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Eating disorders are prevalent among college student populations. Although previous iterations of the instrument did not include specific measurement of eating pathology, the Minnesota multiphasic personality inventory-3 (MMPI-3) now includes a specific scale (i.e., Eating Concerns [EAT]) to assess problematic eating behaviors. The current study examined the MMPI-3 assessment of eating pathology among 249 undergraduate women. A pattern emerged where symptoms of internalizing psychopathology on the MMPI-3 were generally associated with symptoms of eating disorder. However, the newly included EAT scale demonstrated the strongest associations with most areas of eating dysfunction. Further, hierarchical regression analyses suggested that the EAT scale added substantial incremental predictive utility (up to 23%) over other MMPI-3 scales combined in assessing eating pathology. Classification accuracy statistics yielded high sensitivity and specificity coefficients when predicting eating disorder risk at an EAT scale score cutoff of 75 T or higher. These findings support the use of the MMPI-3 in assessing eating pathology in college women, although its performance with men and with women not of college age remains to be studied.

Rationale Previous research suggests that sleep polysomnography and EEG endpoints can be used to assess GABAergic activity; however, the impact of GABAB receptor positive allosteric modulators on sleep endpoints remains unclear. Objectives This phase 1 study compared a single dose of ASP8062 (35 mg or 70 mg), a GABAB receptor positive allosteric modulator, with placebo and paroxetine (40 mg). Methods Healthy adult volunteers were randomized to four treatments (35 mg ASP8062, 70 mg ASP8062, paroxetine 40 mg, or matching placebo), each separated by a 14-day washout. Primary endpoints obtained by polysomnography were time in stage N3 or SWS and time in rapid eye movement (REM) sleep. Secondary endpoints included impact on sleep stages and electroencephalography parameters, pharmacokinetics, nighttime growth hormone (GH), and safety/tolerability. Results In 20 randomized volunteers, ASP8062 led to a significant and seemingly dose-dependent increase in SWS over the entire night; this increase was mainly observed during the first third of the night. ASP8062 did not impact time in REM sleep. Paroxetine had no effect on SWS but produced a significant reduction in time spent in REM sleep. A dose-dependent trend in increased GH release was also observed with ASP8062. Headache and nausea were the most commonly reported treatment-emergent adverse events (TEAEs) for ASP8062; most TEAEs were mild in severity. Conclusions Single-dose ASP8062 (35 and 70 mg) appeared to result in CNS penetration and enhanced GABAergic activity as measured by increases in slow-wave sleep and growth hormone release.

ASP8062 is an orally active γ-amino-butyric acid type B (GABAB ) receptor positive allosteric modulator currently in phase 2 development. Safety and pharmacokinetic (PK) profiles of ASP8062 were evaluated in 2 studies in healthy subjects. The first study (a first-in-human study) evaluated single ascending doses (SAD) of ASP8062. The second study was composed of 2 parts: part 1 evaluated multiple ascending doses (MAD) of ASP8062 for 14 days, and part 2 was a single-dose arm to assess the PK of ASP8062 in cerebrospinal fluid (CSF). Fifty-six men (SAD) and 56 subjects (24 women and 32 men; MAD) were enrolled. Across the SAD dosing range, area under the concentration-time curve was dose proportional; increases in maximum plasma concentration appeared linear but were slightly less than dose proportional. Time to maximal concentration and half-life were 1-4 hours and ∼40-50 hours, respectively; no food effect was observed. ASP8062 PK properties at steady state were similar to those following a single dose. Steady state was achieved by ∼day 9 with ∼2-fold accumulation, and ASP8062 was detected in CSF. ASP8062 was well tolerated; no clear evidence of ASP8062's effects on safety, cognition, drug withdrawal, or suicidal ideation/behavior was observed. These data support the development of ASP8062 in indications where the GABAB receptor is a target.

Psychopathology among liver and kidney transplant patients is prevalent. Although pre-surgical psychological evaluations are routinely conducted, understanding which specific psychological test to use is under-developed. The purpose of this review is to examine the psychometric properties of broadband and narrowband psychological measures in pre-surgical liver and kidney transplant evaluations. Overall, there is a paucity of research in this domain that hamper abilities to make clear recommendations on what to use alongside a clinical interview. This review highlights the need for additional research examining instruments that may predict patients' successful recovery from transplant surgery. Despite the scarcity of research, instruments that appear to be useful in this population include the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the Personality Assessment Inventory (PAI), the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), and the Transplant Evaluation and Rating Scale (TERS).

The Minnesota Multiphasic Personality Inventory (MMPI) family of instruments has been commonly used for the evaluation of patients seeking surgical intervention for back pain. A new version of the MMPI, the Minnesota Multiphasic Personality Inventory-3 (MMPI-3), has been released with updated normative data, expanded and revised item content, and updated scales. The purpose of this investigation is to report reliability and validity findings for MMPI-3 scale scores of patients seeking spine surgery. Using a sample of 761 spine surgery candidates (390 men and 371 women), descriptive data, reliability and standard error of measurement, and zero-order correlations using external criteria (self-report and information gathered from a medical record review/clinical interview) were calculated. By and large, men and women produced MMPI-3 scale scores that were similar with a few exceptions. Many reliability estimates and standard errors of measurement were replicable compared to those reported for the MMPI-3 normative sample for scales that yielded adequate range. The scale scores of the MMPI-3 also yielded evidence of good convergent and discriminant validity when correlated with external criteria. Indeed, MMPI-3 scale scores accounted for 2%-15% of incremental variance in data obtained via the clinical interview and medical chart, once other self-report measures were accounted for. Overall, many of the MMPI-3 scale scores used in spine surgery evaluations appear to be reliable and valid. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) represents a potential mechanism for improving pain conditions. ASP3662 is a potent and selective inhibitor of 11β-HSD1. Two phase I clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single and multiple ascending doses of ASP3662 in healthy young and elderly non-Japanese and young Japanese subjects. Nonlinear, more than dose-proportional PKs were observed for ASP3662 after single-dose administration, particularly at lower doses (≤ 6 mg); the PKs at steady state were dose proportional, although the time to ASP3662 steady state was dose dependent at lower doses (≤ 2 mg). Similar PKs were observed among young Japanese, young non-Japanese, and elderly non-Japanese subjects. Specific inhibition of 11β-HSD1 occurred after both single and multiple doses of ASP3662. A marked dissociation between PKs and PDs was observed after single but not multiple doses of ASP3662. ASP3662 was generally safe and well tolerated.

