Anxiety Disorders: University of Michigan

Albucher RC, Liberzon I. · Department of Psychiatry/PCT 116C, Veterans Administration Medical Center, University of Michigan, 2215 Fuller Road, Ann Arbor, MI 481105, USA. · J Psychiatr Res. · Pubmed #12393304 No free full text.

Abstract: INTRODUCTION: Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder that is heterogeneous in its nature, and often presents with other psychiatric comorbidities. As a result, empirical research on effective pharmacotherapy for PTSD has produced complex findings. This article reviews the existing research literature on pharmacological treatments for PTSD, identifies the most effective treatments, and where possible examines their mechanism of action with respect to the neurobiology of PTSD. METHODS: We examined reports of clinical trials of psychotropic agents carried out with PTSD patients and published in peer-reviewed journals, as well as reports from presentations at scientific meetings between 1966 and 2001. RESULTS: Numerous medications are effective in treating PTSD. These include tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin reuptake inhibitors. Considering reported overall efficacy and side effects profiles, selective serotonin reuptake inhibitors emerge as the preferred first line treatment for PTSD. Mood stabilizers, atypical neuroleptics, adrenergic agents, and newer antidepressants also show promise, but require further controlled trials to clarify their place in the pharmacopoeia for PTSD. DISCUSSION: There is clear evidence for effective pharmacotherapy of PTSD. Future improvements in the treatment of this disorder await further clinical trials and neurobiological research.

Nesse RM. · The University of Michigan, Department of Psychiatry, 426 Thompson St, Rm 5057, Ann Arbor, MI 48104, USA. · West J Med. · Pubmed #11342524 links to  free full text

This publication has no abstract.

Glass JM, Park DC. · Institute for Social Research, The University of Michigan, 426 Thompson Street, Ann Arbor, MI 48106, USA. · Curr Rheumatol Rep. · Pubmed #11286668 No free full text.

Abstract: Fibromyalgia is a puzzling syndrome of widespread musculoskeletal pain. In addition to pain, patients with fibromyalgia frequently report that cognitive function, memory, and mental alertness have declined. A small body of literature suggests that there is cognitive dysfunction in fibromyalgia. This article addresses several questions that physicians may have regarding cognitive function in their patients. These questions concern the types of cognitive tasks that are problematic for patients with fibromyalgia, the role of psychological factors such as depression and anxiety, the role of physical factors such as pain and fatigue, the nature of patients' perceptions of their cognitive abilities, and whether patients can be tested for cognitive dysfunction. Critical areas for further investigation are highlighted.

Fontana RJ. · Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich., USA. · Dig Dis. · Pubmed #11279329 No free full text.

Abstract: Dose-dependent, reversible neuropsychiatric toxicity is reported in up to 30-40% of chronic hepatitis C patients treated with 6-12 months of interferon-alpha or interferon-alpha plus ribavirin combination therapy. Although risk factors remain poorly defined, neuropsychiatric side effects may be severe and dose-limiting in as many as 10-20% of treated patients. Diagnosis relies upon the detection of clinically apparent neuropsychiatric symptoms and the emerging use of self-administered mood inventories and questionnaires. The current stepwise approach to management includes evaluation and treatment of systemic side effects, early use of adjuvant medications, and interferon-alpha and ribavirin dose reduction or cessation with psychiatric referral in selected cases. Although the cellular basis of the neuropsychiatric toxicity of interferon-alpha remains unknown, several hypothesis involving changes in central adrenergic, seratonergic, opioid and neuroendocrine pathways have been proposed. Recognition and management of the neuropsychiatric side effects of antiviral therapy will be of growing clinical importance as additional patients with chronic hepatitis C are treated and longer durations of therapy are utilized.

Zamorski MA, Ward RK. · Department of Family Medicine, University of Michigan Medical School, Ann Arbor 48109-2702, USA. · J Am Board Fam Pract. · Pubmed #10933289 No free full text.

