Psychopathological profile before and after bariatric surgery.

Presurgical psychopathological assessment usually focuses on detecting severe mental disorders. However, mild intensity psychopathology and eating behaviour pattern may also influence postsurgical outcomes. The aim was to identify psychopathology and eating behaviour pattern in candidates prepared for bariatric surgery compared to a normative population before and after surgery. A cohort of 32 patients seeking bariatric surgery in a university hospital between March 2016 and March 2017 were evaluated with Personality Assessment Inventory (PAI), 36-item EDE-Q and BES before and after surgery. Thirty-two patients before and 26 one year after surgery were included. The PAI presurgical psychometric profile suggested a mild mixed adjustment disorder focused on somatic complaints. After surgery, patients improved in somatic complaints (p < 0.001), and depression (p = 0.04). Related eating disorders were more common than those of the normative group and improved significantly after surgery in scores for compulsive intake (BES p < 0.001) and overall key behaviours of eating disorders and related cognitive symptoms (EDE-Q/G p < 0.001). In our cohort ready for bariatric surgery a mild psychopathological profile is still present and becomes closer to that of the normative group after surgery. Further studies are needed to evaluate the effects of mild psychopathology on outcomes after bariatric surgery.

Central Sensitization and Chronic Pain Personality Profile: Is There New Evidence? A Case-Control Study.

BACKGROUND: Personality traits are relevant for pain perception in persistent pain disorders, although they have not been studied in depth in sensitized and nonsensitized patients with knee osteoarthritis (OA). OBJECTIVE: To explain and compare the personality profile of patients with OA, with and without central sensitization (CS), and fibromyalgia (FM). SETTING: Participants were selected at the Rheumatology Department in two major hospitals in Spain. PARTICIPANTS: Case-control study where the sample consists of 15 patients with OA and CS (OA-CS), 31 OA without CS (OA-noCS), 47 FM, and 22 controls. We used a rigorous and systematic process that ensured the sample strictly fulfilled all the inclusion/exclusion criteria, so the sample is very well delimited. PRIMARY OUTCOME MEASURES: Personality was assessed by the Temperament and Character Inventory of Cloninger. RESULTS: The percentile in harm-avoidance dimension for the FM group is higher compared to OA groups and controls. The most frequent temperamental profiles in patients are cautious, methodical, and explosive. Patients with FM are more likely to report larger scores in harm-avoidance, with an increase in logistic regression adjusted odds ratio (ORadj) between 4.2% and 70.2%. CONCLUSIONS: Harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.

Distinctive alterations in the functional anatomy of the cerebral cortex in pain-sensitized osteoarthritis and fibromyalgia patients.

BACKGROUND: Pain-sensitized osteoarthritis and fibromyalgia patients characteristically show nociceptive system augmented responsiveness as a common feature. However, sensitization can be originally related to the peripheral injury in osteoarthritis patients, whereas pain and bodily discomfort spontaneously occur in fibromyalgia with no apparent origin. We investigated the distinct functional repercussion of pain sensitization in the cerebral cortex in both conditions. METHODS: Thirty-one pain-sensitized knee osteoarthritis patients and 38 fibromyalgia patients were compared with matched control groups. And new samples of 34 sensitized knee osteoarthritis and 63 fibromyalgia patients were used to directly compare each condition. A combined measure of local functional connectivity was estimated to map functional alterations in the cerebral cortex at rest. RESULTS: In osteoarthritis, weaker local connectivity was identified in the insula, which is a cortical area processing important aspects of the brain response to painful stimulation. In contrast, fibromyalgia patients showed weaker connectivity in the sensorimotor cortex extensively affecting the cortical representation of the body. CONCLUSIONS: In osteoarthritis, weaker insular cortex connectivity is compatible with reduced neural activity during metabolic recovery after repeated activation. In the fibromyalgia neurophysiological context, weaker connectivity may better express both reduced neural activity and increased excitability, particularly affecting the sensorimotor cortex in patients with spontaneous body pain. Such a combination is compatible with a central gain enhancement mechanism, where low sensory tolerance results from the over-amplification of central sensory reception to compensate a presumably weak sensory input. We propose that deficient proprioception could be a factor contributing to weak sensory input.

Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?

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.

Central sensitization in knee osteoarthritis and fibromyalgia: Beyond depression and anxiety.

