The Effect of Singular Nonverbal Behaviours of Experimenters on Pain Reports.

Introduction: Studies suggest facial expressions of caregivers may be important in placebo effects; however, this has not been systematically tested. This experiment investigated the effects of caregivers' singular positive nonverbal behaviours (NBs) on pain reports. Methods: Fifty-one males and 53 females (total of 104) participants were randomized to four groups that were displayed positive facial expressions, tone of voice, body movement, or neutral NBs of videotaped experimenters. Subjective reports of pain, stress, arousal, and cardiac activity were obtained in a pre-test, a conditioning phase, and at a post-test. Four minutes of heat pain was induced in each test, and a placebo cream was administered before the conditioning and post-test in all groups. Results: There were no differences between the NB groups in the reduced pain. Males had larger reduction in pain in the post-test, and females had lower arousal than the opposite sex. During the conditioning, females had larger reduction in pain ie, unconditioned pain response (UPR). In females, the UPR predicted the reinforced expectation ie, increase in expectations from conditioning to post-test, and fear of minor pain negatively predicted both the UPR and reinforced expectation. Discussion: Singular NBs of caregiver were weak to enhance placebo effects. Females had lower pain during conditioning, and the UPR amplitude in females was associated with positive expectations. Moreover, for females, fear of minor pain weakened the UPR and expectations of cream. Conclusion: No NB of caregivers is more effective in reducing pain. Caregivers' NBs are less effective when displayed individually. Males and females may be different in underlying mechanisms of placebo effects.

Systematic manipulation of experimenters' non-verbal behaviors for the investigation of pain reports and placebo effects.

Objective: Non-verbal behaviors (NBs) of caregivers affect pain reports and placebo effects. However, little experimental research has systematically examined the caregivers' NBs. This study protocol and preparatory study report a systematic manipulation of experimenters' NBs to investigate pain report and placebo effects. Methods: We propose an experiment in which videotaped experimenters (VEs) conduct a pain stimulation and a placebo treatment study. The VEs express one positively enhanced NB and keep the other NBs neutral. Participants will be randomized to either the positive facial expressions (+FE), tone of voice (+TV), body movement (+BM), or neutral NBs (i.e., neutral condition; NC) of the VEs. As a preparatory study for proof of concept, two groups of NB coders from Norway and the USA separately rated the degree of NBs (eye contact, body postures and movements, and tone of voice), and impressions of dominance and being in charge, positivity, and expressivity from each NB video. The NB videos had construct validity and reliability. The +BM and +FE were rated as more dominant and in charge than the +TV and the NC. The +FE and +BM were rated as the most positive and expressive NBs, respectively. Expected results: +FE will have the largest placebo effects on pain and stress levels. However, transmitting the NBs to patients by VEs is challenging. Moreover, controlling for the effects of research assistants present in the testing room is challenging. Discussion: We propose that caregivers' NBs affect pain reports and placebo effects. Moreover, different NBs elicit different impressions, and a better understanding of the role of caregiver NBs requires more rigorous investigations. Lastly, aiming to investigate the caregiver NBs, the varying degrees of micro-NBs and their effects on the formation of impressions should be considered.

A global meta-analysis of depression, anxiety, and stress before and during COVID-19.

OBJECTIVE: This meta-analysis compared negative emotions (NEs) as depression, anxiety, and stress, from before the pandemic to during the pandemic. METHOD: A total of 59 studies (19 before, 37 during-pandemic, and 3 that included both) using the Depression, Anxiety and Stress Scale (DASS) were included. A random effects model estimated the means of NEs before and during the pandemic. RESULTS: Studies from 47 countries involving 193,337 participants were included. Globally, NEs increased during the pandemic, and depression had the largest elevation. In Asia, depression and stress were elevated, whereas in Europe, only depression increased, and in America, no differences in NEs between before and during the pandemic were observed. The later time phase of the pandemic was associated with lower stress globally, and lower stress and anxiety in Europe. Being younger was associated with more stress globally, and being older was associated with higher anxiety in Asia. Students had higher anxiety globally, and higher NEs in all three aspects in Europe compared to the general population. The COVID-19 infection rate was associated with more stress globally, and stress and anxiety in Europe. During the pandemic, females reported higher levels of depression, anxiety, and stress compared to males, most pronounced in Europe. CONCLUSION: NEs increased during the pandemic, with younger and student populations, females and Asians having the highest elevations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Experiencing COVID-19 symptoms without the disease: The role of nocebo in reporting of symptoms.

