Marilyn L. Piccirillo

Characterization of extrastriatal D2 in vivo specific binding of [18F](N‐methyl)benperidol using PET

PET imaging studies of the role of the dopamine D2 receptor family in movement and neuropsychiatric disorders are limited by the use of radioligands that have near‐equal affinities for D2 and D3 receptor subtypes and are susceptible to competition with endogenous dopamine. By contrast, the radioligand [18F]N‐methylbenperidol ([18F]NMB) has high selectivity and affinity for the D2 receptor subtype (D2R) and is not sensitive to endogenous dopamine. Although [18F]NMB has high binding levels in striatum, its utility for measuring D2R in extrastriatal regions is unknown. A composite MR‐PET image was constructed across 14 healthy adult participants representing average NMB uptake 60 to 120 min after [18F]NMB injection. Regional peak radioactivity was identified using a peak‐finding algorithm. FreeSurfer and manual tracing identified a priori regions of interest (ROI) on each individuals MR image and tissue activity curves were extracted from coregistered PET images. [18F]NMB binding potentials (BPNDs) were calculated using the Logan graphical method with cerebellum as reference region. In eight unique participants, extrastriatal BPND estimates were compared between Logan graphical methods and a three‐compartment kinetic tracer model. Radioactivity and BPND levels were highest in striatum, lower in extrastriatal subcortical regions, and lowest in cortical regions relative to cerebellum. Age negatively correlated with striatal BPNDs. BPND estimates for extrastriatal ROIs were highly correlated across kinetic and graphical methods. Our findings indicate that PET with [18F]NMB measures specific binding in extrastriatal regions, making it a viable radioligand to study extrastriatal D2R levels in healthy and diseased states. Synapse 66:770–780, 2012.

Safety Behaviors in Adults With Social Anxiety: Review and Future Directions

Safety behaviors are considered an important factor in the maintenance of social anxiety disorder (SAD). Safety behaviors are typically employed by socially anxious individuals to reduce anxiety in feared social situations. However, by preventing individuals with social anxiety from gathering evidence that would disconfirm their maladaptive beliefs about social situations, the use of safety behaviors ultimately maintains social anxiety over time. Twenty years ago, Wells and colleagues (1995) demonstrated that use of safety behaviors diminishes the efficacy of exposure treatment for SAD, suggesting that reduction in the use of safety behaviors during exposure can enhance treatment response. Research on safety behaviors has expanded considerably since Wells et al.s seminal publication, and our understanding of the role safety behaviors may play in the maintenance of social anxiety has grown in breadth and depth. In this paper, we present a detailed review of the published research on safety behaviors relevant to social anxiety and social-anxiety-related processes. Finally, we evaluate the impact of safety behaviors on the outcome of treatment for SAD, and we look to the literature on safety behaviors in other anxiety disorders to inform our understanding of use of safety behaviors during exposure and to facilitate future research in SAD.

Patient characteristics but not virulence factors discriminate between asymptomatic and symptomatic E. coli bacteriuria in the hospital

BackgroundEscherichia coli is a common cause of asymptomatic and symptomatic bacteriuria in hospitalized patients. Asymptomatic bacteriuria (ASB) is frequently treated with antibiotics without a clear indication. Our goal was to determine patient and pathogen factors suggestive of ASB.MethodsWe conducted a 12-month prospective cohort study of adult inpatients with E. coli bacteriuria seen at a tertiary care hospital in St. Louis, Missouri, USA. Urine cultures were taken at the discretion of treating physicians. Bacterial isolates were tested for 14 putative virulence genes using high-throughput dot-blot hybridization.ResultsThe median age of the 287 study patients was 65 (19–101) years; 78% were female. Seventy percent had community-acquired bacteriuria. One-hundred ten (38.3%) patients had ASB and 177 (61.7%) had symptomatic urinary tract infection (sUTI). Asymptomatic patients were more likely than symptomatic patients to have congestive heart failure (p = 0.03), a history of myocardial infarction (p = 0.01), chronic pulmonary disease (p = 0.045), peripheral vascular disease (p = 0.04), and dementia (p = 0.03). Patients with sUTI were more likely to be neutropenic at the time of bacteriuria (p = 0.046). Chronic pulmonary disease [OR 2.1 (95% CI 1.04, 4.1)] and dementia [OR 2.4 (95% CI 1.02, 5.8)] were independent predictors for asymptomatic bacteriuria. Absence of pyuria was not predictive of ASB. None of the individual virulence genes tested were associated with ASB nor was the total number of genes.ConclusionsAsymptomatic E. coli bacteriuria in hospitalized patients was frequent and more common in patients with dementia and chronic pulmonary disease. Bacterial virulence factors could not discriminate symptomatic from asymptomatic bacteriurias. Asymptomatic E. coli bacteriuria cannot be predicted by virulence screening.

