Effects of Mindfulness-Based Stress Reduction on Experimental Pain Sensitivity and Cortisol Responses in Women With Early Life Abuse: A Randomized Controlled Trial.

OBJECTIVE: Early life abuse (ELAb) initiates pathophysiological cascades resulting in long-term maladaptive stress responsivity, hyperalgesia, and an increased risk of psychopathology. Mindfulness-based stress reduction (MBSR) is effective in modifying psychological and somatic symptoms; thus, we predicted that MBSR would be particularly efficacious for women with ELAb. METHOD: Medically healthy women (mean age = 31 years) with or without a history of early (≤13 years) physical or sexual abuse provided self-report measures and were tested in the laboratory before and after randomization to standard MBSR (n = 52) or social support (SSG) (n = 60) for 8 weeks. The laboratory procedure involved pain testing using the cold pressor and temporal summation of heat pain (indexing central sensitization) procedures, and exposure to the Trier Social Stress Test. Plasma cortisol in response to the experimental protocol was assessed as area under the curve (AUC). RESULTS: The interventions differentially impacted pain sensitivity and cortisol AUC for women with ELAb, as MBSR increased the temporal summation of heat pain intensity ratings (p = .024) and reduced cortisol AUC (p = .004). For women without ELAb, MBSR decreased cold pressor tolerance (p = .045) and decreased the temporal summation of heat pain intensity ratings relative to SSG (p = .024). Both MBSR and SSG improved depression symptoms and emotion regulation abilities (p values < .001); however, MBSR was associated with greater benefits in describing emotions (p = .008) and impulse control (p = .017) for women with ELAb. CONCLUSIONS: Women with ELAb benefited from MBSR-specific improvements in central sensitization, mindfulness skills, and emotion regulation abilities. This is the first study to examine the efficacy of MBSR in modifying affective and somatic symptoms based on ELAb status and provides evidence for considering ELAb in tailoring treatment approaches.Trial Registration: ClinicalTrials.gov Identifier: NCT01995916; https://clinicaltrials.gov/ct2/show/NCT01995916.

Active ghrelin and the postpartum.

Postpartum depression (PPD) occurs in 10-15 % of women. The appetite hormone ghrelin, which fluctuates during pregnancy, is associated with depression in nonpregnant samples. Here, we examine the association between PPD and active ghrelin from pregnancy to postpartum. We additionally examine whether ghrelin changes from pregnancy to postpartum and differs between breastfeeding and non-breastfeeding women. Sixty women who participated in a survey examining PPD and had information in regard to ghrelin concentrations were included in the study. The Edinburgh Postnatal Depression Scale was used to assess symptoms of PPD. Raw ghrelin levels and ghrelin levels adjusted for creatinine were included as outcomes. Women screening positive for PPD at 12 weeks postpartum had higher pregnancy ghrelin concentrations. Ghrelin concentrations significantly decreased from pregnancy to 6 weeks postpartum and this change differed based on pregnancy depression status. Finally, ghrelin levels were lower in women who breastfed compared with women who were bottle-feeding. No significant findings remained once ghrelin levels were adjusted for creatinine. Although results do not suggest an association between PPD and ghrelin after adjusting for creatinine, future research should continue to explore this possibility extending further across the postpartum period with larger sample sizes.

Partner burden in irritable bowel syndrome.