Abstract: BACKGROUND: Social anxiety disorder (also known as social phobia) is characterized by extreme fear, avoidance, or both of one or more social or performance situations, such as making a presentation, meeting new people, or eating in front of others. This condition is common, with a lifetime prevalence of up to 13%, and one third of affected persons have major dysfunction. METHODS: The English-language literature on social anxiety disorder indexed on MEDLINE was searched using the phrases "social phobia" or "social anxiety disorder;" this search was supplemented with other data sources, such as recent textbooks, to determine common clinical symptoms, differential diagnosis, and management in the primary care setting. RESULTS: Recognition and treatment of social anxiety disorder is poor; only a small minority of patients with this condition have it appropriately diagnosed or treated. Primary care physicians should suspect social anxiety disorder in patients who have specific symptoms and signs (such as hyperhidrosis, flushing, tremor, and white-coat hypertension), in patients who have symptoms of anxiety (such as chest pain, palpitations, or dizziness), or in patients who have another known anxiety disorder, depression, or substance abuse. Drug treatment consists of serotonin-reuptake inhibitors, monoamine oxidase inhibitors, or high-potency benzodiazepines. A specific type of psychotherapy called cognitive behavioral therapy is another effective treatment, but it is not acceptable or accessible to most patients. CONCLUSIONS: Because social anxiety disorder is common, disabling, and treatable, primary care physicians should intensify their efforts to recognize it.

Trask PC, Esper P, Riba M, Redman B. · Behavioral Medicine Program, Department of Internal Medicine, and Department of Psychiatry, University of Michigan, Ann Arbor 48108, USA. · J Clin Oncol. · Pubmed #10829053 No free full text.

Abstract: The increasing use of interferon (IFN) in treating a variety of disorders including, malignant melanoma and hepatitis C, has resulted in the identification and increasing concern about the psychiatric side effects that can result from treatment. These effects can occur either shortly after beginning IFN therapy or later as a result of continued treatment. Studies have reported the incidence of later side effects, which include symptoms of depression, anxiety, and occasional suicidal ideation, to be from 0% to 70%. Case studies have demonstrated that pharmacologic interventions are beneficial in reducing iatrogenic psychiatric symptoms while allowing patients to maintain IFN therapy. The present article provides an overview of the psychiatric effects of IFN therapy, the proposed mechanisms of these side effects, and case studies that provide mechanistic support. In addition, limitations of the current literature are provided with suggestions for treating physicians and a discussion of possible future research directions.

Hasan JS. · University of Michigan Medical School, Ann Arbor, USA. · Ann Plast Surg. · Pubmed #10651374 No free full text.

Abstract: The relevance of psychological issues in cosmetic surgery has been well established in the literature. Early articles considered psychopathology to be prevalent in the plastic surgery population, whereas more recent views consider the typical cosmetic surgery candidate to be more psychologically stable. Despite these changes, the potential for psychopathology continues to be recognized. Consequently, screening for psychopathology during the preoperative interview has remained essential. To facilitate a working knowledge of psychological issues that may be useful in preoperative screening, this article reviews the current literature on the psychology of plastic surgery. In addition to discussing the psychological impact of cosmetic surgery, patient's motivations and expectations for surgery are discussed in the context of self-image. After reviewing potential types of psychopathology, various preoperative screening techniques are discussed.

Milner KK, Florence T, Glick RL. · Department of Psychiatry, University of Michigan Health System, Ann Arbor, USA. · Psychiatr Clin North Am. · Pubmed #10623969 No free full text.

Abstract: Mood and anxiety disorders are common in the general population and in the emergency setting. As psychiatric emergency care moves from the realm of triage and referral to a more definitive initiation of treatment, clinicians must approach the assessment and initial management of patients with mood and anxiety disorder in a rational and safe way. In the ED, the next step in assessing patients with mood or anxiety symptoms, after any immediate safety concerns are addressed, is to rule out medical or substance-induced causes. Treatment of these patients is directed at the underlying condition. When a primary psychiatric diagnosis is made, initial management, including definitive pharmacologic or psychotherapeutic intervention, can be started in the ED.

