Faculty Bibliography

Sézary syndrome (SS) is the leukemic form of cutaneous T-cell lymphoma (CTCL) and can be associated with various nail irregularities, though they are infrequently reported. In this retrospective study, we reviewed medical records from a CTCL clinic database at the University of Texas MD Anderson Cancer Center (Houston, Texas) for reported nail abnormalities in patients with a diagnosis of SS. Findings for 2 select cases are described in more detail and are compared to prior case reports to establish a comprehensive list of nail irregularities that have been associated with SS.

BACKGROUND:Alcohol use disorder (AUD) is a wide-spread, heritable brain disease, but few studies have linked genetic variants or epigenetic factors to brain structures related to AUD in humans, due to many factors including the high-dimensional nature of imaging and genomic data. METHODS:To provide potential insights into the links among epigenetic regulation, brain structure, and AUD, we have performed an integrative analysis of brain structural imaging and blood DNA methylome data from 52 AUD and 58 healthy control (HC) subjects collected in the Nathan Kline Institute-Rockland Sample. RESULTS:We first found that AUD subjects had significantly larger insular surface area than HC in both left and right hemispheres. We then found that 7,827 DNA methylation probes on the HumanMethylation450K BeadChip had significant correlations with the right insular surface area (false discovery rate [FDR] < 0.05). Furthermore, we showed that 44 of the insular surface area-correlated methylation probes were also strongly correlated with AUD status (FDR < 0.05). These AUD-correlated probes are annotated to 36 protein-coding genes, with 16 genes (44%) having been reported by others to be related to AUD or alcohol response, including TAS2R16 and PER2. The remaining 20 genes, in particular ARHGAP22, might represent novel genes involved in AUD or responsive to alcohol. CONCLUSIONS:We have identified 36 insular surface area- and AUD-correlated protein-coding genes that are either known to be AUD- or alcohol-related or not yet reported by prior studies. Therefore, our study suggests that the brain imaging-guided epigenetic analysis has a potential of identifying possible epigenetic mechanisms involved in AUD.

The analysis of medical image time-series is becoming increasingly important as longitudinal imaging studies are maturing and large scale open imaging databases are becoming available. Image regression is widely used for several purposes: as a statistical representation for hypothesis testing, to bring clinical scores and images not acquired at the same time into temporal correspondence, or as a consistency filter to enforce temporal correlation. Geodesic image regression is the most prominent method, but the geodesic constraint limits the flexibility and therefore the application of the model, particularly when the observation time window is large or the anatomical changes are non-monotonic. In this paper, we propose to parameterize diffeomorphic flow by acceleration rather than velocity, as in the geodesic model. This results in a nonparametric image regression model which is completely flexible to capture complex change trajectories, while still constrained to be diffeomorphic and with a guarantee of temporal smoothness. We demonstrate the application of our model on synthetic 2D images as well as real 3D images of the cardiac cycle.

AIM/OBJECTIVE:To evaluate the preliminary effectiveness of the BRief Evaluation of Asthma THerapy intervention, a 7-min primary care provider-delivered shared decision-making protocol that uses motivational interviewing to address erroneous asthma disease and medication beliefs. DESIGN/METHODS:A multi-centre masked two-arm group-randomized clinical trial. METHODS:This 2-year pilot study is funded (September 2016) by the National Institute of Nursing Research. Eight providers will be randomized to one of two arms: the active intervention (N = 4) or a dose-matched attention control (N = 4). Providers will deliver the intervention to which they were randomized to 10 Black adult patients with uncontrolled asthma (N = 80). Patients will be followed three months postintervention to test the preliminary intervention effects on asthma control (primary outcome) and on medication adherence, lung function, and asthma-related quality of life (secondary outcomes). DISCUSSION/CONCLUSIONS:This study will evaluate the preliminary impact of a novel shared decision-making intervention delivered in a real world setting to address erroneous disease and medication beliefs as a means of improving asthma control in Black adults. Results will inform a future, large-scale randomized trial with sufficient power to test the intervention's effectiveness. IMPACT/CONCLUSIONS:Shared decision-making is an evidence-based intervention with proven effectiveness when implemented in the context of labour- and time-intensive research protocols. Medication adherence is linked with the marked disparities evident in poor and minority adults with asthma. Addressing this requires a novel multifactorial approach as we have proposed. To ensure sustainability, shared decision-making interventions must be adapted to and integrated into real-world settings. TRIAL REGISTRATION/BACKGROUND:Registered at clincialtrials.gov as NCT03036267 and NCT03300752.

