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Biomedical subjects

R Hoehn-Saric

Publications and source records attributed to R Hoehn-Saric.

At least 19 recordsLinked to original sources

Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex.

Evidence from twin and family studies supports a genetic etiology for obsessive-compulsive disorder (OCD). The purpose of this study was to test whether a major gene is implicated in a proportion of families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a major gene. A Mendelian-dominant model, with significant sex effects and with residual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogeneity with respect to familial aggregation. Segregation analyses of 86 families with a female proband and of the 67 families with a male proband suggested that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups.

Adolescent↗

The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study.

BACKGROUND: The familial relationship between obsessive-compulsive disorder (OCD) and "obsessive-compulsive spectrum" disorders is unclear. This study investigates the relationship of OCD to somatoform disorders (body dysmorphic disorder [BDD] and hypochondriasis), eating disorders (e.g., anorexia nervosa and bulimia nervosa), pathologic "grooming" conditions (e.g., nail biting, skin picking, trichotillomania), and other impulse control disorders (e.g., kleptomania, pathologic gambling, pyromania) using blinded family study methodology. METHODS: Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives, were examined by psychiatrists or Ph.D. psychologists using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. Two experienced psychiatrists independently reviewed all diagnostic information and made final consensus diagnoses using DSM-IV criteria. RESULTS: Body dysmorphic disorder, hypochondriasis, any eating disorder, and any grooming condition occurred more frequently in case probands. In addition, BDD, either somatoform disorder, and any grooming condition occurred more frequently in case relatives, whether or not case probands also had the same diagnosis. CONCLUSIONS: These findings indicate that certain somatoform and pathologic grooming conditions are part of the familial OCD spectrum. Though other "spectrum" conditions may resemble OCD, they do not appear to be important parts of the familial spectrum.

Adult↗

Multicenter double-blind comparison of sertraline and desipramine for concurrent obsessive-compulsive and major depressive disorders.

BACKGROUND: Serotonin reuptake inhibitors (SRIs) have demonstrated consistent efficacy in the treatment of obsessive-compulsive disorder (OCD), while agents that are primarily norepinephrine reuptake inhibitors have not. Comparable efficacy has been demonstrated for SRI and non-SRI antidepressants in uncomplicated major depressive disorder (MDD). This multicenter trial is the first comparison of an SRI (sertraline) and a non-SRI antidepressant (desipramine) in the treatment of OCD with concurrent MDD. METHODS: One hundred sixty-six patients diagnosed using structured clinical interviews and recruited from 16 treatment sites were randomly assigned to double-blind treatment with either sertraline (up to 200 mg/d) or desipramine (up to 300 mg/d) over 12 weeks. Measures of severity of OCD and MDD symptoms, as well as adverse effects of the medications, were monitored over the course of the treatment period. RESULTS: Patients assigned to sertraline responded significantly better at end point on measures of OCD and MDD symptoms compared with patients assigned to desipramine. Sertraline was also associated with a significantly greater number of patients who achieved a "robust" improvement in OCD symptoms (> or =40% reduction) compared with desipramine. More patients receiving desipramine than sertraline discontinued treatment because of adverse events. CONCLUSIONS: The SRI sertraline was more effective in reducing MDD and OCD symptoms than the primarily norepinephrine reuptake inhibitor desipramine for patients with concurrent OCD and MDD.

Adrenergic Uptake Inhibitors↗

A family study of obsessive-compulsive disorder.

BACKGROUND: The causes of obsessive-compulsive disorder (OCD) are as yet unknown. Evidence of familial aggregation is one approach for investigating the role of genetics in the etiology of this condition. The current study was conducted to determine ifOCD is familial and to investigate possible familial subtypes. METHODS: Eighty case probands were identified in 5 specialty OCD clinics and 73 community control probands were identified by random-digit dialing. These probands and their first-degree relatives (343 case and 300 control relatives) were blinded to group and evaluated by psychiatrists and doctoral-level clinical psychologists using semistructured instruments. Final diagnoses were assigned by a blinded-consensus procedure. The results were analyzed using logistic regression by the method of generalized estimating equations. RESULTS: The lifetime prevalence of OCD was significantly higher in case compared with control relatives (11.7% vs 2.7%) (P<.001). Case relatives had higher rates of both obsessions and compulsions; however, this finding is more robust for obsessions. Age at onset of obsessive-compulsive symptoms in the case proband was strongly related to familiality (odds ratio, 0.92; confidence interval, 0.85-0.99) (P = .05); no case of OCD symptoms was detected in the relatives of probands whose age at onset of symptoms was 18 years or older. Probands with tics or obsessive-compulsive personality disorder were not more likely to have relatives with OCD than those without these features. CONCLUSIONS: Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.