López JF, Akil H, Watson SJ. · Department of Psychiatry, University of Michigan, Ann Arbor 48109, USA. · Biol Psychiatry. · Pubmed #10599476 No free full text.

Abstract: Stress has been linked to the pathophysiology and pathogenesis of mood and anxiety disorders. Over the past few years, our understanding of the brain and neuroendocrine circuits that are linked to the stress response have increased dramatically. This article reviews a series of animal and human studies aimed at understanding what are the pathways by which stress is perceived, processed, and transduced into a neuroendocrine response. We focus on the classic stress circuit: the limbic-hypothalamic-pituitary-adrenal (LHPA) axis. These studies indicate that the LHPA stress circuit is a complex system with multiple control mechanisms and that these mechanisms are altered in pathological states, such as chronic stress and depression. These studies also suggest that the interactions between the LHPA and other neurotransmitters, such as serotonin, may provide the neurobiological substrate by which stress may affect mood.

Tsai LY. · Child and Adolescent Psychiatric Hospital, University of Michigan Medical School, Ann Arbor 48109-0390, USA. · Psychosom Med. · Pubmed #10511014 links to  free full text

Abstract: Autism is a neurobiological disorder. The core clinical features of autism include impairment in social interaction, impairments in verbal and nonverbal communication, and restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. Autism often has coexisting neuropsychiatric disorders, including seizure disorders, attention deficit hyperactivity disorder, affective disorders, anxiety disorder, obsessive-compulsive disorder, and Tourette disorder. No etiology-based treatment modality has been developed to cure individuals with autism. However, comprehensive intervention, including parental counseling, behavior modification, special education in a highly structured environment, sensory integration training, speech therapy, social skill training, and medication, has demonstrated significant treatment effects in many individuals with autism. Findings from preliminary studies of major neurotransmitters and other neurochemical agents strongly suggest that neurochemical factors play a major role in autism. The findings also provide the rationale for psychopharmacotherapy in individuals with autism. This article reviews studies of neurochemical systems and related psychopharmacological research in autism and related neuropsychiatric disorders. Clinical indications for pharmacotherapy are described, and uses of various medications are suggested. This article also discusses new avenues of investigation that may lead to the development of more effective medication treatments in persons with autism.

Warschausky S, Kewman D, Kay J. · Department of Physical Medicine and Rehabilitation University of Michigan Hospitals, Ann Arbor, Michigan 49109-0050, USA. · J Head Trauma Rehabil. · Pubmed #10407210 No free full text.

Abstract: This article examines the empirical support for psychological therapies for children with traumatic brain injury (TBI). Empirical support for psychological treatments of noninjured children provides a foundation upon and a framework in which to discuss applications to children with neurobehavioral dysfunction. Behavioral interventions to address externalizing behaviors have received the greatest focus, whereas there is a paucity of work that pertains to internalizing features and prosocial behavior such as assertiveness. Although the systematic study of psychological intervention lags far behind the rapidly increasing knowledge of neurobehavioral sequelae to TBI, there are promising directions that stem from initial findings.

Rauch SA, Defever E, Favorite T, Duroe A, Garrity C, Martis B, Liberzon I. · Mental Health Service, Veterans Administration Ann Arbor Healthcare System and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA. · J Trauma Stress. · Pubmed #19145643 No free full text.

Abstract: With the move toward dissemination of empirically supported treatments in the Veterans Health Administration (VHA), dissemination of additional data concerning the effectiveness of prolonged exposure (PE) among veterans is important. The authors present clinical treatment data from veterans with chronic posttraumatic stress disorder (PTSD) treated in a VHA PTSD clinic (N = 10). Veterans demonstrated significant reductions in total PTSD symptoms from pre- to posttreatment. Returning veterans from the conflicts in Afghanistan and Iraq and other era veterans (Vietnam Veterans and military sexual trauma veterans) demonstrated significant reductions in PTSD. In addition, veterans demonstrated significant reductions in depression from pre- to posttreatment. In conclusion, PE is effective in reducing the symptoms of PTSD in veterans.

