Yihong Zhao

Is Exposure Necessary ? A Randomized Clinical Trial of Interpersonal Psychotherapy for PTSD

OBJECTIVE Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). The authors tested interpersonal psychotherapy (IPT), which has demonstrated antidepressant efficacy and shown promise in pilot PTSD research as a non-exposure-based non-cognitive-behavioral PTSD treatment. METHOD The authors conducted a randomized 14-week trial comparing IPT, prolonged exposure (an exposure-based exemplar), and relaxation therapy (an active control psychotherapy) in 110 unmedicated patients who had chronic PTSD and a score >50 on the Clinician-Administered PTSD Scale (CAPS). Randomization stratified for comorbid major depression. The authors hypothesized that IPT would be no more than minimally inferior (a difference <12.5 points in CAPS score) to prolonged exposure. RESULTS All therapies had large within-group effect sizes (d values, 1.32-1.88). Rates of response, defined as an improvement of >30% in CAPS score, were 63% for IPT, 47% for prolonged exposure, and 38% for relaxation therapy (not significantly different between groups). CAPS outcomes for IPT and prolonged exposure differed by 5.5 points (not significant), and the null hypothesis of more than minimal IPT inferiority was rejected (p=0.035). Patients with comorbid major depression were nine times more likely than nondepressed patients to drop out of prolonged exposure therapy. IPT and prolonged exposure improved quality of life and social functioning more than relaxation therapy. CONCLUSIONS This study demonstrated noninferiority of individual IPT for PTSD compared with the gold-standard treatment. IPT had (nonsignificantly) lower attrition and higher response rates than prolonged exposure. Contrary to widespread clinical belief, PTSD treatment may not require cognitive-behavioral exposure to trauma reminders. Moreover, patients with comorbid major depression may fare better with IPT than with prolonged exposure.

Aberrant gene expression in the Arabidopsis SULTR1;2 mutants suggests a possible regulatory role for this sulfate transporter in response to sulfur nutrient status

Sulfur is required for the biosynthesis of cysteine, methionine and numerous other metabolites, and thus is critical for cellular metabolism and various growth and developmental processes. Plants are able to sense their physiological state with respect to sulfur availability, but the sensor remains to be identified. Here we report the isolation and characterization of two novel allelic mutants of Arabidopsis thaliana, sel1-15 and sel1-16, which show increased expression of a sulfur deficiency-activated gene β-glucosidase 28 (BGLU28). The mutants, which represent two different missense alleles of SULTR1;2, which encodes a high-affinity sulfate transporter, are defective in sulfate transport and as a result have a lower cellular sulfate level. However, when treated with a very high dose of sulfate, sel1-15 and sel1-16 accumulated similar amounts of internal sulfate and its metabolite glutathione (GSH) to wild-type, but showed higher expression of BGLU28 and other sulfur deficiency-activated genes than wild-type. Reduced sensitivity to inhibition of gene expression was also observed in the sel1 mutants when fed with the sulfate metabolites Cys and GSH. In addition, a SULTR1;2 knockout allele also exhibits reduced inhibition in response to sulfate, Cys and GSH, consistent with the phenotype of sel1-15 and sel1-16. Taken together, the genetic evidence suggests that, in addition to its known function as a high-affinity sulfate transporter, SULTR1;2 may have a regulatory role in response to sulfur nutrient status. The possibility that SULTR1;2 may function as a sensor of sulfur status or a component of a sulfur sensory mechanism is discussed.

C-terminal domain (CTD) phosphatase links Rho GTPase signaling to Pol II CTD phosphorylation in Arabidopsis and yeast

