Faculty Bibliography

OBJECTIVE:Research on pediatric bipolar disorder (PBD) has grown substantially in the past 7 years; updating a 2011 meta-analysis of PBD prevalence could improve understanding of factors that influence prevalence. DATA SOURCES:A literature review of papers published in English was updated in 2018 using PubMed and PsycINFO. Search terms included pediatric, child, "bipolar disorder," bipolar, mania, prevalence, epidemiology, community, adolescent, and youth. STUDY SELECTION:Inclusion criteria were (1) youth epidemiologic sample, (2) number of youth with bipolar spectrum disorders reported, and (3) prevalence rates for youth differentiated from prevalence for those over age 21 years (if both included). Of 2,400 articles retrieved, 44 were evaluated and 8 new were included. DATA EXTRACTION:Prevalence rates for each bipolar subtype were recorded as reported; hypothesized moderators (eg, study characteristics, environmental factors) were also coded. RESULTS:Eight additional studies resulted in a total sample of 19 studies, tripling the sample size to N = 56,103 and n = 1,383 with bipolar disorder. Seven studies were from the United States, and 12 were from South America, Central America, or Europe. Weighted average prevalence of bipolar spectrum disorders was 3.9% (95% CI, 2.6%-5.8%). There was significant heterogeneity across studies (Q = 759.82, df = 32, P < .0005). The pooled rate of bipolar I was 0.6% (95% CI, 0.3%-1.2%); these rates were also heterogeneous (Q = 154.27, df = 13, P < .0001). Predictors of higher bipolar spectrum disorder prevalence were the use of broad bipolar criteria (P < .0001), older minimum age (P = .005), and lifetime prevalence (P = .002). Newer studies were associated with lower rates (P < .0001). CONCLUSIONS:The updated meta-analysis confirms that rates of bipolar spectrum disorders are not higher in the United States than in other Western countries, nor are rates increasing over time. Nonstandard diagnostic criteria result in highly variable prevalence rates, as does focusing on narrow definitions of PBD to the exclusion of the full spectrum. Consistent application of validated criteria could help to settle questions regarding PBD prevalence. Studies from non-Western countries are needed to refine understanding of international prevalence and risk factors.

Objective/UNASSIGNED:The current meta-analysis synthesizes previous findings on the effect of gabapentin on alcohol withdrawal and craving. Data Sources/UNASSIGNED:Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, a search for relevant English-language literature published between January 1999 and February 2019 was conducted using PubMed and Google Scholar with the keywords alcohol use disorder, alcohol dependence, alcohol withdrawals, alcohol craving, "gabapentin in alcohol use, consumption," and "gabapentin in alcohol withdrawals." Study Selection and Data Extraction/UNASSIGNED:Studies were included wherein gabapentin was used as an adjunctive or primary treatment of alcohol dependence/withdrawal. Studies included participants diagnosed with alcohol use disorder using DSM-IV, DSM-IV-TR, DSM-5, or the International Classification of Diseases, Tenth Revision (ICD-10). The search, as well as data extraction, was carried out by 3 blinded authors to preserve precision, using a template in Microsoft Excel to extract the needed data. Following the review of the initial 65 returns, 2 authors independently judged each trial by applying the inclusionary and exclusionary criteria, and any remaining disagreements were resolved by involving a third independent author. A total of 10 studies met the inclusion criteria and were selected for analysis. Subjects in these 10 studies were pooled using standard techniques of meta-analysis. Data Synthesis/UNASSIGNED:Three sets of meta-analyses examined outcomes from (1) single-group pretest-posttest changes, (2) posttest differences between independent groups, and (3) differences in pretest-posttest change scores between independent groups. Statistically significant effect sizes were found for craving (P < .01) and withdrawal (P < .01, P < .001) in the meta-analysis of single-group pretest-posttest outcome changes and were associated with a high level of heterogeneity. In contrast, the meta-analyses of posttest differences between independent groups-that of differences in pretest-posttest change scores between independent groups-did not yield significant effect sizes. Conclusions/UNASSIGNED:Our analysis of pooled data provides evidence that the use of gabapentin to manage alcohol withdrawal symptomatology and related cravings is at least moderately effective. However, given the limited number of available well-designed studies, these findings require further support through more rigorously designed studies.

Transcranial magnetic stimulation (TMS), a research tool with various effects on brain cells, can depolarize cerebral neurons noninvasively. This method offers temporal and spatial resolution and can be combined with other neurocognitive and neuro-experimental techniques. Prefrontal TMS therapy repeated daily for four to six weeks is a neuromodulation technique approved by the US Food and Drug Administration for the treatment of major depressive disorder (MDD) in patients resistant to medications. This technique utilizes electromagnetic induction to excite neuronal cells. Several recent studies have enhanced our understanding of this novel treatment intervention. This report reviews recent studies on the mechanism of action, patient eligibility, effectiveness, and safety of TMS in treating depression.