Background Bariatric surgery usually results in substantial weight loss and a reduction in medical comorbidities. Many patients, as a consequence of the weight loss, subsequently evidence loose, redundant skin. Objectives This investigation seeks to examine the prevalence of body contouring surgery (BCS) by patients approximately 4 to 5 years after Roux-en-Y gastric bypass surgery. Demographics, change in BMI, and psychosocial variables were also used to predict body dissatisfaction, desire for BCS, and patients who reported obtaining BCS. Setting The clinical sites involved in the Longitudinal Assessment of Bariatric Surgery project, which included 10 hospitals across the United States. Methods The sample comprised 1159 patients who underwent Roux-en-Y gastric bypass and were enrolled in the Longitudinal Assessment of Bariatric Surgery-2 study. Participants were surveyed using the Excessive Skin Survey and other psychosocial measures at their 4- or 5-year postoperative outcome. The participants were predominately women (80.5%), Caucasian (88.3%), and middle-aged (mean = 46.1 yr, standard deviation = 11.11 yr). Results Participants reported modest degrees of being bothered by excessive skin, primarily in their waist/abdomen, thighs, and chest/breasts body areas. Only 11.2% of the sample had undergone any BCS procedure, and a majority of those participants paid "out of pocket" for BCS. Desire for BCS and body dissatisfaction 4 to 5 years postsurgery was associated with higher depression scores and poorer quality of life scores. Conclusions Excessive skin is associated with poorer psychosocial functioning. Despite reporting modest levels of being bothered by excessive skin and body dissatisfaction, only a small fraction of participants underwent BCS. Cost of BCS was reported to be a primary barrier for not obtaining BCS. All rights reserved.

Psychopathology has been associated with patient reports of poor outcome and an algorithm has been useful in predicting short-term outcomes. The objective of this study is to investigate whether a pre-surgical psychological algorithm could predict 1-year spine surgery outcome reports, including pain, functional disability, and emotional functioning. A total of 1,099 patients consented to participate. All patients underwent spine surgery (e.g., spinal fusion, discectomy, etc.). Pre-operatively, patients completed self-report measures prior to surgery. An algorithm predicting patient prognosis based on data from the pre-surgical psychological evaluation was filled out by the provider for each patient prior to surgery. Post-operatively, patients completed self-report measures at 3- and 12-months after surgery. Longitudinal latent class growth analysis (LCGA) was used to derive patient outcome groups. These outcome groups were then compared to pre-surgical predictions made. LCGA analyses derived three groups of patients from the reported outcome data (entropy = .84): excellent outcomes, good outcomes, and poor outcomes. The excellent and good groups demonstrated improvements over time, but the poor outcome groups, on some measures, reported worsening of pain, functional disability, and emotional functioning over time. The pre-surgical algorithm yielded good concordance with the statistically derived outcome groups (Kendall's W = .81). Using a pre-surgical psychological evaluation algorithm for predicting long-term spine surgery outcomes can identify patients who are unlikely to report good outcomes, and point to areas for psychological intervention that can either improve surgery results or to be utilized as alternatives to elective spine surgery. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Chronic pain has become a significant medical issue. The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a broadband psychological test that has been validated for use across various medical settings and can aid in the assessment and treatment planning of chronic pain. In the current investigation, it was hypothesized that the somatic complaints scales of the MMPI-2-RF would demonstrate good convergent validity from a structured psychodiagnostic interview and other measures of pain and somatization, and lack gender bias. Patients (n = 200) who produced valid MMPI-2-RFs in an outpatient chronic pain clinic were included in the study. Patients were also administered the Modified Somatic Perception Questionnaire (MSPQ), Pain Disability Index (PDI), and the Structured Clinical Interview for DSM-IV-TR (SCID). Zero-order and partial correlations (controlling for gender) were calculated between MMPI-2-RF scale scores and other criteria. Stepdown hierarchical regression analyses were used to detect bias. By and large, higher scale scores on the somatic/cognitive scales of the MMPI-2-RF were modestly or substantially correlated with MSPQ scores, PDI scores, and SCID Somatization symptom count, even after controlling for gender. Regression analyses suggested that the MMPI-2-RF scale scores were not biased as a function of gender. These findings support the validity of specific MMPI-2-RF scales to help identify somatization and psychosocial functioning among patients with chronic pain. Identification of somatization early within the course of treatment of chronic pain may help focus treatment targets, including referrals for psychological interventions such as cognitive behavior therapy for chronic pain.

Both an agonist and its associated prodrug for metabotropic glutamate(2/3) (mGlu(2/3)) receptors demonstrated anxiolytic efficacy in large, randomized, multicenter, double-blind, placebo-controlled trials studying patients with generalized anxiety disorder (GAD). These mGlu(2/3) receptor agonists produced robust preclinical anxiolytic-like effects in rodent models. Several different metabotropic glutamate(2) receptor positive allosteric modulators have been found to produce antidepressant-like effects on several preclinical screening paradigms, including differential-reinforcement-of-low-rate 72-second (DRL 72-s) behavior [increased reinforcers, decreased response rate, and cohesive rightward shifts in inter-response time distributions]. Although mGlu(2/3) receptor agonists have not been tested formally for therapeutic effects in treating patients with major depressive disorder, these compounds generally fail to exert antidepressant-like effects in preclinical screening paradigms and did not improve depressive symptoms in GAD trials. Thus, the present studies were designed to test the potential antidepressant-like effects of the mGlu(2/3) receptor agonist 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicarboxylate monohydrate (LY354740) on the DRL 72-s schedule. LY354740 did not test similarly to clinically validated antidepressant drugs when administered alone or when coadministered with the selective serotonin reuptake inhibitor fluoxetine in rats. Another glutamate-based antidepressant drug, the uncompetitive N-methyl-D-aspartate channel blocker racemic ketamine, exerted antidepressant-like effects when administered at subanesthetic doses in rats. The findings further support the specificity of rat DRL 72-s behavior when screening for anxiolytic versus antidepressant drugs and extend testing of compounds with glutamatergic mechanisms of action. SIGNIFICANCE STATEMENT: The metabotropic glutamate(2/3) receptor agonist and clinically validated anxiolytic drug 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicarboxylate monohydrate did not test similar to antidepressant drugs (increased reinforcers, decreased response rate, and cohesive rightward shifts in the inter-response time distribution) when tested on differential-reinforcement-of-low-rate 72-second (DRL 72-s) behavior and also did not enhance the antidepressant-like effects of the serotonin reuptake inhibitor fluoxetine. The uncompetitive N-methyl-D-aspartate receptor antagonist ketamine increased the reinforcement rate, decreased the response rate, and induced a rightward shift in the inter-response time distribution similar to antidepressant drugs; these results confirm the utility of DRL 72-s schedule of reinforcement when testing clinically validated anxiolytic versus antidepressant glutamatergic drugs.

