Biomedical subjects

R Noyes

Publications and source records attributed to R Noyes.

At least 19 recordsLinked to original sources

PubMed1999

A 5-year follow-up study of generalized anxiety disorder and panic disorder.

To examine the course and outcome of subjects with generalized anxiety disorder (GAD) and panic disorder, we compared 64 patients with GAD and 68 patients with panic disorder who had participated in drug treatment studies and were interviewed an average of 5 years earlier. At baseline GAD subjects were significantly older, had an earlier onset, and longer duration of illness than panic subjects. GAD subjects also had less severe symptoms. At follow-up, diagnostic stability was observed for both GAD and panic disorder. Significantly fewer GAD subjects achieved full remission at follow-up (18% vs. 45%, p < .01). Subjects with GAD were significantly less anxious at baseline than the panic disorder comparison group, but at follow-up there were few significant differences between groups on most severity of illness variables. This change was due in great part to improvement in the panic disorder group with a concomitant lack of change in the GAD group.

Adult↗

PubMed1998

Possible association of a cholecystokinin promotor polymorphism (CCK-36CT) with panic disorder.

We searched for mutations in the CCK gene in panic disorder with single-strand conformational polymorphism (SSCP) analysis of the three exons and promotor region of the gene. We found a C-->T transition at position -36 (CCK(-36C-->T)) in a GC box, a binding site for transcription factor Sp1, in the promotor region. The allele frequency was 0.168 (95% CI, 0.116-0.221) in 98 persons with panic disorder and 0.083 (95% CI, 0.059-0.107) in 247 geographically matched, unscreened controls. A transmission disequilibrium test based on panic disorder as the affected phenotype was nonsignificant (chi2 = 0.93), but when panic disorder or attacks were considered as affected, statistically significant transmission disequilibrium was detected (chi2 = 4.00, P < 0.05). Linkage analysis was uninformative. In exploratory analyses to search for clinical correlations, the "T" allele was found in 59% of 22 persons with panic attacks but not panic disorder, compared with 31% of those who met the criteria for panic disorder. An association between the CCK polymorphism and panic disorder cannot be considered established due to the inconsistencies in the results noted above, but if the provisional association can be replicated, the findings are consistent with CCK(-36C-->T) being a disease-susceptibility allele that alone is neither necessary nor sufficient to cause panic disorder but that increases vulnerability by acting epistatically.

Adult↗

PubMed1998

Fluvoxamine for somatoform disorders: an open trial.

Although the pharmacologic treatment of somatoform disorders has scarcely been investigated, there is reason to believe that antidepressants might be useful. We examined the response of 29 patients with somatoform disorders from a general medicine clinic to a selective serotonin reuptake inhibitor, fluvoxamine. The drug was administered in doses of up to 300 mg daily for 8 weeks. Sixty-one percent of the patients who took medication for at least 2 weeks were at least moderately improved. In addition to antidepressant effects, fluvoxamine had other beneficial effects and was well-tolerated. The benefits of drug therapy were modest but appear to warrant a placebo-controlled trial.

Adult↗

PubMed1997

Charles Darwin and panic disorder.

Charles Darwin (1809-1882) suffered from a chronic illness that, throughout much of his adult life, impaired his functioning and severely limited his activities. The writings of this famous scientist as well as biographical materials indicate that he probably suffered from an anxiety disorder. His symptoms, when considered individually, suggest a variety of conditions, but taken together they point toward panic disorder with agoraphobia. This diagnosis brings coherence to Darwin's activities and explains his secluded lifestyle, including difficulty in speaking before groups and meeting with colleagues.

Agoraphobia↗

PubMed1997

Moclobemide in social phobia: a controlled dose-response trial.

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.

Adult↗

PubMed1997

A family study of hypochondriasis.

To examine the diagnostic validity of hypochondriasis, we undertook a preliminary family study. Nineteen probands with and 24 without DSM-III-R hypochondriasis were identified among outpatients attending a general medicine clinic. Seventy-two first-degree relatives of hypochondriasis probands and 97 relatives of control probands were personally interviewed with the use of the Structured Clinical Interview for DSM-IV. These relatives also completed self-administered measures of hypochondriasis, psychological and somatic symptoms, and personality traits. No increase in the rate of hypochondriasis was found among the relatives of hypochondriasis probands compared with the relatives of control probands. With respect to other mental disorders, only somatization disorder was more frequent among the hypochondriacal relatives. These relatives also scored higher on measures of hostility, antagonism, and dissatisfaction with medical care. The findings of this study suggest that hypochondriasis may not be an independent disorder but a variable feature of other psychopathology, one that may include somatization disorder.

Adult↗

PubMed1997

Candidate gene study of eight GABAA receptor subunits in panic disorder.

