Placebo treatment affects brain systems related to affective and cognitive processes, but not nociceptive pain.

Placebo analgesia is a replicable and well-studied phenomenon, yet it remains unclear to what degree it includes modulation of nociceptive processes. Some studies find effects consistent with nociceptive effects, but meta-analyses show that these effects are often small. We analyzed placebo analgesia in a large fMRI study (N = 392), including placebo effects on brain responses to noxious stimuli. Placebo treatment caused robust analgesia in both conditioned thermal and unconditioned mechanical pain. Placebo did not decrease fMRI activity in nociceptive pain regions, including the Neurologic Pain Signature (NPS) and pre-registered spinothalamic pathway regions, with strong support from Bayes Factor analyses. However, placebo treatment affected activity in pre-registered analyses of a second neuromarker, the Stimulus Intensity Independent Pain Signature (SIIPS), and several associated a priori brain regions related to motivation and value, in both thermal and mechanical pain. Individual differences in behavioral analgesia were correlated with neural changes in both thermal and mechanical pain. Our results indicate that processes related to affective and cognitive aspects of pain primarily drive placebo analgesia.

Anxiety trajectories among cancer survivors during the COVID-19 pandemic.

PURPOSE: To describe trajectories of general and bodily vigilance anxiety among cancer survivors during COVID-19 and examine associated factors. DESIGN: Longitudinal survey study (May-December 2020). SAMPLE: Colorado-based cancer survivors (N = 147). METHODS: Latent class growth analyses were used to examine trajectories for two types of anxiety (general and body vigilance), and to evaluate associations with fear of cancer recurrence (FCR), loneliness, and emotional approach coping. FINDINGS: Anxiety levels remained stable over time. Most participants were best characterized by the mild general anxiety and moderate bodily vigilance anxiety classes. FCR predicted both general and bodily vigilance anxiety class, and loneliness distinguished between mild and moderate bodily vigilance anxiety classes. CONCLUSIONS: Current cancer survivors experienced mild general anxiety and moderate body vigilance anxiety during the early pandemic with no detectable improvement over time, and FCR consistently predicted anxiety outcomes. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: These findings provide insight into the anxiety profiles of cancer survivors during COVID-19 and possible therapeutic targets.

Testosterone-Secreting Ovarian Tumor: A Rare Cause of Erythrocytosis and Pulmonary Embolus.

OBJECTIVE: To raise awareness of the clinical presentation of a testosterone-secreting steroid cell tumor, not otherwise specified, causing pulmonary embolus (PE) and erythrocytosis. METHODS: Report of the first known case of ovarian steroid cell tumor not otherwise specified leading to PE. RESULTS: A 67-year-old Caucasian postmenopausal woman was referred for endocrine evaluation of a 1-year history of hirsutism, weight gain, and elevated total testosterone level of 672 ng/dL (normal, <75 ng/dL). She reported increased hair growth on her chin for the past year, unintentional weight gain, and low energy levels. Laboratory data from the initial visit included a total testosterone level of 672 ng/dL (normal, <75 ng/dL), hemoglobin level of 18.0 g/dL (normal, 11.7-15 g/dL), and hematocrit level of 50.4% (normal, 35%-45%). Four months after initial presentation, the patient developed acute-onset chest pain and shortness of breath and was diagnosed with a right PE on computed tomography chest angiogram. Evaluation with imaging for an ovarian mass revealed a negative workup including computed tomography abdomen pelvis, transvaginal ultrasound, and pelvic magnetic resonance imaging. Despite negative findings during imaging, because of the markedly elevated testosterone levels, this presentation was thought to correspond to a testosterone-secreting ovarian tumor. The patient was referred for bilateral oophorectomy. Pathology of the right ovary revealed a 2-cm steroid cell tumor, not otherwise specified. CONCLUSIONS: PE and erythrocytosis can be presentations of a testosterone-secreting ovarian tumor, not otherwise specified. This case is the first known presentation of an ovarian steroid cell tumor, not otherwise specified, leading to PE and erythrocytosis.

Multi-Polygenic Analysis of Nicotine Dependence in Individuals of European Ancestry.

INTRODUCTION: Heritability estimates of nicotine dependence (ND) range from 40% to 70%, but discovery GWAS of ND are underpowered and have limited predictive utility. In this work, we leverage genetically correlated traits and diseases to increase the accuracy of polygenic risk prediction. METHODS: We employed a multi-trait model using summary statistic-based best linear unbiased predictors (SBLUP) of genetic correlates of DSM-IV diagnosis of ND in 6394 individuals of European Ancestry (prevalence = 45.3%, %female = 46.8%, µâ€Šage = 40.08 [s.d. = 10.43]) and 3061 individuals from a nationally-representative sample with Fagerström Test for Nicotine Dependence symptom count (FTND; 51.32% female, mean age = 28.9 [s.d. = 1.70]). Polygenic predictors were derived from GWASs known to be phenotypically and genetically correlated with ND (i.e., Cigarettes per Day [CPD], the Alcohol Use Disorders Identification Test [AUDIT-Consumption and AUDIT-Problems], Neuroticism, Depression, Schizophrenia, Educational Attainment, Body Mass Index [BMI], and Self-Perceived Risk-Taking); including Height as a negative control. Analyses controlled for age, gender, study site, and the first 10 ancestral principal components. RESULTS: The multi-trait model accounted for 3.6% of the total trait variance in DSM-IV ND. Educational Attainment (ß = -0.125; 95% CI: [-0.149,-0.101]), CPD (0.071 [0.047,0.095]), and Self-Perceived Risk-Taking (0.051 [0.026,0.075]) were the most robust predictors. PGS effects on FTND were limited. CONCLUSIONS: Risk for ND is not only polygenic, but also pleiotropic. Polygenic effects on ND that are accessible by these traits are limited in size and act additively to explain risk. IMPLICATIONS: These findings enhance our understanding of inherited genetic factors for nicotine dependence. The data show that genome-wide association study (GWAS) findings across pre- and comorbid conditions of smoking are differentially associated with nicotine dependence and that when combined explain significantly more trait variance. These findings underscore the utility of multivariate approaches to understand the validity of polygenic scores for nicotine dependence, especially as the power of GWAS of broadly-defined smoking behaviors increases. Realizing the potential of GWAS to inform complex smoking behaviors will require similar theory-driven models that reflect the myriad of mechanisms that drive individual differences.