OBJECTIVES: To determine the psychopathological profile of patients with central sensitization (CS) in a sample of knee osteoarthritis, with and without CS, and fibromyalgia, and to compare their psychopathological profiles. METHODS: The final sample consists of 19 patients with osteoarthritis and CS (mean 66.37 years ± 8.77), 41 osteoarthritis patients without CS (mean 66.8 ± 7.39 years), 47 fibromyalgia patients (mean 46.47 years ± 7.92) and 26 control subjects (mean 51.56 years ± 11.41). The psychopathological profile was evaluated with the Millon Multiaxial Clinical Inventory. RESULTS: The average score of MCMI-III reflect higher scores in the fibromyalgia and osteoarthritis-CS groups. Patients with osteoarthritis-CS are more likely to report larger scores in Borderline and Major Depression scales. Fibromyalgia patients are more likely to report more increased scores in Somatoform and Major Depression, versus osteoarthritis-CS group. Fibromyalgia patients versus osteoarthritis without CS are more likely to report higher scores in Schizoid, Depression, Histrionic, Sadistic, Borderline, Somatoform, Posttraumatic Stress Disorder and Major Depression scales. DISCUSSION: Patients with CS have less differences in their psychopathological profiles as well as in both osteoarthritis groups and greatest differences are obtained between the fibromyalgia and osteoarthritis without CS, so perhaps presence of CS is the key to differentiate those groups and not chronic pain. An exhaustive assessment brings more accurate psychopathological profiles, thus better psychological treatment could be applied.

Depression and Apathy After Transient Ischemic Attack or Minor Stroke: Prevalence, Evolution and Predictors.

Few previous studies have focused on affective impairment after transient ischemic attack (TIA) and/or minor stroke. The aim was to establish the prevalence, evolution and predictors of post-stroke depression (PSD) and post-stroke apathy (PSA) over a 12-month follow-up period. We prospectively included TIA and minor stroke patients (NIHSS ≤4) who had undergone magnetic resonance imaging <7 days. PSD was diagnosed according to DSM-5 criteria and PSA was defined based on an Apathy Evaluation Scale (AES-C) score of ≥37. Clinical and neuroimaging variables (presence and patterns of lesion, cerebral bleeds and white matter disease) were analysed in order to find potential predictors for PSD and PSA. Follow-up was performed at 10 days and after 2, 6, 9 and 12 months. 82 patients were included (mean 66.4 [standard deviation11.0] years) of whom 70 completed the follow-up. At 10 days, 36 (43.9%) and 28 (34.1%) patients respectively were diagnosed with PSD and PSA. At 12 months, 25 of 70 (35.7%) patients still had PSA, but only 6 of 70 (8.6%) had PSD. Beck Depression Inventory-II score, mini mental state examination (MMSE) and a previous history of depression or anxiety were predictors for PSD. While MMSE score, The Montgomery Asberg Depression Rating Scale and having previously suffered a stroke were also risk factors for PSA. Acute basal ganglia lesion and periventricular leukoaraiosis were associated with PSA while deep leukorariosis with PSD. Despite the presence of few or only transient symptoms, PSD and PSA frequent appear early after TIA and minor stroke. Unlike PSD, apathy tends to persist during follow-up.

Testing the effects of gentle vibrotactile stimulation on symptom relief in fibromyalgia.

BACKGROUND: Sensory disturbances in fibromyalgia extend beyond nociception. It has been proposed that imbalance in the mutual competition between painful input and non-painful sensory activity may, to a significant extent, account for the augmented subjective perception of pain. In this context, non-nociceptive somatosensory stimulation could arguably attenuate fibromyalgia symptoms by restoring the sensory balance. We specifically tested the effect of vibrotactile stimulation on symptom relief in fibromyalgia patients with a randomized, double-blind, sham-controlled, crossover clinical trial. METHODS: Seventy-seven female patients were randomized and data from 63 valid cases were analyzed. Active intervention involved extensive body stimulation with gentle mechanical vibrations administered during 3 h at night for 3 weeks, and the placebo effect was controlled using identical instruments to simulate an alternative treatment option. The primary outcome measure combined pain, fatigue, and complaints of poor cognition. RESULTS: Vibrotactile stimulation was significantly superior to sham in alleviating fibromyalgia symptoms globally. However, univariate analyses showed that the effect was not universal. Benefits were perceived on unpleasant somatic sensations such as generalized pain and fatigue, but not on poor cognition, anxiety, and depression. Vibrotactile stimulation was notably well tolerated and sleep quality significantly improved despite the fact that vibrations were administered at night. CONCLUSIONS: Results thus provide new evidence that non-nociceptive somatosensory stimulation may favorably act upon altered somatosensory balance in fibromyalgia. From a clinical perspective, both the degree of improvement and the easy application of our proposal would seem to support a potential role for vibrotactile stimulation in the symptomatic treatment of fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT03227952 . Registered 24 July, 2017.

