Disinhibition and Persistent Maladaptive Behavior

Objective: There is an urgent need to reduce overpopulation in U.S. prisons, which are inundated with individuals needing substance use treatment. Research on both substance use and antisocial behaviors highlight maladaptive beliefs and behaviors, while also implicating disinhibition as an important factor. Disinhibition is a dynamic trait that can be targeted with therapeutic interventions. The current study explored the relationships between neurocognitive disinhibition, substance use, and recidivism among incarcerated men. The study hypothesized that disinhibition would be associated with history of substance use, history of antisocial behavior, and institutional misconduct, as well as predicting recidivism over and above history of substance use. Method: This study analyzed an archival dataset of demographic, clinical, and neuropsychological measures among a sample of incarcerated men (N = 95). Results: Descriptive analyses showed meaningful relationships among history of substance use, history of antisocial behavior, institutional misconduct, disinhibition, and recidivism outcomes. Disinhibition was meaningfully associated with history of substance use (ß = 0.33, t = 3.07, p = .003, adjusted R2 = .09), history of antisocial behavior (ß = .25, t = 2.19, p = .032, adjusted R2 = .18), and institutional misconduct (ß = .270, t = 2.04, p = .047, adjusted R2 = .30), but not recidivism outcome (df = 1, Х2 = 0.73, p = .393). Conclusion: Limitations with statistical analyses may have contributed to a lack of support for neuroprediction of recidivism. Nonetheless, neurocognitive disinhibition may be a worthwhile construct in further research on biopsychosocial treatment of incarcerated or substance use populations

Predicting Opioid Prescribing Behaviors: Influence of an Expert Opioid-Risk Evaluation

Opioid analgesics have been shown to be effective for short-term pain reduction; however, chronic opioid therapy does not improve functioning, and may lead to problems with dependence and abuse. Physicians report having difficulty discerning substance abuse or drug diversion, which can lead to over- or under- prescribing, poor pain management, and may contribute to the growing number of opioid-related overdose deaths. The primary aim of this study was to determine if a psychological opioid risk evaluation influenced opioid prescribing in physicians at the West Virginia University (WVU) Family Medicine Clinic. For this retrospective study, participants were 151 (89 female) adult patients being considered for long-term opioid therapy. Patients participated in a psychological opioid risk evaluation, which included several questionnaires and a clinical interview. This evaluation resulted in an opioid risk level (i.e., low, low-moderate, moderate, moderate-high, high) being assigned to each patient representing clinical judgment about their potential risk for misusing or abusing opioid medication. An electronic medical record review was conducted on each patient, abstracting information about if an opioid was prescribed, in addition to several other factors, which later were included in logistic regression analyses. Patients prescribed an opioid were more likely to be married or with a long term partner and have a higher level of education. Patients not prescribed an opioid were more likely to report a higher pain rating at the time of the evaluation, a history of abuse or substance abuse, or have higher total scores for questionnaires measuring pain catastrophizing, misuse or diversion behaviors, and depression symptoms. Risk status and substance abuse history significantly predicted opioid prescribing, with a decrease in risk status resulting in an increase in opioid prescribing, and those with a history of substance abuse being less likely to be prescribed an opioid; however, substance abuse did not significantly improve the overall model and was removed. Additionally, demographic variables (i.e., age, sex, ethnicity/race) were not significant predictors of prescribing as found in other studies. These findings suggest that providing physicians with additional information about their patient\u27s opioid abuse potential aids in prescribing decisions and may reduce prescribing bias based on demographic factors. Risk status may allow physicians to integrate evidence-based factors into their decision-making process in a simplified manner, and possibly improve patient care. Future work should continue to address physicians\u27 prescribing perspective, accuracy of evaluations, effect on patient care, and cost analyses for the healthcare system

The psychosocial variables contributing to treatment expectancies in individuals with irritable bowel syndrome