Background Cognitive impairment is a core feature of schizophrenia. While first- and second-generation antipsychotic drugs treat psychotic exacerbations, no treatment is approved for the cognitive dysfunction. We have identified ASP4345, a positive allosteric modulator of the dopamine type 1 (D1) receptor that selectively binds to, and enhances the activity of, D1 receptors. ASP4345 has the potential to be an effective and well-tolerated treatment option for cognitive impairment associated with schizophrenia. Objective The objective of this study was to determine the pharmacokinetics of ASP4345 in two phase I single ascending-dose and multiple ascending-dose studies. Methods Both phase I studies were randomized, double blind, and placebo controlled. The single dose-ascending study assessed pharmacokinetics of single oral doses of 3–900 mg of ASP4345 or placebo in the fasted state in healthy adult volunteers. This study also assessed cerebrospinal fluid pharmacokinetics, as well as the effects of food on pharmacokinetic parameters. The multiple ascending-dose study (NCT02720263) assessed the pharmacokinetics of multiple oral doses of 3–150 mg of ASP4345 in patients with schizophrenia or schizoaffective disorder receiving stable antipsychotic drug treatment. The pharmacokinetic data from both studies were summarized using descriptive statistics. Results The plasma concentration–time profile in both studies showed a rapid increase in concentrations of ASP4345. The median time to maximum concentration range was 1.00–2.26 h in the single ascending-dose study in the fasted state and 1.25–3.02 h in the multiple ascending-dose study at steady state. There were less than dose-proportional increases in maximum concentration and area under the curve in the single ascending-dose study, where doses had a range from 3 to 900 mg, and in the multiple ascending-dose study in patients with stabilized schizophrenia or schizoaffective disorder, where doses had a range from 3 to 150 mg. The mean terminal elimination half-life was dose independent and had a range from 9.12 to 14.3 h in the single ascending-dose study and from 11.1 to 26.8 h in the multiple ascending-dose study. Additionally, in the single ascending-dose study, absorption of 300 mg of ASP4345 was slightly delayed when administered in the fed state compared with the fasted state; median time to maximum concentration was 1.5 h under the fasting state and 4.0 h under fed states. All other pharmacokinetic parameters were comparable for both conditions. ASP4345 appeared in the cerebrospinal fluid with some delay; time to maximum concentration range was from 2.48 to 7.98 h in cerebrospinal fluid compared with 0.75 to 1.03 h in plasma (median cerebrospinal fluid/plasma = 0.188). The ratio of cerebrospinal fluid to total plasma for area under the curve from 0 to 24 h (0.157–0.573%) and maximum concentration (0.0899–0.311%) and the ratio of cerebrospinal fluid to unbound plasma for maximum concentration (25.0–86.4%) confirm the distribution of ASP4345 into the brain. Conclusions The pharmacokinetics of ASP4345 suggest that single daily dosing is appropriate for ASP4345. Furthermore, the concentration of ASP4345 in cerebrospinal fluid compared to free drug concentrations in plasma provides evidence of penetration of ASP4345 into the brain.

Previous studies suggest the importance of understanding what factors increase risk of lack of physical activity (PA) prior to bariatric surgery, which may increase risk of suboptimal postoperative outcomes. Therefore, the current study sought to explore which Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scales were associated with lack of pre-surgical PA. The mean age of the sample (N = 1170) was 45.97 years [standard deviation (SD) = 11.59]. Bivariate correlations and relative risk ratios were utilized to examine associations between MMPI-2-RF scale scores and regular preoperative PA. Of the ten hypothesized associations, seven MMPI-2-RF scales in the internalizing and somatic domains were associated with increased risk of preoperative lack of PA. Interventions designed to increase levels of preoperative PA are especially important because individuals with higher levels of preoperative cardiorespiratory fitness experience less complications in surgery and greater weight loss postoperatively.

Solid organ transplant candidates who display alexithymia tend to report psychological distress with some displaying symptoms associated with depression which in turn has a negative impact on their quality of life. This study sought to examine the mediating role of depression on the relationship between alexithymia and physical and psychological quality of life. The sample comprised 707 patients who were under consideration for solid organ transplantation. Mediation models were used to examine the proposed hypotheses, specifically that alexithymia would predict quality of life, and that depression would mediate the relationship between alexithymia and physical and psychological quality of life. Findings revealed that alexithymia predicted both physical and psychological quality of life. Depression scores partially mediated the relationship between alexithymia and both physical and psychological quality of life. Transplant candidates with higher levels of alexithymia who report poor physical and psychological quality of life may be at increased risk for depression. Results highlight the need to assess alexithymia within this unique patient population, who may understate symptoms of depression due to attempts at positive impression management.

The aim of this study was to evaluate the use of a mobile application (app) in patients already using total body photography (TBP) to increase skin self-examination (SSE) rates and pilot the effectiveness of examination reminders and accountability partners. Randomized controlled trial with computer generated randomization table to allocate interventions. University of Pennsylvania pigmented lesion clinic. 69 patients aged 18 years or older with an iPhone/iPad, who were already in possession of TBP photographs. A mobile app loaded with digital TBP photos for all participants, and either (1) the mobile app only, (2) skin examination reminders, (3) an accountability partner, or (4) reminders and an accountability partner. Change in SSE rates as assessed by enrollment and end-of-study surveys 6 months later. Eighty one patients completed informed consent, however 12 patients did not complete trial enrollment procedures due to device incompatibility, leaving 69 patients who were randomized and analyzed [mean age 54.3 years, standard deviation 13.9). SSE rates increased significantly from 58% at baseline to 83% at 6 months (odds ratio 2.64, 95% confidence interval 1.20–4.09), with no difference among the intervention groups. The group with examination reminders alone had the highest (94%) overall satisfaction, and the group with accountability partners alone accounted for the lowest (71%). A mobile app alone, or with reminders and/or accountability partners, was found to be an effective tool that can help to increase SSE rates. Skin examination reminders may help provide a better overall experience for a subset of patients. ClinicalTrials.gov Identifier: NCT02520622.

Background Thirty-day readmissions occur in 5% or more of bariatric surgery patients. Some readmissions relate directly to surgical risks, whereas others relate to more nonspecific complaints or nonadherence and may reflect risks outside of the surgical procedure. Objective To investigate whether presurgical psychosocial factors are related to readmission. Setting Tertiary/quaternary academic referral center. Methods Bariatric surgery patients readmitted within 30 days of surgery during 2012–2015 were identified (n = 102). Patients were matched (2:1) on body mass index, age, sex, and race to 204 nonreadmitted patients. Psychiatric variables and psychological testing (Minnesota Multiphasic Personality Inventory-2-Restructured Form) at intake were compared between the 2 groups. Among those readmitted, the indication for readmission was investigated. Those with specific complications (n = 61) were delineated from those with nonspecific indications (n = 33). Results Those with nonspecific readmissions were younger and more likely to be female. These patients were also less likely to be in outpatient psychiatric care than nonreadmitted patients. Significant differences were found on the Uncommon Virtues scale of the Minnesota Multiphasic Personality Inventory-2-Restructured Form, which reflects a tendency to underreport disinhibited behaviors. Those with nonspecific readmissions had significantly higher underreporting scores compared to those with specific indications or those not readmitted. Conclusions Readmitted patients, particularly those with nonspecific indications, were more likely to presurgically present themselves in an overly positive manner. The tendency to underreport may affect the team's ability to identify risk factors that could be ameliorated before surgery. Readmitted patients were also less likely to be receiving mental health care. Such ongoing treatment may increase monitoring and/or adherence after surgery.

It is well established that psychological factors can affect spine surgery results. A widely utilized presurgical psychological screening (PPS) algorithm that combines established psychosocial risk factors to determine patients' likelihood of achieving successful spine surgery results is evaluated in this study. Patients (n = 603) underwent a PPS, including a diagnostic interview, psychometric testing, and review of medical records. The evaluator completed a PPS algorithm for patients, placing them into one of five prognosis categories, ranging from excellent to poor. For analysis purposes, these categories were collapsed into three prognosis groups: Excellent, Good, and Fair to Very Poor. Patients classified as having an Excellent prognosis achieved the best outcomes following surgery, whereas those in the Fair to Very Poor category obtained the worst results. Analyses of specific components of the PPS algorithm demonstrated that algorithm items were modestly associated with reduced spine surgery results. Implications for presurgical assessments of spine surgery candidates are discussed.

