A culturally adapted unified protocol for transdiagnostic treatment of anxiety disorders in adolescents (UP-A): a randomized waitlist-controlled trial.

BACKGROUND: Anxiety disorders are highly prevalent and debilitating conditions that show high comorbidity rates in adolescence. The present article illustrates how Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) was adapted for Iranian adolescents with anxiety disorders. METHODS: A total of 54 adolescents with comorbid anxiety disorders participated in a randomized, waitlist-controlled trial of group weekly sessions of either UP-A or waitlist control (WLC). Primary and process of change outcomes were assessed at baseline, posttreatment, and 1-month follow-up. RESULTS: Significant changes were observed over time on major DSM-5 anxiety disorder symptoms (F(2, 51) = 117.09, p < 0.001), phobia type symptoms (F(2, 51) = 100.67, p < 0.001), and overall anxiety symptoms (F(2, 51) = 196.29, p < 0.001), as well as on emotion regulation strategies of reappraisal (F(2, 51) = 17.03, p < 0.001), and suppression (F(2, 51) = 21.13, p < 0.001), as well as on intolerance of uncertainty dimensions including prospective (F(2, 51) = 74.49, p < 0.001), inhibitory (F(2, 51) = 45.94, p < 0.001), and total intolerance of uncertainty (F(2, 51) = 84.42, p < 0.001), in favor of UP-A over WLC. CONCLUSION: Overall, results provide a cultural application of the UP-A and support the protocol as useful for improving anxiety disorders as well as modifying of emotion regulation strategies and intolerance of uncertainty dimensions in Iranian adolescents. Future directions and study limitations are discussed.

Outcomes of People of Color in an Efficacy Trial of Cognitive-Behavioral Treatments for Anxiety, Depression, and Related Disorders: Preliminary Evidence.

ABSTRACT: Although evidence-based psychological treatments such as cognitive behavioral therapy (CBT) have strong empirical support for reducing anxiety and depression symptoms, CBT outcome research often does not report race and ethnicity variables, or assess how well CBT works for people from historically excluded racial and ethnic groups. This study presents post hoc analyses comparing treatment retention and symptom outcomes for participants of color ( n = 43) and White participants ( n = 136) from a randomized controlled efficacy trial of CBT. χ 2 tests and one-way ANCOVA showed no observable differences between the two samples on attrition or on clinician-rated measures of anxiety and depression at posttreatment and follow-up. Moderate to large within-group effect sizes on anxiety and depression were found for Black, Latinx, and Asian American participants at almost all time points. These preliminary findings suggest that CBT for anxiety and comorbid depression may be efficacious for Black, Asian American, and Latinx individuals.

Agreement in patient-therapist alliance ratings and its relation to dropout and outcome in a large sample of cognitive behavioral therapy for panic disorder.

Objective The therapeutic alliance is related to treatment outcome but less is known about the agreement on alliance between patients and therapists and its relationship to outcomes. We examined the association of patient-therapist congruence of alliance perceptions, early and late in cognitive behavioral therapy for panic disorder in relation to symptom reduction and dropout. Method: Patients (n = 181) and their therapists provided alliance ratings early and late during 11-session treatment. Independent evaluators rated patients' symptomatic levels post-treatment. Polynomial regression and response surface analysis were used to examine congruence as a predictor of outcome. Results: Early in therapy, stronger combined patient-therapist alliances, regardless of agreement, predicted lower symptom severity at the end of therapy and a lower likelihood of dropout. Late in treatment, the outcome was worse when therapist ratings of the alliance were higher than those of the patient. Conclusions: Therapist-patient agreement on the strength of the alliance is important for symptom improvement and dropout. The study highlights the importance of understanding the dyadic nature of the alliance and its impact on therapeutic change.

The Impact of Lipid Digestion on the Dynamic and Structural Properties of Micelles.