BACKGROUND: A nocebo effect occurs when inactive factors lead to worsening of symptoms or reduce treatment outcomes. Believing that one is or has been infected with COVID-19 may act as a nocebo. However, not much is known about potential nocebo effects associated with the reporting of COVID-19 symptoms. AIM: An online survey investigated whether certainty of being infected with COVID-19, age, sex, cognitive, emotional and personality factors were associated with perceived severity of COVID-19 symptoms. METHODS: Participants (N=375) filled out an online survey containing 57 questions asking about symptoms resembling COVID-19, certainty of being infected with COVID-19, anxiety, stress and personality dimensions. RESULTS: Certainty of being infected with COVID-19 and anxiety predicted 27% of the variance in reporting of COVID-like symptoms. The mediation analysis showed that both higher certainty of being infected and anxiety independently predicted increased reports of COVID-like symptom. Females had higher anxiety and stress levels, and reported more COVID-like symptoms than males did. Older age was not associated with reporting COVID-like symptoms. CONCLUSIONS: Believing to be infected with COVID-19, along with anxiety, can enhance the severity of COVID-like symptoms. Thus, the nocebo effect was due to both cognitive and emotional factors and was higher in females.

Placebo Effects on Stress, but Not on Pain Reports. A Multi-Experiment Study.

BACKGROUND: Contextual factors, such as participant/experimenter sex may moderate the placebo effects. We tested whether the participant and experimenter sex modulated placebo effects on experimentally induced pain and associated stress. OBJECTIVE: To investigate if (i) participant sex and (ii) experimenter sex influence placebo analgesia and subjective and physiological stress in two experiments employing a within-subjects and a mixed design, respectively. Placebo effects were investigated in pain reports, stress, and blood pressure. METHODS: Participants received painful stimulations and a placebo cream. In Experiment One (N = 59) participants underwent a placebo condition (PC) and a natural history condition (NHC) in random order. A placebo cream was applied in the PC and then the heat stimulation temperature was surreptitiously lowered. Identical stimulations were administered in the NHC, but with no cream, no information, and no lowered temperature. In Experiment Two, participants (N = 93) were randomly assigned to three groups receiving either a placebo cream with surreptitiously lowered intensity of electric stimuli (Placebo, PG), a placebo cream (Cream-Control, CCG) without changing the stimuli, or lowered intensity, but with no cream (Pain-Control, PCG) in a mixed design. All participants in both experiments received the same stimuli in the post-test as in the pre-test. Four experimenters (two females) in Experiment One, and five experimenters (two females) in Experiment Two conducted the studies. RESULTS: No placebo effect was seen on pain. However, there were placebo effects on stress, moderated by participant and experimenter sex: in Experiment One males in the PC had lower diastolic blood pressure (DBP) compared to males in the NHC. Participants in the PC had lower DBP compared to the NHC when tested by a female. In Experiment Two, participants expected more cream effectiveness when a female experimenter administered it, and reported lower stress in the PG compared to the PCG when tested by females. CONCLUSION: Our findings highlight a distinction between placebo effects on pain and on associated stress. Secondly, female experimenters recorded lower physiological and subjective stress, higher effectiveness expectations, and lower pain from both sexes compared to male experimenters. Possible reasons for the failure to find a pain placebo effect are discussed.

What Psychological Factors Make Individuals Believe They Are Infected by Coronavirus 2019?