Adolescent↗

Anxiety and arousal: physiological changes and their perception.

Contrary to self-reports, most patients with chronic anxiety disorders exhibit increased muscle tension but not autonomic hyperarousal when at rest. Under everyday stress they tend to react with less physiological flexibility than normal controls. However, they overreact subjectively and physiologically to stimuli that are anxiety-provoking. Diminished physiological flexibility may be either a constitutional trait in anxious individuals, a partial but inadequate adaptation to prolonged stress or the result of a disregard for stressors that are not related to psychopathology. The effects of diminished physiological flexibility on general health are not known. There is only a weak relationship, and in some instances a desynchrony, between physiological changes and perception of change under stress. The inconsistencies between self-reports of physiological states and physiological recordings can be explained by alterations of body sensations through psychological factors, predominantly expectations and attention to bodily states, that lead to perceptual distortions.

Adaptation, Psychological↗

Therapeutic effects of imipramine are counteracted by its metabolite, desipramine, in patients with generalized anxiety disorder.

Imipramine has been shown to reduce anxiety in patients with generalized anxiety disorder (GAD). However, some properties of imipramine may diminish or counteract its anxiolytic effects. The authors previously found that the greater the reduction in cardiac vagal control after 6 weeks of imipramine treatment, the smaller the improvement in anxiety-related symptoms. The purpose of this study was to determine whether the authors' previous findings were replicable and to gather information on the plasma levels of imipramine, desipramine (the major metabolite of imipramine), and anticholinergic levels. Fourteen patients with GAD were administered imipramine for 6 weeks. Their scores from self-administered and investigator-administered rating scales were obtained before and after the treatment, and the changes in these scores were contrasted with the changes in cardiac vagal tone, along with the absolute plasma levels of imipramine, desipramine, and anticholinergic activity at the end of week 6. The authors observed a greater improvement in symptoms of anxiety in those who showed the smallest decreases in cardiac vagal tone and in those who showed the smallest increases in desipramine and anticholinergic plasma levels. Moreover, strong relationships were observed between desipramine and anticholinergic levels. These results demonstrate that imipramine not only has therapeutic effects, but it may also have properties that result in physiologic states that counteract its therapeutic effects. Future research should investigate the direct anticholinergic effects of desipramine and determine whether there is a parallel between the anticholinergic effects and the clinical outcome of other pharmacologic treatments, including antidepressants with predominantly norepinephrine or serotonin reuptake inhibitory properties.

Adrenergic Uptake Inhibitors↗

Personality disorders and normal personality dimensions in obsessive-compulsive disorder.

BACKGROUND: Little is known about personality disorders and normal personality dimensions in relatives of patients with obsessive-compulsive disorder (OCD). AIMS: To determine whether specific personality characteristics are part of a familial spectrum of OCD. METHOD: Clinicians evaluated personality disorders in 72 OCD case and 72 control probands and 198 case and 207 control first-degree relatives. The selfcompleted Revised NEO Personality Inventory was used for assessment of normal personality dimensions. The prevalence of personality disorders and scores on normal personality dimensions were compared between case and control probands and between case and control relatives. RESULTS: Case probands and case relatives had a high prevalence of obsessive-compulsive personality disorder (OCPD) and high neuroticism scores. Neuroticism was associated with OCPD in case but not control relatives. CONCLUSIONS: Neuroticism and OCPD may share a common familial aetiology with OCD.

Adult↗

Influence of age on the parasympatholytic property of tricyclic antidepressants.

Clinical evidence indicates that parasympatholytic effects of tricyclic antidepressants increase with age. The aim of the present study was to determine the possible physiological reason for this phenomenon. Subjects included 23 patients (14 female) with major depression, melancholic type, and 23 age- and sex-matched healthy control subjects. Cardiac vagal tone was measured at rest using both spectral analysis and a time domain beat-to-beat method. Results of the spectral and time domain methods for the estimation of vagal tone used in this study were highly correlated in control subjects as well as in medicated depressed subjects. Both patients and control subjects showed an age-related decline in cardiac vagal tone. Tricyclic antidepressants decreased vagal tone significantly by 25-49% depending on age (20-60 years), although the age difference was not significant. The greater effect of tricyclic antidepressants on parasympathetic activity typically seen in older age groups may reflect the fact that predrug levels of vagal tone are already low in older patients. Measurement of vagal tone prior to drug administration may therefore be of prognostic value for anticholinergic side effects.