Khan S, Briggs H, Abelson JL. · Trauma, Stress and Anxiety Research Group, Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA. · Psychiatry Res. · Pubmed #18222546 links to  free full text

Abstract: Pentagastrin is a cholecystokinin (CCK)-B agonist and laboratory panicogenic agent that produces endocrine (ACTH and cortisol), symptom (anxiety, panic) and cardiovascular (heart rate) responses. Although in vitro data have supported its chemical stability, preliminary data suggested that increasing time between drug preparation and drug infusion could reduce the magnitude of endocrine and symptom responses. The current study examined this possibility. Twenty-one healthy subjects presented at the University of Michigan General Clinical Research Center (GCRC) and had an intravenous catheter inserted. Heart rate, cortisol levels and subjective anxiety were measured before and after pentagastrin and placebo injections. Pentagastrin was prepared either within 60 min of IV infusion (Normal Preparation group) or at least 3.5 h prior to infusion (Early Preparation group). Relative to the Normal Preparation group, Early Preparation subjects had similar heart rate responses but significantly smaller cortisol and subjective anxiety responses. Early preparation of pentagastrin thus appears to weaken endocrine and subjective anxiety responses, highlighting the importance of attending to often overlooked procedural variables (e.g., time between preparation and administration) in studies of this type. The sensitivity of cortisol and anxiety responses to preparation time, but insensitivity of heart rate, is consistent with previous studies suggesting different thresholds of activation for the three response modalities. These differential sensitivities may suggest different and separable CCK-B stimulated pathways for each response, which combine to produce panic, rather than a single, unified CCK-B mediated panicogenic response.

Abelson JL, Liberzon I, Young EA, Khan S. · Department of Psychiatry and Mental Health Research Institute, Trauma, Stress and Anxiety Research Group, University of Michigan, Ann Arbor 48109-0118, USA. · Arch Gen Psychiatry. · Pubmed #15939844 links to  free full text

Abstract: CONTEXT: The hypothalamic-pituitary-adrenal (HPA) axis may mediate the deleterious effects of stress on health. It is sensitive to cognitive and emotional aspects of organism-environment interactions, such as familiarity, control, and social support. Scientific study of how such factors moderate human HPA axis activity has been limited. Their relevance to HPA axis disturbances in psychiatric patients is largely unexplored. OBJECTIVE: To determine whether cognitive manipulation can alter HPA axis activity in laboratory studies and whether patients with panic disorder are differentially sensitive to the manipulated factors. DESIGN: Pharmacological activation paradigm (cholecystokinin-B agonist pentagastrin) by which we examined symptom and endocrine effects on subjects randomly assigned to a standard introduction or a cognitive intervention. SETTING: Clinical research center. PARTICIPANTS: Recruited from university clinic and newspaper advertisements. Fourteen patients with panic disorder and 14 controls, individually matched for age and sex.Intervention Half of each group received a 9-minute cognitive intervention designed to reduce novelty, increase cognitive coping, and provide a sense of control. MAIN OUTCOME MEASURES: Corticotropin (ACTH) and cortisol levels. RESULTS: The cognitive intervention significantly reduced cortisol (P = .02) and ACTH (P = .01) levels, despite pentagastrin's robust stimulation of both hormones (P<.001). The intervention effect was evident in patients and controls, who did not differ in basal HPA axis activity or response to pentagastrin. They did differ in panic symptom responses, which were unaffected by the intervention, and in ACTH effects of the intervention. Patients' exaggerated anxiety responses to pentagastrin were normalized by the intervention. CONCLUSIONS: Cognitive/emotional manipulation can substantially modulate HPA axis responses to pharmacological activation in humans, and HPA disturbances in panic disorder may be secondary to manipulable cognitive/emotional sensitivities. Further study of such factors as novelty, control, and coping may help clarify the origins of HPA axis disturbance in psychiatric disorders and the mediators linking psychosocial stress to disease.