Background: We previously showed, by means of an online-based survey, that the belief of being infected by coronavirus disease 2019 (COVID-19) acted as a nocebo and predicted higher perception of symptoms similar to COVID-19 symptoms. However, there is little known about the psychological mechanisms that give rise to beliefs such as certainty of being infected by COVID-19, and this was investigated in the present study. Objective: Using the same data from the previous online survey with the same research team, we further investigated whether certainty of being infected by COVID-19 is associated with age, sex, health anxiety, and/or personality traits. Methods: Respondents (N = 375) filled out an online survey with 57 questions about symptoms similar to COVID-19, certainty of being infected by COVID-19, anxiety, stress, health anxiety, and personality dimensions (based on the five-factor model of personality). Results: Higher levels of conscientiousness and health anxiety were independently associated with certainty of being infected by COVID-19. The model predicted 29% of the variance in certainty of being infected by COVID-19. Conclusion: Being conscientious and worried about health issues were associated with the belief of being infected by COVID-19. Such finding may have implications for health care personnel who provide COVID-19 testing or consulting services to general population, as individuals high in these traits may over-report COVID-like symptoms. Theoretically, these findings point to psychological factors that may increase nocebo and possibly placebo effects. Clinically, the findings suggest that individuals high in conscientiousness and health anxiety may be more likely to over-report their bodily experiences.

Placebo Analgesia, Nocebo Hyperalgesia, and the Cardiovascular System: A Qualitative Systematic Review.

Background: Placebo/nocebo effects involve the autonomic nervous system, including cardiac activity, but studies have reported inconsistent findings on how cardiac activity is modulated following a placebo/nocebo effect. However, no systematic review has been conducted to provide a clear picture of cardiac placebo responses. Objective: The main goal of the present study is to review the effects of placebo analgesia and nocebo hyperalgesia on cardiac activity as measured by blood pressure, heart rate, and heart rate variability. Methods: Using several Boolean keyword combinations, the PubMed, EMBASE, PsycINFO, Cochrane Review Library, and ISI Web of Knowledge databases were searched until January 5, 2020, to find studies that analyzed blood pressure, heart rate, or heart rate variability indexes following a placebo analgesic/nocebo hyperalgesic effect. Results: Nineteen studies were found, with some reporting more than one index of cardiac activity; eight studies were on blood pressure, 14 studies on heart rate, and six on heart rate variability. No reliable association between placebo/nocebo effects and blood pressure or heart rate was found. However, placebo effects reduced, and nocebo effects increased low-frequency heart rate variability, and heart rate variability significantly predicted placebo effects in two studies. Conclusion: Placebo/nocebo effects can have reliable effects on heart rate variability, but not on heart rate and blood pressure.

European Headache Federation recommendations for placebo and nocebo terminology.

BACKGROUND AND AIM: Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. METHODS: The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented. RESULTS/RECOMMENDATIONS: Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term "placebo response" should be used, and for any unfavorable outcome recorded after placebo administration, the term "nocebo response" should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms "placebo" and "nocebo" ("placebos" and "nocebos" in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement). CONCLUSION: The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).

Reactive Heart Rate Variability and Cardiac Entropy in Children with Internalizing Disorder and Healthy Controls.

Atypical vagal reactivity has been linked to internalizing psychopathology and less adaptive emotion regulation, but reactive cardiac entropy is largely unexplored. Therefore, this study investigated reactive vagally-mediated heart-rate variability (vmHRV) and cardiac entropy in relation to emotion regulation. Electrocardiograms of 32 children (9-13 years) with internalizing difficulties and 25 healthy controls were recorded during a baseline and a sad film. Reactivity-measures were calculated from the root mean square of successive differences (RMSSD) and sample entropy (SampEn). Emotion regulation was assessed using the emotion regulation checklist (ERC). Determinants of reactive SampEn and RMSSD were analyzed with marginal and generalized linear models. The study also modeled the relationship between cardiac reactivity and emotion regulation while controlling for psychopathology. The two groups differed significantly in vmHRV-reactivity, with seemingly higher vagal-withdrawal in the control group. SampEn increased significantly during the film, but less in subjects with higher psychopathology. Higher reactive entropy was a significant predictor of better emotion regulation as measured by the ERC. Internalizing subjects and controls showed significantly different vmHRV-reactivity. Higher reactive cardiac entropy was associated with lower internalizing psychopathology and better emotion regulation and may reflect on organizational features of the neurovisceral system relevant for adaptive emotion regulation.

A Qualitative Systematic Review of Effects of Provider Characteristics and Nonverbal Behavior on Pain, and Placebo and Nocebo Effects.

