Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

The relations between C-reactive protein and trauma exposure, PTSD and depression symptoms, and PTSD psychotherapy treatment response in treatment seeking veterans and service members.

While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (ß = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally.

Integration of peripheral transcriptomics, genomics, and interactomics following trauma identifies causal genes for symptoms of post-traumatic stress and major depression.

Posttraumatic stress disorder (PTSD) is a debilitating syndrome with substantial morbidity and mortality that occurs in the aftermath of trauma. Symptoms of major depressive disorder (MDD) are also a frequent consequence of trauma exposure. Identifying novel risk markers in the immediate aftermath of trauma is a critical step for the identification of novel biological targets to understand mechanisms of pathophysiology and prevention, as well as the determination of patients most at risk who may benefit from immediate intervention. Our study utilizes a novel approach to computationally integrate blood-based transcriptomics, genomics, and interactomics to understand the development of risk vs. resilience in the months following trauma exposure. In a two-site longitudinal, observational prospective study, we assessed over 10,000 individuals and enrolled >700 subjects in the immediate aftermath of trauma (average 5.3 h post-trauma (range 0.5-12 h)) in the Grady Memorial Hospital (Atlanta) and Jackson Memorial Hospital (Miami) emergency departments. RNA expression data and 6-month follow-up data were available for 366 individuals, while genotype, transcriptome, and phenotype data were available for 297 patients. To maximize our power and understanding of genes and pathways that predict risk vs. resilience, we utilized a set-cover approach to capture fluctuations of gene expression of PTSD or depression-converting patients and non-converting trauma-exposed controls to find representative sets of disease-relevant dysregulated genes. We annotated such genes with their corresponding expression quantitative trait loci and applied a variant of a current flow algorithm to identify genes that potentially were causal for the observed dysregulation of disease genes involved in the development of depression and PTSD symptoms after trauma exposure. We obtained a final list of 11 driver causal genes related to MDD symptoms, 13 genes for PTSD symptoms, and 22 genes in PTSD and/or MDD. We observed that these individual or combined disorders shared ESR1, RUNX1, PPARA, and WWOX as driver causal genes, while other genes appeared to be causal driver in the PTSD only or MDD only cases. A number of these identified causal pathways have been previously implicated in the biology or genetics of PTSD and MDD, as well as in preclinical models of amygdala function and fear regulation. Our work provides a promising set of initial pathways that may underlie causal mechanisms in the development of PTSD or MDD in the aftermath of trauma.

Associations among civilian mild traumatic brain injury with loss of consciousness, posttraumatic stress disorder symptom trajectories, and structural brain volumetric data.

Posttraumatic stress disorder (PTSD) is prevalent and associated with significant morbidity. Mild traumatic brain injury (mTBI) concurrent with psychiatric trauma may be associated with PTSD. Prior studies of PTSD-related structural brain alterations have focused on military populations. The current study examined correlations between PTSD, acute mTBI, and structural brain alterations longitudinally in civilian patients (N = 504) who experienced a recent Criterion A traumatic event. Participants who reported loss of consciousness (LOC) were characterized as having mTBI; all others were included in the control group. PTSD symptoms were assessed at enrollment and over the following year; a subset of participants (n = 89) underwent volumetric brain MRI (M = 53 days posttrauma). Classes of PTSD symptom trajectories were modeled using latent growth mixture modeling. Associations between PTSD symptom trajectories and cortical thicknesses or subcortical volumes were assessed using a moderator-based regression. mTBI with LOC during trauma was positively correlated with the likelihood of developing a chronic PTSD symptom trajectory. mTBI showed significant interactions with cortical thickness in the rostral anterior cingulate cortex (rACC) in predicting PTSD symptoms, r = .461-.463. Bilateral rACC thickness positively predicted PTSD symptoms but only among participants who endorsed LOC, p < .001. The results demonstrate positive correlations between mTBI with LOC and PTSD symptom trajectories, and findings related to mTBI with LOC and rACC thickness interactions in predicting subsequent chronic PTSD symptoms suggest the importance of further understanding the role of mTBI in the context of PTSD to inform intervention and risk stratification.

Prior trauma-related experiences predict the development of posttraumatic stress disorder after a new traumatic event.