Young EA, Abelson JL, Cameron OG. · Department of Psychiatry, University of Michigan, Ann Arbor, 48109-0720, USA. · Psychoneuroendocrinology. · Pubmed #15896919 No free full text.

Abstract: BACKGROUND: Numerous interactions between the brainstem locus coeruleus system and the HPA axis have been shown in experimental animals. This relationship is less well characterized in humans and little is known about the influence of psychiatric disorders, which disturb one of these systems, on this relationship. METHODS: Untreated subjects with pure MDD (n = 13), MDD with comorbid anxiety disorders (n = 17), and pure anxiety disorders (n = 15) were recruited by advertising. Age and sex matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 45). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for ACTH assay. These same subjects also underwent a clonidine challenge study for assessment of growth hormone release as a marker of tonic noradrenergic activation. RESULTS: Examining log transformed area under the curve response for each hormone, a significant negative relationship (simple regression) was observed between systems in normal subjects. This relationship was preserved in anxiety subjects. However, both pure depressed and comorbid depressed and anxiety subjects demonstrated disruption of this relationship. CONCLUSIONS: Under normal circumstances, noradrenergic systems can influence the magnitude of the HPA axis response to stress. However, in subjects with major depression, HPA axis activation appears autonomous of noradrenergic influence.

Britton JC, Phan KL, Taylor SF, Fig LM, Liberzon I. · Neuroscience Program, University of Michigan, Michigan, USA. · Biol Psychiatry. · Pubmed #15820703 No free full text.

Abstract: BACKGROUND: Functional neuroimaging experiments targeting personal recall of emotional events may help elucidate neural substrates underlying posttraumatic stress disorder (PTSD). Studies suggest that limbic and paralimbic function might be altered in PTSD, as compared with trauma-exposed control subjects; however, little is known about functional changes resulting from traumatic experience itself. The present study examined both PTSD-specific and trauma-specific regional cerebral blood flow (rCBF) patterns during script-driven imagery. METHODS: Sixteen combat veterans with PTSD (PP); 15 combat veterans without PTSD (CC); and 14 healthy, aged-matched noncombat control subjects (NC) underwent [15O] H20 positron emission tomography (PET) scanning during script-driven imagery of emotionally evocative and neutral autobiographic events. RESULTS: Differential patterns of activation were detected in amygdala and medial frontal cortex. Past trauma experience was associated with decreased amygdala activity (i.e., less activity than healthy control subjects); however, combat control subjects deactivated this region (i.e., greater activity to neutral scripts). All subjects deactivated medial frontal cortex; PTSD patients had greater rostral anterior cingulate (rACC) deactivation compared with control groups, who deactivated ventromedial prefrontal cortex (vmPFC). CONCLUSIONS: Trauma-specific patterns may represent potential compensatory changes to traumatic reminders, while patterns observed only in the PTSD group may reflect neural substrates specific to PTSD pathophysiology.

Abelson JL, Curtis GC, Sagher O, Albucher RC, Harrigan M, Taylor SF, Martis B, Giordani B. · Department of Psychiatry, University of Michigan, Trauma, Stress and Anxiety Research Group, Ann Arbor, Michigan, USA. · Biol Psychiatry. · Pubmed #15737666 No free full text.

Abstract: BACKGROUND: Neurosurgery (anterior capsulotomy) has been beneficial to many patients with debilitating, refractory obsessive-compulsive disorder (OCD), but the irreversibility of the procedure is an important limitation to its use. Nondestructive, electrical stimulation (deep brain stimulation; DBS) has proven an effective alternative to ablative surgery for neurological indications, suggesting potential utility in place of capsulotomy for OCD. METHODS: The effects of DBS for OCD were examined in four patients in a short-term, blinded, on-off design and long-term, open follow-up. The patients had incapacitating illness, refractory to standard treatments. Hardware developed for movement disorder treatment was surgically implanted, with leads placed bilaterally in the anterior limbs of their internal capsules. Patients received stimulation in a randomized "on-off" sequence of four 3-week blocks. Ongoing, open stimulation was continued in consenting patients after the controlled trial. RESULTS: Patients tolerated DBS well. Dramatic benefits to mood, anxiety, and OCD symptoms were seen in one patient during blinded study and open, long-term follow-up. A second patient showed moderate benefit during open follow-up. CONCLUSIONS: It appears that DBS has potential value for treating refractory psychiatric disorders, but additional development work is needed before the procedure is utilized outside of carefully controlled research protocols.

