Faculty Bibliography

Early trauma (ET), though broadly and inconsistently defined, has been repeatedly linked to numerous psychological disturbances, including various developmental stages of psychotic disorders. The prodromal phase of psychosis highlights a unique and relevant population that provides insight into the critical periods of psychosis development. As such, a relatively recent research focus on individuals at clinical high risk (CHR) for psychosis reveals robust associations of early life trauma exposures with prodromal symptoms and function in these cohorts. While prevalence rates of ET in CHR cohorts remain consistently high, methodological measures of traumatic experiences vary across studies, presenting potential problems for reliability and validity of results. This review aims to 1) highlight the existing evidence identifying associations of ET, of multiple forms, with both symptom severity and transition rates to psychosis in CHR individuals, 2) present data on the variability among trauma assessments and its implications for conclusions about its relationship with clinical variables, 3) describe cognitive deficits common in CHR cohorts, including perceptual and neurocognitive impairments, and their neural correlates, that may modify the relationship of ET to symptoms, and 4) propose future directions for standardization of trauma assessment in CHR cohorts to better understand its clinical and cognitive correlates.

Alcohol use, particularly binge drinking (BD), is a major public health concern among adolescents. Recent national data show that the gender gap in alcohol use is lessening, and BD among girls is rising. Considering the increase in BD among adolescent girls, as well as females' increased risk of experiencing more severe biopsychosocial negative effects and consequences from BD, the current review sought to examine gender differences in risk factors for BD. The review highlights gender differences in (1) developmental-related neurobiological vulnerability to BD, (2) psychiatric comorbidity and risk phenotypes for BD, and (3) social-related risk factors for BD among adolescents, as well as considerations for BD prevention and intervention. Most of the information gleaned thus far has come from preclinical research. However, it is expected that, with recent advances in clinical imaging technology, neurobiological effects observed in lower mammals will be confirmed in humans and vice versa. A synthesis of the literature highlights that males and females experience unique neurobiological paths of development, and although there is debate regarding the specific nature of these differences, literature suggests that these differences in turn influence gender differences in psychiatric comorbidity and risk for BD. For one, girls are more susceptible to stress, depression, and other internalizing behaviors and, in turn, these symptoms contribute to their risk for BD. On the other hand, males, given gender differences across the lifespan as well as gender differences in development, are driven by an externalizing phenotype for risk of BD, in part, due to unique paths of neurobiological development that occur across adolescence. With respect to social domains, although social and peer influences are important for both adolescent males and females, there are gender differences. For example, girls may be more sensitive to pressure from peers to fit in and impress others, while male gender role stereotypes regarding BD may be more of a risk factor for boys. Given these unique differences in male and female risk for BD, further research exploring risk factors, as well as tailoring intervention and prevention, is necessary. Although recent research has tailored substance use intervention to target males and females, more literature on gender considerations in treatment for prevention and intervention of BD in particular is warranted.

The health of people ever incarcerated in New York City (NYC) jails during 2001 to 2005 was characterized by matching jail, shelter, mortality, sexually transmitted infection, HIV, and tuberculosis (TB) data from the NYC Departments of Health and Mental Hygiene, Correction, and Homeless Services. Compared with nonincarcerated people and those living in the lowest income NYC neighborhoods, those ever incarcerated had higher HIV prevalence and HIV case rates. Ever-incarcerated females also had higher rates of gonorrhea and syphilis than nonincarcerated females. Ever-incarcerated people who used the single adult homeless shelter system had higher HIV, gonorrhea, and TB case rates and all-cause mortality rates than ever-incarcerated people without shelter use, when adjusting for other variables. People ever incarcerated in NYC jails are at risk for conditions of public health importance. Sex-specific jail- and community-based interventions are needed.

