Dyspnea-related cues engage the prefrontal cortex - evidence from functional brain imaging in COPD

Dyspnea is the major source of disability in chronic obstructive pulmonary disease (COPD). In COPD, environmental cues (e.g. the prospect of having to climb stairs) become associated with dyspnea, and may trigger dyspnea even before physical activity commences. We hypothesised that brain activation relating to such cues would be different between COPD patients and healthy controls, reflecting greater engagement of emotional mechanisms in patients. Methods: Using FMRI, we investigated brain responses to dyspnea-related word cues in 41 COPD patients and 40 healthy age-matched controls. We combined these findings with scores of self-report questionnaires thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enables identification of brain networks responsible for pain processing despite absence of a physical challenge. Results: COPD patients demonstrate activation in the medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) which correlated with the visual analogue scale (VAS) response to word cues. This activity independently correlated with patient-reported questionnaires of depression, fatigue and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex (lPFC) and precuneus correlated with the VAS dyspnea scale but not the questionnaires. Conclusions: Our findings suggest that engagement of the brain's emotional circuitry is important for interpretation of dyspnea-related cues in COPD, and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and our findings suggest such mechanisms may be relevant in COPD.

Frequency of infant stroking reported by mothers moderates the effect of prenatal depression on infant behavioural and physiological outcomes

Animal studies find that prenatal stress is associated with increased physiological and emotional reactivity later in life, mediated via fetal programming of the HPA axis through decreased glucocorticoid receptor (GR) gene expression. Post-natal behaviours, notably licking and grooming in rats, cause decreased behavioural indices of fear and reduced HPA axis reactivity mediated via increased GR gene expression. Post-natal maternal behaviours may therefore be expected to modify prenatal effects, but this has not previously been examined in humans. We examined whether, according to self-report, maternal stroking over the first weeks of life modified associations between prenatal depression and physiological and behavioral outcomes in infancy, hence mimicking effects of rodent licking and grooming. From a general population sample of 1233 first time mothers recruited at 20 weeks gestation we drew a stratified random sample of 316 for assessment at 32 weeks based on reported inter-partner psychological abuse, a risk to child development. Of these 271 provided data at 5, 9 and 29 weeks post delivery. Mothers reported how often they stroked their babies at 5 and 9 weeks. At 29 weeks vagal withdrawal to a stressor, a measure of physiological adaptability, and maternal reported negative emotionality were assessed. There was a significant interaction between prenatal depression and maternal stroking in the prediction of vagal reactivity to a stressor (p = .01), and maternal reports of infant anger proneness (p = .007) and fear (p = .043). Increasing maternal depression was associated with decreasing physiological adaptability, and with increasing negative emotionality, only in the presence of low maternal stroking. These initial findings in humans indicate that maternal stroking in infancy, as reported by mothers, has effects strongly resembling the effects of observed maternal behaviours in animals, pointing to future studies of the epigenetic, physiological and behavioral effects of maternal stroking.

Evidence for sex differences in fetal programming of physiological stress reactivity in infancy

Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.

The accuracy of HADS and GHQ-12 in detecting psychiatric morbidity in breast cancer patients

Objective: Psychological problems should be identified in breast cancer patients proactively if doctors and nurses are to help them cope with the challenges imposed by their illness. Screening is one possible way to identify emotional problems proactively. Self-report questionnaires can be useful alternatives to carrying out psychiatric interviews during screening, because interviewing a large number of patients can be impractical due to limited resources. Two such measures are the Hospital Anxiety and Depression Scale (HADS) and the General Health Questionnaire-12 (GHQ-12). Method: The present study aimed to compare the performance of the GHQ-12, and the HADS Unitary Scale and its subscales to that of the Schedule for Affective Disorders and Schizophrenia (SADS) in identifying patients with affective disorders, including DSM major depression and generalized anxiety disorder. The sample consisted of 296 female breast cancer patients who underwent surgery for breast cancer a year previously. Results: A small number of patients (11%) were identified as having DSM major depression or generalized anxiety disorder based on SADS score. The findings indicate that the optimal thresholds in detecting generalized anxiety disorder and DSM major depression with the HADS anxiety and depression subscales were ≥ 8 and ≥ 7, with 93.3% and 77.3% sensitivity, respectively, and 77.9% and 87.1% specificity, respectively. They also had a 21% and 36% positive predictive value, respectively. Using the HADS Unitary Scale the optimal threshold for detecting affective disorders was ≥ 12, with 88.9% sensitivity, 80.7% specificity, and a 35% positive predictive value. In detecting affective disorders, the optimal threshold on the GHQ-12 was ≥ 2, with 77.8% sensitivity and 70.2% specificity. This scale also had a 24% positive predictive value. In detecting generalized anxiety disorder and DSM major depression, the optimal thresholds on the GHQ-12 were ≥ 2 and ≥ 4 with 73.3% and 77.3% sensitivity, respectively, and 67.5% and 82% specificity, respectively. The scale also had 12% and 29% positive predictive values, respectively. Conclusion: The HADS Unitary Scale and its subscales were effective in identifying affective disorders. They can be used as screening measures in breast cancer patients. The GHQ-12 was less accurate in detecting affective disorders than the HADS, but it can also be used as a screening instrument to detect affective disorders, generalized anxiety disorder, and DSM major depression.