Significance Rho GTPase and polymerase II (Pol II), two key molecules involved in cellular signaling and transcription in eukaryotic organisms, have been separately studied for more than 2 decades without evidence showing their functional linkage. We provide genetic and biochemical evidence linking these two molecules in an intracellular signaling pathway. Rho GTPases in Arabidopsis and yeast can modulate the phosphorylation status of the Pol II C-terminal domain (CTD) by inhibiting the CTD phosphatases. Our finding renders strong support for a direct or “shortcut” model in transcriptional control. Compared with the classical transcriptional activator/repressor-mediated indirect model, this shortcut model of targeting the core of Pol II likely provides an efficient transcriptional control to rapidly bring about the broad changes in gene expression. Rho GTPases, including the Rho, Cdc42, Rac, and ROP subfamilies, act as pivotal signaling switches in various growth and developmental processes. Compared with the well-defined role of cytoskeletal organization in Rho signaling, much less is known regarding transcriptional regulation. In a mutant screen for phenotypic enhancers of transgenic Arabidopsis plants expressing a constitutively active form of ROP2 (designated CA1-1), we identified RNA polymerase II (Pol II) C-terminal domain (CTD) phosphatase-like 1 (CPL1) as a transcriptional regulator of ROP2 signaling. We show that ROP2 activation inhibits CPL1 activity by promoting its degradation, leading to an increase in CTD Ser5 and Ser2 phosphorylation. We also observed similar modulation of CTD phosphorylation by yeast Cdc42 GTPase and enhanced degradation of the yeast CTD phosphatase Fcp1 by activated ROP2 signaling. Taken together, our results suggest that modulation of the Pol II CTD code by Rho GTPase signaling represents an evolutionarily conserved mechanism in both unicellular and multicellular eukaryotes.

Integrated Systems Biology Analysis of Transcriptomes Reveals Candidate Genes for Acidity Control in Developing Fruits of Sweet Orange (Citrus sinensis L. Osbeck)

Organic acids, such as citrate and malate, are important contributors for the sensory traits of fleshy fruits. Although their biosynthesis has been illustrated, regulatory mechanisms of acid accumulation remain to be dissected. To provide transcriptional architecture and identify candidate genes for citrate accumulation in fruits, we have selected for transcriptome analysis four varieties of sweet orange (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). Fruits of these varieties at 45 days post anthesis (DPA), which corresponds to Stage I (cell division), had similar acidity, but they displayed differential acid accumulation at 142 DPA (Stage II, cell expansion). Transcriptomes of fruits at 45 and 142 DPA were profiled using RNA sequencing and analyzed with three different algorithms (Pearson correlation, gene coexpression network and surrogate variable analysis). Our network analysis shows that the acid-correlated genes belong to three distinct network modules. Several of these candidate fruit acidity genes encode regulatory proteins involved in transport (such as AHA10), degradation (such as APD2) and transcription (such as AIL6) and act as hubs in the citrate accumulation gene networks. Taken together, our integrated systems biology analysis has provided new insights into the fruit citrate accumulation gene network and led to the identification of candidate genes likely associated with the fruit acidity control.

Effects of a Risk and Resilience Course on Stress, Coping Skills, and Cognitive Strategies in College Students.

This study tested the impact of the skills-building component of a two-semester risk and resilience (R&R) course on the stress, coping skills, and cognitive style of 36 undergraduates compared to 62 students enrolled in a child and adolescent psychopathology course. In the fall, students learned about risk taking and decision-making as well as coping skills and positive cognitive styles. In the spring, students taught these skills to ninth graders. Upon completion of the fall semester, R&R students reported improvements in stress, coping, and dysfunctional attitudes. Although maintained, these gains did not increase after the spring semester. We conclude that the course, particularly the fall semester, is an effective, practical classroom intervention for reducing stress and improving resilience in undergraduates.

Analysis of alcohol use disorders from the Nathan Kline Institute—Rockland Sample: Correlation of brain cortical thickness with neuroticism

BACKGROUND Although differences in both neuroanatomical measures and personality traits, in particular neuroticism, have been associated with alcohol use disorders (AUD), whether lifetime AUD diagnosis alters the relationship between neuroticism and neuroanatomical structures remains to be determined. METHODS Data from 65 patients with lifetime AUD diagnoses and 65 healthy comparisons (HC) group-matched on age, sex and race were extracted from the Nathan Kline Institute - Rockland Sample data set. Each subject completed personality trait measures and underwent MRI scanning. Cortical thickness measures at 68 Desikan-Killiany Atlas regions were obtained using FreeSurfer 5.3.0. Regression analyses were performed to identify brain regions at which the neuroticism-cortical thickness relationship was altered by lifetime AUD status. RESULTS As expected, AUDs had higher neuroticism scores than HCs. Correlations between neuroticism and cortical thickness in the left insula and right fusiform differed significantly across groups. Higher neuroticism score in AUD and the interaction between the insular cortical thickness-neuroticism correlation and AUD status were confirmed in a replication study using the Human Connectome Project data set. CONCLUSIONS Results confirmed the relationship between neuroticism and AUD and suggests that specific cortical regions, particularly the left insula, represent anatomic substrates underlying this association in AUD.