Faculty Bibliography

OBJECTIVE:Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). METHOD/METHODS:Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. RESULTS:After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). CONCLUSION/CONCLUSIONS:BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability.

PURPOSE OF REVIEW/OBJECTIVE:Many children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have difficulties in their social skills and peer relationships. Because social problems exacerbate later maladjustment in ADHD populations, it is important to address this serious impairment. Although social skills training (SST) is a common intervention approach, evidence to date suggests that SST has limited efficacy, at least when provided in traditional, clinic-based settings. The current review summarizes recent advances to traditional SST approaches that may potentially enhance their efficacy. RECENT FINDINGS/RESULTS:We identify two promising directions in which SST may be modified to make it more efficacious for ADHD populations. The first direction involves providing increased reinforcement and reminders of appropriate social behavior at the point of performance to youth with ADHD (e.g., in vivo, in real life peer situations as opposed to in the clinic). We note the importance of ensuring that youth with ADHD are receptive to such reminders. The second direction involves encouraging peers to be more socially accepting and inclusive of youth with ADHD. This avenue has been understudied in the literature to date. SST for children and adolescents with ADHD may be enhanced by providing more in vivo reminders and feedback at the point of performance and by making efforts to alter peers' impressions about youth with ADHD.

Latent class models are widely used to identify unobserved subgroups (i.e., latent classes) based upon one or more manifest variables. The probability of belonging to each subgroup is typically modeled as a function of a set of measured covariates. In this paper, we extend existing latent class models to incorporate matrix covariates. This research is motivated by a randomized placebo-controlled depression clinical trial. One study goal is to identify a subgroup of subjects who experience symptoms improvement early on during antidepressant treatment, which is considered to be an indication of a placebo rather than a true pharmacological response. We want to relate the likelihood of belonging to this subgroup of early responders to baseline electroencephalography (EEG) measurement that takes the form of a matrix. The proposed method is built upon a low rank Candecomp/Parafac (CP) decomposition of the target coefficient matrix through low-dimensional latent variables, which effectively reduces the model dimensionality. We adopt a Bayesian hierarchical modeling approach to estimate the latent variables, which allows a flexible way to incorporate prior knowledge about covariate effect heterogeneity and offers a data-driven method of regularization. Simulation studies suggest that the proposed method is robust against potentially misspecified rank in the CP decomposition. With the motivating example we show how the proposed method can be applied to extract valuable information from baseline EEG measurements that explains the likelihood of belonging to the early responder subgroup, helping to identify placebo responders and suggesting new targets for the study of placebo response.

OBJECTIVE:To examine the association between 9/11-related exposures and self-reported hearing problems among 16,579 rescue/recovery workers in the World Trade Center (WTC) Health Registry. METHODS:Using Registry Waves 1 (2003 to 2004) and 2 (2006 to 2007), we modeled the association between two metrics of 9/11-related exposures and hearing difficulties. RESULTS:The prevalence of incident, persistent hearing problems was 4.4%. In a fully adjusted model, workers with higher environmental hazards scores were twice as likely (interquartile range OR 2.1; 95% confidence interval [CI] 1.8, 2.5) to report hearing problems. Based on the same fully adjusted model, workers unable to hear in the dust cloud were 2.3 (95% CI 1.8, 3.0) times more likely to report hearing problems as compared with workers not in the dust cloud. CONCLUSIONS:We observed a consistent association between WTC-related exposures and self-reported hearing problems among rescue/recovery workers.

OBJECTIVE:Neural hypo-sensitivity to cues predicting positive reinforcement has been observed in ADHD using the Monetary Incentive Delay (MID) task. Here we report the first study using an electrophysiological analogue of this task to distinguish between (i) cue related anticipation of reinforcement and downstream effects on (ii) target engagement and (iii) performance in a clinical sample of adolescents with ADHD and controls. METHODS:Thirty-one controls and 32 adolescents with ADHD aged 10-16 years performed the electrophysiological (e)-MID task - in which preparatory cues signal whether a response to an upcoming target will be reinforced or not - under three conditions; positive reinforcement, negative reinforcement (response cost) and no consequence (neutral). We extracted values for both cue-related potentials known to be, both, associated with response preparation and modulated by reinforcement (Cue P3 and Cue CNV) and target-related potentials (target P3) and compared these between ADHD and controls. RESULTS:ADHD and controls did not differ on cue-related components on neutral trials. Against expectation, adolescents with ADHD displayed Cue P3 and Cue CNV reinforcement-related enhancement (versus neutral trials) compared to controls. ADHD individuals displayed smaller target P3 amplitudes and slower and more variable performance - but effects were not modulated by reinforcement contingencies. When age, IQ and conduct problems were controlled effects were marginally significant but the pattern of results did not change. DISCUSSION/CONCLUSIONS:ADHD was associated with hypersensitivity to positive (and marginally negative) reinforcement reflected on components often thought to be associated with response preparation - however these did not translate into improved attention to targets. In the case of ADHD, upregulated CNV may be a specific marker of hyper-arousal rather than an enhancement of anticipatory attention to upcoming targets. Future studies should examine the effects of age, IQ and conduct problems on reinforcement sensitivity in ADHD.

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.

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.

Functional brain imaging has revealed two types of dynamic patterns of brain in the resting-state: the dynamics of spontaneous brain activities and the dynamics of functional interconnections between spontaneous brain activities. Although these two types of brain dynamics are usually investigated separately in the literature, recent functional magnetic resonance imaging (fMRI) studies have shown that they exhibit similar spatial patterns, suggesting the dynamics of spontaneous brain activities and the dynamics of their interconnections are associated with each other. In this study, we characterized the local blood oxygenation level dependent (BOLD) dynamics and the functional connectivity dynamics (FCD) in the resting-state, and then investigated their between-region associations. Time-varying FC was estimated as time-varying correlation coefficients using a sliding-window method, and the temporal variability of BOLD and time-varying FC were used to quantify the BOLD dynamics and the FCD, respectively. Our results showed that the BOLD dynamics and the FCD exhibit similar spatial patterns, and they are significantly associated across brain regions. Importantly, such associations are opposite for different types of FC (e.g., within-network FCD are negatively correlated with the BOLD dynamics but the between-network FCD are positively correlated with the BOLD dynamics), and they are spatially heterogeneous across brain networks. The identified heterogeneous associations between the BOLD dynamics and the FCD appear to convey related or even distinct information and might underscore the potential mechanism of brain coordination and co-evolution.

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.

Resting-state functional connectivity is the synchronization of brain regions with each another. Alterations are suggestive of neurologic or psychological disorders. This article discusses methods and approaches used to describe resting-state brain connectivity and the results in neurotypical and diseased brains.