Anxiety Disorders: Naliboff BD

Levy RL, Olden KW, Naliboff BD, Bradley LA, Francisconi C, Drossman DA, Creed F. · University of Washington, Seattle, Washington 98105, USA. · Gastroenterology. · Pubmed #16678558 No free full text.

Abstract: This report reviews recent research on the psychosocial aspects of the functional gastrointestinal disorders (FGIDs). A review and evaluation of existing literature was conducted by a multidisciplinary committee of experts in this field. This report is a synopsis of a chapter published in the Rome III book. The committee reached consensus in finding considerable evidence supporting the association between psychological distress, childhood trauma and recent environmental stress, and several of the FGIDs but noted that this association is not specific to FGIDs. There is also considerable evidence that psychosocial variables are important determinants of the outcomes of global well-being, health-related quality of life, and health care seeking. In line with these descriptive findings, there is now increasing evidence that a number of psychological treatments and antidepressants are helpful in reducing symptoms and other consequences of the FGIDs in children and adults. The FGIDs are a result of complex interactions between biological, psychological, and social factors, and they can only be treated satisfactorily when all these factors are considered and addressed. Therefore, knowledge about the psychosocial aspects of FGIDs is fundamental and critical to the understanding, assessment, and treatment of these disorders. More extensive physician training is needed if these aspects of treatment are to be used effectively and widely in clinical practice.

Mayer EA, Craske M, Naliboff BD. · Department of Medicine, University of California, Los Angeles, USA. · J Clin Psychiatry. · Pubmed #12108819 No free full text.

Abstract: Functional disorders of the digestive system, such as irritable bowel syndrome, are often associated with affective disorders, such as depression, anxiety, panic, and posttraumatic stress disorder (PTSD). Some of these associations are observed not only in clinical populations, but also in population-based samples, suggesting a relationship with pathophysiologic mechanisms underlying both gastrointestinal (GI) dysfunction and certain affective disorders. Sustained and acute life-threatening stressors play an important role in the onset and modulation of GI symptoms as well as in the development of affective disorders and PTSD. A neurobiological model is proposed that attempts to explain the development of visceral hypersensitivity, the neuroendocrine and autonomic dysfunction characteristic of functional GI disorders, as well as the overlap with affective disorders.

Berman SM, Naliboff BD, Suyenobu B, Labus JS, Stains J, Ohning G, Kilpatrick L, Bueller JA, Ruby K, Jarcho J, Mayer EA. · Department of Medicine, University of California, Los Angeles Center for Neurovisceral Sciences and Women's Health, David Geffen School of Medicine at University of California, Los Angeles, 90073, USA. · J Neurosci. · Pubmed #18184777 links to  free full text

Abstract: Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls. During cued anticipation of distention, activity decreased in the insula, supragenual anterior cingulate cortex (sACC), amygdala, and dorsal brainstem (DBS) of controls. IBS patients showed less anticipatory inactivation. Group differences were significant in the right posterior insula and bilateral DBS. Self-rated measures of negative affect during scanning were higher in patients than controls (p < 0.001), and the anticipatory BOLD decreases in DBS were inversely correlated with these ratings. During subsequent distention, both groups showed activity increases in insula, dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, producing significant group differences in dorsal ACC and DBS. The amplitude of the anticipatory decrease in the pontine portion of DBS was associated with greater activation during distention in right orbitofrontal cortex and bilateral sACC. Both regions have been associated previously with corticolimbic inhibition and cognitive coping. Deficits in preparatory inhibition of DBS, including the locus ceruleus complex and parabrachial nuclei, may interfere with descending corticolimbic inhibition and contribute to enhanced brain responsiveness and perceptual sensitivity to visceral stimuli in IBS.

Twiss C, Kilpatrick L, Craske M, Buffington CA, Ornitz E, Rodríguez LV, Mayer EA, Naliboff BD. · Department of Urology, Center for Neurobiology of Stress, Los Angeles, California, USA. · J Urol. · Pubmed #19286199 No free full text.