Background: Previous research has indicated that the sex, status, and nonverbal behaviors of experimenters or clinicians can contribute to reported pain, and placebo and nocebo effects in patients or research participants. However, no systematic review has been published. Objective: The aim of this study was to investigate the effects of experimenter/clinician characteristics and nonverbal behavior on pain, placebo, and nocebo effects. Methods: Using EmBase, Web of Knowledge, and PubMed databases, several literature searches were conducted to find studies that investigated the effects of the experimenter's/clinician's sex, status, and nonverbal behaviors on pain, placebo, and nocebo effects. Results: Thirty-four studies were included, 20 on the effects of characteristics of the experimenter/clinician, 11 on the role of nonverbal behaviors, and 3 on the effects of both nonverbal behaviors and characteristics of experimenters/clinicians on pain and placebo/nocebo effects. There was a tendency for experimenters/clinicians to induce lower pain report in participants of the opposite sex. Furthermore, higher confidence, competence, and professionalism of experimenters/clinicians resulted in lower pain report and higher placebo effects, whereas lower status of experimenters/clinicians such as lower confidence, competence, and professionalism generated higher reported pain and lower placebo effects. Positive nonverbal behaviors (e.g., smiling, strong tone of voice, more eye contact, more leaning toward the patient/participant, and more body gestures) contributed to lower reported pain and higher placebo effects, whereas negative nonverbal behaviors (i.e., no smile, monotonous tone of voice, no eye contact, leaning backward from the participant/patient, and no body gestures) contributed to higher reported pain and nocebo effects. Conclusion: Characteristics and nonverbal behaviors of experimenters/clinicians contribute to the elicitation and modulation of pain, placebo, and nocebo effects.

Failure to Find a Conditioned Placebo Analgesic Response.

Background: Associative learning has, in several studies, been modulated by the sex of the participant. Consistent with this, a recent review found that conditioned nocebo effects are stronger in females than in males. Purpose: It has been suggested that conditioned placebo responses are stronger in females, and this hypothesis was investigated in the present study. Cortisol and measures of negative emotions were taken to investigate if these processes could mediate any conditioned placebo effects. Methods: Cold pain was applied to the volar forearm. The Conditioned group received inert capsules prior to two presentations of less painful stimulations, to associate intake of the capsules with reduced pain. The pain control group received the same painful stimulation as the Conditioned group, but no capsules. The Capsule control group received the capsules in the same way as the Conditioned group, but no decrease in the painful stimulation. Participant sex was crossed across groups. It was hypothesized that in the Conditioned group, an expectation of reduced pain should be induced after administration of the capsules, and this should generate placebo analgesia, and mostly so in females. Results: The Conditioned group reported lower pain during conditioning, and rated the capsules as more effective painkillers than the capsule control group. However, placebo analgesia was not reliably observed in the Conditioned group. Conclusion: The placebo capsules were rated as effective painkillers, but this did not translate into a placebo analgesic effect. This could be due to violation of response expectancies, too few conditioning trials, and differences in pain ratings in the pre-test that could be due to previous experience with painkillers.

Non-linear Heart Rate Variability as a Discriminator of Internalizing Psychopathology and Negative Affect in Children With Internalizing Problems and Healthy Controls.

Background: Internalizing psychopathology and dysregulated negative affect are characterized by dysregulation in the autonomic nervous system and reduced heart rate variability (HRV) due to increases in sympathetic activity alongside reduced vagal tone. The neurovisceral system is however, a complex nonlinear system, and nonlinear indices related to psychopathology are so far less studied in children. Essential nonlinear properties of a system can be found in two main domains: the informational domain and the invariant domain. sample entropy (SampEn) is a much-used method from the informational domain, while detrended fluctuation analysis (DFA) represents a widely-used method from the invariant domain. To see if nonlinear HRV can provide information beyond linear indices of autonomic activation, this study investigated SampEn and DFA as discriminators of internalizing psychopathology and negative affect alongside measures of vagally-mediated HRV and sympathetic activation. Material and Methods: Thirty-Two children with internalizing difficulties and 25 healthy controls (aged 9-13) were assessed with the Child Behavior Checklist and the Early Adolescent Temperament Questionnaire, Revised, giving an estimate of internalizing psychopathology, negative affect and effortful control, a protective factor against psychopathology. Five minute electrocardiogram and impedance cardiography recordings were collected during a resting baseline, giving estimates of SampEn, DFA short-term scaling exponent α1, root mean square of successive differences (RMSSD), and pre-ejection period (PEP). Between-group differences and correlations were assessed with parametric and non-parametric tests, and the relationships between cardiac variables, psychopathology and negative affect were assessed using generalized linear modeling. Results: SampEn and DFA were not significantly different between the groups. SampEn was weakly negatively related to heart rate (HR) in the controls, while DFA was moderately negatively related to RMSSD in both groups, and moderately positively related to HR in the clinical sample. SampEn was significantly associated with internalizing psychopathology and negative affect. DFA was significantly related to internalizing psychopathology. Conclusions: Higher invariant self-similarity was linked to less psychopathology. Higher informational entropy was related to less psychopathology and less negative affect, and may provide an index of the organizational flexibility of the neurovisceral system.