The present study investigated the comparability of laptop computer- and tablet-based administration modes for the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Employing a counterbalanced within-subjects design, the MMPI-2-RF was administered via both modes to a sample of college undergraduates ( N = 133). Administration modes were compared in terms of mean scale scores, internal consistency, test-retest consistency, external validity, and administration time. Mean scores were generally similar, and scores produced via both methods appeared approximately equal in terms of internal consistency and test-retest consistency. Scores from the two modalities also evidenced highly similar patterns of associations with external criteria. Notably, tablet administration of the MMPI-2-RF was substantially longer than laptop administration in the present study (mean difference 7.2 minutes, Cohen's d = .95). Overall, results suggest that varying administration mode between laptop and tablet has a negligible influence on MMPI-2-RF scores, providing evidence that these modes of administration can be considered psychometrically equivalent.

Prospective data are needed to ascertain the impact of iron chelation therapy in patients with myelodysplastic syndromes. The present 5-year prospective registry analysis was conducted to compare clinical outcomes between chelated and nonchelated patients with lower-risk myelodysplastic syndromes and transfusional iron overload. In an interim analysis at 24 months, we previously reported that chelation therapy was associated with longer median overall survival and a tendency toward longer leukemia-free survival and fewer cardiac events. In the present report, we detail findings from the final analysis at 5 years. We confirm, at the conclusion of this 5-year, prospective, non-interventional study, that overall survival was significantly longer in patients who received iron chelation therapy vs those who did not. Causes of death in the overall population were predominantly myelodysplastic syndromes/acute myeloid leukemia followed by cardiac disease. Time to progression to acute myeloid leukemia was also significantly longer in patients receiving chelation therapy, and significantly fewer patients progressed to leukemia vs those not receiving chelation therapy. Limitations of the study include a potential for clinical bias, as patients with longer predicted survival may have been chosen for chelation therapy, the differences present in concomitant conditions at baseline, and the possibility that some high-risk patients were not identified due to limited cytogenetic classification.

Background The reasons why some patients who begin the presurgical process for bariatric surgery fail to complete the procedure are understudied. Previous research implies that psychological factors play a role. Objectives To examine whether scores from baseline psychological testing incrementally predict failure to proceed with bariatric surgery beyond demographic information in patients' medical charts and data derived from a clinical interview. Setting Cleveland Clinic Bariatric and Metabolic Institute. Methods The sample (n = 1160) was mainly female (72.41%), middle aged (mean age=46.07 yr, SD=11.70) and of Caucasian descent (65.76%). Hierarchical logistic regressions were conducted to test the incremental validity of baseline Minnesota Multiphasic Personality Inventory-2 Restructured Form scores after controlling for information gathered from the psychological interview and medical charts. Relative risk ratios were calculated to reflect the clinical utility of the results. Results In total, 27.16% of patients failed to proceed with bariatric surgery after 1 year or more after a recommendation for surgery from their psychological evaluations. Psychological test scores were substantially associated with failure to proceed with surgery and significantly accounted for up to 6% of additional variance after controlling for psychological interview variables and medical chart data. Elevated scores on Minnesota Multiphasic Personality Inventory-2 Restructured Form scales, such as anxiety and substance use, identify patients at up to 2.5 times greater risk for failing to proceed with bariatric surgery. Conclusions Objective psychological test data—notably, scale scores assessing for substance abuse, anxiety, and demoralization—add to information obtained from a clinical interview and medical records in identifying patients at risk for failing to proceed with bariatric surgery.

Research using a categorical-polythetic classification system for mental illness has raised concern regarding the validity of categorical classification systems. Recent efforts suggest psychopathology is better understood from a dimensional framework, though there has been varying evidence of a somatization factor. The current investigation seeks to produce and validate a dimensional model of psychopathology, with a particular emphasis on the placement of somatization, across three nonoverlapping medical samples. Using a bariatric surgery seeking sample (n = 1,268), a spine surgery/spinal cord stimulator seeking sample (n = 1,711), and a chronic pain treatment seeking sample (n = 1,388), a dimensional model of psychopathology was replicated across all three samples using a dimensional measure of psychopathology (the Minnesota Multiphasic Personality Inventory-2-Restructured Form [MMPI-2-RF]). Clear evidence of a separate somatization factor was found in addition to broad internalizing, externalizing, and social detachment factors. Constructs assessable with the model yielded good convergent and discriminant validity coefficients with external criteria, and further supported the presence of a higher-order somatization construct. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

Background Graze eating is defined as repetitive, unplanned eating of small amounts of food throughout the day. Little consensuses exist regarding whether graze eating, like binge eating disorder (BED), is characterized by feelings of loss of control (LOC). Furthermore, little is known about how patients who graze eat with and without LOC differ psychologically. Objectives The present study seeks to better characterize graze eating by examining differences between graze eating with LOC (+LOC) and without LOC (–LOC) among presurgical bariatric patients. Setting A large, Midwestern academic medical center. Methods The sample consisted of 288 adult bariatric surgery candidates (mean age 45.8, standard deviation [SD] 12.57) who underwent a presurgical psychological evaluation. Graze eating, BED, and other mental health diagnoses were evaluated using a semistructured interview. Participants were also administered the Minnesota Multiphasic Personality Inventory–2–Restructured Form (MMPI-2-RF) and binge eating scale (BES). Data were collected using a retrospective chart review. Results Among the 33% (n = 95) of the sample who reported preoperative graze eating, 32% (n = 30) also endorsed LOC. Graze eating, particularly with LOC, was associated with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnoses of anxiety disorders and BED, and multiple measures of internalizing dysfunction on the MMPI-2-RF. Conclusions Bariatric surgery candidates who graze eat experience a greater degree of overall distress and psychopathology including anxiety and depression. The minority who experience grazing+LOC appear to have even greater risk of psychopathology. Moreover, there appears to be significant overlap with BED. Future research should explore whether these 2 maladaptive eating patterns benefit from similar treatment.