The placebo effect has become recognized as an excellent example of mind-body interaction and as a mechanism of therapeutic action in its own right. Theoretical and empirical work has shown that expectations of treatment are important mediators of placebo effects, as well as treatment outcomes in diverse areas of health care. Modern theorists agree that situational and individual factors both contribute to the formation of treatment expectancies; however, only the former has received adequate study. The current research was designed to identify psychosocial variables associated with positive treatment expectations, using irritable bowel syndrome (IBS) as an illness model. People with IBS (n = 289) were recruited online to read hypothetical vignettes about treatments for IBS and to rate their expectations to benefit from treatment on a continuous scale. Participants completed a questionnaire battery measuring various individual difference factors, health belief variables and context-specific psychosocial variables, all identified from the literature as potentially relevant correlates of levels of expectation. Correlation and regression analyses revealed that several of these variables were positively associated with ratings of expected treatment benefit, in particular, perceived somatic focus of treatment, beliefs of personal control over symptoms, levels of optimism and self-focused attention. Weaker relationships were identified for acute health status, coping self-efficacy, catastrophizing and patient-provider relationship; whereas no relationships were found for trait anxiety or motivational factors. Among those with past experience with similar treatments, previous treatment satisfaction was a strong predictor of current expectations. Supplemental analyses revealed that among a sub-sample having previous treatment experience, along with higher levels of self-focused attention, significant relationships between treatment expectancies and independent psychosocial variables were more numerous and more robust. Results are discussed in light of contributions to theory, directions for future research as well as potential clinical applications

Children and adolescents with chronic pain: parental factors, functioning, and neurodevelopmental comorbidity

Background: Pediatric chronic pain affects between 11 and 38% of all children. Although pain may result from injury or disease, the cause of chronic pain is commonly unclear. The interaction between biological, psychological, and social aspects has been emphasized as key to the understanding of the chronic pain experience, as well as risk and resilience factors. Pediatric chronic pain may result in significant impairment affecting both child and family functioning, and addressing family factors such as parental distress and protective behaviors, are generally considered important to pediatric chronic pain management. However, there is still a need to identify resilience factors that can be targeted in parental support programs, and to develop and evaluate effective parent support interventions. The complexity of the pain experience in pediatric chronic pain is well known with a large number of patients suffering from co-occurring disorders such as depression or insomnia. However, despite a considerable number of clinical observations suggesting an elevated prevalence of attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) among children with chronic pain, and similarities in terms of clinical correlates, the empirical support has been scarce. More research on the co-occurrence of pediatric chronic pain, ADHD, and ASD, including relationships with functioning, is therefore warranted. Purpose and aims: The purpose of the present research project was to identify and assess parental and child factors of importance for functioning and treatment effects in pediatric chronic pain. More specifically, the aims of the project were to: validate an instrument for parental psychological flexibility (Study I); evaluate the effects of a brief parental ACTintervention on parent outcomes (Study II); assess the prevalence of clinically significant traits and symptoms of ASD and ADHD in children, and relations to pain- and demographic variables (Study III); and, to explore the relationships between traits and symptoms of ASD and ADHD, functioning, and health-related quality of life (HRQoL) (Study IV). Methods: In Study 1, utilizing a cross-sectional design, the Parent Psychological Flexibility Questionnaire (PPFQ) was translated and psychometrically evaluated in a sample of parents (n=263) of children with chronic pain using principal component analysis (PCA), correlation and regression analyses, and analysis of internal consistency. In Study II, the effects of individual and group ACT-interventions for adolescents (n=48) with chronic pain, and a brief support program for their parents (n=28), were evaluated using a randomized (group/individual) uncontrolled pilot design and non-parametric analyses of differences between groups and over time. In Study III, the prevalence of clinically significant ASD-traits and ADHD-symptoms was evaluated in a descriptive cross-sectional study on children with chronic pain (n=146) and their parents (n=146). Differences in painand demographic variables between children below and above cutoff for clinically significant traits and symptoms of ADHD or ASD were also assessed. Study IV, using the same sample as Study III, examined the relationships between ASD-traits and ADHDsymptoms, functioning (depression and pain interference), and HRQoL in correlation- and regression analyses and with independent t-tests, and assessed the indirect effects of insomnia and psychological inflexibility on the relationships between ASD-traits or ADHD-symptoms as predictors and functioning and HRQoL as dependents. Results: In Study 1, results supported a three-factor solution for the PPFQ with 10 items (PPFQ-10), showing good internal consistency and explaining a significant amount of variance in the criteria variables anxiety (29%) and depression (35.6%). In Study II, significant improvements in parental pain reactivity and psychological flexibility were found with clinically significant changes in the direction of better functioning for 54-76% of parents, with no differences between individual and group formats. In Study III, 13.7% of the sample presented with clinically significant ASD-traits and 19.9% of the sample presented with clinically significant ADHD-symptoms. The combined prevalence of clinically significant ASD/ADHD-traits and symptoms was 26%. Children with clinically significant ASD-traits were more likely to be girls and clinically significant ADHDsymptoms showed no gender differences. In Study IV, children with clinically significant ASD-traits and ADHD-symptoms presented with significantly higher levels of depressive symptoms and pain interference, and significantly lower HRQoL, compared to the rest of the sample. ASD-traits and ADHD-symptoms explained a significant amount of variance in pain interference and depressive symptoms, as well as in HRQoL. Psychological inflexibility was shown to mediate the influence of both ADHD-symptoms and ASD-traits, and insomnia the effect of ADHD-symptoms, on depression, pain interference, and HRQoL. Conclusions: Although tentative, the results suggests the utility of addressing parental psychological flexibility in relation to pediatric chronic pain. However, more research is warranted and future studies should e.g. evaluate the predictive utility of the PPFQ for child treatment outcomes, and evaluate if parental support programs that increase parental psychological flexibility also have positive effects on the children. Also, the results provide empirical support regarding elevated levels of clinically significant ADHD-symptoms and ASD-traits in pediatric chronic pain, and illustrate significant relationships between such traits and symptoms and functioning in children. Children with debilitating chronic pain, particularly girls, may be at risk for having a comorbid, and possibly undetected highfunctioning neurodevelopmental disorder. Results thus suggest the utility of screening for neurodevelopmental disorders in children with chronic pain, and may indicate insomnia, and psychological flexibility as potential treatment targets to improve functioning and HRQoL. The results also warrant further research to e.g. validate these findings in larger studies, evaluate the utility of tailored interventions, and examine the shared neuropathophysiology of chronic pain and neurodevelopmental disorders, including dopamine function and sensory abnormalities