OBJECTIVE: gamma-Aminobutyric acid type A (GABAA) receptor subunit genes are candidate genes for panic disorder. Benzodiazepine agonists acting at this receptor can suppress panic attacks, and both inverse agonists and antagonists can precipitate them. The human GABAA receptor subtypes are composed of various combinations of 13 subunits, each encoded by a unique gene. The authors tested eight of these subunits in a candidate gene linkage study of panic disorder. METHOD: In 21 U.S. and five Icelandic multiplex pedigrees of panic disorder, 104 individuals had DSM-III-R panic disorder (the narrowly defined affected phenotype) and 134 had either this diagnosis or subsyndromal panic disorder characterized by panic attacks that failed to meet either the criterion of attack frequency or the number of criterion symptoms necessary for a definite diagnosis (the broadly defined affected phenotype). The authors conducted lod score linkage analyses with both phenotypes using both a dominant and a recessive model of inheritance for the following loci: GABRA1-GABRA5 (alpha 1-alpha 5), GABRB1 (beta 1), GABRB3 (beta 3), and GABRG2 (gamma 2). RESULTS: The results failed to support the hypothesis that any of these genes cause panic disorder in a majority of the pedigrees. CONCLUSIONS: Within the limitations of the candidate gene linkage method, panic disorder does not appear to be caused by mutation in any of the eight GABAA receptor genes tested.

Adult↗

PubMed1996

Preliminary confirmation of the proposed link between reward-dependence traits and norepinephrine.

The tridimensional theory of personality posits that traits belonging to a personality spectrum called 'reward dependence' are determined in part by the neurotransmitter norepinephrine (NE). We hypothesized that urinary levels of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) would be significantly correlated to the reward dependence score on the Tridimensional Personality Questionnaire (TPQ). Twenty-seven never psychiatrically ill subjects collected urine for MHPG measurements and completed the TPQ. There was a significant correlation between the reward dependence score and the level of MHPG. MHPG levels was not associated with the other two personality dimensions, novelty seeking and harm avoidance. This preliminary study supports the hypothesis that reward-dependence traits are in part determined by NE.

Adult↗

PubMed1996

Association of levels of N-acetyl-beta-glucosaminidase with severity of psychiatric symptoms in panic disorder.

Urinary levels of N-acetyl-beta-glucosaminidase (NAG) were measured in 58 patients with panic disorder. NAG levels were found to be significantly related to the severity of 23 of 72 mood states, measured by the Profile of Mood States, which were grouped in three categories: hostility or irritability, sadness, and panic. A similar result was found in a previous study of bipolar patients. NAG levels were also related to scores on the Hamilton Rating Scale for Anxiety and the Sheehan Patient-Rated Anxiety Scale. It is speculated that NAG could be a marker for serotonin.

Acetylglucosaminidase↗

PubMed1996

Physician recognition of hypochondriacal patients.

To examine primary care physician recognition of hypochondriacal patients, we identified a series of such patients in a general medicine clinic using the Whiteley Index. Clinic physicians made blind global ratings of severity of physical disease and unreasonable fear of illness (hypochondriasis) and completed a checklist of somatizing characteristics. Patient records were audited for diagnoses, laboratory tests, consultations, and medications prescribed. Twenty-nine (14%) of 210 patients scored above an established cutoff on the Whiteley Index. These hypochondriacal patients were rated by clinic physicians as more hypochondriacal and were more often given psychiatric diagnoses. Also, clinic physicians identified more somatizing features among hypochondriacal patients including their own reaction to them. This recognition of hypochondriac characteristics may have contributed to better management but may need to be raised to the diagnostic level for maximum benefit.

Adult↗

PubMed1996

Diazepam versus alprazolam for the treatment of panic disorder.

BACKGROUND: Alprazolam has proven efficacy as a treatment for panic disorder, but the place of other benzodiazepines is less well established. METHOD: To compare the efficacy and tolerability of diazepam and alprazolam for the disorder, a placebo-controlled, double-blind trial was undertaken in two sites. Two hundred forty-one subjects with panic disorder or agoraphobia with panic attacks were randomly assigned to flexible doses of diazepam, alprazolam, or placebo for 8 weeks. RESULTS: At the end of the trial, over 60% of subjects taking either diazepam or alprazolam were at least moderately improved compared with less than 30% of those taking placebo. On all measures of efficacy, subjects taking diazepam and alprazolam showed an equally favorable response. Despite some sedation early in the trial, both drugs were tolerated well. More severely ill subjects responded less well to either benzodiazepine. CONCLUSION: The results indicate that diazepam is an effective alternative to alprazolam for the treatment of panic disorder.

Adult↗

PubMed1995

Relationship of generalized anxiety symptoms to urinary 5-hydroxyindoleacetic acid and vanillylmandelic acid.

Urinary levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the norepinephrine metabolite vanillylmandelic acid (VMA) were measured in 45 patients with generalized anxiety disorder. Multiple regression analysis demonstrated that the severity of several anxiety symptoms was predicted by levels of 5-HIAA and VMA. These data are consistent with the proposal that serotonin and norepinephrine may be involved in the pathophysiology of anxiety.

Adult↗

PubMed1995

Somatization. Diagnosis and management.