Brain imaging of pain sensitization in patients with knee osteoarthritis.

A relevant aspect in osteoarthritic pain is neural sensitization. This phenomenon involves augmented responsiveness to painful stimulation and may entail a clinically worse prognosis. We used functional magnetic resonance imaging (fMRI) to study pain sensitization in patients with knee osteoarthritis. Sixty patients were recruited and pain sensitization was clinically defined on the basis of regional spreading of pain (spreading sensitization) and increased pain response to repeated stimulation (temporal summation). Functional magnetic resonance imaging testing involved assessing brain responses to both pressure and heat stimulation. Thirty-three patients (55%) showed regional pain spreading (simple sensitization) and 19 patients (32%) showed both regional spreading and temporal summation. Sensitized patients were more commonly women. Direct painful pressure stimulation of the joint (articular interline) robustly activated all of the neural elements typically involved in pain perception, but did not differentiate sensitized and nonsensitized patients. Painful pressure stimulation on the anterior tibial surface (sensitized site) evoked greater activation in sensitized patients in regions typically involved in pain and also beyond these regions, extending to the auditory, visual, and ventral sensorimotor cortices. Painful heat stimulation of the volar forearm did not discriminate the sensitization phenomenon. Results confirm the high prevalence of pain sensitization secondary to knee osteoarthritis. Relevantly, the sensitization phenomenon was associated with neural changes extending beyond strict pain-processing regions with enhancement of activity in general sensory, nonnociceptive brain areas. This effect is in contrast to the changes previously identified in primary pain sensitization in fibromyalgia patients presenting with a weakening of the general sensory integration.

Vulnerability to Psychopathology and Dimensions of Personality in Patients With Fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) patients may present psychopathology and some characteristic personality traits that may affect their adaptation to the disease. The aim of this paper was to study the relationship between personality dimensions according to the psychobiological model of Cloninger and the presence of psychopathology. MATERIALS AND METHODS: The study sample consisted of 42 patients with FM and 38 pain-free controls. The assessment instruments administered were the Temperament and Character Inventory-Revised and the Millon Clinical Multiaxial Inventory. RESULTS: A higher proportion of clinical psychopathologic syndromes (CPS) was observed in the FM group than in the control group, the most prevalent being anxiety disorder and dysthymia. Patients with FM (with CPS or without CPS) presented higher Harm Avoidance than the control group, and the presence of a CPS also increased Harm Avoidance scores. FM patients with CPS had low Self-directedness (SD) compared with both the control group and with their FM peers without CPS. Purposefulness and Anticipatory worry-Pessimism explained 38% of the variance of dysthymia, and anticipatory worry-Pessimism explained 18% of the variance of anxiety disorders. CONCLUSIONS: Patients with FM have a high probability of anxious-depressive-type psychopathologic alterations. Their vulnerability to these conditions may be determined by personality traits. The SD character dimension may have implications for therapy, as low SD is associated with the presence of psychopathology and with a low capacity to cope with the disease.

Towards a neurophysiological signature for fibromyalgia.