Sexual abuse in childhood and postoperative depression in women with breast cancer who opt for immediate reconstruction after mastectomy

INTRODUCTION Breast reconstruction is routinely offered to women who undergo mastectomy for breast cancer. However, patient-reported outcomes are mixed. Child abuse has enduring effects on adults’ well-being and body image. As part of a study into damaging effects of abuse on adjustment to breast cancer, we examined: (i) whether women with history of abuse would be more likely than other women to opt for reconstruction; and (ii) whether mood problems in women opting for reconstruction can be explained by greater prevalence of abuse. PATIENTS AND METHODS We recruited 355 women within 2-4 days after surgery for primary breast cancer; 104 had mastectomy alone and 29 opted for reconstruction. Using standardised questionnaires, women self-reported emotional distress and recollections of childhood sexual abuse. Self-report of distress was repeated 12 months later. RESULTS Women who had reconstruction were younger than those who did not. Controlling for this, they reported greater prevalence of abuse and more distress than those having mastectomy alone. They were also more depressed postoperatively, and this effect remained significant after controlling for abuse. CONCLUSIONS One interpretation of these findings is that history of abuse influences women's decisions about responding to the threat of mastectomy, but it is premature to draw inferences for practice until the findings are replicated. If they are replicated, it will be important to recognise increased vulnerability of some patients who choose reconstruction. Studying the characteristics and needs of women who opt for immediate reconstruction and examining the implications for women's adjustment should be a priority for research.

Sex and STEM occupation predict Autism-spectrum Quotient (AQ) scores in half a million people

This study assesses Autism-Spectrum Quotient (AQ) scores in a ‘big data’ sample collected through the UK Channel 4 television website, following the broadcasting of a medical education program. We examine correlations between the AQ and age, sex, occupation, and UK geographic region in 450,394 individuals. We predicted that age and geography would not be correlated with AQ, whilst sex and occupation would have a correlation. Mean AQ for the total sample score was m = 19.83 (SD = 8.71), slightly higher than a previous systematic review of 6,900 individuals in a non-clinical sample (mean of means = 16.94) This likely reflects that this big-data sample includes individuals with autism who in the systematic review score much higher (mean of means = 35.19). As predicted, sex and occupation differences were observed: on average, males (m = 21.55, SD = 8.82) scored higher than females (m = 18.95; SD = 8.52), and individuals working in a STEM career (m = 21.92, SD = 8.92) scored higher than individuals non-STEM careers (m = 18.92, SD = 8.48). Also as predicted, age and geographic region were not meaningfully correlated with AQ. These results support previous findings relating to sex and STEM careers in the largest set of individuals for which AQ scores have been reported and suggest the AQ is a useful self-report measure of autistic traits

Threat interpretation bias in anxious children and their mothers

The role of parents in the development of anxiety disorders in children is of increasing research and clinical interest. This study investigated interpretation biases of anxious children and their mothers using the ambiguous stimuli task developed by Hadwin, Frost, French, and Richards (1997). Three groups of children (aged 7 to 12 years) and their mothers were recruited; 23 non-clinical controls, 18 children with an anxiety disorder and 15 children with an externalising disorder. Following diagnostic assessments of the children, children and their mothers independently completed the homophone task and self-report measures of anxiety. Mothers of anxious children had significantly higher self-reported anxiety than mothers of non-clinical children. As hypothesised, children in the anxious group had higher threat interpretation scores than the non-clinical group. The hypothesis that mothers of anxious children would make more threat interpretations was not supported. Paired correlations showed no significant association between threat interpretations made by children and their mothers. There was a significant positive correlation between maternal threat interpretation and child anxiety. The results suggest that there is a complex association between mother's anxiety and cognitions and those of their children, which requires further examination in controlled observational and experimental studies, including treatment trials.