BACKGROUND & AIMS: Studies have described the burden experienced by caregivers and next of kin to patients with diseases such as cancer. However, the burden of functional gastrointestinal disorders on partners of patients has not been determined. We aimed to quantify the degree of burden to partners of patients with irritable bowel syndrome (IBS), to describe the factors that affect the burden perceived, and to identify the areas of relationship that are affected. METHODS: We surveyed 152 patients diagnosed with IBS at a tertiary gastrointestinal clinic, on the basis of Rome III criteria, and their partners. Their partners completed questionnaires including the Zarit Burden Interview (ZBI), Relationship Satisfaction Scale, and questions on sexual relationships. Patients with IBS were rated for disease severity by using the Functional Bowel Disease Severity Index. We compared findings with those from 39 partners of healthy individuals (controls). RESULTS: There were no significant demographic differences between the partners of patients with IBS and controls; demographics had no effect on burden. Burden was significantly higher among partners of IBS patients (mean ZBI score, 22.1) than controls (mean ZBI score, 11.5) (P = .0002). The degree of burden was directly related to IBS severity (P < .0001). There were inverse relationships between partners' rating of burden (ZBI) and relationship quality (R = -0.60; P < .001) and sexual satisfaction (R = -0.56; P < .0001). There was no difference in the Relationship Satisfaction Scale scores (4.25 vs 4.19; P = .78) or sexual relationship (6.47 vs 6.21; P = .64) between partners of IBS patients and controls, respectively. CONCLUSIONS: Partners of patients with IBS have a significant burden (on the basis of ZBI score), compared with partners of healthy individuals. Perceived burden increases with IBS severity and poorer sexual and relationship satisfaction.

Intranasal oxytocin blocks alcohol withdrawal in human subjects.

BACKGROUND: The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. METHODS: In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. RESULTS: All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01). CONCLUSIONS: This is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients.

Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome.

UNLABELLED: OBFECTIVES: Narcotic bowel syndrome (NBS) is characterized by a paradoxical increase in abdominal pain associated with continued or escalating dosages of narcotics. This study evaluated the clinical and psychosocial features of patients with NBS and the response to detoxification treatment. METHODS: For 2 years, 39 patients seen by the GI consult service at the University of North Carolina at Chapel Hill (UNC) with presumed NBS were placed on a detoxification program. Clinical, psychosocial, health status, and outcome data were obtained before and after detoxification. Our aims were to: (i) clinically characterize patients with presumed NBS, (ii) assess the clinical response and adverse effects to detoxification, (iii) identify clinical and psychosocial predictors of treatment response, and (iv) determine the clinical outcome at 3 months after detoxification and the time frame for patients who revert back to narcotics. RESULTS: Of the 39 patients detoxified, 89.7% met predefined criteria. Patients were mostly well educated (14.5 ± 2.3 years of school), female (92.3%), and with a variety of diagnoses (21% irritable bowel syndrome IBS/functional, 37% inflammatory bowel disease and other structural, 29% fibromyalgia and other functional somatic, or orthopedic, and 13% postoperative or other). They reported high health-care use (15.3 ± 10.1 MD visits/6 months; 6.5 ± 6.1 hospitalizations/2 years, 6.4 ± 2.0 surgeries/lifetime), and 82.1% were jobless. Despite high dosages of narcotics (total intravenous (IV) morphine equivalent 75.3 ± 78.0 mg/day), pain scores were rated severe (52.9 ± 28.8 visual analog scale (VAS); 257.1 ± 139.6 functional bowel disorder severity index (FBDSI); 17.2 ± 10.2 (McGill Pain and greater than labor or postoperative pain). Multiple symptoms were reported (n = 17.8 ± 9.2) and rated as moderate to severe. Psychosocial scores showed high catastrophizing (19.9 ± 8.6); poor daily function (Short Form-36 (SF-36) physical 28.3 ± 7.7, mental 34.3 ± 11.0; worse than tetraplegia); 28.2% were clinically depressed and 33.3% anxious (Hospital Anxiety and Depression Scale (HADS)). Detoxification was successfully completed by 89.7%; after detoxification, abdominal pain was reduced by 35% (P < 0.03) and nonabdominal pain by 42% (P < 0.01) on VAS, and catastrophizing significantly improved (P < 0.01). Responder status was met in 56.4% with 48.7% achieving a ≥ 30% reduction in pain. By 3 months after detoxification, 45.8% had returned to using narcotics. For those who remained off narcotics at 3 months, the VAS abdominal pain score was 75% lower than pretreatment when compared with those who went back on narcotics (24% lower). Successful detoxification and a good clinical response was associated with low abuse potential (Current Opioid Misuse Measure (COMM) score < 9). CONCLUSIONS: Despite severe pain, poor coping, and poor health status, almost all patients with NBS undergoing detoxification were able to stop using narcotics and have significant improvement in pain and coping. However, almost ½ reverted to narcotic use at 3 months. Those who stayed off narcotics showed greater improvement in pain scores. This study provides a rationale for treating patients with NBS by detoxification in order to improve their clinical status. Further work is needed to understand the reasons for the high recidivism rate.