The Influence of Placebo Analgesia Manipulations on Pain Report, the Nociceptive Flexion Reflex, and Autonomic Responses to Pain.

Expectations for pain relief and experience/conditioning are psychological factors that contribute to placebo analgesia, yet few studies have studied the physiological mechanisms underlying their effects. This study randomized 133 participants to 4 groups: an expectation only (E-only) group, a conditioning only (C-only) group, an expectation plus conditioning (E+C) group, and a natural history (NH) control group. Painful electric stimulations were delivered before and after an inert cream was applied to the site of stimulation. Pain-related outcomes (pain ratings, nociceptive flexion reflex [NFR], skin conductance response, and heart rate acceleration) were recorded after each stimulation. NFR (a measure of spinal nociception) assessed if placebo analgesia inhibited spinal processing of pain. E+C was the only manipulation that significantly inhibited pain and skin conductance response. Surprisingly, NFR was facilitated in the E+C and E-only groups. No effects were noted for C-only. Mediation analysis suggested 2 descending processes were engaged during E+C that influenced spinal nociception: 1) descending facilitation and 2) descending inhibition that was also responsible for pain reduction. These results suggest that E+C manipulations produce the strongest analgesia and have a complex influence on spinal nociception involving both inhibitory and facilitatory processes. PERSPECTIVE: This study assessed whether placebo analgesia manipulations that include expectations, conditioning, or both modulate the NFR (measure of spinal nociception). Only the manipulation that involved expectations and conditioning inhibited pain, but both expectation manipulations facilitated NFR. This suggests a complex modulation of spinal neurons by placebo manipulations.

Influence of catechol-O-methyltransferase Val158Met on fear of pain and placebo analgesia.

Higher levels of fear have been shown to partly explain individual differences in placebo analgesic responding. The catechol-O-methyltransferase (COMT) rs4680 Val158Met polymorphism has been associated with both increased placebo analgesia and increased fear-related behavior, in what appears to be inconsistent findings in the literature. The aim of the study was therefore to investigate placebo analgesia and fear-related processes with regard to the COMT genotype, to sort out whether the Met-allele is associated with increased placebo analgesia or increased fear of pain (FOP). A 3 Group (Emla, placebo and natural history) by 5 Test (2 pretest, 3 posttests) mixed design was used (N = 223). A contact heat-evoked stimulator was used to induce pain, and FOP was quantified with the Fear of Pain Questionnaire-III. Saliva was obtained for genotyping. As expected, we observed a significant interaction of test by group (P < 0.01), with lower pain report in the placebo group compared with the natural history group (P < 0.01). There was a main effect of the COMT genotype on fear of medical pain (P = 0.032), and Met-allele carriers reported significantly higher fear of medical pain compared with the Val-allele (P = 0.044). We observed no effect of the COMT genotype on mean pain-level report or placebo analgesia. Thus, we conclude that the Met-allele seems to be associated with the negative emotional process of fear, but not with placebo analgesia.

Developing a model for measuring fear of pain in Norwegian samples: The Fear of Pain Questionnaire Norway.

