Introduction: Many drug trials for chronic pain fail because of high placebo response rates in primary endpoints. Neurophysiological measures can help identify pain-linked pathophysiology and treatment mechanisms. They can also help guide early stop/go decisions, particularly if they respond to verum treatment but not placebo. The neurologic pain signature (NPS), an fMRI-based measure that tracks evoked pain in 40 published samples and is insensitive to placebo in healthy adults, provides a potentially useful neurophysiological measure linked to nociceptive pain. Objectives: This study aims to validate the NPS in knee osteoarthritis (OA) patients and test the effects of naproxen on this signature. Methods: In 2 studies (50 patients, 64.6 years, 75% females), we (1) test the NPS and other control signatures related to negative emotion in knee OA pain patients; (2) test the effect of placebo treatments; and (3) test the effect of naproxen, a routinely prescribed nonsteroidal anti-inflammatory drug in OA. Results: The NPS was activated during knee pain in OA (d = 1.51, P < 0.001) and did not respond to placebo (d = 0.12, P = 0.23). A single dose of naproxen reduced NPS responses (vs placebo, NPS d = 0.34, P = 0.03 and pronociceptive NPS component d = 0.38, P = 0.02). Naproxen effects were specific for the NPS and did not appear in other control signatures. Conclusion: This study provides preliminary evidence that fMRI-based measures, validated for nociceptive pain, respond to acute OA pain, do not appear sensitive to placebo, and are mild-to-moderately sensitive to naproxen.

We compared body composition, biochemical parameters, motor function, and brain neural activation in 27 adults with Prader–Willi syndrome and growth-hormone deficiency versus age-and sex-matched controls and baseline versus posttreatment values of these parameters after one year of recombinant human growth hormone (rhGH) treatment. To study body composition, we analyzed percentage of fat mass, percentage of lean mass, and muscle-mass surrogate variables from dual X-ray absorptiometry. Biochemical parameters analyzed included IGF-I, glucose metabolism, and myokines (myostatin, irisin, and IL6). To explore muscle function, we used dynamometer-measured handgrip strength, the Timed Up and Go (TUG) test, and the Berg Balance Scale (BBS). To study brain activation, we acquired functional magnetic resonance images during three motor tasks of varying complexity. After one year of treatment, we observed an increase in lean mass and its surrogates, a decrease in fat mass, improvements in TUG test and BBS scores, and increased neural activation in certain cerebellar areas. The treatment did not significantly worsen glucose metabolism, and no side-effects were reported. Our findings support the benefits of rhGH treatment in adults with Prader–Willi syndrome and growth-hormone deficiency on body composition and suggest that it may also improve balance and brain neural activation.

Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination.

Background: Despite a large body of schizophrenia research, we still have no reliable predictors to guide treatment from illness onset. The present study aimed to identify baseline clinical or neurobiological factors — including peripheral brain-derived neurotrophic factor (BDNF) levels and amygdala or hippocampal relative volumes — that could predict negative symptomatology and persistent negative symptoms in first-episode psychosis after 1 year of follow-up. Methods: We recruited 50 drug-naive patients with first-episode psychosis and 50 age- and sex-matched healthy controls to study brain volumes. We performed univariate and multiple and logistic regression analyses to determine the association between baseline clinical and neurobiological variables, score on the PANSS negative subscale and persistent negative symptoms after 1 year of follow-up. Results: Low baseline serum BDNF levels (p = 0.011), decreased left amygdala relative volume (p = 0.001) and more severe negative symptomatology (p = 0.021) predicted the severity of negative symptoms at 1 year, as measured by the PANSS negative subscale. Low baseline serum BDNF levels (p = 0.012) and decreased left amygdala relative volume (p = 0.010) predicted persistent negative symptoms at 1 year. Limitations: We were unable to assess negative symptoms and their dimensions with next-generation scales, which were not available when the study was initiated. Conclusion: This study shows that a set of variables at baseline, including low BDNF levels, smaller left amygdala relative volume and score on the PANSS negative subscale are significant predictors of outcomes in first-episode psychosis. These findings might offer an initial step for tailoring treatments in first-episode psychosis.

Hyperphagia is one of the main problems of patients with Prader-Willi syndrome (PWS) to cope with everyday life. The underlying mechanisms are not yet well understood. Gut-brain hormones are an interrelated network that may be at least partially involved. We aimed to study the hormonal profile of PWS patients in comparison with obese and healthy controls. Thirty adult PWS patients (15 men; age 27.5 ± 8.02 years; BMI 32.4 ± 8.14 kg/m²), 30 obese and 30 healthy controls were studied before and after eating a hypercaloric liquid diet. Plasma brain-derived neurotrophic factor (BDNF), leptin, total and active ghrelin, peptide YY (PYY), pancreatic polypeptide (PP), Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and amylin were determined at times 0′, 30′, 60′ and 120′. Cluster analysis was used. When considering all peptides together, two clusters were established according to fasting hormonal standardized concentrations. Cluster 1 encompassed most of obese (25/30) and healthy controls (28/30). By contrast, the majority of patients with PWS were located in Cluster 2 (23/27) and presented a similar fasting profile with hyperghrelinemia, high levels of leptin, PYY, GIP and GLP-1, compared to Cluster 1; that may reflect a dysfunction of these hunger/satiety hormones. When peptide behavior over the time was considered, PP concentrations were not sustained postprandially from 60 min onwards in Cluster 2. BDNF and amylin did not help to differentiate the two clusters. Thus, cluster analysis could be a good tool to distinguish and characterize the differences in hormone responses between PWS and obese or healthy controls.