Hypothalamic-pituitary-thyroid axis function in women with a menstrually related mood disorder: association with histories of sexual abuse.

INTRODUCTION: We previously reported a unique hypothalamic-pituitary-thyroid (HPT) axis profile in women with a menstrually related mood disorder (MRMD) who also had a history of sexual abuse (SA). In the present study, we sought to extend that work by examining the association of an SA history with HPT-axis disturbance in both women with MRMD and women without MRMD. METHODS: Fifty-seven women met the prospective criteria for MRMD (23 with an SA history), and 52 women were non-MRMD (18 with an SA history). Thyroid-stimulating hormone, thyroxin (T4; total and free), and triiodothyronine (T3; total and free) were evaluated in serum, together with thyroid hormone ratios reflecting T4 to T3 conversion. RESULTS: Women with MRMD, compared with women without MRMD, had elevated T3/T4 ratios (p values ≤ .01; reflecting increased conversion of T4 to T3) and lower free and total T4 concentrations (p values = .01). Higher T3/T4 ratios and lower T4 concentrations predicted more severe premenstrual symptoms in all women. An SA history, irrespective of MRMD status, was associated with elevated thyroid-stimulating hormone concentrations (p = .03). However, in women with MRMD, an SA history was associated with elevated T3 concentrations (p = .049), whereas in women without MRMD, an SA history was associated with decreased T3 concentrations (p = .02). CONCLUSIONS: An MRMD and an SA history are associated with independent and interactive effects on the HPT axis. The evidence that an MRMD moderates the influence of SA on T3 concentrations contributes to a growing body of work suggesting that an SA history may identify a distinct subgroup of women with MRMD.

Relationship between trauma and high-risk behavior among HIV-positive men who do not have sex with men (MDSM).

The incidence of heterosexual HIV transmission continues to increase in the USA. However, little is known about factors that influence high-risk behavior among men who do not have sex with men (MDSM). This study examines the association of childhood sexual abuse and high-risk behaviors among MDSM. The Coping with HIV/AIDS in the Southeast (CHASE) study included 611 HIV-positive individuals in the Southeastern US Bivariate statistics were used to examine the influence of childhood sexual abuse among MDSM, men who have sex with men (MSM), and women. Study findings indicated that among MDSM with HIV, childhood sexual abuse predicted a higher number of sexual partners, alcohol and drug use problems, depression, post-traumatic stress disorder (PTSD), and less trust in medical providers. Similar statistically significant relationships between childhood sexual abuse and negative outcomes were not found for MSM and women with the exception of childhood sexual abuse predicting PTSD and alcohol use in women. Study findings indicate a need for more in-depth research to examine the role of childhood sexual abuse in shaping adult risk behaviors among MDSM as well as a need to assess for and address childhood sexual abuse in this population.

Characterization of episodes of irritable bowel syndrome using ecological momentary assessment.