Prediction and causal inference in the transition from acute to chronic low back pain

The overarching aim of this thesis was to enhance our understanding of the neurobiological risk factors associated with the transition from acute to chronic Low back pain (LBP). To achieve this aim, the Understanding persistent Pain Where it ResiDes (UPWaRD) study was conducted. In this thesis, six chapters describe the background, methods, and results of the UPWaRD study. Chapter 2 describes the protocol, published ‘a priori’ for developing a multivariable prediction model, including candidate predictors selected from the neurobiological (e.g. sensorimotor cortical excitability assessed by sensory and motor evoked potentials, Brain Derived Neurotrophic Factor [BDNF] genotype), psychological (e.g. depression and anxiety), symptom-related (e.g. LBP history) and demographic domains. Chapter 3 builds on the study protocol in the form of a cohort profile, describing baseline characteristics of 120 people experiencing an acute LBP episode and 57 pain-free control participants that form the UPWaRD cohort. Chapter 4 reports the results of the multivariable prediction model developed in 120 people experiencing acute LBP. To further understand the importance of these prognostic factors we developed a causal model of chronic LBP using directed acyclic graphs. The methodology and statistical analysis plan for drawing causal inferences, thus transparently reporting our causal assumptions, are reported in Chapter 5. Chapter 6 then provides the first evidence that low sensory cortex excitability during an acute LBP episode is a causal mechanism underpinning the development of chronic LBP. Finally, in Chapter 7, we report the results of a proteomic analysis, using hydrophobic interaction chromatography and electrospray ionization tandem mass spectrometry. Taken together this thesis makes an extensive and original contribution to our understanding of neurobiological risk factors involved in the transition from acute to chronic LBP. Not only is the inclusion of neurobiological prognostic factors in multivariable clinical prediction models a promising direction for future research that aims to identify people at high risk of poor outcome, but low sensory cortex excitability during acute LBP may be a promising causal mechanism that future treatments could target during acute LBP in the hope of expediting recovery and preventing the development of chronic LBP. Further, this thesis provides some of the earliest evidence to suggest sex-specific differential expression of proteins, measured from human serum, contributes to recovery status at three-month follow-up. This work provides foundational evidence for future research exploring strategies targeting distinct immune system processes in males and females that may interfere with the transition from acute to chronic LBP