BACKGROUND: Fear of pain is highly correlated with pain report and physiological measures of arousal when pain is inflicted. The Fear of Pain Questionnaire III (FPQ-III) and The Fear of Pain Questionnaire Short Form (FPQ-SF) are self-report inventories developed for assessment of fear of pain (FOP). A previous study assessed the fit of the FPQ-III and the FPQ-SF in a Norwegian non-clinical sample and proved poor fit of both models. This inspired the idea of testing the possibility of a Norwegian FOP-model. AIMS AND METHODS: A Norwegian FOP-model was examined by Exploratory Factor Analysis (EFA) in a sample of 1112 healthy volunteers. Then, the model fit of the FPQ-III, FPQ-SF and the Norwegian FOP-model (FPQ-NOR) were compared by Confirmatory Factor Analysis (CFA). Sex neutrality was explored by examining model fit, validity and reliability of the 3 models amongst male and female subgroups. RESULTS: The EFA suggested either a 4-, a 5- or a 6-factor Norwegian FOP model. The eigenvalue criterion supported the suggested 6-factor model, which also explained most of the variance and was most interpretable. A CFA confirmed that the 6-factor model was better than the two 4- and 5-factor models. Furthermore, the CFA used to test the fit of the FPQ-NOR, the FPQ-III and the FPQ-SF showed that the FPQ-NOR had the best fit of the 3 models, both in the whole sample and in sex sub-groups. CONCLUSION: A 6-factor model for explaining and measuring FOP in Norwegian samples was identified and termed the FPQ-NOR. This new model constituted six factors and 27 items, conceptualized as Minor, Severe, Injection, Fracture, Dental, and Cut Pain. The FPQ-NOR had the best fit overall and in male- and female subgroups, probably due to cross-cultural differences in FOP. IMPLICATIONS: This study highlights the importance on exploratory analysis of FOP-instruments when applied to different countries or cultures. As the FPQ-III is widely used in both research and clinical settings, it is important to ensure that the models construct validity is high. Country specific validation of FOP in both clinical and non-clinical samples is recommended.

The Fear of Pain Questionnaire-III and the Fear of Pain Questionnaire-Short Form: a confirmatory factor analysis.

BACKGROUND: The Fear of Pain Questionnaire-III (FPQ-III) is a widely used instrument to assess the fear of pain (FOP) in clinical and nonclinical samples. The FPQ-III has 30 items and is divided into three subscales: Severe Pain, Minor Pain and Medical Pain. Due to findings of poor fit of the original three-factor FPQ-III model, the Fear of Pain Questionnaire-Short Form (FPQ-SF) four-factor model has been suggested as an alternative. The FPQ-SF is a revised version of the FPQ-III, reduced to 20 items and subdivided into four subscales: Severe Pain, Minor Pain, Injection Pain and Dental Pain. AIMS AND METHODS: The purpose of the study was to investigate the model fit, reliability and validity of the FPQ-III and the FPQ-SF in a Norwegian nonclinical sample, using confirmatory factor analysis (CFA). The second aim was to explore the model fit of the two scales in male and female subgroups separately, since previous studies have uncovered differences in how well the questionnaires measure FOP across sex; thus, the questionnaires might not be sex neutral. It has been argued that the FPQ-SF model is better because of the higher fit to the data across sex. To explore model fit across sex within the questionnaires, the model fit, validity and reliability were compared across sex using CFA. RESULTS: The results revealed that both models' original factor structures had poor fit. However, the FPQ-SF had a better fit overall, compared to the FPQ-III. The model fit of the two models differed across sex, with better fit for males on the FPQ-III and for females on the FPQ-SF. CONCLUSION: The FPQ-SF is a better questionnaire than the FPQ-III for measurement of FOP in Norwegian samples and across sex subgroups. However, the FPQ-III is a better questionnaire for males than for females, whereas the FPQ-SF is a better questionnaire for females than for males. The findings are discussed and directions for future investigations outlined.

Cardiac complexity and emotional dysregulation in children.