OBJECTIVES: Patients with irritable bowel syndrome (IBS) report that symptoms occur as episodes. The nature and frequency of episodes have not been well studied. METHODS: Using modified ecological momentary assessment (EMA), we examined clinical factors attributed to IBS symptom episodes and compared them with nonsymptom episode periods in patients with IBS-D (N=21), IBS-C (N=18), or IBS-M (N=19), and healthy controls (N=19). Symptoms were rated over 14 days on a visual ordinal scale (VOS: 0-10) randomly in morning, midday, and evening, and at wake up, bedtime, prebowel movement, and postbowel movement. Scores were evaluated for total group and across subgroups and between EMA and daily diary cards on the same day. RESULTS: Subjects (n=57/59) reported symptom episodes 34% of the time. Episodes showed significantly higher pain levels (3.6 vs. 1.64, P<0.0001), bloating (4.57 vs. 3.02, P<0.0001), stress (3.54 vs. 2.59, P<0.0001), and decreased well-being (5.29 vs. 6.16, P<0.0001). Episode frequency/2 weeks was greatest for IBS-D (10.7±7.05) than IBS-C (8.4±5.76) and IBS-M (7.1±4.45) (P=nonsignificant). IBS-D also had shorter episodes (9 h 23 min) compared with IBS-M (15 h 01 min) and IBS-C (15 h 25 min) (P<0.04). Stool frequency and looser consistency were greater with IBS-D and similar between IBS-C and IBS-M. Abdominal pain was the greatest predictor of episode status. Diary card ratings of pain and stool frequency overestimate levels reported by EMA. CONCLUSIONS: Episodes of IBS are associated with greater pain (strongest relationship), bloating, and stress scores, and poorer global well-being. Compared with IBS-D, IBS-C and IBS-M are similar in clinical features. Patients overreport pain and stool frequency by diary compared with EMA.

Highly stressed: stressful and traumatic experiences among individuals with HIV/AIDS in the Deep South.

A history of traumatic and/or stressful experiences is prevalent among HIV-infected individuals and has been consistently associated with poorer health outcomes. However, little is known about incident stressful experiences and the factors that predict these experiences among HIV-infected individuals. Data from a longitudinal study of 611 HIV-infected individuals in the Southeastern USA were used to examine the frequency and types of incident stress reported in a 27-month period and to determine predictors associated with three incident stress measures (all stressful events, severe stressful events, and traumatic events such as physical assault). Incident stressful experiences frequently occurred among study participants, as 91% reported at least one stressful experience (median=3.5 experiences) and 10% of study participants reported traumatic stress in any given nine-month reporting period. Financial stressors were the most frequently reported by study participants. Greater emotional distress, substance use, and a higher number of baseline stressful experiences were significantly associated with reporting a greater number of incident stressful experiences and any traumatic experiences. Study results indicate that efforts are needed to identify individuals at risk for traumatic events and/or substantial stressors and to address the factors, including mental health and substance abuse, that contribute to these experiences.

Psychiatric comorbidity in women with chronic pelvic pain.

Chronic pain syndromes are often treatment refractory and pose an enormous burden of suffering for the individual. Chronic pelvic pain (CPP) is generally defined as noncyclic pain of at least 6 months duration and severe enough to require medical care or cause disability. CPP has been estimated to have a prevalence of 15% among women of reproductive age. Women are at increased risk for both major depression and chronic pain syndromes such as CPP, and are more likely to report antecedent stressful events, have higher rates of physical and sexual abuse, and subsequently develop posttraumatic stress disorder. High rates of sexual and physical abuse and other trauma have been shown among women with CPP, including symptoms of dyspareunia (pain during intercourse), dysmenorrhea (pain during menstruation), and vulvar pain. A detailed and comprehensive evaluation of the patient with CPP should include a thorough gynecologic exam and a full mental health assessment. Treatment of CPP must include an integrated approach targeted at both the psychiatric comorbidity and pain symptoms. A multidisciplinary treatment team offers the best chance for success with CPP, and it is critical to suggest psychiatric treatment (psychopharmacology and/or psychotherapy) in addition to traditional medical and surgical approaches.

Cognitive factors affect treatment response to medical and psychological treatments in functional bowel disorders.