Cameron OG, Abelson JL, Young EA. · Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, Michigan, USA. · Biol Psychiatry. · Pubmed #15576065 No free full text.

Abstract: BACKGROUND: Although comorbidity of anxiety with depression is common, investigations of physiologic abnormalities related specifically to comorbidity are rare. This study examined relationships of DSM-IV-defined depression, anxiety, and their comorbidity to noradrenergic function measured by blunting of the growth hormone (GH) response to the alpha2 adrenoreceptor agonist (and imidazoline receptor agent) clonidine and by blood pressure and symptom responses. METHODS: Fifteen subjects with pure social anxiety or panic disorder, 15 with pure major depression, and 18 with both depression and anxiety were compared with healthy control subjects matched for age and gender. Other factors known to affect GH (weight, menstrual status, prior antidepressant, or other drug exposure) were controlled. RESULTS: Anxiety produced GH blunting, but depression was associated with normal GH responses. The comorbid state did not affect results beyond the impact of anxiety. Preclonidine stress-related GH elevations were observed, to the greatest degree in anxious subjects. Relevant symptom, but not blood pressure, changes were significantly associated with blunting. CONCLUSIONS: With use of pure depression and anxiety groups and careful control of other factors known to affect GH, these results demonstrate central nervous system noradrenergic dysfunction in anxiety disorders. In contrast to less rigorously controlled studies, noradrenergic function in depression was normal.

Abelson JL, Curtis GC, Uhde TW. · Department of Psychiatry, University of Michigan, Anxiety and Stress Disorders Program, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0118, USA. · Psychoneuroendocrinology. · Pubmed #15358444 No free full text.

Abstract: BACKGROUND: Patients with panic disorder have blunted growth hormone (GH) responses to clonidine, suggesting subsensitivity of post-synaptic alpha(2)-adrenoreceptors, presumably in response to excessive central noradrenergic outflow. However, basal levels of GH release over a full circadian cycle have not been examined in panic. Reduced basal GH release would suggest an overall hypo-active GH system rather than a specific alpha-adrenergic abnormality. METHODS: To determine whether panic patients show reduced basal GH secretion, 20 patients and 12 healthy controls were studied. Blood samples were drawn every 15 min for 24 h and plasma was assayed for GH. Patients were restudied during successful treatment with alprazolam. Groups were compared on overnight and daytime GH secretion and circadian patterns of release. RESULTS: Patients showed normal levels on all measures of GH release. Treatment may have reduced nocturnal GH release slightly, but treated patients still did not differ from controls. The normal predominance of sleep over waking GH secretion was seen in both groups. CONCLUSIONS: Panic patients, in contrast to depressed patients, have normal somatotrophic axis activity when measured in a resting state over a full circadian cycle. GH dysregulation may only be evident in these patients in activation paradigms and has been most consistently demonstrated by challenges with the alpha(2)-noradrenergic agonist, clonidine.

Young EA, Abelson JL, Cameron OG. · Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0720, USA. · Biol Psychiatry. · Pubmed #15231443 No free full text.

Abstract: BACKGROUND: Major depressive disorder (MDD) is often complicated by anxiety symptoms, and anxiety disorders occur in approximately 30% of mood cases. This study examined the influence of anxiety comorbidity on the hypothalamic-pituitary-adrenal (HPA) axis response to stress in patients with MDD. METHODS: Untreated subjects with pure MDD (n = 15), MDD with comorbid anxiety disorders (n = 18), and pure anxiety disorders (n = 15) were recruited by advertising. Age- and gender-matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 48). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for adrenocorticotropic hormone (ACTH) and cortisol assay. RESULTS: When all depressed patients (n = 33) were compared with their matched control subjects (n = 33), they showed a significantly greater ACTH response to the stressor; however, this exaggerated ACTH response was exclusively due to the depressed group with comorbid anxiety disorders. A similar but nonsignificant effect was observed in the cortisol response. Subjects with pure mood or pure anxiety disorders showed normal ACTH and cortisol responses to the TSST. All patient groups showed similar levels of TSST-induced anxiety. CONCLUSIONS: Comorbid anxiety disorders might play a role in the increased activation of the HPA axis observed in patients with major depression.