Factors that influence the detection of psychological problems in adolescents attending general practices

Background Epidemiological studies indicate that the prevalence of psychological problems in patients attending primary care services may be as high as 25%. Aim To identify factors that influence the detection of psychological difficulties in adolescent patients receiving primary care in the UK. Design of study A prospective study of 13-16 year olds consecutively attending general practices. Setting General practices, Norfolk, UK. Method Information was obtained from adolescents and parents using the validated Strengths and Difficulties Questionnaire (SDQ) and from GF`s using the consultation assessment form. Results Ninety-eight adolescents were recruited by 13 GPs in Norfolk (mean age = 14.4 years, SD = 1.08; 38 males, 60 females). The study identified psychological difficulties in almost one-third of adolescents (31/98, 31.6%). Three factors significant to the detection of psychological disorders in adolescents were identified: adolescents' perceptions of difficulties according to the self-report SDQ, the severity of their problems as indicated by the self-report SDQ, and whether psychological issues were discussed in the consultation. GPs did not always explore psychological problems with adolescents, even if GPs perceived these to be present. Nineteen of 31 adolescents with psychological difficulties were identified by GPs (sensitivity = 61.2%, specificity = 85.1%). A management plan or follow-up was made for only seven of 19 adolescents identified, suggesting that ongoing psychological difficulties in many patients are not being addressed. Conclusions GPs are in a good position to identify psychological issues in adolescents, but GPs and adolescents seem reluctant to explore these openly. Open discussion of psychological issues in GP consultations was found to be the most important factor in determining whether psychological difficulties in adolescents are detected by GPs.

Resting-state functional connectivity following a single dose treatment with CB1 neutral antagonist tetrahydrocannabivarin (THCv) in healthy volunteers

BACKGROUND: The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. METHOD: We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. RESULTS: Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. CONCLUSION: Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions.

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience.

Intraindividual relations between achievement goals and discrete achievement emotions: an experience sampling approach

Theories on the link between achievement goals and achievement emotions focus on their within-person functional relationship (i.e., intraindividual relations). However, empirical studies have failed to analyze these intraindividual relations and have instead examined between-person covariation of the two constructs (i.e., interindividual relations). Aiming to better connect theory and empirical research, the present study (N = 120 10th grade students) analyzed intraindividual relations by assessing students’ state goals and emotions using experience sampling (N = 1,409 assessments within persons). In order to replicate previous findings on interindividual relations, students’ trait goals and emotions were assessed using self-report questionnaires. Despite being statistically independent, both types of relations were consistent with theoretical expectations, as shown by multi-level modeling: Mastery goals were positive predictors of enjoyment and negative predictors of boredom and anger; performance-approach goals were positive predictors of pride; and performance-avoidance goals were positive predictors of anxiety and shame. Reasons for the convergence of intra- and interindividual findings, directions for future research, and implications for educational practice are discussed.

The relationship between challenging parenting behaviour and childhood anxiety disorders

Background: This research investigates the relationship between challenging parenting behaviour and childhood anxiety disorders proposed by Bögels and Phares (2008). Challenging parenting behaviour involves the playful encouragement of children to go beyond their own limits, and may decrease children’s risk for anxiety (Bögels & Phares, 2008). Method: Parents (n = 164 mothers, 144 fathers) of 164 children aged between 3.4 and 4.8 years participated in the current study. A multi-method, multi-informant assessment of anxiety was used, incorporating data from diagnostic interviews as well as questionnaire measures. Parents completed self-report measures of their parenting behaviour (n = 147 mothers, 138 fathers) and anxiety (n = 154 mothers, 143 fathers). Mothers reported on their child’s anxiety via questionnaire as well as diagnostic interview (n = 156 and 164 respectively). Of these children, 74 met criteria for an anxiety disorder and 90 did not. Results: Fathers engaged in challenging parenting behaviour more often than mothers. Both mothers’ and fathers’ challenging parenting behaviour was associated with lower report of child anxiety symptoms. However, only mothers’ challenging parenting behaviour was found to predict child clinical anxiety diagnosis. Limitations: Shared method variance from mothers confined the interpretation of these results. Moreover, due to study design, it is not possible to delineate cause and effect. Conclusions: The finding with respect to maternal challenging parenting behaviour was not anticipated, prompting replication of these results. Future research should investigate the role of challenging parenting behaviour by both caregivers as this may have implications for parenting interventions for anxious children.