It is not uncommon for patients to report diminished outcomes as a result of spine surgery or a spinal cord stimulator implant. Presurgical psychological evaluations are increasingly used to identify patients at increased risk for such outcomes and use of personality assessment instruments in these evaluations provides incremental information beyond a clinical interview and medical chart review. This investigation explores the psychometric properties of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) in a sample of spine surgery patients (

Background The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) has empirically validated utility in presurgical psychological evaluations of bariatric surgery patients. However, clinicians may prefer shorter, symptom-focused measures. Objectives The purpose of the present study is to evaluate the feasibility and potential administration time savings of a proposed flexible and conditional (FCA) administration of the MMPI-2-RF in presurgical evaluations of bariatric surgery candidates. Setting Bariatric surgery candidates evaluated at a large hospital as well as a private practice in the Midwest. Methods MMPI-2-RF scores were available for a total of 4099 adult bariatric surgery candidates from 2 separate samples. The hospital sample included 911 males and 2430 females. The average BMI was 49.3 kg/m2 (SD = 11.0). The private practice sample included 105 males, 640 females, and 13 individuals who did not report gender. The average BMI was 48.8 kg/m2 (SD = 8.4). The authors used a simulation design in which existing MMPI-2-RF responses were used to simulate an FCA administration. Results The findings indicated that an FCA of the MMPI-2-RF closely approximates the amount of information typically gained from a full administration of the test in the 2 samples of bariatric surgery candidates. Items savings and estimated time savings ranged from 44% to 88% in both samples, depending on the number of conditionally administered scales. Conclusions The present study supports the feasibility of an FCA of the MMPI-2-RF, potentially shortening administration time and reducing patient burden. However, the findings are limited because the accuracy and time savings are based on a simulation, not actual FCA administrations.

Although spine surgery (SS) and spinal cord stimulators (SCSs) can provide significant relief for patients with intractable pain, their effectiveness is variable. Previously, a number of pre-operative psychosocial risk factors have predicted suboptimal outcomes of these procedures. However, recent research has found that “patient activation”—the extent to which patients are engaged and active in their own health care—can predict positive surgical results. The purpose of the current investigation was to determine whether patient activation helps explain associations between established psychosocial risk factors and suboptimal outcomes. Candidates for SS and SCS (n = 1254; 56.3% women, mean age 50.4 years) consented to participate in an outcome study prior to their pre-surgical psychological evaluation. Of those, 46.3% returned self-report measures an average of 180 days (SD = 79.1) post-surgery. Bootstrapped mediation analyses indicated that patient activation mediates numerous associations between psychosocial risk factors and suboptimal outcomes. That is, patients’ involvement in obtaining information, decision making, and their resilience can explain why some patients do not experience adverse surgical results when pre-surgical psychosocial risk factors are present. Pre-surgical psychological evaluations should include examination of patient strengths in addition to psychosocial risk factors, so that treatments can be appropriately individualized and the most effective surgical results obtained.

The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme converts cortisone to cortisol and participates in the regulation of glucocorticoid levels in tissues. 11β-HSD1 is expressed in the liver, kidney, adipose tissue, placenta, and brain. 11β-HSD1 is a target for treatment of depression, anxiety, posttraumatic stress disorder, and also against age-related cognitive function and memory loss. In this study, we evaluated the radiotracer

Background The Binge Eating Scale (BES) is a widely-used self-report measure of binge eating severity. Hood et al. [1] reported a 2-factor structure for the BES in a sample of bariatric surgery candidates, with factors labeled feelings/cognitions and behavioral manifestations. The present study aims to replicate and extend the factor structure obtained by Hood et al. [1] by testing the utility of a bifactor model that removes binge eating severity variance, which the total BES score purports to assess, in another sample of bariatric surgery candidates. Methods Bariatric surgery candidates (n = 517; 71.2% women; mean body mass index=49.50 kg/m 2 ; SD=10.17) were sampled. Twenty-four percent met DSM-IV-TR diagnostic criteria for binge eating disorder. Results Consistent with previous research, a 2-factor structure for the BES was supported; however, the 2 factors were substantially correlated ( r = .89). A bifactor model significantly improved model fit, supporting the presence of a higher-order severity factor accounting for a significant amount of variance. This factor was primarily marked by binge eating severity as demonstrated by associations with number of objective binge eating episodes and DSM-IV-TR diagnosis. In the bifactor model, the feelings/cognitions factor was modestly associated with self-reported mood psychopathology. However, contrary to expectations, the behavioral manifestation factor was not associated with empirically derived behavioral problems. Conclusions The current findings partially converge with those of Hood et al. [1] However, the use of the BES as a 2-factor measure is not recommended at this point because of lack of incremental validity demonstrated by the behavioral manifestation factor. Continued use of the BES as a unidimensional measure of binge eating severity, in conjunction with a comprehensive clinical interview, can provide useful guidance for presurgical treatment recommendations.

Background Presurgical psychological screening is used to identify factors that may impact postoperative adherence and surgical outcomes in bariatric surgery candidates. Minnesota Multiphasic Personality Inventory – 2 Restructured Form (MMPI-2-RF) findings have demonstrated utility for this task. Objectives To explore whether there are clinically meaningful gender, ethnicity, or age differences in presurgical MMPI-2-RF scores and the validity of these scores in bariatric surgery candidates. Methods The sample was composed of 872 men and 2337 women. Ethnicity/race groups included 2,204 Caucasian, 744 African American, and 96 Hispanic individuals. A sample of 165 were not included in the ethnicity/race analyses because they were of another descent. Ages groups included 18–35 year olds (n = 454), 36–49 year olds (n = 1154), 50–64 year olds, (n = 1246), and 65 years old or older (n = 355). Validity data, obtained via a retrospective chart review, were available for a subset patients (n = 1,268) who were similarly distributed. Step-down hierarchical regression analyses were conducted to assess for differential validity. Results Bariatric surgery candidates produced comparable MMPI-2-RF scores in all subsamples, indicating that the test norms generalize across demographic groups. Validity findings were also generally comparable, indicating that MMPI-2-RF scores have the same interpretive implications in demographically diverse subgroups of bariatric surgery candidates. Conclusions The MMPI-2-RF can assist in presurgical psychological screening of demographically diverse bariatric surgery candidates.

A substantial proportion of individuals who undergo surgical procedures to relieve spine pain continue to report significant pain and dysfunction after recovery. Psychopathology and patient expectations have been linked to poor results, leading to an increasing reliance on presurgical psychological screening (PPS) as part of the surgical diagnostic process. The original Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1943) and the MMPI-2 (Butcher, Graham, Ben-Porath, Tellegen, & Dahlstrom, 2001) were among the measures most commonly used in PPS evaluations and research. This study focuses on the newest version of the test, the MMPI-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008/2011; Tellegen & Ben-Porath, 2008/2011) as a predictor of outcomes for spine surgery candidates. Using a sample of 172 men and 210 women who underwent a PPS, we examined the ability of MMPI-2-RF scale scores to predict early surgical outcomes independent of other presurgical risk factors identified by other means, as well as patients' presurgical expectations. MMPI-2-RF results accounted for up to 11% of additional variance in measures of early postoperative functioning. MMPI-2-RF scales that assess for emotional/internalizing problems, specifically Demoralization, measures of somatoform dysfunction, and interpersonal problems contributed most to the prediction of diminished outcome.

