Faculty Bibliography

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.

Importance:Associations between in utero exposure to maternal SARS-CoV-2 infection and neurodevelopment are speculated, but currently unknown. Objective:To examine the associations between maternal SARS-CoV-2 infection during pregnancy, being born during the COVID-19 pandemic regardless of maternal SARS-CoV-2 status, and neurodevelopment at age 6 months. Design, Setting, and Participants:A cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls was enrolled in the COVID-19 Mother Baby Outcomes Initiative at Columbia University Irving Medical Center in New York City. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were approached. Women with unexposed infants were approached based on similar gestational age at birth, date of birth, sex, and mode of delivery. Neurodevelopment was assessed using the Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at age 6 months. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 were included in secondary analyses. Exposures:Maternal SARS-CoV-2 infection during pregnancy and birth during the COVID-19 pandemic. Main Outcomes and Measures:Outcomes were scores on the 5 ASQ-3 subdomains, with the hypothesis that maternal SARS-CoV-2 infection during pregnancy would be associated with decrements in social and motor development at age 6 months. Results:Of 1706 women approached, 596 enrolled; 385 women were invited to a 6-month assessment, of whom 272 (70.6%) completed the ASQ-3. Data were available for 255 infants enrolled in the COVID-19 Mother Baby Outcomes Initiative (114 in utero exposed, 141 unexposed to SARS-CoV-2; median maternal age at delivery, 32.0 [IQR, 19.0-45.0] years). Data were also available from a historical cohort of 62 infants born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences on any ASQ-3 subdomain, regardless of infection timing or severity. However, compared with the historical cohort, infants born during the pandemic had significantly lower scores on gross motor (mean difference, -5.63; 95% CI, -8.75 to -2.51; F1,267 = 12.63; P<.005), fine motor (mean difference, -6.61; 95% CI, -10.00 to -3.21; F1,267 = 14.71; P < .005), and personal-social (mean difference, -3.71; 95% CI, -6.61 to -0.82; F1,267 = 6.37; P<.05) subdomains in fully adjusted models. Conclusions and Relevance:In this study, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, was associated with differences in neurodevelopment at age 6 months. These early findings support the need for long-term monitoring of children born during the COVID-19 pandemic.

OBJECTIVE:Evaluating the impact of the Inversion Time (TI) on regional perfusion estimation in a pediatric cohort using Arterial Spin Labeling (ASL). MATERIALS AND METHODS/METHODS:Pulsed ASL (PASL) was acquired at 3 T both at TI 1500 ms and 2020 ms from twelve MRI-negative patients (age range 9-17 years). A volume of interest (VOIs) and a voxel-wise approach were employed to evaluate subject-specific TI-dependent Cerebral Blood Flow (CBF) differences, and grey matter CBF Z-score differences. A visual evaluation was also performed. RESULTS:CBF was higher for TI 1500 ms in the proximal territories of the arteries (PTAs) (e.g. insular cortex and basal ganglia - P < 0.01 and P < 0.05 from the VOI analysis, respectively), and for TI 2020 ms in the distal territories of the arteries (DTAs), including the watershed areas (e.g. posterior parietal and occipital cortex - P < 0.001 and P < 0.01 from the VOI analysis, respectively). Similar differences were also evident when analyzing patient-specific CBF Z-scores and at a visual inspection. CONCLUSIONS:TI influences ASL perfusion estimates with a region-dependent effect. The presence of intraluminal arterial signal in PTAs and the longer arterial transit time in the DTAs (including watershed areas) may account for the TI-dependent differences. Watershed areas exhibiting a lower perfusion signal at short TIs (~ 1500 ms) should not be misinterpreted as focal hypoperfused areas.

This study investigated motor preparation and action-consequence prediction using the lateralized readiness potential (LRP). Motor impairments are common in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. Alterations in predictive processes may impact motor planning. Whether motor planning deficits are characteristic of ASD broadly or magnified in the context of co-morbid ADHD is unclear. ASD children with (ASD + ADHD; n = 12) and without (ASD - ADHD; n = 9) comorbid ADHD and typical controls (n = 29) performed voluntary motor actions that either did or did not result in auditory consequences. ASD - ADHD children demonstrated LRP enhancement when their action produced an effect while ASD + ADHD children had attenuated responses regardless of action-effect pairings. Findings suggest influence of ADHD comorbidity on motor preparation and prediction in ASD.

Adverse childhood experiences (ACEs) are associated with poor mental health in adulthood. Comprehensive prevalence data encompassing all 10 ACE questionnaire items has not previously been described in a hospital-based outpatient psychiatric clinic. This study assessed the prevalence of 10 ACEs in such a clinic and correlated ACEs with indicators of case severity. For 252 patients newly evaluated in an urban clinic, a retrospective chart review was completed and data was collected on ACE questionnaire responses, psychiatric, substance-related, and medical diagnoses, psychiatric hospitalizations, suicide attempts, and suicide and violence risk. Patients in the clinic had an average of 3.4 ACEs, higher than national community sample averages of 1.6. The percentages of patients with at least one, two, and four ACEs were 82% (n = 207), 68% (n = 172), and 42% (n = 106) respectively (compared with 61%, 38%, and 15% nationally). ACEs had statistically significant correlations with an increased number of psychiatric diagnoses, substance use disorders, medical illnesses, suicide attempts, and suicide risk level. This study demonstrated that patients seeking psychiatric care from a hospital-based outpatient clinic are likely to be traumatized to a degree far exceeding what is typical in the general population. While a high prevalence of ACEs in a psychiatric population is an expected finding given the literature to date, this is the first study presenting data on the prevalence of ACEs in such a hospital-based community clinic. Additionally this study reinforces prior research correlating childhood adversity and case severity.