Levodopa effects on [ 11 C]raclopride binding in the resting human brain

Rationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [ 11C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS). Objective: Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS. Methods: This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BP ND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BP ND voxel by voxel over the entire brain. Results: DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa’s effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BP ND by 74% in TS subjects. Discussion: Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.

Anger profiles in social anxiety disorder

Individuals with social anxiety disorder (SAD) exhibit elevated levels of anger and anger suppression, which are both associated with increased depression, diminished quality of life, and poorer treatment outcomes. However, little is known about how anger experiences differ among individuals with SAD and whether any heterogeneity might relate to negative outcomes. This investigation sought to empirically define anger profiles among 136 treatment-seeking individuals with SAD and to assess their association with distress and impairment. A latent class analysis was conducted utilizing the trait subscales of the State-Trait Anger Expression Inventory-2 as indicators of class membership. Analysis revealed four distinct anger profiles, with greatest distress and impairment generally demonstrated by individuals with elevated trait anger, a greater tendency to suppress the expression of anger, and diminished ability to adaptively control their anger expression. These results have implications for tailoring more effective interventions for socially anxious individuals.

Does centrality in a cross-sectional network suggest intervention targets for social anxiety disorder?

Objective: Network analysis allows us to identify the most interconnected (i.e., central) symptoms, and multiple authors have suggested that these symptoms might be important treatment targets. This is because change in central symptoms (relative to others) should have greater impact on change in all other symptoms. It has been argued that networks derived from cross-sectional data may help identify such important symptoms. We tested this hypothesis in social anxiety disorder. Method: We first estimated a state-of-the-art regularized partial correlation network based on participants with social anxiety disorder (n = 910) to determine which symptoms were more central. Next, we tested whether change in these central symptoms were indeed more related to overall symptom change in a separate dataset of participants with social anxiety disorder who underwent a variety of treatments (n = 244). We also tested whether relatively superficial item properties (infrequency of endorsement and variance of items) might account for any effects shown for central symptoms. Results: Centrality indices successfully predicted how strongly changes in items correlated with change in the remainder of the items. Findings were limited to the measure used in the network and did not generalize to three other measures related to social anxiety severity. In contrast, infrequency of endorsement showed associations across all measures. Conclusions: The transfer of recently published results from cross-sectional network analyses to treatment data is unlikely to be straightforward.

Evaluation of Ecological Momentary Assessment for Tinnitus Severity

Importance Existing patient-reported outcome measures of tinnitus assess the severity and disability retrospectively, which may result in adequate reliability, but cannot capture the fluctuating and individualized nature of tinnitus. Experience sampling may provide an alternative. Objective To use an ecological momentary assessment (EMA) to measure tinnitus disability and associated constructs. Design, Setting, and Participants Forty adults with tinnitus provided self-report of their tinnitus bother using 5 questions measured by EMA, as well as standard retrospective outcome measures. In this 6-week longitudinal observational study conducted from July 15 to December 22, 2014, participants provided EMA data for 2 weeks (part 1); then after a 2-week break, they provided EMA data for an additional 2 weeks (part 2). A text message with a link to the EMA survey was sent for a total of 56 assessments during each 2-week assessment period. Ecological momentary assessment responses were evaluated using multilevel confirmatory factor analysis to assess the fluctuating nature of bothersome tinnitus across the group and within the pool of individuals over time. Main Outcomes and Measures Ecological momentary assessment questions measured tinnitus disability and associated constructs. Compliance in each study part was assessed based on response rates. The Tinnitus Functional Index and the Overall Global Rating of Bother Scale were assessed at the beginning and end of each 2-week assessment period to explore the effect of the frequent EMAs on the perceived level of bother from tinnitus. Results Of the 40 participants in the study (10 women and 30 men; mean [SD] age, 60.0 [10.5] years), the median survey response rate was high (49 responses to 56 surveys sent [88%] for part 1 and 47 responses of 56 surveys sent [84%] for part 2). The latent factor identified by the 2-level confirmatory factor analysis models demonstrates that within-individual tinnitus bother, loudness, and stress vary together over time. In addition, tinnitus bother, feeling, and stress symptoms all vary together across individuals, which means that bother and stress covary strongly both across time and across individuals. Conclusions and Relevance Ecological momentary assessment evaluates the moment-to-moment perception of tinnitus and the effect of emotional and environmental factors, which suggests that it is a superior tool to measure tinnitus outcomes compared with standard retrospective self-reports. Taken together, information from emotional and environmental factors can be summarized in an underlying (latent) factor that represents a vulnerability to bothersome tinnitus and that can be used to comprehensively describe the tinnitus experience. Momentary variability in tinnitus bother is strongly associated with levels of perceived stress.