The current investigation aims to predict 3-year postoperative percent total weight loss among a sample of bariatric surgery patients with super-super obesity.Previous research implies that persons with presurgical super-super obesity (body mass index [BMI] ≥60 kg/mCleveland Clinic, BariatricMetabolic Institute, Cleveland, OH.Bariatric surgery candidates (N = 1231; 71.9% female; 65.8% Caucasian) completed a presurgical psychological evaluation and the Minnesota Multiphasic Personality Inventory-2-Restructured Form. Participants with a baseline BMI ≥60 (n = 164) were compared with BMI60 (n = 1067) on psychosocial and demographic factors, the Minnesota Multiphasic Personality Inventory-2-Restructured Form, and in the subset that had surgery (n = 870), percent total weight loss extending to the 3-year follow-up.Patients with a BMI ≥60 were younger, less educated, and more likely to be male compared with lower BMI patients. Patients with a BMI ≥60 had greater psychosocial sequelae as evidenced by being more likely to have a history of sexual abuse, history of psychiatric hospitalization, more binge eating episodes, and higher prevalence of major depression disorder and binge eating disorder. On the Minnesota Multiphasic Personality Inventory-2-Restructured Form, those with BMI ≥60 reported greater demoralization, low positive emotions, ideas of persecution, and dysfunctional negative emotions. After controlling for surgery type, weight loss for individuals with BMI ≥60 did not greatly differ from weight loss in patients with BMI60. Variables predictive of less weight loss at 3 years regardless of presurgical BMI, included being older, having a sexual abuse history, and higher ideas of persecution scores.Although patients with BMI ≥60 evidenced more psychopathology before surgery, findings suggest that the relationship between higher BMI and poorer outcome may better be explained by other co-morbid factors.

Focusing on average weight loss (WL) from interventions provides useful efficacy data but masks large variability across patients. In this study, parameters of weight loss trajectories were determined that differentiated individuals during a 15-week clinical lifestyle intervention.Patients (n = 595) were in a fee-for-service WL lifestyle program with a partial meal replacement diet and lifestyle change counseling. Parameters used in latent class analyses were percent WL (%WL), weight nadir, number of weekly weight gains, maximum weekly percent weight gain, standard deviation of weekly weight changes, linear slope values, and change in slope.Average %WL was 9.73%. Latent class analyses revealed three groups with considerable overlap in %WL ranges but differing significantly on all trajectory parameters (Ps 0.001). Group 1 had the most variable and least successful pattern of weight changes. Group 3 had the least variable and most successful pattern of weight changes. Group 2 fell between the others on all parameters.Emphasis on average WL likely obscures considerable variability in individual courses of weight change. Moreover, patients with similar %WL can have different WL trajectories. Identification of behavioral/physiological characteristics associated with different weight loss trajectories may facilitate the development of more tailored interventions, particularly for trajectories associated with less optimal outcomes.

Objective Binge eating disorder (BED) was recently included in the DSM-5. The prevalence rate for BED using the DSM-IV-TR research criteria tends to be higher in bariatric surgery candidates than the normative population; however, no studies have examined how many more bariatric surgery candidates will meet the new, less conservative criteria of DSM-5. We explore the current BED prevalence rate change in a sample of bariatric surgery candidates. Method Data were obtained for 1,283 bariatric surgery candidates. 84 men and 213 women were diagnosed with current BED using DSM-IV-TR research criteria. A semi-structured interview, the binge eating scale (BES), and a Minnesota Multiphasic Personality Inventory—2 Restructured Form (MMPI-2-RF) were given to every patient as part of standard procedures mandated by the facility. Results and Discussion An additional 3.43% (p

This 5-year, prospective registry enrolled 600 lower-risk MDS patients (pts) with transfusional iron overload. Clinical outcomes were compared between chelated and nonchelated pts. At baseline, cardiovascular comorbidities were more common in non-chelated pts, and MDS therapy was more common in chelated pts. At 24 months, chelation was associated with longer median overall survival (52.2 months vs. 104.4 months; p

Presurgical psychological screening of bariatric surgery candidates includes some form of standardized psychological assessment. However, associations between presurgical psychological screening and postoperative outcome have not been extensively studied. Here, we explore associations between presurgical Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) scores and early postoperative Somatic Concerns, Psychological Distress, and Maladaptive Eating Behaviors.The sample consisted of male (n = 238) and female (n = 621) patients who were administered the MMPI-2-RF at their presurgical psychological evaluation and received bariatric surgery. Patients were evaluated at their 1- and 3-month postoperative appointments.Confirmatory factor analysis indicated that three latent constructs-somatic concerns, psychological distress, and maladaptive eating behaviors-were represented by responses to a postoperative assessment and that these constructs could be measured consistently over time. Presurgical scores on MMPI-2-RF scales measuring internalizing dysfunction were associated with more psychological distress at postoperative follow-ups, scores on scales measuring somatization were associated with more postoperative somatic concerns, and scores on scales assessing emotional/internalizing, behavioral/externalizing, cognitive complaints, and thought dysfunction prior to surgery were associated with maladaptive eating behaviors after surgery.In conjunction with a presurgical psychological interview, the MMPI-2-RF provides information that can assist in anticipating postoperative outcomes and inform efforts to prevent them.

Psychological comorbidity is common in bariatric surgery candidates. Many multidisciplinary teams incorporate psychometric testing to screen for psychological factors that, if left unattended, may negatively impact surgical results. Here, we report descriptive findings and empirical correlates of Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) scales among of bariatric surgery candidates undergoing a pre-surgical psychological evaluation.The sample consisted of male (n = 324) and female (n = 658) patients seeking bariatric surgery who were administered the MMPI-2-RF at their psychological evaluation. Psychosocial and medical variables were retrospectively coded from the patients' medical records. These criteria included history/current mental health diagnoses and treatments, maladaptive eating behaviors/diagnoses, past/current substance use, abuse history, sleep apnea, and denial of surgery.Descriptive analyses demonstrated similar findings for male and female candidates and replicated previous reports. MMPI-2-RF scales measuring emotional dysfunction were associated with maladaptive eating patterns, a history of Major Depressive Disorder, and previous suicide attempts. Scale scores measuring behavioral dysfunction were associated with current/past substance use and previous physical abuse. MMPI-2-RF scale scores measuring somatic problems were associated with a higher BMI at the time of surgery, sleep apnea diagnosis/adherence, physical/sexual abuse history, active mood disorder, previous mental health diagnoses, and maladaptive eating patterns.The MMPI-2-RF can aid in identifying a broad range of psychological comorbidity among bariatric surgery candidates. When used in conjunction with a pre-surgical psychological interview, it can aid in the assessment of psychological factors relevant to pre-surgical psychological assessment of bariatric surgery candidates.

Background Psychosocial factors contribute to poorer weight loss outcomes following bariatric surgery; however, findings on associations between preoperative psychiatric diagnoses, psychological testing, and weight loss are inconsistent. Objectives Examine associations between presurgical psychiatric diagnoses derived from a semi-structured clinical interview and test scores from the Minnesota Multiphasic Personality-Inventory−2 – Restructured Form (MMPI-2-RF) and 5-year Body Mass Index (BMI) outcomes. Setting Cleveland Clinic Bariatric and Metabolic Institute Methods 446 consecutively consented patients who underwent a Roux-en-Y gastric bypass (RYGB) at least 5 years prior were included in the study. A majority were women (74.2%) and Caucasian (66.2%). Patients' mean presurgical BMI was 49.14 kg/m 2 [SD = 9.50 kg/m 2 ]. Psychiatric diagnoses were obtained from a presurgical, semi-structured clinical interview and all participants were administered the MMPI-2-RF at their presurgical evaluations. BMIs were collected at 4 postoperative time points across a 5-year trajectory. This prospective design utilized latent growth curve modeling. Results Older patients evidenced a slower rate of BMI reduction over time. A presurgical diagnosis of Binge Eating Disorder predicted higher BMIs at the 5-year outcome. Scores on MMPI-2-RF measures of emotional and behavioral dysfunction domains incrementally predicted poorer weight loss outcomes. Conclusion Preoperative indicators of psychopathology, notably indicators that are dimensional in nature, are important in predicting postoperative outcomes. Closer follow-up with patients who evidence presurgical psychological factors, both before and after surgery, may help improve outcomes.