Patients with fibromyalgia (FM) show characteristically enhanced unpleasantness to painful and nonpainful sensations accompanied by altered neural responses. The diagnostic potential of such neural alterations, including their sensitivity and specificity to FM (vs healthy controls) is unknown. We identify a brain signature that characterizes FM central pathophysiology at the neural systems level. We included 37 patients with FM and 35 matched healthy controls, and analyzed functional magnetic resonance imaging responses to (1) painful pressure and (2) nonpainful multisensory (visual-auditory-tactile) stimulation. We used machine-learning techniques to identify a brain-based FM signature. When exposed to the same painful stimuli, patients with FM showed greater neurologic pain signature (NPS; Wager et al., 2013. An fMRI-based neurologic signature of physical pain. N Engl J Med 2013;368:1388-97) responses. In addition, a new pain-related classifier ("FM-pain") revealed augmented responses in sensory integration (insula/operculum) and self-referential (eg, medial prefrontal) regions in FM and reduced responses in the lateral frontal cortex. A "multisensory" classifier trained on nonpainful sensory stimulation revealed augmented responses in the insula/operculum, posterior cingulate, and medial prefrontal regions and reduced responses in the primary/secondary sensory cortices, basal ganglia, and cerebellum. Combined activity in the NPS, FM pain, and multisensory patterns classified patients vs controls with 92% sensitivity and 94% specificity in out-of-sample individuals. Enhanced NPS responses partly mediated mechanical hypersensitivity and correlated with depression and disability (Puncorrected < 0.05); FM-pain and multisensory responses correlated with clinical pain (Puncorrected < 0.05). The study provides initial characterization of individual patients with FM based on pathophysiological, symptom-related brain features. If replicated, these brain features may constitute objective neural targets for therapeutic interventions. The results establish a framework for assessing therapeutic mechanisms and predicting treatment response at the individual level.

Cloninger's psychobiological model of personality and psychological distress in fibromyalgia.

AIM: Personality can play an important role in the clinical symptoms of fibromyalgia (FM). The aim of this study is to identify personality profiles in FM patients and the possible presence of personality disorder (PD) from the Temperament and Character Inventory-Revised (TCI-R), and to assess whether personality dimensions are related to psychological distress in FM. METHOD: The sample consisted of 42 patients with FM and 38 healthy controls. The TCI-R, Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Short-Form-36 Health Survey, Fibromyalgia Impact Questionnaire and McGill Pain Questionnaire were administered. RESULTS: The personality profile of the FM group based on the TCI-R is defined by high Harm Avoidance (HA), low Novelty Seeking (NS), and low Self-Directedness (SD). Only one-third of patients with FM present a possible psychometric PD, principally from Cluster C. In the FM group, HA and SD are associated positively and negatively, respectively, with indicators of emotional distress. Patients with higher HA present higher perceived pain intensity rated via a verbal-numerical scale while Determination (SD2) reduced the perceived level of pain induced by the stimulus. NS is negatively related to the number of work absences caused by FM. CONCLUSIONS: The study suggests that HA and SD play an important role in psychological distress in FM. The fact that SD is prone to modification and has a regulatory effect on emotional impulses is a key aspect to consider from the psychotherapeutic point of view.

Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients.

OBJECTIVE: Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non-nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non-nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity. METHODS: Functional magnetic resonance imaging (MRI) was used to assess brain response to auditory, visual, and tactile motor stimulation in 35 women with FM and 25 matched controls. Correlation and mediation analyses were performed to establish the relationship between brain responses and 3 types of outcomes: subjective hypersensitivity to daily sensory stimulation, spontaneous pain, and functional disability. RESULTS: Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. Functional MRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hypersensitivity and clinical severity measures. CONCLUSION: FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core FM symptoms, suggesting that they may be part of the pathophysiology of the disease.

The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia.

Fibromyalgia typically presents with spontaneous body pain with no apparent cause and is considered pathophysiologically to be a functional disorder of somatosensory processing. We have investigated potential associations between the degree of self-reported clinical pain and resting-state brain functional connectivity at different levels of putative somatosensory integration. Resting-state functional magnetic resonance imaging was obtained in 40 women with fibromyalgia and 36 control subjects. A combination of functional connectivity-based measurements were used to assess (1) the basic pain signal modulation system at the level of the periaqueductal gray (PAG); (2) the sensory cortex with an emphasis on the parietal operculum/secondary somatosensory cortex (SII); and (3) the connectivity of these regions with the self-referential "default mode" network. Compared with control subjects, a reduction of functional connectivity was identified across the 3 levels of neural processing, each showing a significant and complementary correlation with the degree of clinical pain. Specifically, self-reported pain in fibromyalgia patients correlated with (1) reduced connectivity between PAG and anterior insula; (2) reduced connectivity between SII and primary somatosensory, visual, and auditory cortices; and (3) increased connectivity between SII and the default mode network. The results confirm previous research demonstrating abnormal functional connectivity in fibromyalgia and show that alterations at different levels of sensory processing may contribute to account for clinical pain. Importantly, reduced functional connectivity extended beyond the somatosensory domain and implicated visual and auditory sensory modalities. Overall, this study suggests that a general weakening of sensory integration underlies clinical pain in fibromyalgia.