Anxiety has been associated with reliance on reactive (stimulus-driven/reflexive) control strategies in response to conflict. However, this conclusion rests primarily on indirect evidence. Few studies utilize tasks that dissociate the use of reactive ('just in time') vs. proactive (anticipatory/preparatory) cognitive control strategies in response to conflict, and none examine children diagnosed with anxiety. The current study utilizes the AX-CPT, which dissociates these two types of cognitive control, to examine cognitive control in youth (ages 8-18) with and without an anxiety diagnosis (n = 56). Results illustrate that planful behavior, consistent with using a proactive strategy, varies by both age and anxiety symptoms. Young children (ages 8-12 years) with high anxiety exhibit significantly less planful behavior than similarly-aged children with low anxiety. These findings highlight the importance of considering how maturation influences relations between anxiety and performance on cognitive-control tasks and have implications for understanding the pathophysiology of anxiety in children.

Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), is a potentially effective treatment strategy for a number of mental conditions. However, no quantitative evidence synthesis of randomized controlled trials (RCTs) of TMS or tDCS using the same criteria including several mental conditions is available. Based on 208 RCTs identified in a systematic review, we conducted a series of random effects meta-analyses to assess the efficacy of NIBS, compared to sham, for core symptoms and cognitive functioning within a broad range of mental conditions. Outcomes included changes in core symptom severity and cognitive functioning from pre- to post-treatment. We found significant positive effects for several outcomes without significant heterogeneity including TMS for symptoms of generalized anxiety disorder (SMD = -1.8 (95% CI: -2.6 to -1), and tDCS for symptoms of substance use disorder (-0.73, -1.00 to -0.46). There was also significant effects for TMS in obsessive-compulsive disorder (-0.66, -0.91 to -0.41) and unipolar depression symptoms (-0.60, -0.78 to -0.42) but with significant heterogeneity. However, subgroup analyses based on stimulation site and number of treatment sessions revealed evidence of positive effects, without significant heterogeneity, for specific TMS stimulation protocols. For neurocognitive outcomes, there was only significant evidence, without significant heterogeneity, for tDCS for improving attention (-0.3, -0.55 to -0.05) and working memory (-0.38, -0.74 to -0.03) in individuals with schizophrenia. We concluded that TMS and tDCS can benefit individuals with a variety of mental conditions, significantly improving clinical dimensions, including cognitive deficits in schizophrenia which are poorly responsive to pharmacotherapy.

OBJECTIVE/UNASSIGNED:The study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia. METHODS/UNASSIGNED:Preoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non-small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site. RESULTS/UNASSIGNED: = .0003). CONCLUSIONS/UNASSIGNED:Both open and minimally invasive lung resection for clinical early-stage lung cancer are associated with new or enlarging postoperative hiatal hernia, especially after resections involving the left lower lobe.

OBJECTIVE:To model children's mental health policy making dynamics and simulate the impacts of knowledge broker interventions. DATA SOURCES/METHODS:Primary data from surveys (n = 221) and interviews (n = 64) conducted in 2019-2021 with mental health agency (MHA) officials in state agencies. STUDY DESIGN/METHODS:A prototype agent-based model (ABM) was developed using the PARTE (Properties, Actions, Rules, Time, Environment) framework and informed through primary data collection. In each simulation, a policy is randomly generated (salience weights: cost, contextual alignment, and strength of evidence) and discussed among agents. Agents are MHA officials and heterogenous in their properties (policy making power and network influence) and policy preferences (based on salience weights). Knowledge broker interventions add agents to the MHA social network who primarily focus on the policy's research evidence. DATA COLLECTION/EXTRACTION METHODS/METHODS:A sequential explanatory mixed method approach was used. Descriptive and regression analyses were used for the survey data and directed content analysis was used to code interview data. Triangulated results informed ABM development. In the ABM, policy makers with various degrees of decision influence interact in a scale-free network before and after knowledge broker interventions. Over time, each decides to support or oppose a policy proposal based on policy salience weights and their own properties and interactions. The main outcome is an agency-level decision based on policy maker support. Each intervention and baseline simulation runs 250 times across 50 timesteps. PRINCIPAL FINDINGS/RESULTS:Surveys and interviews revealed that barriers to research use could be addressed by knowledge brokers. Simulations indicated that policy decision outcomes varied by policy making context within agencies. CONCLUSIONS:This is the first application of ABM to evidence-informed mental health policy making focusing. Results suggest that the presence of knowledge brokers can: (1) influence consensus formation in MHAs, (2) accelerate policy decisions, and (3) increase the likelihood of evidence-informed policy adoption.

BACKGROUND:The association between adversity and psychopathology in adolescents and adults is characterized by equifinality. These associations, however, have not been assessed during early childhood when psychopathology first emerges. Defining adversity using both dimensional and cumulative risk approaches, we examined whether specific types of adversity are differentially associated with psychopathology in preschool-aged children. METHODS:Measures of threat, deprivation, and total adversities (i.e., cumulative risk) were calculated based on parent-reported information for 755 2- to 5-year old children recruited from pediatric primary care clinics. Logistic regression was used to estimate cross-sectional associations between type of adversity and anxiety, depression, ADHD, and behavioral disorder diagnoses. RESULTS:Threat and cumulative risk exhibited independent associations with psychopathology. Threat was strongly related to behavioral disorders. Cumulative risk was consistently related to all psychopathologies. CONCLUSIONS:Using mutually adjusted models, we identified differential associations between threat and psychopathology outcomes in preschool-aged children. This selectivity may reflect different pathways through which adversity increases the risk for psychopathology during this developmentally important period. As has been observed at other ages, a cumulative risk approach also effectively identified the cumulative impact of all forms of adversity on most forms of psychopathology during early childhood.