OBJECTIVE: Sample entropy (SampEn) gives an estimate of signal complexity in cardiac time series and can give information beyond linear heart rate variability. Lower cardiac SampEn is associated with psychopathology in adults. Emotional dysregulation is widely present in adult psychopathology and a forerunner to later mental problems in children. Therefore, this study investigated whether SampEn relates to emotional dysregulation in children. METHODS: Participants were 32 children between 9 and 13years with internalizing difficulties and 25 controls. Parents filled out the "Emotional Problems" subscale in the Strengths and Difficulties questionnaire and the "Lability/Negativity" scale in the Emotion Regulation Checklist. SampEn, root mean square of successive differences (RMSSD), normalized power of high frequency (HFnu) components of the cardiac signal and pre-ejection period (PEP) were computed at rest. The study investigated the predictive power of SampEn, RMSSD and HFnu on the measures of emotional dysregulation. It also tested whether RMSSD or PEP were related to SampEn. RESULTS: SampEn was a significant predictor of both measures of emotional dysregulation, while RMSSD and HFnu were not. RMSSD and PEP were both significant predictors of SampEn. CONCLUSIONS: SampEn is a potential marker of dysregulation in the underlying neurovisceral processes vital for emotion regulation, and an important complementary measure to linear cardiac indices, explaining more of the variance in emotional dysregulation than RMSSD and HFnu in this study. Lower SampEn can also be linked to both higher vagal and sympathetic activation via RMSSD and PEP.

A systematic review of sex differences in the placebo and the nocebo effect.

OBJECTIVES: The present review investigated whether there are systematic sex differences in the placebo and the nocebo effect. METHODS: A literature search was conducted in multiple electronic databases. Studies were included if the study compared a group or condition where a placebo was administered to a natural history group or similar cohort. RESULTS: Eighteen studies were identified - 12 on placebo effects and 6 on nocebo effects. Chi-square tests revealed that 1) males responded more strongly to placebo treatment, and females responded more strongly to nocebo treatment, and 2) males responded with larger placebo effects induced by verbal information, and females responded with larger nocebo effects induced by conditioning procedures. CONCLUSION: This review indicates that there are sex differences in the placebo and nocebo effects, probably caused by sex differences in stress, anxiety, and the endogenous opioid system.

The Placebo Analgesic Effect in Healthy Individuals and Patients: A Meta-Analysis.

OBJECTIVE: The present meta-analysis investigates whether the magnitude of placebo analgesia is different in patients compared with healthy individuals and whether placebo analgesia is different in experimentally induced pain compared with clinical pain in patients. METHODS: A literature search in Web of Science (ISI) on the terms "placebo analgesia" and "placebo analgesic" was conducted. The search resulted in 71 studies, including 4239 participants. Fifty-five studies included healthy individuals and 16 studies included patients. Of the 16 studies with patients, five studies investigated clinical pain and 11 studies investigated experimentally induced pain. RESULTS: The average effect size was 1.24 for healthy individuals and 1.49 for patients. In the studies with patients, the average effect sizes of placebo treatment were 1.73 for experimentally induced pain and 1.05 for clinical pain. A χ test revealed that there were relatively more studies with patients compared with healthy volunteers in which there was a clinically significant reduction in pain (p = .040). CONCLUSIONS: The findings suggest that patients benefited from placebo treatment to a greater degree than healthy individuals did and that studies on healthy individuals may underestimate the magnitude of the placebo analgesic effect in patients. Patients' clinical pain and experimentally induced pain respond to placebo to the same degree.

Pain-related negative emotions and placebo analgesia.

Individuals undergoing treatment for a symptom like pain expect that the treatment will reduce the pain. Many studies show that healthy volunteers or patients in pain report less pain after inactive treatment, if they believe that active medication has been administrated. The reduction of pain can be partly blocked by systemic administration of naloxone, an opioid antagonist. There is reduced central nervous system activation to painful stimuli in individuals who have been given a placebo and told it is a painkiller. These findings suggest that the expectation of pain relief generates central nervous system opioid activity that inhibits pain transmission to the cerebral cortex. Expectations may thus lead to changes in central nervous system activity that reduces pain. It is proposed that expectations activate a homeostatic system that corrects perturbations to the system via negative feedback. The nocebo effect is the opposite of the placebo effect, and is due to induction of negative emotions. Part of the treatment of many symptoms and diseases is due to autonomic adjustments controlled by the central nervous system. The involvement of emotional processes in placebo effects could have important consequences for interpretation of data from randomized controlled trials.