Introduction Hispanics are the largest ethnic minority group in the United States. The prevalence of depression and co-morbid depression in the Hispanic population is well-recognized. The positive association between physical activity and psychological health improves mood, emotional well-being, and prognostic outcome. Objectives There are two aspects of our research paper. First, it critically reviews the available literature showing the correlation between physical exercise and depression. Second, it analyzes the association between exercise and depression in uncontrolled diabetic Hispanics using data collected from the local community intervention program. Method A chi-square analysis was conducted to examine whether levels of physical activity reported at the baseline were associated with the frequency of depressed mood and anhedonia self-reported for the previous two weeks. This study utilized the use of the PHQ-2 scale for the assessment of depressive symptoms. The PHQ-2 scale is a useful tool to screen for depression in the integrated care setting. Participants from a local community intervention program were stratified on the basis of their gender and preferred language. Data were collected and represented in tables according to demographic characteristics. Results Our study established a statistically significant association between the levels of physical activity and the frequency of depression symptoms among Spanish speaking participants from the local community intervention program. These results provide convincing evidence that biological, developmental, social, and psychological factors facilitate the association between physical activity and depression.

Psychogenic polydipsia or self-induced water intoxication is a potentially lethal condition seen in many chronic psychiatric patients. This is a literature review based on therapeutic significance of Naltrexone in improving compulsive water drinking behavior in chronic psychiatrically ill patients with psychogenic polydipsia. Naltrexone is an opioid antagonist approved by FDA for alcohol dependence. Extensive literature search provides a line of evidence that suggests correlation of opioid receptor with compulsive water ingestion in animals. However, there is limited data regarding clinical utility of naltrexone in improving psychogenic polydipsia in human species. This review highlights the necessity for further research and trials to elucidate the role of naltrexone in human psychogenic drinking behavior.

The anxiety-related attention bias (AB) has been studied for several decades as a clinically-relevant output of the dynamic and complex threat detection-response system. Despite research enthusiasm for the construct of AB, current theories and measurement approaches cannot adequately account for the growing body of mixed, contradictory, and null findings. Drawing on clinical, neuroscience, and animal models, we argue that the apparent complexity and contradictions in the empirical literature can be attributed to the field's failure to clearly conceptualize AB heterogeneity and the dearth of studies in AB that consider additional cognitive mechanisms in anxiety, particularly disruptions in threat-safety discrimination and cognitive control. We review existing research and propose a working model of AB heterogeneity positing that AB may be best conceptualized as multiple subtypes of dysregulated processing of and attention to threat anchored in individual differences in threat-safety discrimination and cognitive control. We review evidence for this working model and discuss how it can be used to advance knowledge of AB mechanisms and inform personalized prevention and intervention approaches.