Self-assembled, lipid-based micelles, such as those formed by the short-chain phosphocholine, dihexanoylphosphatidylcholine (2C6PC), are degraded by the pancreatic enzyme, phospholipase A2 (PLA2). Degradation yields 1-hexanoyl-lysophosphocholine (C6LYSO) and hexanoic acid (C6FA) products. However, little is known about the behavior of these products during and after the degradation of 2C6PC. In this work, a combination of static and time-resolved small angle neutron scattering, as well as all-atom molecular dynamics simulations, is used to characterize the structure of 2C6PC micelles. In doing so a detailed understanding of the substrate and product aggregation behavior before, during and after degradation is gained. Consequently, the formation of mixed micelles containing 2C6PC, C6LYSO and C6FA is shown at every stage of the degradation process, as well as the formation of mixed C6LYSO/C6FA micelles after degradation is complete. The use of atomistic molecular dynamics has allowed us to characterize the structure of 2C6PC, 2C6PC/C6LYSO/C6FA, and C6LYSO/C6FA micelles throughout the degradation process, showing the localization of the different molecular species within the aggregates. In addition, the hydration of the 2C6PC, C6LYSO, and C6FA species both during micellization and as monomers in aqueous solution is documented to reveal the processes driving their micellization.

Does the unified protocol really change neuroticism? Results from a randomized trial.

BACKGROUND: Neuroticism is associated with the onset and maintenance of a number of mental health conditions, as well as a number of deleterious outcomes (e.g. physical health problems, higher divorce rates, lost productivity, and increased treatment seeking); thus, the consideration of whether this trait can be addressed in treatment is warranted. To date, outcome research has yielded mixed results regarding neuroticism's responsiveness to treatment, perhaps due to the fact that study interventions are typically designed to target disorder symptoms rather than neuroticism itself. The purpose of the current study was to explore whether a course of treatment with the unified protocol (UP), a transdiagnostic intervention that was explicitly developed to target neuroticism, results in greater reductions in neuroticism compared to gold-standard, symptom focused cognitive behavioral therapy (CBT) protocols and a waitlist (WL) control condition. METHOD: Patients with principal anxiety disorders (N = 223) were included in this study. They completed a validated self-report measure of neuroticism, as well as clinician-rated measures of psychological symptoms. RESULTS: At week 16, participants in the UP condition exhibited significantly lower levels of neuroticism than participants in the symptom-focused CBT (t(218) = -2.17, p = 0.03, d = -0.32) and WL conditions(t(207) = -2.33, p = 0.02, d = -0.43), and these group differences remained after controlling for simultaneous fluctuations in depression and anxiety symptoms. CONCLUSIONS: Treatment effects on neuroticism may be most robust when this trait is explicitly targeted.

Using Polar Ion-Pairs to Control Drug Delivery to the Airways of the Lungs.

The rapid absorptive clearance of drugs delivered to the airways of the lungs means that many inhaled medicines have a short duration of action. The aim of this study was to investigate whether forming polar ion-pairs can modify drug absorption to slow down clearance from the airways. Salbutamol was used as a model drug and was formulated as ion-pairs in an aqueous solution with three negatively charged hydrophilic counterions: sulfate (molecular weight (MW) 142), gluconate (MW 218), and phytate (MW 736) (association constants of 1.57, 2.27, and 4.15, respectively) and one negatively charged hydrophobic counterion, octanoate (MW 166) (association constant, 2.56). All of the counterions were well tolerated by Calu-3 human bronchial epithelial cells when screened for toxicity in vitro using conditions that in silico simulations suggested maintain >80% drug-counterion association. The transport of salbutamol ion-pairs with higher polar surface area (PSA), i.e., the sulfate (PSA 52%), gluconate (PSA 50%), and phytate (PSA 79%) ion-pairs, was significantly lower compared to that of the drug alone (PSA 30%, p < 0.05). In contrast, the octanoate ion-pair (PSA 23%) did not significantly alter the salbutamol transport. The transport data for the gluconate ion-pair suggested that the pulmonary absorption half-life of the ion-paired drug would be double that of salbutamol base, and this illustrates the promise of increasing drug polarity using noncovalent complexation as an approach to control drug delivery to the airways of the lungs.