Himle JA, Fischer DJ, Van Etten ML, Janeck AS, Hanna GL. · Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109-0840, USA. · Depress Anxiety. · Pubmed #12621595 No free full text.

Abstract: Prior research supports the distinction between tic-related and non-tic-related obsessive-compulsive disorder (OCD) based on phenomenologic, etiologic, and neurobehavioral data. The present study examines whether response to psychosocial treatment differs in adolescents, depending on the presence of comorbid tics. Nineteen adolescents, 12-17 years of age, participated in 7-week, uncontrolled trial of group cognitive-behavioral treatment (CBT) for OCD. Eight of the patients had tic-related and eleven had non-tic-related OCD. The group CBT program included psycho-education, exposure and response prevention, cognitive strategies, and family involvement. Significant improvement was observed for all subjects on the Yale-Brown Obsessive Compulsive Scale ratings of obsessions, compulsions, and total OCD symptoms. Outcomes were similar for subjects with tic-related and non-tic-related OCD. These preliminary results suggest that the presence of comorbid tic disorders may not attenuate response to behavioral group treatment among adolescents.

Abelson JL, Young EA. · Department of Psychiatry, Anxiety Disorders Program, Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109, USA. · Psychoneuroendocrinology. · Pubmed #12510010 No free full text.

Abstract: Intravenous injection of the cholecystokinin (CCK)-B receptor agonist, pentagastrin, produces robust, dose-dependent release of adrenocorticotropin (ACTH) and cortisol, supporting the hypothesis that CCK-B agonists pharmacologically activate the hypothalamic-pituitary-adrenal (HPA) axis. The mechanism of activation and its physiological relevance remain uncertain. Preliminary data suggest that the ACTH response to pentagastrin may be differentiated from the response to exogenous corticotropin releasing hormone (CRH) by its relative resistance to cortisol feedback inhibition. To more directly test the relationship between cortisol levels and ACTH response to pentagastrin, this study examined responses to pentagastrin (a) during a peak (8 a.m.) and a nadir (4 p.m.) period of endogenous cortisol secretion and (b) when cortisol levels were artificially reduced to low levels by administration of metyrapone. ACTH responses to pentagastrin were identical in the morning and afternoon, despite substantial differences in basal cortisol levels. Suppression of cortisol with metyrapone had little impact on ACTH response to pentagastrin. These data support the hypothesis that CCK-B receptor mediated activation of the HPA axis is relatively resistant to cortisol feedback inhibition. This differentiates it from CRH-mediated activation and raises the possibility that CCK could contribute to acute activation of the HPA axis even in the face of elevated basal cortisol levels, such as those seen in chronic stress or some psychiatric disorders.

Warner MD, Dorn MR, Peabody CA. · University of Michigan Medical Center, USA. · Pharmacopsychiatry. · Pubmed #11518472 No free full text.