Umbilical cord blood transplantation (UCBT) is an alternative for patients who need hematopoietic stem cell transplant (HSCT), but lack HLA-matched adult donors. Rabbit anti-thymoglobulin (ATG) has been used in UCBT conditioning to achieve T cell depletion, but ATG-induced immunosuppression is associated with delayed immune reconstitution, increased infectious complications and higher non-relapse mortality. In a clinical trial of reduced intensity double-unit UCBT (dUCBT), we substituted low dose total body irradiation (TBI) for ATG to determine whether dUCBT without ATG would alter kinetics and quality of immune reconstitution. Thirty-one patients with hematopoietic malignancies and a median age of 58 yr were treated with Flu/Mel/TBI, followed by dUCBT and GVHD prophylaxis with tacrolimus and sirolimus. We examined reconstitution of immune cell populations, thymic regeneration by quantifying T cell receptor excision circles (TREC) and serum cytokines (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha, IL-12p70, GM-CSF) using the LUNARISTM Human 11-Plex Cytokine BiochipXX from AYOXXA Biosystems. Assessments were done prior to and at 1, 2, 3, 6, 12 and 24 months after dUCBT. Results are based on 28 evaluable patients. The 2-yr overall survival and progression-free survival were 53% and 48%. Median time to neutrophil and platelet engraftment was 25 and 52 days, respectively. Before UCBT, the median values for most leukocyte subsets were below normal limits, except for monocytes. CD3XX cells remained depressed until 2 months post-transplant when gradually began to re-emerge. However, CD4XX subsets had distinct reconstitution kinetics (Figure 1). CD4XX T cells declined at 1 month but gradually increased and exceeded pre-transplant levels by 9 months after UCBT. In contrast, at 9 months, CD8XX lymphocytes remained depressed to 50% of pre-transplant levels, but increased thereafter and reached normal values by 2-yr. NK cells and monocytes reached normal values at 3 months post-UCBT. B cells were mostly undetectable for the first 6 months, followed by a 10-fold increase at 9 months and exceeded the upper normal limit by 2-yr. TREC, which were within normal range before transplant, decreased after UCBT but remained detectable between 1-6 months and recovered to normal levels by 9 months. Among cytokines, only IL-8, IL-6 and TNF-alpha displayed significant changes. IL-8 and IL-6 peaked at day 100 and 9 months, and subsequently declined. In contrast, TNF-alpha increased by day 100 and remained elevated thereafter. To evaluate functional immunity, we assessed correlations between viral reactivation and reconstitution of immune cell populations and thymic function. Nineteen patients experienced 24 clinically significant viral reactivations or infections, with 1-year cumulative incidence of 62%, which was comparable to 53% observed in dUCBT cohorts receiving ATG-containing conditioning. Although there was no difference in CMV, EBV, adenovirus and VZV reactivation, there was a significant increase in the incidence of HHV-6 reactivation. HHV-6 viremia was observed in 24 of 28 (86%) patients during the first month after dUCBT. Six of these 24 (25%) patients developed HHV-6-related encephalitis. There was a correlation between development of encephalitis and HHV-6 viral load >=50.000 copies/ml (p=0.007). Pre-transplant TREC levels >=1.200 copies/ml negatively correlated with subsequent HHV-6 reactivation (p=0.04), indicating that baseline reserve of thymic function has a significant role in post-transplant immune reconstitution. On days 30, 60 and 100 post-transplant, higher TREC levels correlated with lack of HHV-6 viremia (pXX counts in the first 100 days was also observed in patients without HHV-6 reactivation. Neutrophil and platelet engraftment, reconstitution of CD4XX T effectors, NK cells and monocytes, IL-6, IL-8 and TNF-alpha levels, and development of GVHD did not correlate with HHV-6 reactivation or its absence. Our results indicate that substitution of low dose TBI for ATG in the conditioning regimen is characterized by superior recovery of thymopoiesis and reconstitution of CD4XX T cells, both of which have a protective role against HHV-6 reactivation and end organ disease. Further studies will identify why HHV-6 reactivation is selectively increased in UCBT recipients treated with TBI-containing conditioning. [Formula presented] Disclosures: Defilipp: Incyte: Research Funding. Politikos: Angiocrine Bioscience Inc: Research Funding. Armand: Otsuka: Research Funding; Roche: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Sigma Tau: Research Funding; ADC Therapeutics: Consultancy; Tensha: Research Funding; Genentech: Research Funding; Pfizer: Consultancy. Ho: Jazz Pharmaceuticals: Consultancy. Koreth: Amgen: Consultancy; Equillium: Consultancy; Cugene: Consultancy. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partners Tx: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexel: Consultancy; Takeda: Consultancy. Rosenblatt: Celgene: Research Funding; Amgen: Other: Advisory Board; Merck: Other: Advisory Board; BMS: Other: Advisory Board; Parexel: Consultancy; Imaging Endpoint: Consultancy; Partner Tx: Other: Advisory Board; Dava Oncology: Other: Education; BMS: Research Funding. Chen: Abbvie: Consultancy; Incyte: Consultancy; Magenta: Consultancy; Takeda: Consultancy; Kiadis: Consultancy. Soiffer: Gilead, Mana therapeutic, Cugene, Jazz: Consultancy; Juno, kiadis: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Mana therapeutic: Consultancy; Kiadis: Other: supervisory board; Jazz: Consultancy; Cugene: Consultancy. Cutler: Kadmon: Consultancy; Incyte: Consultancy; Pharmacyclics: Consultancy; Fate Therapeutics: Consultancy. Ritz: Equillium: Research Funding; Merck: Research Funding; Kite Pharma: Research Funding; Aleta Biotherapeutics: Consultancy; Celgene: Consultancy; Avrobio: Consultancy; LifeVault Bio: Consultancy; Draper Labs: Consultancy; Talaris Therapeutics: Consultancy; TScan Therapeutics: Consultancy.XXCopyright

Given the immense harm inflicted on individuals and groups of color via prejudice and discrimination, it becomes imperative for our nation to begin the process of disrupting, dismantling, and disarming the constant onslaught of micro- and macroaggressions. For too long, acceptance, silence, passivity, and inaction have been the predominant, albeit ineffective, strategies for coping with microaggressions. Inaction does nothing but support and proliferate biased perpetrator behaviors which occur at individual, institutional and societal levels. This article introduces a new strategic framework developed for addressing microaggressions that moves beyond coping and survival to concrete action steps and dialogues that targets, allies, and bystanders can perform (microinterventions). A review of responses to racist acts, suggest that microaggression reactions/interventions may be primarily to (a) remain passive, retreat, or give up; (b) strike back or hurt the aggressor; (c) stop, diminish, deflect, or put an end to the harmful act; (d) educate the perpetrator; (e) validate and support the targets; (f) act as an ally; (g) seek social support; (h) enlist outside authority or institutional intervention; or (h) achieve any combination of these objectives. We organize these responses into four major strategic goals of microinterventions: (a) make the invisible visible, (b) disarm the microaggression, (c) educate the perpetrator, and (d) seek external reinforcement or support. The objectives and rationale for each goal are discussed, along with specific microintervention tactics to employ and examples of how they are executed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).