Behavioral economics, wearable devices, and cooperative games: results from a population-based intervention to increase physical activity

Background: Health care literature supports the development of accessible interventions that integrate behavioral economics, wearable devices, principles of evidence-based behavior change, and community support. However, there are limited real-world examples of large scale, population-based, member-driven reward platforms. Subsequently, a paucity of outcome data exists and health economic effects remain largely theoretical. To complicate matters, an emerging area of research is defining the role of Superusers, the small percentage of unusually engaged digital health participants who may influence other members. Objective: The objective of this preliminary study is to analyze descriptive data from GOODcoins, a self-guided, free-to-consumer engagement and rewards platform incentivizing walking, running and cycling. Registered members accessed the GOODcoins platform through PCs, tablets or mobile devices, and had the opportunity to sync wearables to track activity. Following registration, members were encouraged to join gamified group challenges and compare their progress with that of others. As members met challenge targets, they were rewarded with GOODcoins, which could be redeemed for planet- or people-friendly products. Methods: Outcome data were obtained from the GOODcoins custom SQL database. The reporting period was December 1, 2014 to May 1, 2015. Descriptive self-report data were analyzed using MySQL and MS Excel. Results: The study period includes data from 1298 users who were connected to an exercise tracking device. Females consisted of 52.6% (n=683) of the study population, 33.7% (n=438) were between the ages of 20-29, and 24.8% (n=322) were between the ages of 30-39. 77.5% (n=1006) of connected and active members met daily-recommended physical activity guidelines of 30 minutes, with a total daily average activity of 107 minutes (95% CI 90, 124). Of all connected and active users, 96.1% (n=1248) listed walking as their primary activity. For members who exchanged GOODcoins, the mean balance was 4,000 (95% CI 3850, 4150) at time of redemption, and 50.4% (n=61) of exchanges were for fitness or outdoor products, while 4.1% (n=5) were for food-related items. Participants were most likely to complete challenges when rewards were between 201-300 GOODcoins. Conclusions: The purpose of this study is to form a baseline for future research. Overall, results indicate that challenges and incentives may be effective for connected and active members, and may play a role in achieving daily-recommended activity guidelines. Registrants were typically younger, walking was the primary activity, and rewards were mainly exchanged for fitness or outdoor products. Remaining to be determined is whether members were already physically active at time of registration and are representative of healthy adherers, or were previously inactive and were incentivized to change their behavior. As challenges are gamified, there is an opportunity to investigate the role of superusers and healthy adherers, impacts on behavioral norms, and how cooperative games and incentives can be leveraged across stratified populations. Study limitations and future research agendas are discussed.

Could in-home sensors surpass human observation of people with Parkinson’s at high risk of falling? An ethnographic study

Self-report underpins our understanding of falls among people with Parkinson’s (PwP) as they largely happen unwitnessed at home. In this qualitative study, we used an ethnographic approach to investigate which in-home sensors, in which locations, could gather useful data about fall risk. Over six weeks, we observed five independently mobile PwP at high risk of falling, at home. We made field notes about falls (prior events and concerns) and recorded movement with video, Kinect, and wearable sensors. The three women and two men (aged 71 to 79 years) having moderate or severe Parkinson’s were dependent on others and highly sedentary. We most commonly noted balance protection, loss, and restoration during chair transfers, walks across open spaces and through gaps, turns, steps up and down, and tasks in standing (all evident walking between chair and stairs, e.g.). Our unobtrusive sensors were acceptable to participants: they could detect instability during everyday activity at home and potentially guide intervention. Monitoring the route between chair and stairs is likely to give information without invading the privacy of people at high risk of falling, with very limited mobility, who spend most of the day in their sitting rooms.

Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population

Background Lifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity–associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene-lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D). Methods The study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model. Results There was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the ‘A’ allele carriers had 2.46 times increased risk of obesity than those with ‘CC’ genotype (P = 3.0 × 10−5) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3rd tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with ‘T’ allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the ‘A’ allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with ‘CC’ genotype (P = 4.0 × 10−5). Conclusions This is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population.