Applying the Project ECHO Model to Support Implementation and Sustainment of Cognitive Behavioral Therapy for Psychosis.

INTRODUCTION: Project Extension for Community Healthcare Outcomes (ECHO) is a teleconsultation model that leverages technology to sustain specialized interventions in underresourced settings. We present the application of the ECHO model to longitudinal training and consultation for community behavioral health providers learning to deliver cognitive behavioral therapy for psychosis, an evidence-based psychotherapy for individuals with psychotic disorders that has poorly penetrated the US mental health system. METHODS: We analyzed within-group change over practitioners' 6-month ECHO participation cycle using the Expanded Outcomes Framework. We evaluated outcomes associated with participation, satisfaction, knowledge acquisition, performance, patient symptom severity, and functional impairment. RESULTS: In the first 3 years, the cognitive behavioral therapy for psychosis ECHO Clinics supported 150 providers from 12 community agencies. Forty percent did not complete the 6-month ECHO calendar, most commonly due to separation from their agency. Participants reported high degrees of satisfaction. Declarative and procedural knowledge increased over the 6-month period. Of the 24 providers who received a fidelity review, 87.5% met or exceeded the competency benchmark within the 6-month period. Clinical outcomes reflected reductions in hallucinations, negative symptoms, depression, mania, and functional impairment, but no reductions were detected in delusions, disorganized speech, or abnormal psychomotor behavior. DISCUSSION: ECHO Clinics offer a mode of providing continuous access to expert instruction, peer-to-peer consultation, and case-based learning that other workforce training models lack. Our evaluation suggests that the ECHO model supports continuous professional development for practitioners, most of whom had indicated inadequate preparation for their role. We observed improved learner and select patient outcomes.

Associations Between Urological Chronic Pelvic Pain Syndrome Symptom Flares, Illness Impact, and Health Care Seeking Activity: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study.

PURPOSE: Most studies on interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome use typical or average levels of pelvic pain or urological symptom intensity as their outcome, as both are associated with reduced quality of life. Symptom exacerbations or "flares" have also been found to be associated with reduced quality of life, but no studies, to our knowledge, have investigated whether these associations are independent of typical pelvic pain levels and thus might be useful additional outcome measures (or stated differently, whether reducing flare frequency even without reducing mean pain intensity may be important to patients). MATERIALS AND METHODS: We used screening visit and weekly run-in period data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study to investigate associations between flare frequency and multiple measures of illness impact and health care seeking activity, independent of typical nonflare and overall pelvic pain levels. RESULTS: Among the 613 eligible participants, greater flare frequency was associated with worse condition-specific illness impact (standardized ß coefficients=0.11-0.68, P trends < .0001) and health care seeking activity (odds ratios=1.52-3.94, P trends .0039 to < .0001) in analyses adjusted for typical nonflare and overall pelvic pain levels. Experiencing ≥1/d was also independently associated with worse general illness impact (standardized ß coefficients=0.11-0.25). CONCLUSIONS: Our findings suggest that flare frequency and possibly other flare characteristics may be worth considering as additional outcome measures in urological chronic pelvic pain syndrome research to support the development of new preventive and therapeutic flare strategies.

Informal Caregiving Among American Indians and Alaska Natives in the Pacific Northwest.

Unpaid or informal caregivers are people who provide assistance without compensation to adults and children who require care beyond typical needs. Although often rewarding, informal caregiving can be associated with high rates of depression, stress, anxiety, sleep and endocrine system disruption, immunosuppression, and general morbidity and mortality. Few recent studies of informal caregivers have included data from American Indians and Alaska Natives (AI/AN). Given this noteworthy gap in the literature, we surveyed a total of 225 AI/ANs attending two cultural, community functions in the Pacific Northwest to gain a general understanding of frequency of caregiving, caregiver and recipient characteristics, caregiving duties, support needs, and financial, emotional, and physical strains as a consequence of caregiving. Of the 225 participants who completed the survey, 90 (40%) indicated that they had been an unpaid caregiver for a month or more and 28 (12%) were current unpaid caregivers. Consistent with prior research, most caregivers (84%) reported satisfaction from providing help, but 84% of caregivers reported experiencing "increased stress," 40% reported financial strain, and 34% reported decreased health "because of involvement with providing care." Our data also suggested a disproportionate impact on AI/AN women given higher rates of being a caregiver compared to other populations and less support from others in their communities. Our data suggest similarities for AI/AN caregivers with other groups of caregivers but also emphasize the importance of including AI/AN populations in future research in order to understand ways to best serve their unique needs.