Arrangement of Ceramides in the Skin: Sphingosine Chains Localize at a Single Position in Stratum Corneum Lipid Matrix Models.

Understanding the structure of the stratum corneum (SC) is essential to understand the skin barrier process. The long periodicity phase (LPP) is a unique trilayer lamellar structure located in the SC. Adjustments in the composition of the lipid matrix, as in many skin abnormalities, can have severe effects on the lipid organization and barrier function. Although the location of individual lipid subclasses has been identified, the lipid conformation at these locations remains uncertain. Contrast variation experiments via small-angle neutron diffraction were used to investigate the conformation of ceramide (CER) N-(tetracosanoyl)-sphingosine (NS) within both simplistic and porcine mimicking LPP models. To identify the lipid conformation of the twin chain CER NS, the chains were individually deuterated, and their scattering length profiles were calculated to identify their locations in the LPP unit cell. In the repeating trilayer unit of the LPP, the acyl chain of CER NS was located in the central and outer layers, while the sphingosine chain was located exclusively in the middle of the outer layers. Thus, for the CER NS with the acyl chain in the central layer, this demonstrates an extended conformation. Electron density distribution profiles identified that the lipid structure remains consistent regardless of the lipid's lateral packing phase, this may be partially due to the anchoring of the extended CER NS. The presented results provide a more detailed insight on the internal arrangement of the LPP lipids and how they are expected to be arranged in healthy skin.

Correction to: Metabolic relevance for N-hydroxy L-arginine reduction in estrogen-negative breast cancer cells.

We found a unit error with our LC-MS lower limit of quantitation (LLOQ) measurement in the Amino Acids Journal.

The discovery and enhanced properties of trichain lipids in lipopolyplex gene delivery systems.

The formation of a novel trichain (TC) lipid was discovered when a cationic lipid possessing a terminal hydroxyl group and the helper lipid dioleoyl l-α-phosphatidylethanolamine (DOPE) were formulated as vesicles and stored. Importantly, the transfection efficacies of lipopolyplexes comprised of the TC lipid, a targeting peptide and DNA (LPDs) were found to be higher than when the corresponding dichain (DC) lipid was used. To explore this interesting discovery and determine if this concept can be more generally applied to improve gene delivery efficiencies, the design and synthesis of a series of novel TC cationic lipids and the corresponding DC lipids was undertaken. Transfection efficacies of the LPDs were found to be higher when using the TC lipids compared to the DC analogues, so experiments were carried out to investigate the reasons for this enhancement. Sizing experiments and transmission electron microscopy indicated that there were no major differences in the size and shape of the LPDs prepared using the TC and DC lipids, while circular dichroism spectroscopy showed that the presence of the third acyl chain did not influence the conformation of the DNA within the LPD. In contrast, small angle neutron scattering studies showed a considerable re-arrangement of lipid conformation upon formulation as LPDs, particularly of the TC lipids, while gel electrophoresis studies revealed that the use of a TC lipid in the LPD formulation resulted in enhanced DNA protection properties. Thus, the major enhancement in transfection performance of these novel TC lipids can be attributed to their ability to protect and subsequently release DNA. Importantly, the TC lipids described here highlight a valuable structural template for the generation of gene delivery vectors, based on the use of lipids with three hydrophobic chains.

Assessing N w-hydroxy-L-arginine applicability as a novel ethnic specific estrogen-negative breast cancer marker.