In vivo translational imaging techniques, such as positron emission tomography and single-photon emission-computed tomography, are the only ways to adequately determine that a drug engages its target. Unfortunately, there are far more experimental mechanisms being tested in the clinic than there are radioligands, impeding the use of this risk-mitigating approach in modern drug discovery and development. Pharmacological magnetic resonance imaging (phMRI) offers an approach for developing new biomarkers with the potential to determine central activity and dose selection in animals and humans. Using phMRI, we characterized the effects of xanomeline on ketamine-induced activation on blood oxygen level-dependent (BOLD) signal. In the present studies, xanomeline alone dose-dependently increased the BOLD signal across several regions of interest, including association and motor and sensory cortical regions. It is noteworthy that xanomeline dose-dependently attenuated ketamine-induced brain activation patterns, effects that were antagonized by atropine. In conclusion, the muscarinic 1/4-preferring receptor agonist xanomeline suppressed the effects of the N-methyl-D-aspartate channel blocker ketamine in a number of brain regions, including the association cortex, motor cortex, and primary sensory cortices. The region-specific brain activation observed in this ketamine challenge phMRI study may provide a method of confirming central activity and dose selection for novel antipsychotic drugs in early clinical trials for schizophrenia, if the data obtained in animals can be recapitulated in humans.

The neurokinin-1 (NK-1) antagonist LY686017 showed activity in preclinical anxiety models. The clinical development of LY686017 included a PET study and a proof-of-concept in social anxiety disorder (SAD). [ 11 C]GR205171 was used healthy volunteers receiving 1–100 mg/d LY686017 for 28 days to determine brain receptor occupancy (RO). The mean NK-1 RO increased ranged from 25% with 1 mg to 93% with 100 mg. Subsequently, a 12-week randomized clinical trial tested LY686017 vs. paroxetine, or placebo in SAD. Pharmacokinetic (PK)/RO modeling based on the PET results predicted that once daily dosing of > 30 mg LY686017 led to sustained trough RO of over 80%. 189 outpatients 1 suffering from SAD were randomly assigned to 12-weeks treatment with 50 mg/d LY686017 ( N = 77), placebo ( N = 74), or 20 mg/d paroxetine ( N = 38). There was no significant difference between LY686017 and placebo as measured with the Liebowitz Social Anxiety scale (LSAS). The active comparator paroxetine showed positive trends on primary and secondary measures. The plasma concentrations were above the level expected to produce maximal brain NK-1 RO based on the PK/RO relationship obtained in the human PET investigation. Thus, further evaluation of LY686017 for the treatment of SAD does not seem warranted.

Using the 133Xe tissue clearance method, the blood flow in the greater trochanter of the femur was studied in 30 patients with acromegaly. Both the washout rate constant (k2) and blood flow (P2) values are significantly decreased in acromegaly (p less than 0.01). There is a significant negative correlation (r = -0.42, p less than 0.05) between the flow values and mean daily concentrations of growth hormone in serum of acromegalic patients. The observations is presented as a preliminary evidence of a possible influence of growth hormone on the blood flow in bone.

We present the first reported treatment failure of a reconstructed scapula body that proceeded to nonunion. This is a unique case report of an otherwise healthy patient who underwent open reduction and internal fixation of a scapula fracture nonunion, which is very rare. Failure of internal fixation in this application has not been reported, and, to our knowledge, this is only the fifth case report of a scapula body nonunion that was reconstructed. Of 159 reported cases of open reduction and internal fixation for treatment of scapula neck and body fractures (with or without intraarticular glenoid fractures), there is not one reported case of a nonunion. Our case is described in detail, including the method of surgical reconstruction, and a review of the literature regarding surgical treatment of scapula nonunions after nonoperative treatment also is presented.

Down-regulation of 5-hydroxytryptamine 2A (5-HT 2A ) receptors has been a consistent effect induced by most antidepressant drugs. The evidence for down-regulation of 5-HT 2A receptor binding following subchronic treatment with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) is mixed. The question of 5-HT 2A receptor sensitivity during chronic administration of antidepressants is important since activation of 5-HT 2A receptors is associated with impulsivity. Continued activation of 5-HT 2A receptors may functionally oppose activation of other non-5-HT 2A receptors in the prefrontal cortex associated with the clinical efficacy of SSRI treatment. Therefore, the effects of repeated daily administration of fluoxetine (10 mg/kg, i.p. ×3 weeks) on pharmacologically characterized electrophysiological response mediated by 5-HT 2A receptor activation, 5-HT-induced excitatory postsynaptic currents (EPSCs), in rat prefrontal cortical slices was examined. The concentration–response curve for 5-HT-induced EPSCs was unchanged following subchronic fluoxetine treatment. This subchronic fluoxetine treatment failed to modify electrophysiological responses to AMPA in layer V pyramidal cells as well. These findings would be consistent with the hypothesis that blockade of 5-HT 2A receptors may enhance the effects of SSRIs or serotonin/norepinephrine reuptake inhibitors (SNRIs).

Glutamate plays an important role in the psychotomimetic effects of both channel blocking N-methyl d -aspartate (NMDA) receptor antagonists and hallucinogenic drugs which activate 5-hydroxytryptamine2A (5-HT2A) receptors. Previous work suggested that activation of non-NMDA ionotropic glutamate receptors mediates the effects of 5-HT-induced excitatory post-synaptic potentials/currents (EPSPs/EPSCs) when recording from layer V pyramidal cells in the rat medial pre-frontal cortex (mPFC). However, those effects are mediated by either α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or kainate receptors of the iGluk5 subtype. To test whether activation of AMPA receptors is sufficient to mediate 5-HT-induced EPSCs, a 2,3-benzodiazepine that selectively blocks AMPA receptors was assessed. This selective AMPA receptor antagonist potently suppressed 5-HT-induced EPSCs. Since phenethylamine hallucinogens induce head shakes by activating 5-HT2A receptors in the mPFC and this action is modulated by glutamate, we also examined whether selective blockade of AMPA receptors would suppress DOI-induced head shakes. As predicted, we found that selective blockade of AMPA receptors suppressed DOI-induced head shakes. Given evidence that activation of AMPA receptors is an important downstream effect for both channel blocking NMDA receptor antagonists and phenethylamine hallucinogens, we also tested multiple doses of DOI with a sub-anesthetic dose of MK-801. Synergistic action between these two classes of psychotomimetic drugs was demonstrated by MK-801 enhancing DOI-induced head shakes and locomotor activity. These findings expand the dependence of both channel blocking NMDA receptor antagonists and phenethylamine hallucinogens on enhancing extracellular glutamate.