Undiagnosed asthma adds to the burden of asthma and is an especially significant public health concern among urban adolescents. While much is known about individual-level demographic and neighborhood-level factors that characterize those with diagnosed asthma, limited data exist regarding these factors and undiagnosed asthma. This observational study evaluated associations between undiagnosed asthma and individual and neighborhood factors among a large cohort of urban adolescents. We analyzed data from 10,295 New York City adolescents who reported on asthma symptoms and diagnosis; a subset (n = 6220) provided addresses that we were able to geocode into US Census tracts. Multivariable regression models estimated associations between undiagnosed asthma status and individual-level variables. Hierarchical linear modeling estimated associations between undiagnosed asthma status and neighborhood-level variables. Undiagnosed asthma prevalence was 20.2%. Females had higher odds of being undiagnosed (adjusted odds ratio (AOR) = 1.25; 95% confidence interval (CI) = 1.13-1.37). Compared to White, non-Hispanic adolescents, Asian-Americans had higher risk of being undiagnosed (AOR = 1.41; 95% CI = 1.01-1.95); Latinos (AOR = 0.67; 95% CI = 0.45-0.83); and African-Americans/Blacks (AOR = 0.66; 95% CI = 0.52-0.87) had lower risk; Latinos and African-Americans/Blacks did not differ significantly. Living in a neighborhood with a lower concentration of Latinos relative to White non-Latinos was associated with lower risk of being undiagnosed (AOR = 0.66; CI = 0.43-0.95). Living in a neighborhood with health care provider shortages was associated with lower risk of being undiagnosed (AOR = 0.80; 95% CI =0.69-0.93). Public health campaigns to educate adolescents and their caregivers about undiagnosed asthma, as well as education for health care providers to screen adolescent patients for asthma, are warranted.

We conducted a systematic review of studies that have evaluated invariance of the construct of posttraumatic stress disorder (PTSD) to summarize their conclusions related to invariance/noninvariance and sources of noninvariance. In November 2017, we searched Pubmed, PSYCINFO, PILOTS Web of Science, CINAHL, Medline, and Psychological and Behavioral Science Collection for abstracts and articles with these inclusionary criteria: peer-reviewed, including DSM-IV or DSM-5 PTSD invariance as a main study aim, use of multigroup confirmatory factor analyses, and use of an independent PTSD instrument or module. In total, 45 articles out of 1,169 initially identified abstracts met inclusion criteria. Research assistants then followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to complete a secondary search and independently extract data. Results indicated that DSM-IV dysphoric arousal and DSM-5 hybrid model factors demonstrated the most stability; sources of instability were some intrusion (distress to trauma cues), dysphoria/numbing (traumatic amnesia, foreshortened future, emotional numbness, detachment), and arousal (hypervigilance) items. The PTSD Checklist and PTSD Reaction Index were most often used to assess PTSD in studies investigating its invariance; however, these measures demonstrated partial conceptual equivalence of PTSD across subgroups. Instead, clinician-administered measures demonstrated more conceptual equivalence across subgroups. Age, gender, cultural/linguistic factors, and sample diversity had the least moderating effect on PTSD's symptom structure. Our review demonstrates the need to examine invariance of the PTSD construct following recommended guidelines for each empirical and clinical trial study to draw meaningful multigroup comparative conclusions.

The search for objective biological tests, sufficiently reliable, and predictive enough to be diagnostic of psychiatric disorders, continues apace - yet their discovery remains a distant dream. It seems increasingly unlikely that current diagnostic structures and concepts map biologically in a straight forward way - with heterogeneity within, and sharing across, existing diagnostic boundaries being the biological rule rather than the exception. Indeed, it now appears that the science of biological psychiatry is more likely to redraw those boundaries than it is to confirm and mark them (Sonuga-Barke, Journal of Child Psychology and Psychiatry, 2016, 57, 1). Clinical identification of childhood psychiatric disorders therefore remains, for the foreseeable future at least, an exercise in regulated social perception - reliant on the fallible and subjective judgements of parents, teachers and clinicians. Social perception of this sort is an active and motivated process and therefore prone, like all social perception, to bias and distortions - both systematic and idiosyncratic. Progress has certainly been made over the last 50 years in reducing such judgement bias by, for instance filtering perceptions through the lens of standardised instruments (questionnaires and interviews) with carefully operationalised items and a degree of reliability and validity. However, such instruments often play only a peripheral role in actual diagnostic encounters and when they are used, there is still sufficient ambiguity to leave open plenty of room for interpretation. When we acknowledge that psychiatric diagnoses are social constructions - we are not saying that symptoms of inattention, impulsivity and hyperactivity are not real or do not cluster together in meaningful ways or that they do not cause real distress and disability but that their interpretation and meaning are often informed by social constructs such as ethnic or gender norms and stereotypes (Meyer, Stevenson, & Sonuga-Barke, Journal of Attention Disorders, 2019).