OBJECTIVES: For clinical trials in functional bowel disorders (FBD), the definition of a responder, one who meets the predefined criteria for a clinical response, is needed. Factors that determine clinical response aside from treatment itself are unknown. The aim of this study was to determine what baseline and post-treatment factors affect treatment response. METHODS: Females (n=397) with FBD entering a 12-week, four-arm, randomized NIH treatment trial (desipramine (DES), CBT, pill placebo, and education) were studied at baseline and after treatment. Demographic, clinical, psychosocial, and physiological variables were considered in the analysis. A responder was defined as a patient obtaining a score>3.5 on an averaged eight-item, five-point satisfaction-with-treatment questionnaire. Baseline and post-treatment logistic regressions were performed for each treatment condition to predict the responder outcome variable. RESULTS: Similar cognitive features predisposed participants to treatment response across the treatment conditions: sense of control over the condition, positive relationship with therapist or study coordinator, confidence in treatment, improvement in maladaptive cognitions, and quality of life during treatment. Demographic and clinical variables studied were not predictive. Some treatment-specific effects predicting responder status were noted, including a reduction in stool frequency with DES treatment and lack of abuse history in the placebo group. CONCLUSIONS: For medication, psychological, and placebo treatment in FBD, satisfaction with treatment depends on cognitive factors of confidence in treatments, perceived control over illness and symptoms, and reduction in negative cognitions related to symptom experience. Addressing these issues among patients with FBD may enhance treatment response to a variety of treatments.

Incident stressful and traumatic life events and human immunodeficiency virus sexual transmission risk behaviors in a longitudinal, multisite cohort study.

OBJECTIVE: To assess the association between incident stressful life events (e.g., sexual and physical assault; housing instability; and major financial, employment, and legal difficulties) and unprotected anal or vaginal sexual intercourse (unprotected sex) among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (PLWHA). METHODS: We assessed incident stressful events and unprotected sex over 27 months in 611 participants in an eight-site, five-state study in the Southeast United States. Using mixed-effects logistic models and separately estimating between-person and within-person associations, we assessed the association of incident stressful events with unprotected sex with all partners, HIV-positive partners, and HIV-negative/serostatus-unknown partners. RESULTS: Incident stressful events reported at one third or more of interviews included major illness, injury or accident (non-HIV-related); major illness of a family member/close friend; death of a family member/close friend; financial stresses; and relationship stresses. In multivariable models, each additional moderately stressful event an individual experienced at a given time point above his or her norm (within-person association) was associated with a 24% to 27% increased odds of unprotected sex for each partner type. CONCLUSIONS: Risk reduction among PLWHA remains a major focus of efforts to combat the HIV epidemic. Incident stressful events are exceedingly common in the lives of PLWHA and are associated with increased unprotected sex. Efforts to either prevent the occurrence of such events (e.g., financial or relationship counseling) or address their sequelae (e.g., coping skills or other behavioral counseling) may help reduce secondary HIV transmission.

Physiological and psychosocial factors that predict HIV-related fatigue.

Fatigue is one of the most common and debilitating symptoms experienced by HIV-infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue.

Psychosocial factors are more important than disease activity in determining gastrointestinal symptoms and health status in adults at a celiac disease referral center.

BACKGROUND: The relative effects of clinical and psychosocial variables on outcome in celiac disease (CD) has not previously been reported. In adult patients with (CD), we studied the relationships among demographics, psychosocial factors, and disease activity with health-related quality of life (HRQOL), health care utilization, and symptoms. METHODS: Among 101 adults newly referred to a tertiary care center with biopsy-proven CD we assessed: (a) demographic factors and diet status; (b) disease measures (Marsh score, tissue transglutaminase antibody (tTG) level, weight change and additional blood studies); and (c) Psychosocial status (psychological distress, life stress, abuse history, and coping). Multivariate analyses were performed to predict HRQOL, daily function, self-reported health, number of physician visits, and GI symptoms (pain and diarrhea). RESULTS: Impaired HRQOL and daily function was associated with psychological distress and poorer coping. Self-report of poorer health was associated with poorer coping, longer symptom duration, lower education, and greater weight loss. More physician visits were associated with poorer coping, abnormal tTG levels, and milder Marsh classification. Greater pain scores were seen in those with higher psychological distress and greater weight loss. Finally, diarrhea was associated with greater psychological distress and poorer coping. CONCLUSIONS: In patients presenting to a CD referral center, psychosocial factors more strongly affect health status and GI symptoms than disease measures.

Obsessional thoughts and compulsive behaviors in a sample of women with postpartum mood symptoms.