Identifying the relative importance of non-suicidal self-injury features in classifying suicidal ideation, plans, and behavior using exploratory data mining

Individuals with a history of non-suicidal self-injury (NSSI) are at alarmingly high risk for suicidal ideation (SI), planning (SP), and attempts (SA). Given these findings, research has begun to evaluate the features of this multi-faceted behavior that may be most important to assess when quantifying risk for SI, SP, and SA. However, no studies have examined the wide range of NSSI characteristics simultaneously when determining which NSSI features are most salient to suicide risk. The current study utilized three exploratory data mining techniques (elastic net regression, decision trees, random forests) to address these gaps in the literature. Undergraduates with a history of NSSI (N = 359) were administered measures assessing demographic variables, depression, and 58 NSSI characteristics (e.g., methods, frequency, functions, locations, scarring) as well as current SI, current SP, and SA history. Results suggested that depressive symptoms and the anti-suicide function of NSSI were the most important features for predicting SI and SP. The most important features in predicting SA were the anti-suicide function of NSSI, NSSI-related medical treatment, and NSSI scarring. Overall, results suggest that NSSI functions, scarring, and medical lethality may be more important to assess than commonly regarded NSSI severity indices when ascertaining suicide risk.

The stigmatization of nonsuicidal self-injury: BURKE et al.

OBJECTIVE Despite the high prevalence of nonsuicidal self-injury (NSSI), no research has systematically studied the occurrence and effects of stigmatization by others towards NSSI scarring. METHODS The current study measured implicit and explicit attitudes among undergraduates towards NSSI scarring using the implicit association test and questionnaires to compare implicit and explicit biases towards NSSI with biases towards tattoos, a culturally sanctioned form of self-determined marking, as well as nonintentional disfigurement. RESULTS Our study demonstrated strong negative implicit and explicit biases towards NSSI when comparing NSSI to tattoos and nonintentional disfigurement. CONCLUSIONS Results extend previous research describing stigma towards mental illness and suggest a large negative bias towards NSSI. The importance of studying how stigma affects those who bear scarring from NSSI is discussed.

Social anxiety and interpersonal stress generation: the moderating role of interpersonal distress

ABSTRACT Background and Objectives: Existing models of social anxiety scarcely account for interpersonal stress generation. These models also seldom include interpersonal factors that compound the effects of social anxiety. Given recent findings that two forms of interpersonal distress, perceived burdensomeness and thwarted belongingness, intensify social anxiety and cause interpersonal stress generation, these two constructs may be especially relevant to examining social anxiety and interpersonal stress generation together. Design: The current study extended prior research by examining the role of social anxiety in the occurrence of negative and positive interpersonal events and evaluated whether interpersonal distress moderated these associations. Methods: Undergraduate students (N = 243; M = 20.46 years; 83% female) completed self-report measures of social anxiety, perceived burdensomeness, and thwarted belongingness, as well as a self-report measure and clinician-rated interview assessing negative and positive interpersonal events that occurred over the past six weeks. Results: Higher levels of social anxiety were associated only with a higher occurrence of negative interpersonal dependent events, after controlling for depressive symptoms. This relationship was stronger among individuals who also reported higher levels of perceived burdensomeness, but not thwarted belongingness. Conclusions: It may be important to more strongly consider interpersonal stress generation in models of social anxiety.