In our prior study we identified N w-hydroxy-L-arginine (NOHA) as a simple, yet sensitive indicator for estrogen negative (ER-) breast cancer early-prognosis, but not estrogen positive (ER+), and to offer ethnic selectivity for ER- detection. However, the ability of NOHA to assess ER- breast tumor based on disease progression, and tumor severity needs further delineation. Also, the overall NOHA storage stability needs to be validated. To assess the NOHA predictive capability based on disease progression, ER-/ER+ 3D-spheroids (from breast tumor cell lines of human origin) were cultured for 10 weeks. We found only ER- 3D-spheroid cultured for 10 weeks to show a gradual reduction in NOHA (both in culture medium and 3D-spheroid lysates) that correlated with a progressive increase in cellular NOS2 expression and NOS2 activity (measured as total nitrites). We additionally identified the NOHA-NOS2 correlation to be ethnically selective between ER- African American versus ER- Caucasian groups. Interestingly, such NOHA reduction was observed earlier in ER- culture medium (viz., after week 1) than from ER- 3D-spheroids lysates (viz., at the end of 3 weeks). When categorized based on 3D-spheroid grade, we found a ≥ 68% NOHA reduction in ER- spheroids that were ≤ 3 weeks old, that was categorized as "low-grade" (based on tumor size ≤ 250 µm, and with cellular characteristics identical to healthy cells). A substantial reduction in NOHA of ≥ 87% occurred with ER- 3D-spheroids grown for 6 weeks, which were categorized as "intermediate-grade" (with tumor size of ≥ 400 µm, and with less characteristic similarity to control spheroids). These in vitro findings thus suggest a distinct correlation between NOHA reduction and ER- tumor grade. Such distinctive correlation between NOHA and ER- tumor grade was additionally observed in de-identified clinical samples where a onefold higher reduction in NOHA occurred in grade-2 than with grade-1 de-identified patient plasma (when compared with control), and such correlation offered ethnic selectivity between ER- African American and ER- Caucasian groups. Of additional interest, when NOHA overall storage stability was assessed by incubating patient plasma and culture medium spiked with 75 pg/ml NOHA at multiple incubation temperatures and time-points, we found NOHA to maintain its stability for up to 6 weeks in culture medium and for 7 days in plasma at 4 °C and below. These results thus provide the first evidence of NOHA as a stable indicator to monitor ER- disease progression and tumor severity in ethnically distinctive populations.

Metabolic relevance for N-hydroxy L-arginine reduction in estrogen-negative breast cancer cells.

We had shown Nw-hydroxy-L-arginine (NOHA) as a promising blood-based biomarker for estrogen-receptor-negative (ER-) breast cancer (BC) that differentiates ER- BC based on grade and molecular phenotype. In this in vitro study, we assessed the metabolic relevance for ER- BC-specific NOHA modulation and correlated them with NOHA regulatory responses. This study aids future NOHA clinical utility in ER- BC diagnosis and therapy management and would prove useful for potential drug discovery and development process.

Ion-Pairing with Spermine Targets Theophylline To the Lungs via the Polyamine Transport System.

Certain xenobiotics, such as paraquat, are sequestered into the lungs from the systemic circulation by the polyamine transporter system (PTS). The aim of this study was to investigate whether ion-pairing a drug (theophylline) with a PTS substrate (spermine) provides a means of using this active transport mechanism to target drug delivery to the lungs. Fourier transform infrared spectroscopy showed that two of the amine groups of spermine interact with C-N7 and C6═O of theophylline, leaving two free amines to interact with the PTS. In A549 cells, which possess a functional PTS (spermidine Km and Vmax, 0.6 ± 0.3 µM and 1.8 ± 0.3 pmol·min-1 per 105 cells, respectively), uptake of the theophylline-spermine ion-pair was increased 1.8-fold compared to free theophylline at 37 °C, but not at 4 °C. In an isolated perfused rat lung model (IPL) a 3.6-fold increase in lung theophylline concentration was observed after vascular administration of the ion-pair compared to free theophylline. Theophylline was cleared from the IPL with similar kinetics irrespective of whether it was delivered as the free drug or an ion-pair, although lung levels remained elevated after washout following delivery as an ion-pair. In vitro simulation of the theophylline-spermine break down demonstrated that a drop in pH from 9.6 to 7.4, such as that undergone by the ion-pair in biological matrices, induces rapid and almost complete dissociation of the ion-paired species. However, infusion of the ion-pair formulations via the vasculature provides almost immediate delivery to the pulmonary capillary bed permitting PTS-mediated active sequestering of ion-paired theophylline into the lungs.

A Preliminary Examination of the Effects of Transdiagnostic Versus Single Diagnosis Protocols on Anger During the Treatment of Anxiety Disorders.