BACKGROUND: Many reports have documented the relationship between previous traumatic experiences, including childhood trauma, and the development of later life psychopathology, including posttraumatic stress disorder (PTSD). Identification of individuals at greatest risk for the development of PTSD could lead to preventative interventions. The present study examined the developmental course of PTSD after trauma exposure, using histories of previous traumatic experiences and the severity of the reaction to the trauma as predictors. METHODS: Participants (N = 713) were recruited from Emergency Departments in Miami and Atlanta immediately following a traumatic experience. Histories of previous traumatic experiences and the immediate reaction to the new trauma were examined at baseline. Follow-up assessments of PTSD severity were conducted at 1, 3, and 6 months. RESULTS: Histories of child abuse and pre-existing trauma symptoms predicted the immediate response to stress (R2 = .21, p < .001) and the initial trauma reaction (p < .005).) A mixed-model repeated-measures analysis of variance found that immediate stress response and a history of prior trauma (p < .001) significantly predicted the course of PTSD symptoms. Area under the curve (AUC) analyses suggested that the presence of PTSD at each successive assessment was predicted most substantially by the severity of PTSD at the immediately prior follow-up assessment (AUC > 0.86). CONCLUSIONS: The current findings suggest that previous traumatic experiences lead to a greater immediate reaction to trauma and combine to predict the development of PTSD, the maintenance of which is not moderated by these earlier experiences. The identification of people likely to develop PTSD may be aided by the assessment of prior experiences and immediate reactions.

Psychometric Properties of the Personality Inventory for DSM-5-Brief Form in a Community Sample with High Rates of Trauma Exposure.

In the current study, we used a sample of predominantly African-American women with high rates of trauma exposure (N = 434) to examine psychometric properties of the Personality Inventory for DSM-5-Brief Form (PID-5-BF). We compared model fit between a model with five correlated latent factors and a higher-order model in which the five latent factors were used to estimate a single "general pathology" factor. Additionally, we computed estimates of internal consistency and domain interrelations and examined indices of convergent/discriminant validity of the PID-5-BF domains by examining their relations to relevant criterion variables. The expected five-factor structure demonstrated good fit indices in a confirmatory factor analysis, and the more parsimonious, higher-order model was retained. Within this higher-order model, the first-order factors accounted for more variance in the criterion variables than the general pathology factor in most instances. The PID-5-BF domains were highly interrelated (rs = .38 to .66), and convergent/discriminant validity of the domains varied: Negative Affectivity and Detachment generally showed the hypothesized pattern of relations with external criteria, while Antagonism and Disinhibition displayed less consistent and discriminant relations. Results are discussed in terms of the costs and benefits of using brief pathological trait measures in samples characterized by high levels of psychopathology.

A Review of PTSD Augmentation Strategies for Older Adults and Case of rTMS-Augmented Prolonged Exposure.

Evidence-based psychotherapies such as prolonged exposure therapy (PE) are recommended by clinical practice guidelines as first-line treatments for post-traumatic stress disorder (PTSD) and are safe and acceptable for use with older adults. One third to one half of all patients do not achieve a clinically meaningful response to standard outpatient PE and recent research suggests that older adults in particular may experience barriers to full engagement and response. Standard treatment may be challenging in older adults due to cognitive, medical, and psychosocial barriers. This article reviews the current state of the evidence on adjunctive and second-tier interventions that show promise for increasing response and/or engagement in evidence-based psychotherapy for PTSD, including medications such as d-cycloserine and 3,4-methylenedioxy-methamphetamine, neuromodulation techniques such as repetitive transcranial magnetic stimulation, and augmentations to the structure and content of psychotherapy, such as intensive outpatient formats. A case illustration of successful application of multiple augmentations to PE with an initially nonresponsive older adult patient is presented. A creative interdisciplinary approach based in available research may be beneficial for older adults who do not respond to first-line treatments.

Investigation of optimal dose of early intervention to prevent posttraumatic stress disorder: A multiarm randomized trial of one and three sessions of modified prolonged exposure.