Psychophysiological interaction (PPI) is a regression based method to study task modulated brain connectivity. Despite its popularity in functional MRI (fMRI) studies, its reliability and reproducibility have not been evaluated. We investigated reproducibility and reliability of PPI effects during a simple visual task, and examined the effect of deconvolution on the PPI results. A large open-access dataset was analyzed (n = 138), where a visual task was scanned twice with repetition times (TRs) of 645 and 1,400 ms, respectively. We first replicated our previous results by using the left and right middle occipital gyrus as seeds. Then regions of interest (ROI)-wise analysis was performed among 20 visual-related thalamic and cortical regions, and negative PPI effects were found between many ROIs with the posterior fusiform gyrus as a hub region. Both the seed-based and ROI-wise results were similar between the two runs and between the two PPI methods with and without deconvolution. The non-deconvolution method and the short TR run in general had larger effect sizes and greater extents. However, the deconvolution method performed worse in the 645 ms TR run than the 1,400 ms TR run in the voxel-wise analysis. Given the general similar results between the two methods and the uncertainty of deconvolution, we suggest that deconvolution may be not necessary for PPI analysis on block-designed data. Lastly, intraclass correlations (ICC) between the two runs were much lower for the PPI effects than the activation main effects, which raise cautions on performing inter-subject correlations and group comparisons on PPI effects.

Background/UNASSIGNED:Schizophrenia, a neurodevelopmental disorder, involves abnormalities in functional connectivity (FC) across distributed neural networks, which are thought to antedate the emergence of psychosis. In a cohort of adolescents and young adults at clinical high risk (CHR) for psychosis, we applied data-driven approaches to resting-state fMRI data so as to systematically characterize FC abnormalities during this period and determine whether these abnormalities are associated with psychosis risk and severity of psychotic symptoms. Methods/UNASSIGNED:Fifty-one CHR participants and 47 matched healthy controls (HCs) were included in our analyses. Twelve of these CHR participants developed psychosis within 3.9 years. We estimated one multivariate measure of FC and studied its relationship to CHR status, conversion to psychosis and positive symptom severity. Results/UNASSIGNED:Multivariate analyses revealed between-group differences in whole-brain connectivity patterns of bilateral temporal areas, mostly affecting their functional connections to the thalamus. Further, more severe positive symptoms were associated with greater connectivity abnormalities in the anterior cingulate and frontal cortex. Conclusions/UNASSIGNED:Our study demonstrates that the well-established FC abnormalities of the thalamus and temporal areas observed in schizophrenia are also present in the CHR period, with aberrant connectivity of the temporal cortex most associated with psychosis risk.

BACKGROUND:Oppositional defiant disorder (ODD) is a major mental health concern and highly prevalent among children living in poverty-impacted communities. Despite that treatments for ODD are among the most effective, few children living in poverty receive these services due to substantial barriers to access, as well as difficulties in the uptake and sustained adoption of evidence-based practices (EBPs) in community settings. The purpose of this study is to examine implementation processes that impact uptake of an evidence-based practice for childhood ODD, and the impact of a Clinic Implementation Team (CIT)-driven structured adaptation to enhance its fit within the public mental health clinic setting. METHODS/DESIGN/METHODS:This study, a Hybrid Type II effectiveness-implementation research trial, blends clinical effectiveness and implementation research methods to examine the impact of the 4Rs and 2Ss Multiple Family Group (MFG) intervention, family level mediators of child outcomes, clinic/provider-level mediators of implementation, and the impact of CITs on uptake and long-term utilization of this model. All New York City public outpatient mental health clinics have been invited to participate. A sampling procedure that included randomization at the agency level and a sub-study to examine the impact of clinic choice upon outcomes yielded a distribution of clinics across three study conditions. Quantitative data measuring child outcomes, organizational factors and implementation fidelity will be collected from caregivers and providers at baseline, 8, and 16 weeks from baseline, and 6 months from treatment completion. The expected participation is 134 clinics, 268 providers, and 2688 caregiver/child dyads. We will use mediation analysis with a multi-level Structural Equation Modeling (SEM) (MSEM including family level variables, provider variables, and clinic variables), as well as mediation tests to examine study hypotheses. DISCUSSION/CONCLUSIONS:The aim of the study is to generate knowledge about effectiveness and mediating factors in the treatment of ODDs in children in the context of family functioning, and to propose an innovative approach to the adaptation and implementation of new treatment interventions within clinic settings. The proposed CIT adaptation and implementation model has the potential to enhance implementation and sustainability, and ultimately increase the extent to which effective interventions are available and can impact children and families in need of services for serious behavior problems. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov, ID: NCT02715414 . Registered on 3 March 2016.