Genetic Insights into the Heterogeneity and Comorbidity of Substance Use Disorders

[eng] Substance use disorders (SUDs) are psychiatric disorders characterized by a recurring desire to continue taking a substance regardless of its destructive consequences. The etiology of SUDs is complex and multifactorial, where both genetic and environmental factors have an impact on the disease development. In addition, SUDs often co-occur at high prevalence with other psychiatric conditions, significantly impacting life expectancy, disease severity and societal burden. Over the past decade, genome-wide association studies (GWASs) have identified various risk loci for substance-specific SUD, as well as a shared genetic vulnerability for addiction. In addition, post-GWAS analyses have helped unravel the complex genetic architecture of SUDs, which can also involve an interplay of gene-environment interactions, and its relationship with comorbid mental health conditions. Current research in this field is making collective efforts to provide deeper and clearer knowledge into the genetic and environmental factors involved into the co-occurrence of SUDs and psychiatric disorders, which may be partially driving the high heterogeneity observed in SUDs, and the biological mechanisms driving these relationships. The present thesis comprises two studies that leverage in-house clinical cohorts, with both phenotypical and genetic data available, and state-of-the-art genomic techniques to investigate the shared genetic liability between SUDs and co-occurring traits, and to shed light into the genetic underpinnings of SUDs heterogeneity. The first study particularly focused on the relationship between SUDs and attention-deficit and hyperactivity disorder (ADHD). In this study, we tested whether the genetic liability to five SUD-related phenotypes share a common genetic background in both the general population and clinically diagnosed ADHD individuals, using an in-house sample of 989 subjects and polygenic scores (PGSs) analyses. We further explored the genetic overlap and the causal relationship between ADHD and SUDs using genetic correlation and Mendelian randomization analyses. Our results confirmed a significant genetic correlation between ADHD and SUDs and supported the current literature on the causal effect of the genetic liability to ADHD on the risk for SUDs. We provided novel findings on the effect of the genetic liability to lifetime cannabis use on an increased risk for ADHD and found evidence of a shared genetic background underlying SUDs between general population and ADHD, at least for lifetime cannabis use, alcohol dependence and smoking initiation. The second study aimed to disentangle SUDs heterogeneity using multidimensional data from a deeply phenotyped SUDs cohort of 1,427 individuals and PGSs for comorbid psychiatric disorders, behavioral and other related traits. We systematically explored the associations between the PGSs and 39 SUD-related phenotypes, and performed PGSs-environment interaction analyses using information on lifetime emotional, physical and/or sexual abuse. Our results revealed different patterns of associations between the genetic liability for mental health-related traits and SUD-related phenotypes, which may help explain part of the heterogeneity observed in SUDs. We also found evidence of a PGS-environment interaction showing that genetic liability for suicide attempt worsened the psychiatric status in SUDs individuals with a history of emotional physical and/or sexual abuse. Overall, the results of the present thesis provide new insights into the genetic overlap and causal relationships between SUDs and ADHD and contribute to a better understanding of the role of the genetic liability for psychiatric disorders and related traits, as well as its interaction with adverse life experiences, in the complexity of SUD heterogeneity. Lastly, this thesis provides a general discussion of the findings, which offers an extensive interpretation of the results in the context of existing literature, discusses the main methodological implications and outlines prospective directions for advancing in this line of research.