BACKGROUND: Posttraumatic stress disorder (PTSD) is linked to a specific event, providing the opportunity to intervene in the immediate aftermath of trauma to prevent the development of this disorder. A previous trial demonstrated that trauma survivors who received three sessions of modified prolonged exposure therapy demonstrated decreased PTSD and depression prospectively compared to assessment only. The present study investigated the optimal dosing of this early intervention to test one versus three sessions of exposure therapy in the immediate aftermath of trauma. METHODS: Participants (n = 95) recruited from a Level 1 Trauma Center were randomly assigned in a 1.5:1.5:1 ratio in a parallel-group design to the three conditions: one-session exposure therapy, three-session exposure therapy, and assessment only. Follow-up assessments were conducted by study assessors blind to study condition. RESULTS: Mixed-effects model results found no significant differences in PTSD or depression symptoms between the control condition and those who received one or three exposure therapy sessions across 1-12-month follow-up assessment. Results indicate that the intervention did not interfere with natural recovery. Receiver operating characteristic curve analyses on the screening measure used for study inclusion (Predicting PTSD Questionnaire; PPQ) in the larger sample from which the treatment sample was drawn (n = 481) found that the PPQ was a poor predictor of likely PTSD at all follow-up time points (Area under the curve's = 0.55-0.62). CONCLUSIONS: This likely impacted study results as many participants demonstrated natural recovery. Recommendations for future early intervention research are reviewed, including strategies to identify more accurately those at risk for PTSD and oversampling more severe trauma types.

Identifying obstetrics patients in whom RHD genotyping can be used to assess risk of D alloimmunization.

CONCLUSIONS: The D antigen is highly immunogenic and may cause alloimmunization to occur after blood transfusion or pregnancy. Some RHD variant alleles express a D antigen that is missing one or more epitopes, thus putting a presumed D+ patient at risk for alloanti-D and hemolytic disease of the fetus and newborn. It is generally accepted that individuals who have a serologic weak D phenotype due to one of three alleles common in Caucasians, RHD*weak D types 1, 2, or 3, are not at risk for alloimmunization. In this study, blood samples from 46 obstetrics patients from a local health system were identified based on discrepant results between automated gel and manual tube testing (n = 20) or based on presentation with a serologic weak D phenotype (n = 26). RHD genotyping was performed using commercial and laboratory-developed tests. Of the 26 serologic weak D samples, 18 (69.2%) were found to carry alleles RHD*weak D type 1, 2, or 3. The remaining eight samples (30.8%) were found to carry partial D alleles. Of the 20 samples submitted because of D typing discrepancy, 7 (35%) carried alleles RHD*weak D type 1, 2, or 3, while 13 (65%) carried partial RHD alleles. This report summarizes the findings of one hospital system and its approach to integrating RHD genotyping into its assessment of risk of alloimmunization in obstetrics patients. It demonstrates that individuals with partial RHD alleles can present with serologic weak D phenotype, such that, without RHD genotyping, these individuals may not be identified as candidates for Rh immune globulin. The study also demonstrates that use of two methods (automated gel and tube testing) allows for identification of partial D cases that would otherwise be missed. I.

Associations of childhood trauma with food addiction and insulin resistance in African-American women with diabetes mellitus.

Food addiction (FA) describes a group of disordered eating behaviors. Childhood trauma has been associated with adult FA and trauma has known effects on the endocrine system, but it is unclear whether FA is associated with insulin resistance. We hypothesized that severity of childhood trauma will be associated with FA and higher insulin resistance (HOMA-IR) in a sample of obese women with type 2 diabetes mellitus (T2DM), and that FA will mediate the association between childhood trauma and HOMA-IR. Women with a diagnosis of T2DM (N = 73; MBMI = 35.86, SDBMI = 7.72; Mage = 50.59, SDage = 9.72) were recruited from a diabetes clinic at a county hospital. Participants completed the Childhood Trauma Questionnaire and the Yale Food Addiction Scale. Fasting blood samples were obtained from 64 participants to assess plasma hemoglobin A1c (HbA1c), insulin and glucose (used to calculate HOMA-IR); Oral Glucose Tolerance Test (OGTT) was performed to measure change in glucose and insulin secretion. 48% of the sample met diagnostic criteria for FA. Women with FA reported significantly higher HOMA-IR (F = 25.692, p < 0.001, df = 1,62), HbA1c (F = 4.358, p = 0.041, df = 1,62), and OGGT glucose (F = 5.539, p = 0.022, df = 1,62) as well as severity of childhood trauma (F = 10.453, p = 0.002, df = 1,71). In a hierarchical linear regression controlling for BMI, income level, and T2DM treatment, the severity of childhood trauma did not contribute to the prediction of HOMA-IR (ß = -0.011, p = 0.942) whereas FA did (ß = 0.422, p = 0.007). In a bootstrapped mediation analysis, the association between childhood trauma and HOMA-IR was mediated by FA severity (b = 0.596, p = 0.020). Understanding the psychological factors that contribute to HOMA-IR in an underserved population of African American women may lead to more effective diabetes management and prevention strategies.