Postpartum psychiatric disorders are widely recognized by clinicians and researchers, yet while much attention has been paid to perinatal mood disorders, considerably less has been given to anxiety and obsessive-compulsive symptoms in this population. The present study examined anxiety and obsessive-compulsive symptoms among postpartum women with mood complaints, with the aim of delineating the relationship between these symptoms. Sixty postpartum women seeking treatment in a perinatal mood disorders clinic completed measures of depression, anxiety, and obsessive-compulsive symptoms. Obsession-like thoughts and compulsive-like ("neutralizing") strategies were present among the majority of the sample, yet the severity of these symptoms ranged widely. Depressive and anxiety symptoms were associated with obsessive and neutralizing compulsive symptoms. It may be helpful to consider anxiety and depressive symptoms as part of a broad spectrum of perinatal psychiatric illness. Clinicians should assess for anxiety and obsessive-compulsive symptoms as routinely as they assess for depressive symptoms in the perinatal period.

Effect of abuse history on pain reports and brain responses to aversive visceral stimulation: an FMRI study.

BACKGROUND & AIMS: Abuse history is common in irritable bowel syndrome (IBS) and is associated with greater pain reporting, psychologic distress, and poorer health outcome. These effects may be mediated by enhanced responses to aversive visceral stimuli. We investigated the effects of IBS and abuse history on pain reporting and brain activation in response to rectal distentions. METHODS: Ten female patients with IBS and 10 controls were included. Half of patients in each group reported a history of abuse. Brain functional magnetic resonance imaging (fMRI) images and pain ratings were obtained during rectal distentions. Statistical parametric mapping identified activation in subregions of the dorsal cingulate cortex and covariation with rated pain. RESULTS: (1) Distention-elicited pain correlated with anxiety and activation of the posterior (PCC) and middle (MCC) dorsal cingulate subregions. (2) Subjects with a history of abuse showed greater activation in the left MCC (P = .022; t = 5.61) and PCC (P = .033; t = 5.00) than subjects without abuse. (3) Those with IBS and abuse reported greater pain than all others (P = .004), had more activity in the left MCC (P = .021; t = 5.29) and PCC (P = .049; t = 4.81), and had less activity in the left supragenual anterior cingulate (sACC) (P = .01; t = 4.86). CONCLUSIONS: Pain ratings during rectal distention are associated with activation of dorsal cingulate regions implicated in homeostatic afferent processing, and prior abuse enhances this activation. Patients with IBS and abuse report more pain, greater MCC/PCC activation, and reduced activity of a region implicated in pain inhibition and arousal (sACC). These findings suggest a possible explanation for the clinical observation of greater pain reporting and poorer outcome in IBS patients with a history of abuse.

Not all side effects associated with tricyclic antidepressant therapy are true side effects.

BACKGROUND & AIMS: Patients with functional gastrointestinal disorders treated with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it is unclear whether these are drug side effects or reflect a behavioral tendency to report symptoms. We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms. METHODS: Female patients in a multicenter National Institutes of Health trial for functional bowel disorders completed a 15-item symptom questionnaire at baseline (before randomization), 2 weeks after they were given desipramine (n = 81) or placebo (n = 40), and at study completion (12 weeks). Patients were asked about the severity and frequency of 15 symptoms. Results were analyzed from 57 patients given desipramine who completed the questionnaires. RESULTS: Symptoms reported as side effects to have occurred more frequently and also worsened at week 2 in the group given desipramine included dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and flushing. Symptoms that did not change in severity or showed improvement at week 2 in the group given desipramine included morning tiredness, nausea, blurred vision, headaches, appetite reduction, and trouble sleeping. Psychologic distress but not desipramine blood level correlated with symptom reporting. CONCLUSIONS: Most symptoms often attributed to side effects of desipramine were present before treatment; only a few, related to anticholinergic effects, worsened 2 weeks after treatment, suggesting that most so-called side effects were not associated specifically with desipramine use. Such symptoms might instead be associated with psychologic distress.

Overload: impact of incident stressful events on antiretroviral medication adherence and virologic failure in a longitudinal, multisite human immunodeficiency virus cohort study.