[cat] Els trastorns per l'ús de substàncies (TUS) són trastorns psiquiàtrics caracteritzats per un desig recurrent de continuar prenent una o diverses substàncies, independentment de les seves conseqüències destructives. L'etiologia dels TUS és complexa i multifactorial, on tant factors genètics com ambientals tenen un impacte en el desenvolupament de la malaltia. A més, els TUS sovint es presenten simultàniament amb altres trastorns psiquiàtrics, afectant significativament la severitat de la malaltia, l’esperança de vida i la càrrega en la societat. Durant l'última dècada, els estudis d'associació del genoma complet (GWASs) han identificat diverses variants genètiques de risc per a TUS de substàncies específiques, així com una vulnerabilitat genètica compartida per a l'addicció. A més, les anàlisis post-GWAS han ajudat a desxifrar l'arquitectura genètica complexa dels TUS, que també pot implicar la interacció entre gens i ambient, i la seva relació amb trastorns de salut mental comòrbids. La recerca actual en aquest camp està focalitzada en profunditzar en el coneixement sobre els factors genètics i ambientals involucrats en la coexistència del TUS i trastorns psiquiàtrics, el qual pot ser parcialment responsable de l’alta heterogeneïtat observada en el TUS, i els mecanismes biològics implicats. La present tesi està composta per dos estudis que utilitzen cohorts clíniques, amb dades fenotípiques i genètiques disponibles, i tècniques genòmiques actuals per explorar la carga genètica compartida entre els TUS i els trets comòrbids, i per investigar la heterogeneïtat dels TUS des del punt de vista genètic. El primer estudi es centra particularment en la relació entre els TUS i el trastorn per dèficit d’atenció i hiperactivitat (TDAH). En aquest estudi, vam testar si la càrrega genètica per a cinc fenotips de TUS comparteixen una base genètica comuna en la població general i en individus amb TDAH, fent servir un mostra interna de 989 individus i anàlisis de puntuacions poligèniques (PGSs). Seguidament, vam explorar el solapament genètic i la relació causal entre el TDAH i els TUS utilitzant anàlisis de correlació genètica i de randomització mendeliana. Els nostres resultats confirmen una base genètic comuna entre el TDAH i els TUS i donen suport a la literatura actual sobre l'efecte causal de la càrrega genètica pel TDAH en el risc de TUS. A més, descrivim per primera vegada l'efecte causal de la càrrega genètica per a l'ús de cànnabis en el risc de TDAH i trobem evidències d'un component genètic compartit subjacent als TUS en la població general i en els individus amb TDAH, almenys per a l'ús de cànnabis, la dependència a l'alcohol i l'inici del consum de tabac. El segon estudi té com a objectiu desxifrar la heterogeneïtat dels TUS utilitzant dades multidimensionals d'una cohort de TUS de 1,427 individus dels quals es disposa una àmplia informació fenotípica, i PGSs per a trastorns psiquiàtrics comòrbids, trets del comportament i altres trets relacionats. Vam explorar les associacions entre els PGSs i 39 fenotips de TUS, i vam portar a terme anàlisis d’interacció PGS-ambient utilitzant informació sobre abús emocional, físic i/o sexual al llarg de la vida. Els nostres resultats revelen diferents patrons d'associacions entre la càrrega genètica per a trets relacionats amb la salut mental i fenotips de TUS, el que pot ajudar a explicar part de la heterogeneïtat observada en els TUS. També trobem evidència d'una interacció PGS-ambient que mostra que la càrrega genètica per a intents de suïcidi empitjora l'estat psiquiàtric en individus amb TUS que han patit abús emocional, físic i/o sexual. En conjunt, els resultats de la present tesi aporten noves perspectives sobre el solapament genètic i les relacions causals entre els TUS i el TDAH i contribueixen a una millor comprensió del paper de la càrrega genètica pels trastorns psiquiàtrics i trets relacionats, així com la seva interacció amb experiències adverses al llarg de la vida, en la complexitat de la heterogeneïtat dels TUS. Finalment, aquesta tesi ofereix una discussió general, la qual proporciona una extensa interpretació dels resultats en el context de la literatura existent, discuteix les principals implicacions metodològiques i detalla les futures direccions per avançar en aquesta línia de investigació