Mapping brain response to pain in fibromyalgia patients using temporal analysis of FMRI.

BACKGROUND: Nociceptive stimuli may evoke brain responses longer than the stimulus duration often partially detected by conventional neuroimaging. Fibromyalgia patients typically complain of severe pain from gentle stimuli. We aimed to characterize brain response to painful pressure in fibromyalgia patients by generating activation maps adjusted for the duration of brain responses. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-seven women (mean age: 47.8 years) were assessed with fMRI. The sample included nine fibromyalgia patients and nine healthy subjects who received 4 kg/cm(2) of pressure on the thumb. Nine additional control subjects received 6.8 kg/cm(2) to match the patients for the severity of perceived pain. Independent Component Analysis characterized the temporal dynamics of the actual brain response to pressure. Statistical parametric maps were estimated using the obtained time courses. Brain response to pressure (18 seconds) consistently exceeded the stimulus application (9 seconds) in somatosensory regions in all groups. fMRI maps following such temporal dynamics showed a complete pain network response (sensory-motor cortices, operculo-insula, cingulate cortex, and basal ganglia) to 4 kg/cm(2) of pressure in fibromyalgia patients. In healthy subjects, response to this low intensity pressure involved mainly somatosensory cortices. When matched for perceived pain (6.8 kg/cm(2)), control subjects showed also comprehensive activation of pain-related regions, but fibromyalgia patients showed significantly larger activation in the anterior insula-basal ganglia complex and the cingulate cortex. CONCLUSIONS/SIGNIFICANCE: The results suggest that data-driven fMRI assessments may complement conventional neuroimaging for characterizing pain responses and that enhancement of brain activation in fibromyalgia patients may be particularly relevant in emotion-related regions.

[Can we see pain?]. / ¿Se puede ver el dolor?

Pain is a highly subjective experience that is difficult to measure objectively due to its varied expression. It is defined as a complex sensory-emotional experience, it is modulated by cognitive factors and involves a broad neural system. Functional neuroimaging has helped to define that neural circuit involved in the perception, modulation and response to painful experience, both in healthy controls and in patients with acute and chronic pain disorders. However, functional activation of the so-called "pain matrix" may also be differentially modulated by sensory and emotional processing components. The latter, for example, can influence the intensity to which a stimulus is perceived as painful. Such a threshold seems to be lower in patients with clinical diagnosis of fibromyalgia (FM) and has been linked to an abnormal pattern of activation of the "pain matrix" when assessed with functional magnetic resonance imaging (fMRI), considering a "syndrome of central susceptibility". Supporting an aetiological explanation for FM, studies have noted that a significant proportion of patients with FM demonstrate this abnormal pattern of activation to stimuli of low intensity. Additionally, there is an important and significant temporal dimension to this activation pattern observed in FM patients, where areas commonly associated with the emotional experience of pain show a prolonged response to painful stimuli compared to healthy subjects. Accordingly, fMRI may assist in objectifying the experience of pain in patients with FM in response to nociceptive stimulation.

Identification of the sensorimotor cortex with functional MRI: frequency and actual contribution in a neurosurgical context.

BACKGROUND AND PURPOSE: We assessed the actual frequency of motor functional MRI (fMRI) in a neurosurgical environment and estimated the extent to which it aided surgeons' identifications of the sensorimotor cortex. METHODS: During five consecutive years, an fMRI protocol aimed at generating a selective activation of the hand cortical area was prescribed to 147 patients showing a centrally located space-occupying lesion, which represents 6.7% of all assisted surgical candidates showing an intracranial mass. Three senior neurosurgeons indicated the position of the sensorimotor cortex on two different anatomical displays, reporting confidence ratings for each decision. RESULTS: The sensorimotor cortex could not be identified in 16.5% of cases using conventional anatomical MRI, and in 15% of cases using 3-dimensional reconstructions. In an additional 12.5% of cases, the neurosurgeons were not confident when they correctly identified the sensorimotor cortex. The tumor distorting effect on central region anatomy significantly contributed to sensorimotor cortex misidentification. fMRI, by contrast, showed a selective activation indicating the position of the sensorimotor cortex in all but 4% of cases. CONCLUSIONS: In our neurosurgical environment, fMRI was prescribed to a selected group of surgical candidates showing a centrally located brain lesion. Compared to conventional anatomical imaging, fMRI does appear to improve the identification of sensorimotor cortex.