Abstract: PURPOSE: Hypersensitivity to visceral stimuli in interstitial cystitis/painful bladder syndrome may result from enhanced responsiveness of affective circuits (including the amygdala complex) and associated central pain amplification. Potentiation of the eyeblink startle reflex under threat is mediated by output from the amygdala complex and, therefore, represents a noninvasive marker to study group differences in responsiveness in this brain circuit. MATERIALS AND METHODS: Acoustic startle responses were examined in female patients with interstitial cystitis/painful bladder syndrome (13) and healthy controls (16) during context threat (application of muscle stimulation electrodes to the lower abdomen overlying the bladder), and cued conditions for safety (no stimulation possible), anticipation and imminent threat of aversive abdominal stimulation over the bladder. RESULTS: Patients showed significantly greater startle responses during nonimminent threat conditions (baseline, safe and anticipation periods) while both groups showed similar robust startle potentiation during the imminent threat condition. Higher rates of anxiety and depression symptoms in the patient group did not account for the group differences in startle reflex magnitude. CONCLUSIONS: Compared to controls, female patients with interstitial cystitis/painful bladder syndrome showed increased activation of a defensive emotional circuit in the context of a threat of abdominal pain. This pattern is similar to that previously reported in patients with anxiety disorders as well as those with irritable bowel syndrome. Since these circuits have an important role in central pain amplification related to affective and cognitive processes, these results support the hypothesis that the observed abnormality may be involved in the enhanced perception of bladder signals associated with interstitial cystitis/painful bladder syndrome.

Naliboff BD, Waters AM, Labus JS, Kilpatrick L, Craske MG, Chang L, Negoro H, Ibrahimovic H, Mayer EA, Ornitz E. · Center for Neurobiology of Stress, Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles, California, USA. · Psychosom Med. · Pubmed #18842745 No free full text.

Abstract: BACKGROUND AND AIMS: Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (IBS) are both exacerbated by stress. The eye-blink startle response represents a noninvasive measure of central defensive responding. Evidence for central hyperexcitability was studied in IBS patients by examining potentiation of the startle reflex to a nociceptive threat. METHODS: Acoustic startle responses were examined in female IBS patients (n = 42) and healthy controls (n = 22) during cued periods in which an aversive abdominal or biceps stimulation was impossible (safe), possible (imminent threat) or anticipated (period just before the imminent threat), and during a threatening context (muscle stimulation pads attached but no cues for stimulation). RESULTS: Both groups showed potentiation of startle responses during the imminent threat condition compared with both the anticipation and safe conditions. Compared with controls, IBS subjects showed significantly larger startle responses during anticipation and imminent threat conditions after receiving an initial aversive stimulation. There were no group differences during the context threat manipulation. Moreover, in IBS patients but not controls, higher neuroticism was associated with larger startle responses during safe and anticipation conditions but not imminent threat, whereas anxiety symptoms were negatively associated with startle magnitude during imminent threat. CONCLUSIONS: Female IBS patients show increased startle responses to threat of aversive stimulation at both abdominal and nonabdominal sites compared with controls. The data represent the first demonstration of altered threat potentiated startle in a functional pain condition and provide support for the use of these paradigms in further evaluation of affective mechanisms in these disorders.

Waters AM, Craske MG, Bergman RL, Naliboff BD, Negoro H, Ornitz EM. · School of Psychology, Griffith University, Gold Coast, Qld, Australia. · Int J Psychophysiol. · Pubmed #18718853 No free full text.

Abstract: The present study examined the development of elevated startle reactivity in anticipation of mild anxiogenic procedures in school-age children with current anxiety disorders and in those at-risk for their development due to parental anxiety. Startle blink reflexes and skin conductance responses were assessed in 7 to 12 year old anxious children (N=21), non-anxious children at-risk for anxiety by virtue of parental anxiety disorder status (N=16) and non-anxious control children of non-anxious parents (N=13). Responses were elicited by 28 auditory startle stimuli presented prior to undertaking mild anxiogenic laboratory procedures. Results showed that group differences in startle reactivity differed as a function of children's age. Relative to control children for whom age had no effect, startle reflex magnitude in anticipation of anxiogenic procedures increased across the 7 to 12 years age range in children at-risk for anxiety disorders, whereas elevations in startle reactivity were already manifest from a younger age in children with anxiety disorders. These findings may suggest an underlying vulnerability that becomes manifest with development in offspring of anxious parents as the risk for anxiety disorders increases.

Ringel Y, Drossman DA, Leserman JL, Suyenobu BY, Wilber K, Lin W, Whitehead WE, Naliboff BD, Berman S, Mayer EA. · UNC Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina, USA. · Gastroenterology. · Pubmed #18242208 No free full text.

Abstract: 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.

Schieffer BM, Pham Q, Labus J, Baria A, Van Vort W, Davis P, Davis F, Naliboff BD. · Veteran's Administration Greater Los Angles Healthcare System, Los Angeles, CA 90073, USA. · J Pain. · Pubmed #16139781 No free full text.