Comparison of ABO genotyping methods: a study of two low-resolution polymerase chain reaction assays in a clinical testing laboratory.

CONCLUSIONS: The ABO blood group system is the most clinically significant system in transfusion medicine. Although serologic typing for ABO antigens is routine and reliable, molecular methods can be used to predict an ABO type in the absence of a blood specimen as well as to investigate ABO typing discrepancies often caused by ABO subgroups that cause weakened antigen expression, weak or missing serum reactivity, and/or extra red blood cell reactivity. By detecting single nucleotide variants that are hallmarks of the major ABO alleles, low-resolution genotyping methods can be used to make allele assignments and predict phenotypes. This approach has become a dependable tool, initially to resolve typing discrepancies identified in blood banks and donor centers and, more recently, to predict the ABO group in bone marrow transplant donors and in deceased donors of solid organs. The aim of this report is to compare two different low-resolution polymerase chain reaction (PCR)-based methods: a PCRrestriction fragment length polymorphism (RFLP) implemented based on a publication and a commercially available TaqManbased sequence-specific primer-PCR for resolution of ABO typing discrepancies. Fifty-six peripheral blood samples from 31 patients and 25 blood donors were used to isolate genomic DNA and perform genotyping. Results of 49 of the 56 samples (87.5%) were concordant between methods, three samples yielded an unexpected banding pattern on the PCR-RFLP method, and four sample results were discordant between assays. The discordances all involved group A versus A2 discrepancies. Sanger sequencing was used as a high-resolution genotyping method to resolve discrepancies between the two low-resolution methods. This study demonstrates that, in the majority of cases, a low-resolution genotyping method can resolve an ABO discrepancy. Although there is no U.S. Food and Drug Administration-approved genotyping method for ABO determination, molecular testing for investigation of discrepancies is a useful tool for blood banks and transplant programs.

Implementation and Utility of an Automated Text Messaging System to Facilitate Symptom Self-Monitoring and Identify Risk for Post-Traumatic Stress Disorder and Depression in Trauma Center Patients.

Background and Introduction: Comprehensive monitoring and follow-up after traumatic injury is important for psychological recovery. However, scalable services to facilitate this are limited. Automated text message-based symptom self-monitoring (SSM) may be a feasible approach. This study examined its implementation and utility in identifying patients at risk for mental health difficulties after traumatic injury.Materials and Methods: Five hundred two patients admitted to a Level I trauma center between June 20, 2016 and July 31, 2017 were offered enrollment in a text message-based SSM service. Patients who enrolled received daily text message prompts over 30 days and most participated in a mental health screening 30 days postbaseline.Results: Approximately 67% of patients enrolled in the service; of these, 58% responded to the text messages, with an average response rate of 53%. Younger patients and those with elevated peritraumatic distress were more likely to enroll. Patients with higher levels of mental health stigma, who were White, or had been in a motor vehicle collision were more likely to enroll and respond to text messages once enrolled. Patients' daily ratings of distress detected clinically elevated 30-day mental health screens with high sensitivity (83%) and specificity (70%).Discussion and Conclusions: Text message-based SSM can be implemented as a clinical service in Level I trauma centers, and patient participation may increase engagement in mental health follow-up. Further, it can inform the use of risk assessments in practice, which can be used to identify patients with poor psychological recovery who require additional screening.

Using Item Response Theory to Develop a 60-Item Representation of the NEO PI-R Using the International Personality Item Pool: Development of the IPIP-NEO-60.

Given advantages of freely available and modifiable measures, an increase in the use of measures developed from the International Personality Item Pool (IPIP), including the 300-item representation of the Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992a ) has occurred. The focus of this study was to use item response theory to develop a 60-item, IPIP-based measure of the Five-Factor Model (FFM) that provides equal representation of the FFM facets and to test the reliability and convergent and criterion validity of this measure compared to the NEO Five Factor Inventory (NEO-FFI). In an undergraduate sample (n = 359), scores from the NEO-FFI and IPIP-NEO-60 demonstrated good reliability and convergent validity with the NEO PI-R and IPIP-NEO-300. Additionally, across criterion variables in the undergraduate sample as well as a community-based sample (n = 757), the NEO-FFI and IPIP-NEO-60 demonstrated similar nomological networks across a wide range of external variables (rICC = .96). Finally, as expected, in an MTurk sample the IPIP-NEO-60 demonstrated advantages over the Big Five Inventory-2 (Soto & John, 2017 ; n = 342) with regard to the Agreeableness domain content. The results suggest strong reliability and validity of the IPIP-NEO-60 scores.