Clinical Phenotyping for Pain Mechanisms in Urologic Chronic Pelvic Pain Syndromes: A MAPP Research Network Study.

Three categories of pain mechanisms are recognized as contributing to pain perception: nociceptive, neuropathic, and nociplastic (ie, central nervous system augmented pain processing). We use validated questionnaires to identify pain mechanisms in Urologic Chronic Pelvic Pain Syndrome (UCCPS) patients (n = 568, female = 378, male = 190) taking part in the Symptom Patterns Study of the Multidisciplinary Approach to the study of chronic Pelvic Pain Research Network. A cutoff score of 12 on the painDETECT questionnaire (-1 to 38) was used to classify patients into the neuropathic category while the median score of 7 on the fibromyalgia survey criteria (0-31) was used to classify patients into the nociplastic category. Categories were compared on demographic, clinical, psychosocial, psychophysical and medication variables. At baseline, 43% of UCPPS patients were classified as nociceptive-only, 8% as neuropathic only, 27% as nociceptive+nociplastic, and 22% as neuropathic+nociplastic. Across outcomes nociceptive-only patients had the least severe symptoms and neuropathic+nociplastic patients the most severe. Neuropathic pain was associated with genital pain and/or sensitivity on pelvic exam, while nociplastic pain was associated with comorbid pain conditions, psychosocial difficulties, and increased pressure pain sensitivity outside the pelvis. A self-report method classifying individuals on pain mechanisms reveals clinical differences that could inform clinical trials and novel targets for treatment. PERSPECTIVE: This article presents differences in clinical characteristics based on a simple self-report method of classifying pain mechanisms for Urologic Chronic Pelvic Pain Syndrome patients. This method can be easily applied to other chronic pain conditions and may be useful for exploring pathophysiology in pain subtypes.

Temporal Relationships between Pain, Mood and Urinary Symptoms in Urological Chronic Pelvic Pain Syndrome: A MAPP Network Study.

PURPOSE: We sought to determine the time-lagged, bidirectional relationships among clinical variables of pelvic pain, urinary symptoms, negative mood, nonpelvic pain and quality of life in men and women with urological chronic pelvic pain syndrome, incorporating interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 204 female and 166 male patients were assessed up to 24 times over a 48-week period on the 5 primary outcomes. A lagged autoregressive analysis was applied to determine the directional relationship of one variable to another 2 weeks later, beyond that of the concurrent relationships at each time point and autocorrelations and trends over time. RESULTS: The results show clear evidence for a bidirectional positive relationship between changes in pelvic pain severity and urinary symptom severity. Increases in either variable predicted significant increases in the other 2 weeks later, beyond that explained by their concurrent relationship at each time point. Pelvic pain and to a lesser degree urinary frequency also showed similar bidirectional relationships with negative mood and decreased quality of life. Interestingly, neither pelvic pain or urinary symptom severity showed lagged relationships with nonpelvic pain severity. CONCLUSIONS: Results document for the first time specific short-term positive feedback between pelvic pain and urinary symptoms, and between symptoms of urological chronic pelvic pain syndrome, mood and quality of life. The feedforward aspects of these relationships can facilitate a downward spiral of increased symptoms and worsening psychosocial function, and suggest the need for multifaceted treatments and assessment to address this possibility in individual patients.

Natural bladder filling alters resting brain function at multiple spatial scales: a proof-of-concept MAPP Network Neuroimaging Study.