Purpose: To image and analyze individual RPE melanosomes (M), lipofuscin (LF), and melanolipofuscin (MLF) granules using high-resolution structured illumination microscopy (hrSIM) and confocal multispectral laser scanning microscopy (cmLSM). Methods: Human donor RPE-flatmounts (n=35; normal macular status: 9<51yrs, 9>80yrs; age-related macular degeneration (AMD): 17) were scanned apical to basal through RPE cells at the fovea, perifovea, and near periphery using hrSIM (Zeiss Elyra.S1; ex488 nm; em>510 nm; 100 nm step size) and cmLSM (Zeiss LSM780; ex488 nm; em 490-695 nm; 390 nm step size; 8.9 nm spectral channel width). The hrSIM and lower-resolution cmLSM images were co-registered by linear 3D registration and choice of mutual information as the image match criterion (PMID16545965). This results in a 1:1 mapping between the single channel hrSIM and multichannel cmLSM data. Individual granules were segmented from the hrSIM data by expert-guided 3D level-set segmentation. Via the hrSIM-cmLSM mapping, the spectra of individual granules can be extracted for quantitative analysis. M, LF, MLF granules/cell were also counted using a custom FIJI plugin. Results: HrSIM imaging and segmentation enables clear delineation and identification of M, LF, and MLF granules (Fig. A,B). Individual granules can be tracked in the z-direction, and size, shape, dimensions, and intracellular position can be monitored. Each cell contains several hundred granules. A cushion of M localizes apically, while LF/MLF prefer basolateral accumulation. Software-assisted mapping of corresponding z-sections (hrSIM/cmLSM) for spectral characterization (Fig. C,D) demonstrates spectral variability among granules. Conclusions: With the combination of hrSIM and cmLSM imaging, individual autofluorescent RPE granules can be identified, localized in three-dimensions, and spectrally analyzed. The examination of spectral characteristics and changes related to intracellular and tissue localization, age, and disease status, on an individual granule basis, might reveal LF/MLF metabolism, and help elucidate LF's role in human RPE physiology. Ongoing studies are examining RPE granule properties in aging and AMD

Approximately 22% of children in the United States live in poverty, with high rates of caregiver depression and child disruptive behavior disorders (DBD). The current study aims to explore the relationships between living in extreme poverty and both child and parent mental health. Data are comprised of findings from the first effectiveness study of the 4Rs and 2Ss intervention, in addition to preliminary data from an implementation study currently underway (n= 484). Families with an annual income of less than $9,999 reported significantly greater child DBD scores and prevalence of clinically significant levels of caregiver depressive symptoms compared to income levels over $10,000. Findings support the recommendation for parental mental health to be attended to within the context of child mental health services.

Studies have reported associations between cortical thickness (CT) and socioeconomic status (SES), as well as between CT and cognitive outcomes. However, findings have been mixed as to whether CT explains links between SES and cognitive performance. In the current study, we hypothesized that this inconsistency may have arisen from the fact that socioeconomic factors (family income and parental education) may moderate the relation between CT and neurocognitive skills. Results indicated that associations between CT and cognitive performance did vary by SES for both language and executive function (EF) abilities. Across all ages, there was a negative correlation between CT and cognitive skills, with thinner cortices associated with higher language and EF scores. Similarly, across all cognitive skills, children from higher-SES homes outperformed their age-matched peers from lower-SES homes. Moderation analyses indicated that the impact of SES was not constant across CT, with SES more strongly predictive of EF skills among children with thicker cortices and more strongly predictive of language skills among children with thinner cortices. This suggests that socioeconomic advantage may in some cases buffer against a neurobiological risk factor for poor performance. These findings suggest that links between brain structure and cognitive processes vary by family socioeconomic circumstance.