Somatization, the somatic expression of psychological distress, occurs in a large proportion of primary care patients. It is associated with substantial distress and impairment and with increased health care utilization. Some somatizing patients have a history of multiple unexplained complaints (somatization disorder), others are excessively worried about serious illness (hypochondriasis), and still others have psychiatric disorders that present with somatic symptoms (depression and anxiety). In general, somatizing patients are characterized by abnormal illness behavior (eg, failure to respond to treatment, excessive utilization of care) and psychological distress (eg, depressive symptoms, psychosocial stressors). Recognition requires alertness to characteristic features and skillful interview technique. Successful management begins by legitimizing symptoms. Restraint should be used in performing workups and assigning diagnoses to somatizing patients. Treatment goals should be clarified and regular visits scheduled. Also, behaviors that threaten the physician-patient relationship should be dealt with. Depression and anxiety should be treated when present. Pharmacologic and psychological treatments for somatizing patients have been described, although none has proven efficacy.

Diagnosis, Differential↗

PubMed1995

Avoidant personality traits distinguish social phobic and panic disorder subjects.

The purpose of this study was to show that, as a group, patients with social phobia and panic disorder differ with respect to personality traits, further validating the distinction between these anxiety disorders. To show this, we compared the response of 46 subjects with social phobia with the response of 72 subjects with panic disorder with or without agoraphobia on the Personality Diagnostic Questionnaire. The subjects, who were recruited for treatment studies, completed this personality questionnaire after they had been off psychotropic medication for at least 1 week. Responses to the Personality Diagnostic Questionnaire showed that the social phobics had more severe personality pathology. These subjects had higher anxious and schizoid cluster scores and differed from panic subjects in having more avoidant personality traits. Panic subjects had more dependent traits. The results indicate that social phobic and panic disorder patients are distinguishable on the basis of personality characteristics. They also show that the generalized situational subtype of social phobia is closely associated with avoidant personality disorder and that these may be differing categorizations of a single disturbance.

Adult↗

PubMed1995

Psychiatric disorders in relatives of probands with obsessive-compulsive disorder and co-morbid major depression or generalized anxiety.

The authors report findings from a blind, controlled study of obsessive-compulsive disorder (OCD). Prevalence rates of generalized anxiety disorder (GAD) and major depressive disorder (MDD) were compared among first-degree relatives of probands with OCD and co-morbid GAD or MDD, respectively. Rates of MDD were not increased in relatives of probands with OCD and MDD; neither were rates of GAD increased in relatives of probands with OCD and GAD, although rates of GAD were increased among relatives of probands with OCD compared to relatives of healthy controls. The authors explore the implications of the findings.

Adolescent↗

PubMed1995

The association of urinary 5-hydroxyindoleacetic acid and vanillylmandelic acid in patients with generalized anxiety.

There is evidence that serotonin and norepinephrine are in some way involved in the pathophysiology of anxiety disorders. Urinary levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the norepinephrine metabolite vanillylmandelic acid (VMA) were measured in 46 patients with generalized anxiety disorder. There was a significant association between urinary levels of 5-HIAA and VMA: r = 0.79; p = 0.0001. Possible implications of this finding are discussed.

Anxiety Disorders↗

PubMed1995

The association of the serotonin metabolite, 5-HIAA, to the lysosomal enzyme N-acetyl-beta-glucosaminidase.

Twenty-one medication-free patients with generalized anxiety disorder (GAD) collected urine samples for 5-hydroxyindoleacetic acid (5-HIAA) and N-acetyl-beta-glucosaminidase (NAG). Nine patients with no comorbid psychiatric diagnosis showed a significant association between 5-HIAA and NAG, r = -0.683, p = 0.04. The possibility that NAG could be a marker for serotonin metabolism is discussed.

Acetylglucosaminidase↗

PubMed1994

Psychiatric comorbidity among patients with hypochondriasis.

The purpose of this study was to determine the nature and extent of comorbidity among patients with DSM-III-R hypochondriasis and to examine the relationships between this disorder and coexisting psychiatric illness. For this purpose, patients seen in a general medicine clinic were screened using measures of hypochondriacal attitudes and somatic symptoms. Those scoring above an established cutoff were given a structured diagnostic interview. In this manner, 50 patients who met DSM-III-R criteria for hypochondriasis and 50 age- and sex-matched controls were identified. The presence of other psychiatric disorders (current and past) was determined by means of the same diagnostic interview. More hypochondriacal subjects (62.0%) had lifetime comorbidity than did controls (30.0%). Major depression, the most frequent comorbid disturbance, was usually current and most often had an onset after that of hypochondriasis. Panic disorder with agoraphobia, the most frequent anxiety disorder, was also current but often began before or at the same time as hypochondriasis. Few subjects met criteria for somatization disorder but a third qualified for a subsyndromal form of this disorder. The data show that, in medical outpatients with hypochondriasis, mood and anxiety disorders frequently coexist. This comorbidity is subject to varying interpretations including overlap of symptom criteria, treatment-seeking bias, and the possibility that hypochondriasis predisposes to or causes the comorbid disorder, as seems likely in the case of depression. In some instances hypochondriasis may be an associated feature of another illness.

Adult↗