Neural circuitry regulating urine storage in humans has been largely inferred from fMRI during urodynamic studies driven by catheter infusion of fluid into the bladder. However, urodynamic testing may be confounded by artificially filling the bladder repeatedly at a high rate and examining associated time-locked changes in fMRI signals. Here we describe and test a more ecologically-valid paradigm to study the brain response to bladder filling by (1) filling the bladder naturally with oral water ingestion, (2) examining resting state fMRI (rs-fMRI) which is more natural since it is not linked with a specific stimulus, and (3) relating rs-fMRI measures to self-report (urinary urge) and physiologic measures (voided volume). To establish appropriate controls and analyses for future clinical studies, here we analyze data collected from healthy individuals (N = 62) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Participants orally ingested approximately 350 mL of water, and had a 10 min "fuller bladder" rs-fMRI scan approximately 1 h later. A second 10 min "empty bladder" rs-fMRI scan was conducted immediately following micturition. We examined multiple spatial scales of brain function, including local activity, circuits, and networks. We found changes in brain function distributed across micturition loci (e.g., subregions of the salience, sensorimotor, and default networks) that were significantly related to the stimulus (volume) and response (urinary urge). Based on our results, this paradigm can be applied in the future to study the neurobiological underpinnings of urologic conditions.

Central and Peripheral Symptoms in Network Analysis are Differentially Heritable A Twin Study of Anxious Misery.

BACKGROUND: Evidence suggests that depression and anxiety disorders are genetically based. Although symptoms of these internalizing disorders tend to correlate, the degree to which the related symptoms are heritable is unclear. This overlap has been conceptualized as Anxious Misery and existing research examining similar constructs of negative affect has revealed moderate heritability. However, it is unclear if some symptoms that characterize these constructs are more heritable than others. Modeling the symptom structure of Anxious Misery and examining which symptoms are most heritable may have implications for etiological models of internalizing disorders. Accordingly, the present study employed network analysis to explore the relationships across symptoms of Anxious Misery and to test if central symptoms in the network, compared to more peripheral symptoms, differ in their heritabilities. METHODS: Twin pairs (N = 1,344 pairs) with a mean age of 39 years (SD = 16 years) completed measures of anxiety and neuroticism to represent the Anxious Misery network. RESULTS: Panic-related symptoms were the most central in the network and were the most heritable, with genetic factors accounting for up to 59% of phenotypic variance. Peripheral symptoms were less heritable, accounting for as little as 21% of phenotypic variance. The degree of symptom heritability was strongly correlated with the degree of centrality of a symptom in the network (r = .53). LIMITATIONS: Reliance on two self-report measures to represent Anxious Misery limits the generalizability of the findings. CONCLUSIONS: Central and peripheral symptoms of an Anxious Misery network may differ in degree of heritability.

Insomnia and posttraumatic stress symptoms: Evidence of shared etiology.

Posttraumatic stress disorder (PTSD) and insomnia are comorbid clinical conditions that are thought to result from genetic and environmental effects. Though studies have established the heritability of these disorders independently, no study to date has examined the genetic contributions to the relation between insomnia and PTSD symptoms (PTSS). The present study assessed this gap in the literature using a behavioral genetics approach to symptom dimensions. The sample consisted of 242 twin pairs who endorsed lifetime trauma exposure. Insomnia symptoms were assessed with the Women's Health Initiative Survey, and intrusion and avoidance PTSS were assessed with the Impact of Events Scale. Structural equation modeling was then employed to test the relative contributions of genetic, shared environmental, and nonshared environmental components to the relations between insomnia symptoms and intrusions and avoidance. Results indicated a significant association between insomnia symptoms and intrusions (r = 0.33, p < 0.01) and insomnia symptoms and avoidance (r = 0.20, p < 0.01), and 36-44% of phenotypic variance was accounted for by genetic contributions. These findings highlight a significant role for genetic factors in the mechanisms underlying the comorbidity between insomnia and PTSS. The implications for current etiological models of PTSD and insomnia are discussed.

Genome-wide profiling of DNA methylome and transcriptome in peripheral blood monocytes for major depression: A Monozygotic Discordant Twin Study.