OBJECTIVE: To examine the influence of incident stressful experiences on antiretroviral medication adherence and treatment outcomes. Past trauma history predicts poorer medication adherence and health outcomes. Human immunodeficiency virus (HIV)-infected individuals experience frequently traumatic and stressful events, such as sexual and physical assault, housing instability, and major financial, employment, and legal difficulties. METHODS: We measured prospectively incident stressful and traumatic events, medication adherence, and viral load over 27 months in an eight-site, five-state study. Using multivariable logistic and generalized estimating equation modeling, we assessed the impact of incident stressful events on 27-month changes in self-reported medication adherence and virologic failure (viral load = >or=400 c/mL). RESULTS: Of 474 participants on antiretroviral therapy at baseline, 289 persons were interviewed and still received treatment at 27 months. Participants experiencing the median number of incident stressful events (n = 9) had over twice the predicted odds (odds ratio = 2.32) of antiretroviral medication nonadherence at follow-up compared with those with no events. Stressful events also predicted increased odds of virologic failure during follow-up (odds ratio = 1.09 per event). CONCLUSIONS: Incident stressful events are exceedingly common in the lives of HIV-infected individuals and negatively affect antiretroviral medication adherence and treatment outcomes. Interventions to address stress and trauma are needed to improve HIV outcomes.

International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit.

BACKGROUND: Although clinicians generally make treatment decisions in irritable bowel syndrome (IBS) related to the type of symptoms, other factors such as the perceived severity and the risks patients are willing to tolerate for effective treatment are also important to consider. These factors are not fully understood. OBJECTIVE: To describe among patients with IBS their symptoms and severity, quality of life and health status, medications taken, and the risk that they would take to continue medications for optimal relief. METHODS: Adult patients diagnosed with IBS who accessed the websites of the International Foundation for Functional GI Disorders or the University of North Carolina Center for Functional GI Disorders filled out questionnaires to address the study aims. RESULTS: The 1966 respondents (83% female, 91% white, 78% US/Canada) reported impaired health status: restricting on average 73 days of activity in a year, having poor health-related quality of life particularly with dietary restrictions, mood disturbance, and interference with daily activity, and 35% reported their symptoms as severe defined primarily as pain, bowel difficulties, bloating, and eating/dietary restrictions). These symptoms were reported in some combination by over 90%, and 35.1% endorsed all 4 items. To receive a treatment that would make them symptom free, patients would give up 25% of their remaining life (average 15 y) and 14% would risk a 1/1000 chance of death. Most of the medications being taken were for pain relief and 18% were taking narcotics. Complementary and alternative treatments were used by 37%. CONCLUSIONS: Patients accessing IBS informational websites report moderate-to-severe impairments in health status, and would take considerable risk to obtain symptom benefit. There is an unmet need to find effective treatments for patients with IBS and regulatory agencies might consider raising risk-benefit ratios when approving new medications for IBS.

Open-label trial of lamotrigine focusing on efficacy in vulvodynia.

OBJECTIVE: Chronic pelvic pain (CPP) affects 15% of women and has a high rate of psychiatric comorbidity. Vulvodynia, a vulvar pain syndrome that includes vulvar vestibulitis, is the most common subtype of CPP. This study examined the efficacy of lamotrigine for the treatment of CPP using an open-label design. STUDY DESIGN: Forty-three women with CPP were recruited from a specialty pelvic pain clinic. Of these, 31 completed 8 weeks of active treatment. Outcome variables included the McGill Pain Rating Index and subscales of pain intensity and the Hamilton Depression and Anxiety Rating Scales. RESULTS: We found significant reductions in all pain and mood measures at the 8-week visit compared to baseline. In particular, women with vulvodynia-type CPP (N = 17) had robust reductions in pain and mood symptoms. CONCLUSION: CPP is a heterogeneous disorder, with psychiatric comorbidity and poor treatment response. This open-label study suggests that treatment with lamotrigine in women with the vulvodynia subtype of CPP may be helpful in addressing both the pain and mood symptoms associated with this disorder.