Dysregulated anger is often present in the emotional (i.e., anxiety, mood, and related) disorders; however, it is rarely targeted in treatment. Transdiagnostic treatments, which focus on processes that contribute to dysregulated emotions across the range of psychopathology, might represent an efficient way to treat this anger. Using a subset of data from a recently completed equivalency trial comparing the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) to single diagnosis protocols (SDPs) for specific disorders, this study began exploring whether the UP led to great reductions in anger compared with the SDPs. Results indicated that there was a small, nonsignificant, decrease in anger in the UP condition, whereas there was a moderate, nonsignificant increase in anger in the SDP condition. At posttreatment, UP patients had significantly lower anger scores than patients who received an SDP. These preliminary results suggest that transdiagnostic treatments may be well poised to target dyregulated anger in the context of emotional disorders.

The influence of rough lipopolysaccharide structure on molecular interactions with mammalian antimicrobial peptides.

The influence of Escherichia coli rough lipopolysaccharide chemotype on the membrane activity of the mammalian antimicrobial peptides (AMPs) human cathelicidin (LL37) and bovine lactoferricin (LFb) was studied on bilayers using solid state (2)H NMR (ssNMR) and on monolayers using the subphase injection technique, Brewster angle microscopy (BAM) and neutron reflectivity (NR). The two AMPs were selected because of their differing biological activities. Chain-deuterated dipalmitoylphosphatidylcholine (d62-DPPC) was added to the LPS samples, to highlight alterations in the system properties caused by the presence of the different LPS chemotypes and upon AMP challenge. Both LPS chemotypes showed a temperature dependent influence on the packing of the DPPC molecules, with a fluidizing effect exerted below the DPPC phase transition temperature (Tm), and an ordering effect observed above the Tm. The magnitude of these effects was influenced by LPS structure; the shorter Rc LPS promoted more ordered lipid packing compared to the longer Ra LPS. These differential ordering effects in turn influenced the penetrative activity of the two peptides, as the perturbation induced by both AMPs to Ra LPS-containing models was greater than that observed in those containing Rc LPS. The NR data suggests that in addition to penetrating into the monolayers, both LL37 and LFb formed a non-interacting layer below the LPS/DPPC monolayer. The overall activity of LL37, which showed a deeper penetration into the model membranes, was more marked than that of LFb, which appeared to localise at the interfacial region, thus providing evidence for the molecular origins of their different biological activities.

Nicotinamide N-methyltransferase catalyses the N-methylation of the endogenous ß-carboline norharman: evidence for a novel detoxification pathway.

Nicotinamide N-methyltransferase (NNMT) is responsible for the N-methylation of nicotinamide to 1-methylnicotinamide. Our recent studies have demonstrated that NNMT regulates cellular processes fundamental to the correct functioning and survival of the cell. It has been proposed that NNMT may possess ß-carboline (BC) N-methyltransferase activity, endogenously and exogenously produced pyridine-containing compounds which, when N-methylated, are potent inhibitors of Complex I and have been proposed to have a role in the pathogenesis of Parkinson's disease. We have investigated the ability of recombinant NNMT to N-methylate norharman (NH) to 2-N-methylnorharman (MeNH). In addition, we have investigated the toxicity of the BC NH, its precursor 1,2,3,4-tetrahydronorharman (THNH) and its N-methylated metabolite MeNH, using our in vitro SH-SY5Y NNMT expression model. Recombinant NNMT demonstrated NH 2N-methyltransferase activity, with a Km of 90 ± 20 µM, a kcat of 3 × 10(-4) ± 2 × 10(-5) s(-1) and a specificity constant (kcat/Km) of 3 ± 1 s(-1) M(-1) THNH was the least toxic of all three compounds investigated, whereas NH demonstrated the greatest, with no difference observed in terms of cell viability and cell death between NNMT-expressing and non-expressing cells. In NNMT-expressing cells, MeNH increased cell viability and cellular ATP concentration in a dose-dependent manner after 72 and 120 h incubation, an effect that was not observed after 24 h incubation or in non-NNNT-expressing cells at any time point. Taken together, these results suggest that NNMT may be a detoxification pathway for BCs such as NH.