Spinal cord stimulation (SCS) has variable effectiveness in controlling chronic pain. Previous research has demonstrated that psychosocial factors are associated with diminished results of SCS. The objective of this investigation is to examine associations between pre-implant psychological functioning as measured by the Minnesota Multiphasic Personality Inventory–2–Restructured Form (MMPI-2-RF) and SCS outcomes. SCS candidates at two sites (total N = 319) completed the MMPI-2-RF and measures of pain, emotional distress, and functional ability as part of a pre-implant psychological evaluation. At an average of 5 months post-implant, patients completed the measures of pain and emotional distress a second time. Poorer SCS outcomes and poorer patient satisfaction were associated with higher pre-implant MMPI-2-RF scores on scales used to assess emotional dysfunction, somatic/cognitive complaints, and interpersonal problems. Ways through which pre-implant psychological evaluations of spinal cord stimulator candidates can be informed by MMPI-2-RF findings are discussed.

5-Hydroxytryptamine2A (5-HT2A) receptor regulation is atypical compared to most other monoaminergic receptors in that chronic administration of both antagonists and agonists results in down-regulation of cortical 5-HT2A receptor number and the functional in vitro and in vivo effects. We have recently found that midline thalamic lesions, which appeared to block glutamate release induced by activation of 5-HT2A receptors, also increased 5-HT2A receptor binding in layers I and Va of the medial prefrontal cortex (mPFC). These layers contain the highest density of both 5-HT2A receptors and thalamocortical terminals from the midline and intralaminar thalamic nuclei. These findings suggest the hypothesis that excitatory amino acid release plays a role in regulation of postsynaptic 5-HT2A receptors, and that down-regulation of 5-HT2A receptors by 5-HT2A agonists may not be attributed only to simple occupancy of the receptor by direct agonists. Therefore, we examined the effect of a single 30 min pretreatment with the metabotropic glutamate2/3 (mGlu2/3) receptor agonist (1S,2S,5R,6S)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylate monohydrate (LY354740; 10 mg/kg, i.p.) on the second of three consecutive days of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) treatment (1.25 mg/kg, i.p.). The subchronic DOI administration significantly decreased binding of [125I]DOI to 5-HT2A receptors in layers I and Va of the mPFC by approximately 25%. In contrast, a single dose of LY354740 on Day 2 of this regimen completely blocked the DOI-induced down-regulation. Thus, a presumed hypoglutamatergic state secondary to thalamic lesions and increased glutamate release induced by a subchronic regimen of a 5-HT2A agonist (and hallucinogenic drug) differentially regulate prefrontal cortical 5-HT2A receptor binding.

Both a 5-hydroxytryptamine2A (5-HT2A) agonist and immobilization stress previously have been shown to differentially alter brain-derived neurotrophic factor (BDNF) mRNA expression in the neocortex and hippocampus. Both 5-HT2A receptor activation and immobilization stress also increase glutamate release in the rat prefrontal cortex. Given that the metabotropic glutamate2/3 receptor (mGluR2/3) agonist (1S,2S,5R,6S)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylate monohydrate (LY354740) suppressed electrophysiological, behavioral and biochemical effects of 5-HT2A receptor activation in the medial prefrontal cortex (mPFC), we assessed the efficacy of the mGluR2/3 agonist in suppressing the stress-induced increase in BDNF mRNA expression. LY35740 (10 mg/kg, i.p.) attenuated the immobilization stress-induced increase in BDNF mRNA expression in the rat mPFC. This result is consistent with the hypothesis that mGlu2/3 agonists may be an efficacious treatment for stress-induced neuropsychiatric syndromes.

Cushing's syndrome is associated with typical central redistribution of adipose tissue. The aim of the study was to assess lipolysis and catecholamines and their metabolites in subcutaneous abdominal adipose tissue using an in-vivo microdialysis technique. Nine patients with Cushing's syndrome and nine age-, gender- and body mass index (BMI)-matched control subjects were included in the study. Local glycerol concentrations were significantly increased in subcutaneous adipose tissue of patients with Cushing's syndrome (p

Background Some research suggests that higher levels of depression and anxiety-related symptoms at intake are associated with premature termination from psychotherapy, but findings are mixed. However, theoretical and measurement considerations – introduced by a common mood factor – might complicate literature synthesis. Tellegen (1985) demonstrated that demoralization causes multicollinearity between measures of depression and anxiety, and other lines of research have converged to indicate that this construct is an important non-specific factor to consider when assessing mood pathology. Methods We utilized a sample of 557 community mental health center outpatients (188 males, 265 females; 80% Caucasian) with an average age of 32.2 years (SD=10.2). We used self-report indicators to model latent low positive emotionality and negative emotionality constructs, which are temperament markers of core depressive and anxiety symptoms. We further specified a latent demoralization bifactor from these indicators. Results As hypothesized, the bifactor model yielded significantly better fit than competing one-factor and two-factor models. Furthermore, the bifactor was substantially correlated with a demoralization measure (r=.96). As expected, low positive emotionality and negative emotionality were significant predictors of therapist ratings of premature termination. Though demoralization was a non-significant predictor, the structural paths from the other two internalizing constructs markedly increased in the bifactor model relative to the two-factor model. Limitations Replications with other, more diverse clinical populations using multi-method indicators of premature termination are needed. Conclusions This research indicates that after accounting for demoralization patients presenting with core mood disorder symptoms are at substantially increased risk for premature termination.

PURPOSE: Because of the potential risk of malignancy and technical difficulties in achieving complete removal, large colorectal polyps represent a special problem for the endoscopist. The aim of this study was to evaluate the capabilities and risks of endoscopy in complete removal of large colorectal polyps. METHODS: Endoscopic polypectomy of 186 colorectal polyps larger than 3 cm in diameter (range, 3–13 cm) was performed; 141 were sessile and 45 pedunculated. Most of the polyps were located in the rectum (n = 88), sigmoid (n = 63), and cecum (n = 9). The remaining adenomas were situated in other parts of the colon. Sessile polyps were removed using the piecemeal technique. RESULTS: Histology results showed an adenoma in 167 cases, and invasive carcinoma was present in the adenoma in 19 patients. Of the adenomas, 29 were tubulous, 118 tubulovillous, and 20 villous; adenoma with severe dysplasia was found in 49 cases. Complete endoscopic removal was achieved in all sessile and pedunculated polyps. None of the patients with invasive carcinoma who underwent surgical resection (n = 10) had any evidence of tumor in the resected specimen. Bleeding occurred in 4 patients after polypectomy (2 percent). Perforation occurred in 1 patient (0.5 percent), who had an invasive carcinoma of the cecum. There was no procedure-related mortality. During a mean follow-up period of 40 (range, 3–87) months, 6 patients presented with recurrence of a benign adenoma (3 percent), which was treated endoscopically, and 1 patient presented with a recurrent invasive carcinoma, which was treated surgically. CONCLUSIONS: Endoscopic polypectomy is a safe and effective method of treating large colorectal polyps.