Abstract: BACKGROUND: Trazodone is commonly used in the treatment of insonmia and nightmares in patients with PTSD. There is little evidence in the literature for this practice. METHOD: Seventy-four patients from the Palo Alto Veterans Affairs Health Care System in California who were admitted to a specialized 8 week inpatient treatment program for PTSD were surveyed regarding their use of trazodone in the treatment of insomnia or nightmares. Patients were asked to complete a questionnaire regarding trazodone's effectiveness, side effects, and optimal doses. RESULTS: Of 74 patients surveyed, 60 patients were able to maintain an effective dose of trazodone. The other 14 patients were unable to tolerate the medication. Seventy-two percent of the 60 patients assessed found trazodone helpful in decreasing nightmares, from an average of 3.3 to 1.3 nights per week (p<.005). Ninety-two percent found it helped with sleep onset, and 78% reported improvement with sleep maintenance. There was a significant correlation between the effectiveness in decreasing nightmares and improving sleep (r= .57, p < .005). The effective dose range of trazodone for 70% of patients was 50 to 200 mg nightly. Of the 74 patients surveyed, 9 (12%) reported priapism. CONCLUSION: Trazodone appears effective for the treatment of insomnia and nightmares associated with chronic PTSD. However, controlled trials are needed before any definite conclusions can be drawn. The higher than expected occurrence of priapism warrants clinicians asking directly about this side effect.

Abelson JL, Weg JG, Nesse RM, Curtis GC. · Anxiety Disorders Program, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109-0840, USA. · Biol Psychiatry. · Pubmed #11297716 No free full text.

Abstract: BACKGROUND: Dysregulated respiratory control may play a role in the pathophysiology of panic disorder. This could be due to abnormalities in brain stem respiratory nuclei or to dysregulation at higher brain levels. Results from previous studies using the doxapram model of panic have yielded an unclear picture. A brief cognitive manipulation reduced doxapram-induced hyperventilation in patients, suggesting that higher level inputs can substantially alter their respiratory patterns. However, respiratory abnormalities persisted, including a striking irregularity in breathing patterns. METHODS: To directly study respiratory irregularity, breath-by-breath records of tidal volume (V(t)) and frequency (f) from previously studied subjects were obtained. Irregularity was quantified using von Neumann's statistic and calculation of "sigh" frequency in 16 patients and 16 matched control subjects. Half of each group received a standard introduction to the study and half received a cognitive intervention designed to reduce anxiety/distress responses to the doxapram injection. RESULTS: Patients had significantly greater V(t) irregularity relative to control subjects. Neither the cognitive intervention nor doxapram-induced hyperventilation produced significant changes in V(t) irregularity. The V(t) irregularity was attributable to a sighing pattern of breathing that was characteristic of panic patients but not control subjects. Patients also had somewhat elevated f irregularity relative to control subjects. CONCLUSIONS: The irregular breathing patterns in panic patients appear to be intrinsic and stable, uninfluenced by induced hyperventilation or cognitive manipulation. Further study of V(t) irregularity and sighs are warranted in efforts to localize dysregulated neural circuits in panic to brain stem or midbrain levels.

Abelson JL, Le Mellédo J, Bichet DG. · University of Michigan Department of Psychiatry, Anxiety Disorders Program, Ann Arbor, MI, USA. · Neuropsychopharmacology. · Pubmed #11120398 links to  free full text

Abstract: Cholecystokinin (CCK) is a peptide neurotransmitter that modulates hypothalamic-pituitary-adrenal (HPA) axis activity and may be involved in fear or anxiety states. Arginine vasopressin (AVP) also modulates HPA axis activity and may play a role in fear conditioning. Few human studies have examined interactions between CCK and AVP systems. To explore relationships between CCK-B receptor activation, the HPA axis response, and AVP release, a dose-response study using the CCK-B receptor agonist pentagastrin was conducted. Adrenocorticotropin (ACTH) and cortisol results have been previously reported and AVP data is presented here. Thirty-five healthy subjects were randomly assigned to receive placebo, or 0.2, 0.4, 0.6, or 0.8 microg/kg doses of pentagastrin. AVP release appeared to increase with increasing doses of the CCK-B agonist. However, this may have been due to a greater percentage of subjects releasing AVP in the higher dose groups, rather than a direct effect of dose on magnitude of response. AVP and ACTH responses were correlated, but AVP response alone could not account for the magnitude of the ACTH response. AVP release was significantly correlated with anxiety symptom responses. These findings suggest a possible role for the CCK-B receptor in AVP release, which may be at least partially separate from its role in modulation of the HPA axis. Further work is needed to determine whether these are physiologically meaningful interactions and to determine their functional implications.