The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016 Statement.

We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016. As a result of 2 online surveys and a 2-day meeting of experts, the SCRIBE 2016 checklist was developed, which is a set of 26 items that authors need to address when writing about single-case research. This article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016 ) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. We recommend that the SCRIBE 2016 is used by authors preparing manuscripts describing single-case research for publication, as well as journal reviewers and editors who are evaluating such manuscripts. SCIENTIFIC ABSTRACT Reporting guidelines, such as the Consolidated Standards of Reporting Trials (CONSORT) Statement, improve the reporting of research in the medical literature (Turner et al., 2012 ). Many such guidelines exist and the CONSORT Extension to Nonpharmacological Trials (Boutron et al., 2008 ) provides suitable guidance for reporting between-groups intervention studies in the behavioural sciences. The CONSORT Extension for N-of-1 Trials (CENT 2015) was developed for multiple crossover trials with single individuals in the medical sciences (Shamseer et al., 2015 ; Vohra et al., 2015 ), but there is no reporting guideline in the CONSORT tradition for single-case research used in the behavioural sciences. We developed the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016 to meet this need. This Statement article describes the methodology of the development of the SCRIBE 2016, along with the outcome of 2 Delphi surveys and a consensus meeting of experts. We present the resulting 26-item SCRIBE 2016 checklist. The article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016 ) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated.

Interaction of the Antimicrobial Peptides Rhesus θ-Defensin and Porcine Protegrin-1 with Anionic Phospholipid Monolayers.

A combination of Langmuir isotherm, Brewster angle microscopy (BAM), and neutron reflectivity studies have been performed to gain insight into the effects on model bacterial cell membranes of the antimicrobial peptides, Rhesus θ-defensin 1 (RTD-1), and porcine protegrin 1 (PG-1). The peptides were interacted with monolayers spread at the air-water interface and prepared from a 3:1 molar mixture of phosphatidylethanolamine and phosphatidylglycerol used to approximate the cell membranes of Gram positive bacteria. The Langmuir film balance measurements show that both peptides perturb the lipid monolayers causing an increase in surface pressure, and the BAM studies show that each results in the formation of small domains within the lipid films, around 5 µm diameter. The overall change in monolayer surface pressure caused by PG-1, however, is a little more pronounced than that due to RTD-1 (+8.5 mN·m(-1) vs +5.5 mN·m(-1)), and the rate of its initial interaction with the monolayer is a little more rapid than that for RTD-1. The neutron reflectivity studies also show differences for PG-1 and RTD-1, with the model fits to these data showing that the more amphiphilic PG-1 becomes fully embedded within the lipid film-causing an extension of the lipid acyl chains but leaving the thickness of the lipid headgroup layer unaffected-while RTD-1 is seen to insert less deeply-causing the same extension of the lipid acyl chains as PG-1 but also causing a significant increase in thickness of the lipid headgroup layer. The various differing effects of the two peptides on anionic lipid monolayers are discussed in the context of their differing hemolytic activities, and their proposed differing propensities to form transmembrane pores.

SECOND-STAGE TREATMENTS FOR RELATIVE NONRESPONDERS TO COGNITIVE BEHAVIORAL THERAPY (CBT) FOR PANIC DISORDER WITH OR WITHOUT AGORAPHOBIA-CONTINUED CBT VERSUS SSRI: A RANDOMIZED CONTROLLED TRIAL.