DNA methylation plays an important role in major depressive disorder (MDD), but the specific genes and genomic regions associated with MDD remain largely unknown. Here we conducted genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) and gene expression (RNA-seq) in peripheral blood monocytes from 79 monozygotic twin pairs (mean age 38.2 ± 15.6 years) discordant on lifetime history of MDD to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with MDD, followed by replication in brain tissue samples. Integrative DNA methylome and transcriptome analysis and network analysis was performed to identify potential functional epigenetic determinants for MDD. We identified 39 DMRs and 30 DEGs associated with lifetime history of MDD. Some genes were replicated in postmortem brain tissue. Integrative DNA methylome and transcriptome analysis revealed both negative and positive correlations between DNA methylation and gene expression, but the correlation pattern varies greatly by genomic locations. Network analysis revealed distinct gene modules enriched in signaling pathways related to stress responses, neuron apoptosis, insulin receptor signaling, mTOR signaling, and nerve growth factor receptor signaling, suggesting potential functional relevance to MDD. These results demonstrated that altered DNA methylation and gene expression in peripheral blood monocytes are associated with MDD. Our results highlight the utility of using peripheral blood epigenetic markers and demonstrate that a monozygotic discordant co-twin control design can aid in the discovery of novel genes associated with MDD. If validated, the newly identified genes may serve as novel biomarkers or druggable targets for MDD and related disorders.

The Washington State Twin Registry: 2019 Update.

It has been over 5 years since the last special issue of Twin Research and Human Genetics on 'Twin Registries Worldwide: An Important Resource for Scientific Research' was published. Much progress has been made in the broad field of twin research since that time, and the current special issue is a follow-up to update the scientific community about twin registries around the globe. The present article builds upon our 2013 Registry description by summarizing current information on the Washington State Twin Registry (WSTR), including history and construction methods, member characteristics, available data, and major research goals. We also provide a section with brief summaries of recently completed studies and discuss the future research directions of the WSTR. The Registry has grown in terms of size and scope since 2013; highlights include recruitment of youth pairs under 18 years of age, extensive geocoding work to develop environmental exposures that can be linked to survey and administrative health data such as death records, and expansion of a biobank with specimens collected for genotyping, DNA methylation, and microbiome based-studies.

Stepped Care as an Implementation and Service Delivery Model for Cognitive Behavioral Therapy for Psychosis.

Cognitive behavioral therapy for schizophrenia spectrum disorders is an evidence-based treatment that is recommended by United States schizophrenia treatment guidelines. Based on recent estimates, only 0.3% of individuals with a primary psychotic disorder are able to access this treatment in the United States. Stepped care interventions have shown promise as an applied treatment delivery model in other settings and for other psychotherapeutic interventions. The current paper describes how the stepped care model can be applied to CBT for psychosis in the US to increase access to the intervention in community mental health settings by leveraging the multidisciplinary team.

Viral Genetics Modulate Orolabial Herpes Simplex Virus Type 1 Shedding in Humans.

BACKGROUND: Orolabial herpes simplex virus type 1 (HSV-1) infection has a wide spectrum of severity in immunocompetent persons. To study the role of viral genotype and host immunity, we characterized oral HSV-1 shedding rates and host cellular response, and genotyped viral strains, in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 29 MZ and 22 DZ HSV-1-seropositive twin pairs were evaluated for oral HSV-1 shedding for 60 days. HSV-1 strains from twins were genotyped as identical or different. CD4+ T-cell responses to HSV-1 proteins were studied. RESULTS: The median per person oral HSV shedding rate was 9% of days that a swab was obtained (mean, 10.2% of days). A positive correlation between shedding rates was observed within all twin pairs, and in the MZ and DZ twins. In twin subsets with sufficient HSV-1 DNA to genotype, 15 had the same strain and 14 had different strains. Viral shedding rates were correlated for those with the same but not different strains. The median number of HSV-1 open reading frames recognized per person was 16. The agreement in the CD4+ T-cell response to specific HSV-1 open reading frames was greater between MZ twins than between unrelated persons (P = .002). CONCLUSION: Viral strain characteristics likely contribute to oral HSV-1 shedding rates.

Study Design and Rationale for the Mood and Methylation Study: A Platform for Multi-Omics Investigation of Depression in Twins.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future 'multi-omic' analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other 'omic' factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: a MAPP Research Network study.