Novel mutations in KLF1 encoding the In(Lu) phenotype reflect a diversity of clinical presentations.

BACKGROUND: Mutation in the KLF1 gene is the cause of the In(Lu) (Inhibitor of Lutheran) Lu(a-b-) phenotype and more than 60 alleles have been associated with this phenotype. Here we describe findings from investigation of seven cases: six presenting with a Lu(a-b-) phenotype including the historical index case and one referred from a patient with chronic anemia. STUDY DESIGN AND METHODS: Serologic testing was by standard methods. DNA testing included amplification and sequencing of KLF1 and LU coding regions. A StuI polymerase chain reaction-restriction fragment length polymorphism was designed to target c.304T>C in KLF1. RESULTS: Five different KLF1 alleles were identified. Three are new: KLF1*90A (p.Trp30Ter), KLF*911A (p.Thr304Lys), and KLF1*304C,318G (p. Ser102Pro, Tyr106Ter) present in two unrelated individuals. Two, including the index case, had c.954dupG (p.Arg319Glufs*34), that is, KLF1*BGM06. The child with unexplained anemia had c.973G>A (p.Glu325Lys), associated with congenital dyserythropoietic anemia. The common c.304T>C was found in two of the seven samples investigated and in 60 of 100 blood donors. CONCLUSION: Mutations in KLF1 are pleiotropic and although most are benign, others are associated with hematologic abnormalities. We report three new KLF1 alleles associated with benign In(Lu) and document both the molecular basis of the original In(Lu) phenotype using a frozen sample stored for more than 50 years and the cause of unexplained anemia in a child. We also confirm previous observations that c.304C (p.102Pro) is not, by itself, associated with an In(Lu) phenotype in donors self-identified as U.S. minorities.

How Likable Are Personality Disorder and General Personality Traits to Those Who Possess Them?

OBJECTIVE: The goal of the present study was to investigate whether having higher scores on maladaptive personality traits was related to rating these traits as more likable. METHOD: Two studies were conducted, one with personality disorder traits (N = 219; Mage = 19.4; 63.8% female; 76.6% Caucasian) and one with general personality traits (N = 198; Mage = 19.5; 69.7% female; 77.3% Caucasian). In each study, participants self-rated their own personality and separately provided ratings of how "likable" they considered those personality traits. RESULTS: As expected, participants rated maladaptive traits more favorably if they considered themselves to possess those traits as well. Also as expected, individuals with higher Antagonism scores (including self-rated Dark Triad constructs of narcissism, psychopathy, and Machiavellianism) rated Antagonism and its related facets as "tolerable"-not necessarily likable, but as less unlikable than the average participant. CONCLUSIONS: These findings have implications for the ways that individuals with personality pathology perceive the people around them, which may in turn impact their expectations and behaviors.

Vulnerable Narcissism Is (Mostly) a Disorder of Neuroticism.

OBJECTIVE: Increasing attention has been paid to the distinction between the dimensions of narcissistic grandiosity and vulnerability. We examine the degree to which basic traits underlie vulnerable narcissism, with a particular emphasis on the importance of Neuroticism and Agreeableness. METHOD: Across four samples (undergraduate, online community, clinical-community), we conduct dominance analyses to partition the variance predicted in vulnerable narcissism by the Five-Factor Model personality domains, as well as compare the empirical profiles generated by vulnerable narcissism and Neuroticism. RESULTS: These analyses demonstrate that the lion's share of variance is explained by Neuroticism (65%) and Agreeableness (19%). Similarity analyses were also conducted in which the extent to which vulnerable narcissism and Neuroticism share similar empirical networks was tested using an array of criteria, including self-, informant, and thin slice ratings of personality; interview-based ratings of personality disorder and pathological traits; and self-ratings of adverse events and functional outcomes. The empirical correlates of vulnerable narcissism and Neuroticism were nearly identical (MrICC = .94). Partial analyses demonstrated that the variance in vulnerable narcissism not shared with Neuroticism is largely specific to disagreeableness-related traits such as distrustfulness and grandiosity. CONCLUSIONS: These findings demonstrate the parsimony of using basic personality to study personality pathology and have implications for how vulnerable narcissism might be approached clinically.