BACKGROUND: Cognitive behavioral therapy (CBT) and pharmacotherapy are efficacious for the short-term treatment of panic disorder. Less is known about the efficacy of these therapies for individuals who do not respond fully to short-term CBT. METHOD: The current trial is a second-step stratified randomized design comparing two treatment conditions-selective serotonin reuptake inhibitor (SSRI; paroxetine or citalopram; n = 34) and continued CBT (n = 24)-in a sample of individuals classified as treatment nonresponders to an initial course of CBT for panic disorder. Participants were randomized to 3 months of treatment and then followed for an additional 9 months. Only treatment responders after 3 months were maintained on the treatment until 12-month follow-up. Data analysis focused on panic disorder symptoms and achievement of response status across the first 3 months of treatment. Final follow-up data are presented descriptively. RESULTS: Participants in the SSRI condition showed significantly lower panic disorder symptoms as compared to continued CBT at 3 months. Results were similar when excluding individuals with comorbid major depression or analyzing the entire intent-to-treat sample. Group differences disappeared during 9-month naturalistic follow-up, although there was significant attrition and use of nonstudy therapies in both arms. CONCLUSIONS: These data suggest greater improvement in panic disorder symptoms when switching to SSRI after failure to fully respond to an initial course of CBT. Future studies should further investigate relapse following treatment discontinuation for nonresponders who became responders. Clinicaltrials.gov Identifier: NCT00000368; https://clinicaltrials.gov/show/NCT00000368.

Focused vs. Broad enhanced cognitive behavioral therapy for bulimia nervosa with comorbid borderline personality: A randomized controlled trial.

OBJECTIVE: A subset of individuals with bulimia nervosa (BN) have borderline personality disorder (BPD) symptoms, including chronic negative affect and interpersonal problems. These symptoms predict poor BN treatment outcome in some studies. The broad version of Enhanced Cognitive Behavior Therapy (CBT-E) was developed to address co-occurring problems that interfere with treatment response. The current study investigated the relative effects, predictors, and moderators of CBT-E for BN with BPD and co-occurring mood/anxiety disorders. METHOD: Fifty patients with BN and threshold or sub-threshold BPD and current or recent Axis I mood or anxiety disorders were randomly assigned to receive focused CBT-E (CBT-Ef) or broad CBT-E (CBT-Eb) specifically including an interpersonal module and additional attention to mood intolerance. RESULTS: Forty-two percent of the sample reported remission from binge eating and purging at termination. Significant changes across symptom domains were observed at termination and at 6-month follow-up. Though CBT-Ef predicted good outcomes in multivariate models, the severity of affective/interpersonal problems moderated treatment effects: participants with higher severity showed better ED outcomes in CBT-Eb, whereas those with lower severity showed better outcomes in CBT-Ef. Severity of affective/interpersonal BPD symptoms at baseline predicted negative outcomes overall. Follow-up BPD affective/interpersonal problems were predicted by baseline affective/interpersonal problems and by termination EDE score. DISCUSSION: This study supports the utility of CBT-E for patients with BN and complex comorbidity. CBT-Ef appears to be more efficacious for patients with relatively less severe BPD symptoms, whereas CBT-Eb appears to be more efficacious for patients with more severe BPD symptoms.

A Transcultural Model of the Centrality of "Thinking a Lot" in Psychopathologies Across the Globe and the Process of Localization: A Cambodian Refugee Example.

We present a general model of why "thinking a lot" is a key presentation of distress in many cultures and examine how "thinking a lot" plays out in the Cambodian cultural context. We argue that the complaint of "thinking a lot" indicates the presence of a certain causal network of psychopathology that is found across cultures, but that this causal network is localized in profound ways. We show, using a Cambodian example, that examining "thinking a lot" in a cultural context is a key way of investigating the local bio-cultural ontology of psychopathology. Among Cambodian refugees, a typical episode of "thinking a lot" begins with ruminative-type negative cognitions, in particular worry and depressive thoughts. Next these negative cognitions may induce mental symptoms (e.g., poor concentration, forgetfulness, and "zoning out") and somatic symptoms (e.g., migraine headache, migraine-like blurry vision such as scintillating scotomas, dizziness, palpitations). Subsequently the very fact of "thinking a lot" and the induced symptoms may give rise to multiple catastrophic cognitions. Soon, as distress escalates, in a kind of looping, other negative cognitions such as trauma memories may be triggered. All these processes are highly shaped by the Cambodian socio-cultural context. The article shows that Cambodian trauma survivors have a locally specific illness reality that centers on dynamic episodes of "thinking a lot," or on what might be called the "thinking a lot" causal network.