Background and aims.- Prevalence of psychiatric disorders differs in males and females, and neurological studies suggest that sex-linked variation in the brain may underlie this dissociation. However, the origin of this difference, and how early in human life sexual dimorphism in brain function emerges is a topic that requires further investigation. Here, we address this gap by assessing brain resting-state functional connectivity (RSFC) between and within brain networks as it relates to fetal sex and gestational age (GA). Methods.- We examined 118 typical human fetuses (70 male; 48 female) between 25.9 and 39.6 weeks GA. Infomap was used to derive 16 separable fetal neural networks distributed across cortical, subcortical, and cerebellar regions. Using enrichment analysis, we identified network pairs revealing distinct patterns of GArelated change in males and females. Results.- Sex-dependent variation of between- and within- network RSFC-GA associations was observed: while females exhibited GA-related variation in connectivity between posterior cingulate and temporal pole regions, and between pre-frontal and cerebellar regions, males demonstrated increased intracerebellar RSFC with advancing age. Conclusions.- Such observations confirm that sex-related differences in functional brain development are present before birth. An important next step in this line of research will be to follow children across early development and discover how sex-related variation in network development relates to future health outcomes

Introduction: Short sleep duration promotes metabolic dysregulation and obesity. We have previously shown that acute sleep restriction increases neuronal activity in response to food stimuli in areas of interoception and reward, such as the insula and orbitofrontal cortex. However, whether chronic mild sleep restriction impacts food reward valuation in the brain remains unknown. In an ongoing study, we assess the effects of mild 6-week sleep restriction on intrinsic functional connectivity (iFC) across reward and interoception- related brain circuitry.
Method(s): To date, 16 adult men and women (age 29.0+/-5.3 years and BMI 26.9+/-2.6 kg/m²at study entry) took part in this randomized, crossover, outpatient trial of 2 phases: habitual sleep (HS; >=7 h/night) and sleep restriction (SR; -1.5 h/night relative to HS). All participants were screened with actigraphy over a two-week period to ensure adequate sleep duration of 7-9 h/night (average screening total sleep time: 7.65+/-0.58 h/night). Two resting-state (task-free) functional MRI scans (Siemens Skyra 3T, TR=2.5s, two 5-min runs) were collected during the final week of each phase. Here we report preliminary analyses using the Data Processing & Analysis of Brain Imaging V2.3-170105 toolbox with paired-sample t-tests across the whole brain.
Result(s): Average sleep duration in the HS phase was 7.55+/-0.55 h/ night vs. 6.10+/-0.49 h/night during SR (p<0.0001). Examining iFC of 17 previously studied regions-of-interest relevant to food valuation and interoception yielded two significant results after correction for Gaussian Random Field (p<0.001 at voxel level, cluster p<0.05). iFC was greater following SR than HS for (1) left inferior frontal gyrus with medial prefrontal cortex (mPFC); and (2) mPFC with bilateral superior temporal gyrus.
Conclusion(s): This study provides preliminary evidence of decreased segregation between a key anterior node of the default mode network (mPFC) and nodes of the salience and somatosensory (auditory) networks under prolonged mild SR. Such iFC changes, suggesting atypical network coupling, if confirmed in the completed sample, will be examined in the future in relation to key measures of metabolism and cardiovascular risks

Active avoidance is the prototypical paradigm for studying aversively-motivated instrumental behavior. However, avoidance research stalled amid heated theoretical debates and the hypothesis that active avoidance is essentially Pavlovian flight. Here I reconsider key "avoidance problems" and review neurobehavioral data collected with modern tools. Although the picture remains incomplete, these studies strongly suggest that avoidance has an instrumental component and is mediated by brain circuits that resemble appetitive instrumental actions more than Pavlovian fear reactions. Rapid progress may be possible if investigators consider important factors like safety signals, response-competition, goal-directed vs. habitual control and threat imminence in avoidance study design. Since avoidance responses likely contribute to active coping, this research has important implications for understanding human resilience and disorders of control.