Chronic overlapping pain conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This "centralized pain" phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here, we used 3 cohorts, including patients with urologic chronic pelvic pain syndrome, a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified 2 general factors in all 3 cohorts, one characterized by a broad increased sensitivity to internal somatic sensations,environmental stimuli, and diffuse pain, termed Generalized Sensory Sensitivity, and one characterized by constitutional symptoms-Sleep, Pain, Affect, Cognition, Energy (SPACE). Longitudinal analyses in the urologic chronic pelvic pain syndrome cohort found the same 2-factor structure at month 6 and 1 year, suggesting that the 2-factor structure is reproducible over time. In secondary analyses, we found that Generalized Sensory Sensitivity particularly is associated with the presence of comorbid COPCs, whereas SPACE shows modest associations with measures of disability and urinary symptoms. These factors may represent an important and distinct continuum of symptoms that are indicative of the centralized pain phenotype at high levels. Future research of COPCs should accommodate the measurement of each factor.

Childhood Trauma, DNA Methylation of Stress-Related Genes, and Depression: Findings From Two Monozygotic Twin Studies.

OBJECTIVE: DNA methylation has been associated with both early life stress and depression. This study examined the combined association of DNA methylation at multiple CpG probes in five stress-related genes with depressive symptoms and tested whether these genes methylation mediated the association between childhood trauma and depression in two monozygotic (MZ) twin studies. METHODS: The current analysis comprised 119 MZ twin pairs (84 male pairs [mean = 55 years] and 35 female pairs [mean = 36 years]). Peripheral blood DNA methylation of five stress-related genes (BDNF, NR3C1, SLC6A4, MAOA, and MAOB) was quantified by bisulfite pyrosequencing or 450K BeadChip. We applied generalized Poisson linear-mixed models to examine the association between each single CpG methylation and depressive symptoms. The joint associations of multiple CpGs in a single gene or all five stress-related genes as a pathway were tested by weighted truncated product method. Mediation analysis was conducted to test the potential mediating effect of stress gene methylation on the relationship between childhood trauma and depressive symptoms. RESULTS: Multiple CpG probes showed nominal individual associations, but very few survived multiple testing. Gene-based or gene-set approach, however, revealed significant joint associations of DNA methylation in all five stress-related genes with depressive symptoms in both studies. Moreover, two CpG probes in the BDNF and NR3C1 mediated approximately 20% of the association between childhood trauma and depressive symptoms. CONCLUSIONS: DNA methylation at multiple CpG sites are jointly associated with depressive symptoms and partly mediates the association between childhood trauma and depression. Our results highlight the importance of testing the combined effects of multiple CpG loci on complex traits and may unravel a molecular mechanism through which adverse early life experiences are biologically embedded.

Dexamethasone-suppressed Salivary Cortisol and Pain Sensitivity in Female Twins.

OBJECTIVES: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with chronic pain. Studying pain sensitivity and the HPA axis could elucidate the role of stress in chronic pain development, which might be influenced by familial factors, including genes. METHODS: Associations between pain sensitivity and salivary cortisol and familial confounding in these associations were examined in 88 female, community-based twin pairs (75% monozygotic, mean age 29 y). Cortisol was assessed after 0.25 mg dexamethasone (DEX), recovery from 0.25 mg DEX, and after 0.5 mg DEX. Cold pressor task (CPT) pain ratings were obtained at threshold and at tolerance. Conditioned pain modulation (CPM) was examined using thermal heat as the testing stimulus and hot water as the conditioning stimulus. Generalized estimating equation models were used and adjusted for baseline pain rating, age, and other relevant covariates. RESULTS: After controlling for baseline cortisol, greater cortisol suppression following DEX administration and lower recovery cortisol levels were associated with higher pain ratings at tolerance during the CPT (Bs=-2.42 to -17.82; Ps=0.031 to<0.001) as well as with reduced CPM (Bs=-0.92 to -1.68; Ps=0.003 to 0.046). Interestingly, familial confounding was evident in the CPT and CPM during recovery from DEX administration, but not immediately following DEX administration. DISCUSSION: These findings contribute to understanding possible mechanisms underlying chronic pain by demonstrating that HPA axis response to negative feedback is related to pain sensitivity.

Resilient Coping Moderates the Effect of Trauma Exposure on Depression.