Abstract: This study assessed the influence of medication beliefs, symptom severity, disability, mood, and psychiatric history on opiate medication misuse behaviors in 288 chronic pain patients. Data were gathered by questionnaires and systematic reviews of electronic medical records. The results demonstrate that patients with a history of substance abuse, compared to those without, showed greater medication misuse despite similar dosages and self-rated opiate effectiveness. Misusers believed more strongly in the potential for opiate addiction and that they required higher doses than others, but also had greater belief in opiate effectiveness and the importance of free access. Although both anxiety and substance abuse history are related to medication misuse, a multivariate analysis indicated that these factors can be seen as mediated by medication beliefs. These data suggest important roles for historical, affective, and cognitive variables in understanding medication misuse. Patients with a history of substance abuse report stronger beliefs in opiate effectiveness while simultaneously showing awareness of their addiction potential. Providers may help patients by addressing these issues prior to prescribing opiates. PERSPECTIVE: History of substance abuse is associated with increased opiate medication misuse independent of differences in reported opiate effectiveness. Self-attributions regarding opiate treatment related to need for higher doses, dose control, and addiction potential, may be important mediators of this relationship and interact with anxiety to produce heightened risk of opiate misuse.

Tillisch K, Labus JS, Naliboff BD, Bolus R, Shetzline M, Mayer EA, Chang L. · CNS/WH: Center for Neurovisceral Sciences & Women's Health, Department of Medicine, UCLA, and the VA Greater Los Angeles Healthcare System, Los Angeles, California, USA. · Am J Gastroenterol. · Pubmed #15784038 No free full text.

Abstract: BACKGROUND: Due to a wide range of symptom patterns, patients with irritable bowel syndrome (IBS) are often subgrouped by bowel habit. However, the IBS subgroup with alternating bowel habits (IBS-A) has been poorly characterized. OBJECTIVES: (i) To determine a set of bowel habit symptom criteria, which most specifically identifies IBS patients with an alternating bowel habit, (ii) to describe IBS-A bowel symptom patterns, and (iii) to compare clinical characteristics among IBS-A, constipation-predominant (IBS-C), and diarrhea-predominant IBS (IBS-D). METHODS: One thousand one hundred and two Rome I positive IBS patients were analyzed. Three sets of potential criteria for IBS-A were developed and compared by multirater Kappa test. Gastrointestinal, psychological, extraintestinal symptoms, and health-related quality of life were compared in IBS-A, IBS-C, and IBS-D using chi(2) test and analysis of variance (ANOVA). RESULTS: Stool consistency was determined to be the most specific criteria for alternating bowel habits. IBS-A patients reported rapid fluctuations in bowel habits with short symptom flares and remissions. There was a greater prevalence of psychological and extraintestinal symptoms in the IBS-A subgroup compared to IBS-C and IBS-D. No differences were seen between bowel habit subtypes in health-related quality of life. CONCLUSIONS: IBS-A patients have rapidly fluctuating symptoms and increased psychological comorbidity, which should be taken into account for clinical practice and clinical trials.

Naliboff BD, Mayer M, Fass R, Fitzgerald LZ, Chang L, Bolus R, Mayer EA. · Center for Neurovisceral Sciences & Women's Health, Department of Medicine, UCLA, Los Angeles, CA, USA. · Psychosom Med. · Pubmed #15184707 links to  free full text

Abstract: OBJECTIVE: Psychosocial stressors have been associated with exacerbations of symptoms in functional and inflammatory disorders of the gastrointestinal tract. The present longitudinal study tests the general hypothesis that life stressors can exacerbate symptoms in patients with chronic heartburn. METHODS: Sixty subjects with current heartburn symptoms were recruited by community advertisement and assessed for presence of stressful life events retrospectively over the preceding 6 months and prospectively for 4 months. Symptom severity by daily diary, quality of life, and psychological symptoms of anxiety, depression, and vital exhaustion were also measured. RESULTS: The presence of a severe, sustained life stress during the previous 6 months significantly predicted increased heartburn symptoms during the following 4 months. In addition, symptoms showed a strong, independent correlation with vital exhaustion. Affective and subjective stress ratings were not strongly related to heartburn severity; however, anxiety showed the strongest relationship to impaired quality of life and depression to heartburn medication use. CONCLUSIONS: As with other chronic conditions such as irritable bowel syndrome (IBS), heartburn severity appears to be most responsive to major life events and not an accumulation of more minor stressors or fluctuations in mood. In addition, vital exhaustion, which may in part result from sustained stress, may represent the psychophysiological symptom complex most closely associated with heartburn exacerbation. Potential mechanisms for these results include increased level and frequency of esophageal acid exposure, inhibition of gastric emptying of acid, or stress-induced hypersensitivity.