Aspects of Pain in Special Age Groups

Kivun arviointiin, kipukokemukseen ja kivun hoitoon liittyy erityispiirteitä ja haasteita erityisikäryhmissä (lapset, ikääntyneet). Tutkimuksen tavoitteena oli tutkia kipuun sopeutumista lapsilla ja nuorilla sekä löytää tekijöitä, jotka ovat yhteydessä koettuun kipuun ikääntyneillä. Tutkimuksen tavoite oli siten kehittää keinoja ymmärtää paremmin näiden erityisikäryhmien kipukokemusta. Tutkimuksessa määritettiin englannista suomeksi käännetyn kipusopeutumismittarin (PCQ) faktorirakenne, ja suomenkielinen PCQ validoitiin. PCQ on ensimmäinen nimenomaan lapsille kehitetty kipusopeutumismittari. Tutkimuksessa tarkasteltiin myös ikääntyneiden SF-36-mittarilla arvioitua kivun voimakkuutta ja haittaavuutta sekä näihin liittyviä tekijöitä. Lisäksi tarkasteltiin ikääntyneiden reseptikipulääkeostoja, jotta saataisiin enemmän tietoa ikääntyvän väestön kipulääkkeiden käytöstä sekä kipulääkeprofiilista. Päähuomio kohdennettiin opioidiostoihin, sillä opioidien käytön tiedetään lisääntyneen ikääntyneessä väestössä. Lastenreumaa sairastavien ja pitkittyneestä kivusta kärsivien lasten (N=91, ikä 8– 15 vuotta) kipuoireet jaoteltiin ensimmäisen ja korkeamman asteen luokkiin käyttäen eksploratiivista faktorianalyysiä. Satunnaisotannalla valikoidut, kotona asuvat ikääntyneet (N=1420) raportoivat SF-36-mittarilla kokemaansa ruumiillista kipua viimeisen kuukauden ajalta. Kipuraportoinnin perusteella tutkittavat jaettiin neljään kipuryhmään (ryhmä I [0–45, kohtalainen–erittäin kova kivun voimakkuus sekä kipuun liittyvä haitta], ryhmä II [47,5–70], ryhmä III [77,5–90], ryhmä [100, ei lainkaan kipua]). Ikääntyneiden raportoimia kyselytietoja sekä kliinistä aineistoa tarkasteltiin suhteessa kipuun. Ikääntyneiden reseptikipulääkeostot kuudelta kuukaudelta ennen kyselykaavakkeen täyttöä ja kuudelta kuukaudelta sen jälkeen kerättiin Kansaneläkelaitoksen reseptitietokeskuksesta. Kipulääkeostoja tarkasteltiin erikseen kolmessa ikäryhmässä (62–66-, 72–76- ja 82–86-vuotiaat). Kulttuurisesti ja tilastollisesti tyydyttävä suomenkielisen PCQ:n ensimmäisen ja korkeamman asteen faktorirakenne saavutettiin 38 muuttujalla. Ikääntyneistä 78 % raportoi kokeneensa kipua viimeisen kuukauden aikana (SF-36 kipu < 100); 17 % oli kokenut sekä kohtalaista tai erittäin kovaa kipua että kohtalaista tai erittäin voimakasta kipuun liittyvää haittaa. Ne henkilöt, jotka raportoivat eniten kipua, asuivat useammin yksin, sijoittuivat matalampaan sosioekonomiseen luokkaan ja olivat useammin ylipainoisia sekä monisairaampia. Ikääntyneistä 84 % oli vuoden aikana noutanut apteekista jotakin reseptillä määrättyä kipulääkettä; 77 % oli noutanut tulehduskipulääkkeitä ja 32 % opioideja. Ainoastaan sairauksien määrä oli itsenäisesti yhteydessä kipulääkeostoihin. Eri ikäryhmien välillä ei löytynyt mainittavaa eroa kipulääkejakaumassa tai noutojen esiintyvyydessä. Metabolinen oireyhtymä ja yleinen sairastavuus olivat itsenäisesti yhteydessä opioidien käyttöön niillä henkilöillä, jotka olivat noutaneet reseptillä määrättyjä opioideja mutta eivät olleet raportoineet lainkaan kipua. Lapsilta voi puuttua keinoja käsitellä epämiellyttäviä fyysisiä ja psyykkisiä kokemuksia. Validi kipusopeutumismittari voi edistää heikon kivun käsittelykyvyn tunnistamista ennen kuin kipu kroonistuu. Merkittävä osa ikääntyneistä oli raportoinut kipua viimeksi kuluneen kuukauden aikana. Useiden tekijöiden, joiden todettiin olevan yhteydessä kipuun näillä henkilöillä, tiedetään olevan yhteydessä sosiaaliseen syrjäytymiseen. Huomiota tulee kiinnittää kyseisten tekijöiden varhaiseen tunnistamiseen kipua kokevilla henkilöillä. Tulehduskipulääkkeiden ja opioidien käyttö ikääntyneillä oli runsasta. Huolellista harkintaa tulee käyttää näiden lääkkeiden määräämisessä ikääntyneelle väestölle, ja vasta-aiheet ja mahdolliset riskit tulee tuntea. Erityishuomiota tulee kiinnittää niihin ikääntyviin henkilöihin, jotka sijoittuvat matalampaan sosioekonomiseen luokkaan, ovat ylipainoisia ja joilla on metabolinen oireyhtymä.Special age groups (children, adolescents, older adults) have special characteristics when it comes to pain assessment, pain experience, and pain management. The first