Comparison Between Etest and Broth Microdilution Methods for Testing Itraconazole-Resistant Aspergillus fumigatus Susceptibility to Antifungal Combinations.

The checkerboard broth microdilution assay (BMD) is the most frequently used method for the in vitro evaluation of drug combinations. However, its use to evaluate the effect of antifungal drugs on filamentous fungi is sometimes associated with endpoint-reading difficulties, and different degrees of interaction are assigned to the same drug combination. We evaluated combinations of the azoles, itraconazole, posaconazole, and voriconazole, with the echinocandins, anidulafungin, caspofungin, and micafungin, against 15 itraconazole-resistant Aspergillus fumigatus clinical strains via the checkerboard BMD and Etest assay. Readings after 24 and 48 h, considering the two reading endpoints, the minimum inhibitory concentration (MIC) and minimum effective concentration (MEC), were performed for both methods. Our results showed that the correlation coefficients between the BMD and Etest methods were quite diverse to the drug combinations tested. The highest correlation coefficients of the Etest with the BMD assays (MEC and MIC reading) were the Etest-MIC reading at 24 h and the Etest-MEC reading at 48 h. Improvements in experimental conditions may increase the correlation between the two methods and ensure that Etest assay can be safely used in the evaluation of antifungal combinations against Aspergillus species.

Targeting memory reconsolidation to prevent the return of fear in patients with fear of flying.

BACKGROUND: When a memory is recalled, it may again exist in a labile state and stored information becomes amenable to change, a psychobiological process known as reconsolidation. Exposure therapy for anxiety disorders involves accessing a fear memory and modifying it with less fearful information. A preclinical study reported that providing a reminder of a fear memory 10 min prior to extinction training in humans decreased fear up to 1 year later (Schiller et al., 2010). METHODS: For this pilot clinical study, we used virtual reality exposure therapy (VRE) for fear of flying (FoF) to determine if using a cue to reactivate the memory of the feared stimulus 10 min prior to exposure sessions leads to fewer anxiety-related behaviors and a more durable response compared to a neutral cue. FoF participants (N = 89) received four sessions of anxiety management training followed by four sessions of VRE. Participants were randomly assigned to receive an FoF cue (reactivation group) or a neutral cue (control group) prior to the VRE sessions. Heart rate (HR) and skin conductance levels (SCLs) were collected during posttreatment and 3-month follow-up assessments as objective markers of fear responding. RESULTS: Treatment was effective and all clinical measures improved equally between groups at posttreatment with maintained gains through follow-ups. Significant differences were identified with regard to HR and SCL indices. CONCLUSIONS: These results suggest that memory reactivation prior to exposure therapy did not have an impact on clinical measures but may enhance the effect of exposure therapy at the physiological level.

Psychopathy and Machiavellianism: A Distinction Without a Difference?

A robust literature has emerged on the Dark Triad (DT) of personality-Machiavellianism (MACH), psychopathy, and narcissism. Questions remain as to whether MACH and psychopathy are distinguishable and whether MACH's empirical and theoretical networks are consistent. In Study 1 (N = 393; MTurk research participants), factor analyses were used to compare two-factor (MACH and psychopathy combined + narcissism) and three-factor models, with both fitting the data equally well. In Studies 1 and 2 (N = 341; undergraduate research participants), DT scores were examined in relation to a variety of external criteria, including self- and informant ratings of personality, adverse developmental experiences, and psychopathological symptoms/behaviors. In both studies, MACH and psychopathy manifested nearly identical empirical profiles and both were significantly related to disinhibitory traits thought to be antithetical to MACH. In Study 3 (N = 36; expert raters), expert ratings of the Five-Factor Model traits prototypical of MACH were collected and compared with empirically derived profiles. Measures of MACH yielded profiles that were inconsistent with the prototypical expert-rated profile due to their positive relations with a broad spectrum of impulsivity-related traits. Ultimately, measures of psychopathy and MACH appear to be measuring the same construct, and MACH assessments fail to capture the construct as articulated in theoretical descriptions.