypical children and not required for joint attention in either group.

BACKGROUND:Children in low-and-middle-income countries (LMICs) are facing tremendous mental health challenges. Numerous evidence-based interventions (EBIs) have been adapted to LMICs and shown effectiveness in addressing the needs, but most EBIs have not been adopted widely using scalable and sustainable implementation models that leverage and strengthen existing structures. There is a need to apply implementation science methodology to study strategies to effectively scale-up EBIs and sustain the practices in LMICs. Through a cross-sector collaboration, we are carrying out a second-generation investigation of implementation and effectiveness of a school-based mental health EBI, ParentCorps Professional Development (PD), to scale-up and sustain the EBI in Uganda to promote early childhood students' mental health. Our previous studies in Uganda supported that culturally adapted PD resulted in short-term benefits for classrooms, children, and families. However, our previous implementation of PD was relied on mental health professionals (MHPs) to provide PD to teachers. Because of the shortage of MHPs in Uganda, a new scalable implementation model is needed to provide PD at scale. OBJECTIVES/OBJECTIVE:This study tests a new scalable and sustainable PD implementation model and simultaneously studies the effectiveness. This paper describes use of collaboration, task-shifting, and Train-the-Trainer strategies for scaling-up PD, and protocol for studying the effectiveness-implementation of ParentCorps-PD for teachers in urban and rural Ugandan schools. We will examine whether the new scale-up implementation approach will yield anticipated impacts and investigate the underlying effectiveness-implementation mechanisms that contribute to success. In addition, considering the effects of PD on teachers and students will influence by teacher wellness. This study also examines the added value (i.e. impact and costs) of a brief wellness intervention for teachers and students. METHODS:Using a hybrid-type II effectiveness-implementation cluster randomized controlled trial (cRCT), we will randomize 36 schools (18 urban and 18 rural) with 540 teachers and nearly 2000 families to one of three conditions: PD + Teacher-Wellness (PDT), PD alone (PD), and Control. Primary effectiveness outcomes are teachers' use of mental health promoting strategies, teacher stress management, and child mental health. The implementation fidelity/quality for the scale-up model will be monitored. Mixed methods will be employed to examine underlying mechanisms of implementation and impact as well as cost-effectiveness. DISCUSSION/CONCLUSIONS:This research will generate important knowledge regarding the value of an EBI in urban and rural communities in a LMIC, and efforts toward supporting teachers to prevent and manage early signs of children's mental health issues as a potentially cost-effective strategy to promote child population mental health in low resource settings. TRIAL REGISTRATION/BACKGROUND:This trial was registered with ClinicalTrials.gov (registration number: NCT04383327; https://clinicaltrials.gov/ct2/show/NCT04383327 ) on May13, 2020.

Grief is the physical or mental suffering experienced after a major loss, usually the death of a loved one. It is a universal experience, but sociocultural factors, such as cultural or ethnic identity and religious beliefs predict and shape the expression of grief. The circumstances under which people are experiencing grief during the coronavirus outbreak have adversely affected the grieving process. Unexpected deaths, social distancing rules and visitor restrictions in healthcare facilities have posed a heavier burden on the loss and have heightened the risk of grievers experiencing complicated or persistent grief. This concern led us, as early career psychiatrists (ECPs) from 14 different countries connected by the Early Career Psychiatrists Section of the World Psychiatric Association (WPA), to share our country-specific experiences on the mourning, grief tradition, and burial rites during the COVID-19 pandemic. In this paper, we discuss our experiences, similarities and differences with relation to the: 'Effect of the pandemic on mourning', 'Restrictions and Guideline on burial rites due to the pandemic', 'Effect of the pandemic on social support' and 'Role of media and telecommunication on mourning practices and burial rites'. We conclude that while telecommunication means have attempted to bridge the gap and provide some form of social connectedness, the total and global effect of the pandemic is yet to be fully seen and understood.

Most psychiatric disorders are chronic, associated with high levels of disability and distress, and present during pediatric development. Scientific innovation increasingly allows researchers to probe brain-behavior relationships in the developing human. As a result, ambitions to (1) establish normative pediatric brain development trajectories akin to growth curves, (2) characterize reliable metrics for distinguishing illness, and (3) develop clinically useful tools to assist in the diagnosis and management of mental health and learning disorders have gained significant momentum. To this end, the NKI-Rockland Sample initiative was created to probe lifespan development as a large-scale multimodal dataset. The NKI-Rockland Sample Longitudinal Discovery of Brain Development Trajectories substudy (N = 369) is a 24- to 30-month multi-cohort longitudinal pediatric investigation (ages 6.0-17.0 at enrollment) carried out in a community-ascertained sample. Data include psychiatric diagnostic, medical, behavioral, and cognitive phenotyping, as well as multimodal brain imaging (resting fMRI, diffusion MRI, morphometric MRI, arterial spin labeling), genetics, and actigraphy. Herein, we present the rationale, design, and implementation of the Longitudinal Discovery of Brain Development Trajectories protocol.