Posttraumatic depression rates are increasing in the United States, and there is a great need to identify malleable factors that could moderate posttraumatic depression levels. The purpose of this study was to examine whether resilient coping moderates the effects of trauma exposure on depression, while controlling for neuroticism-an established predictor of depressive symptoms. This study used data from 3,734 pairs of twins from the community-based University of Washington Twin Registry. Each twin pair was randomized with twin A in one subsample and twin B in the second subsample. The four-item Brief Resilient Coping Scale measured resilient coping. The two-item Patient Health Questionnaire measured depression. Multiple linear regression analyses were performed on each subsample, controlling for neuroticism. In addition to significant effects of neuroticism and trauma exposure on depression (p < .001), the effect of the interaction of resilient coping and trauma exposure on depression was significant in both subsamples (p < .01). High levels of resilient coping were associated with lower depression scores in the context of previous trauma exposure. Individuals high in resilient coping who experienced significant life traumas were less depressed after trauma exposure, even after controlling for neuroticism. Because coping skills may be learned, interventions that teach resilient coping to individuals with traumatic histories merit investigation. © 2016 Wiley Periodicals, Inc.

Familial Contributions to Self-Reported Sleep and Pain in Female Twins.

OBJECTIVE: The relationship between sleep quality and pain has been studied in populations with chronic pain and in nonclinical populations using experimental paradigms. Little is known about the familial contributions to this relationship. This study examines self-reported sleep quality and pain in a nonclinical sample and to explore familial (i.e., shared genetic and common family environment) confounding in those relationships. DESIGN: Cross-sectional. SUBJECTS: Ninety nine community-based female twin pairs (N = 198) with a mean age of 29 years; 72% monozygotic. METHODS: The short form McGill Pain Questionnaire (McGill), a visual analog scale (VAS), a body map, and the Pittsburgh Sleep Quality Index (PSQI) measured self-reported pain and sleep quality. Mixed model regression adjusted for age was used to examine relationships between the pain indices and PSQI in overall and within-pair models. RESULTS: Higher PSQI total scores were significantly associated with higher scores across the McGill sensory (B = 0.37, p < 0.001), affective (B = 0.16, p < 0.001), total scores (B = 0.54, p < 0.001), the VAS (B = 2.41, p < 0.001), and number of sites with any pain on the body map (B = 0.42, p = 0.001). All of these associations were diminished and rendered nonsignificant in within-pair analyses that accounted for genetic and familial factors (all p's ≥ 0.01; Bonferroni α = 0.01). CONCLUSIONS: These findings support an association between poor sleep quality and pain and suggest that this relationship may be confounded by shared genetic and environmental factors, which could elucidate biological mechanisms that underlie the development and maintenance of pain and sleep problems.

Alterations in Connectivity on Functional Magnetic Resonance Imaging with Provocation of Lower Urinary Tract Symptoms: A MAPP Research Network Feasibility Study of Urological Chronic Pelvic Pain Syndromes.

PURPOSE: Urological chronic pelvic pain syndromes have refractory bladder or pelvic pain as the dominant symptom. This has been attributed to changes in the central nervous system caused by a chronic barrage of noxious stimuli. We developed what is to our knowledge a novel challenge protocol that induced bladder distention in study participants to reproduce pain and urinary symptoms. We tested to see whether it could discriminate between persons with urological chronic pelvic pain syndrome-like symptoms and asymptomatic controls. MATERIALS AND METHODS: We recruited 10 female twin pairs who were discordant for urological chronic pelvic pain syndrome-like symptoms. Before scanning each twin urinated to completion and then consumed 500 cc water. Each twin was scanned with our resting state functional magnetic resonance imaging protocol immediately and approximately 50 minutes after consumption. Time series were extracted from the right and left periaqueductal gray, and the right and left amygdala subregions. We performed the repeated measures 2-sample t-test to assess differences in connectivity between symptomatic and asymptomatic twins before and after bladder distention. RESULTS: Group by condition interaction effects were found from the periaqueductal gray to the right cerebellum VIIIa, the amygdala, the right premotor cortex/supplementary motor area and the insular cortex, and between the amygdala and the frontal pole/medial orbital frontal cortex, the hypothalamus, the insular cortex, the thalamus and the anterior cingulate cortex. CONCLUSIONS: These findings demonstrate that our noninvasive bladder distention protocol can detect differences in the processing of urinary sensation between twins discordant for lower urinary tract pain.