Tsao JC, Dobalian A, Naliboff BD. · Pediatric Pain Program, Department of Pediatrics, David Geffen School of Medicine at UCLA, 10940 Wilshire Blvd, Suite 1450, Los Angeles, CA 90024, USA. · Pain. · Pubmed #15082139 No free full text.

Abstract: Research to date has focused on depression and co-existing pain in HIV with relatively little attention devoted to the study of anxiety disorders and concurrent pain. We therefore examined the relationships among panic disorder, posttraumatic stress disorder (PTSD), major depression and pain in a US national sample of persons with HIV, controlling for key sociodemographic and clinical variables, including HIV disease status. The study sample comprised 1489 HIV+ individuals (representing 219 667 persons). In multivariate analyses, panic disorder showed a strong association with pain ( beta= -15.70; 99% confidence interval [CI]=-21.33 to -10.08; P<0.001, which was significantly greater than PTSD (P=0.002) but only marginally greater than major depression (P=0.002). Longitudinal analyses of the three psychological disorders revealed that increasing pain from baseline to follow-up (an approximately 6-month period) was associated with panic disorder only (relative risk ratio=2.18, 99% CI=1.02-4.69; P<0.01), after controlling for baseline pain scores, baseline HIV disease status and change in disease stage across time. We discuss specific mechanisms by which clinical anxiety and chronic pain may be mutually maintained in HIV+ individuals. Our findings suggest that panic disorder, as well as PTSD and major depression are associated with greater pain in HIV patients.

Hazlett-Stevens H, Craske MG, Mayer EA, Chang L, Naliboff BD. · Department of Psychology/298, University of Nevada, Reno, NV 89557, USA. · J Psychosom Res. · Pubmed #14642979 No free full text.

Abstract: OBJECTIVE: Relationships between presence of irritable bowel syndrome (IBS) and generalized anxiety disorder (GAD), chronic worry, neuroticism, anxiety sensitivity and anxiety about visceral sensations were examined among university students. METHODS: College student participants were administered self-report diagnostic measures of IBS and GAD, the Penn State Worry Questionnaire (PSWQ), the Neuroticism subscale of the Eysenck Personality Questionnaire, the Anxiety Sensitivity Index (ASI) and five additional items designed to measure visceral anxiety. RESULTS: The prevalence of IBS and its associated characteristics among students were similar to previous community survey studies, with the exception of lower symptom severity in the university sample. IBS was associated with a higher frequency of GAD and greater worry, neuroticism, anxiety sensitivity and visceral anxiety. Logistic regression analyses further showed that the measure of anxiety specific to visceral sensations was the strongest predictor of IBS diagnostic status. CONCLUSIONS: While various aspects of anxiety appear related to IBS, specific anxiety about visceral sensations appears to be the most significant factor. Implications of the associations between anxiety-related variables, particularly anxiety about visceral sensations, are discussed.

Berman SM, Naliboff BD, Chang L, Fitzgerald L, Antolin T, Camplone A, Mayer EA. · CURE Digestive Diseases Research Center, Department of Medicine, University of California, Los Angeles 90073, USA. · Am J Gastroenterol. · Pubmed #12425550 No free full text.

Abstract: OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder characterized by enhanced perceptual sensitivity and hypervigilance toward afferent signals from the viscera. We hypothesize that the increased responsiveness of IBS patients is a generalized phenomenon applying to stimuli other than visceral and attempt to demonstrate increased responsiveness to sounds as measured by the P1 scalp potential. METHODS: Event-related potentials were recorded from IBS patients and control subjects in an auditory task requiring detection of rare pitch targets in a designated ear. Visual words served as targets in an additional block. RESULTS: Compared to control subjects, IBS patients displayed a robust increase in the amplitude of the P1 scalp potential elicited by both attended and unattended sounds. CONCLUSIONS: Enhanced P1 indicates preattentive central nervous system dishabituation in response to repeated sounds. A generalized preattentive increase in central nervous system reactivity may be a feature that IBS shares with several anxiety disorders that frequently co-occur in these patients.