objectives of the current study were to examine pain coping in children and to identify factors related to pain in older adults, in order to improve the understanding of the pain experience in these special age groups. First, the factor structure of the Finnish translation of the Pain Coping Questionnaire (PCQ), the first validated pain coping measurement developed specifically for children, was determined and validated. Secondly, the pain intensity and interference as well as pain-related factors according to the SF-36 were examined among community-dwelling older adults. In addition, purchases of prescribed analgesics among older adults were considered in order to estimate the analgesic administration prevalence in the aging population. The main focus was in opioid purchases due to the known increase in opioid use among older adults. Exploratory factor analysis was used for the first-order and higher-order classification of 91 juvenile idiopathic arthritis patients and patients with chronic non-inflammatory musculoskeletal pain symptoms, aged 8–15. A total of 1,420 randomly selected community-dwelling older adults self-reported SF-36 bodily pain (pain intensity and pain-related interference) during the previous month. Based on the pain reports, four pain groups were formed (group I [0–45, moderate to very severe pain intensity and interference], group II [47.5–70], group III [77.5–90], and group IV [100, no pain at all]). The relationship between questionnaire and clinical data in these groups was explored. Data regarding older adults’ analgesic purchases for six months prior to and six months after the self-report were retrieved from the Social Insurance Institution of Finland. Analgesic purchases were examined separately in three age groups (62–66, 72–76, and 82–86 years). Factors related to analgesic purchases were explored. With 38 items, the exploratory factor analysis of the PCQ provided a both culturally and statistically satisfactory structure of eight first-order factors (Internalizing/Catastrophizing [IC], Positive Self-Statements [PSS], Information Seeking [IS], Seeking Social Support [SSS], Cognitive Distraction [CD], Externalizing [EXT], Behavioural Distraction [BD], Problem Solving [PS]) and three higher-order factors (Approach [APP], Emotion-Focused Avoidance [EFA], Distraction [DIS]) in the Finnish translation. Regarding older adults, the overall pain prevalence was 78% (SF-36 bodily pain < 100); 17% had experienced both moderate to severe pain intensity and pain-related interference. The prevalence of cohabiting as well as socioeconomic status decreased, and obesity and morbidity increased with increasing SF-36 bodily pain. In total, 84% of the participants had purchased at least one prescribed analgesic over the period of one year; 77% had purchased non-steroidal anti-inflammatory drugs (NSAIDs), and 32% had purchased opioids. Of all examined factors, only morbidities were independently associated with analgesic purchases. Age did not make a marked difference in drug distribution or purchasing prevalence. Of the opioid purchasers, 16% had reported no pain of any intensity and 30% no pain-related interference. Metabolic syndrome and morbidities were independently associated with opioid purchases among these participants. Children may lack understanding and the means to deal with ongoing unwanted physical and mental health conditions. A valid pain coping scale may enhance the distinguishing of vulnerable pain coping at the very early stage of pain becoming chronic. In older adults, a high prevalence of intense and interfering pain was reported. Multiple factors that were found to relate to pain are known to associate with social exclusion. Increasing efforts should be targeted towards identifying these factors in persons with pain. The use of NSAIDs and opioids emerged as being substantial in the older adult population. Careful deliberation in terms of contraindications and potential risks needs to be executed when prescribing NSAIDs and opioids to older adults, especially in older adults with a lower socio-economic status, obesity, and metabolic syndrome

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40