Adult↗

Increased heart rate in depressed subjects in spite of unchanged autonomic balance?

A clinical study was conducted to examine the effects of depression on cardiac autonomic control. Cardiac autonomic control was measured in 26 nonmedicated patients (19 females) suffering from Major Depression, melancholic type, and in 26 age- and sex-matched normal controls. We measured heart rate and high frequency heart rate variability (respiratory sinus arrhythmia), pulsewave velocity and blood pressure, during 10 min of supine rest under controlled conditions. Using a log transformed time domain measure of respiratory sinus arrhythmia (logRSA), we found an inverse linear dependence between cardiac vagal tone and age in the healthy subjects as well as the depressed patients. logRSA was 0.22+/-0.25 in the patients and 0.25+/-0.16 in the control group. While this difference was not significant (P > 0.1), the deviations from the regression line were significantly (P < 0.0005) greater in the patients (0.21+/-0.12) than in the control group (0.09+/-0.07), indicating a more heterogeneous vagal tone in the depressed patients. Heart rate was also significantly (P < 0.03) greater in the depressed patients (76.6+/-12.4) than in the control group (69.5+/-6.9). No between-group differences were found in pulsewave velocity or systolic blood pressure, but diastolic blood pressure was lower in depressed patients (73.5+/-8.7 vs. 80.8+/-9.1). We discuss the possibility that the increased heart rate seen in the absence of vagal tone changes may not be due to altered vagal or sympathetic tone, as measured in this study. Other factors, including altered autonomous heart rate, may be responsible for the higher heart rate in the depressed group.

Adolescent↗

Psychic and somatic anxiety: worries, somatic symptoms and physiological changes.

Contrary to self-reports, patients with generalized anxiety disorder exhibit increased muscle tension but not autonomic hyperarousal. Under stress they tend to react autonomically in a less flexible manner than normal controls. There is only a weak relationship, and in some instances a desynchrony, between physiological changes and perception of change. The inconsistencies between self-reports of physiological states and physiological recordings can be explained by alterations of body sensations through psychological factors, predominantly expectations of and attention to bodily states, that lead to perceptual distortions.

Anxiety Disorders↗

Major depression and cardiac autonomic control.

We investigated autonomic control of heart rate in patients with major depression, melancholic type. Twenty-three depressed inpatients who were being treated with tricyclic antidepressants and 23 depressed patients who were taking no medications were compared with age- and sex-matched control groups on resting cardiac vagal tone and heart rate. In unmedicated depressed patients, cardiac vagal tone was comparable to that of control subjects, but heart rate was significantly higher. This increase in heart rate may have been due to sympathetic activation caused by anxiety, since the depressed patients were significantly more anxious than the control subjects. Medicated patients exhibited diminished cardiac vagal tone and higher heart rate than unmedicated patients and controls. This was probably due to the anticholinergic effects of the antidepressants. Our findings suggest that cardiac vagal tone is not lower than normal in patients with depression, melancholic type.

Adult↗

Does muscle tension reflect arousal? Relationship between electromyographic and electroencephalographic recordings.

Increased muscle tension and heightened arousal are the most consistent finding in patients with anxiety disorders. This study examined the relationship between frontalis and gastrocnemius electromyographic (EMG) and electroencephalographic activity on 14 female generalized anxiety disorder patients and 14 female control subjects. In GAD patients, gastrocnemius but not frontalis EMG was correlated with right but not left hemisphere activity. For the non-anxious subjects, there was a pattern for both beta 1 and beta 2 waves to be positively associated with both frontalis and gastrocnemius muscle tension levels. The results, while preliminary, suggest that EMG activity may reflect central nervous system arousal.

Adult↗

Explained and unexplained medical symptoms in generalized anxiety and panic disorder: relationship to the somatoform disorders.

We have examined the numbers and types of symptoms in a sample of 90 patients with generalized anxiety disorder (GAD) and 77 patients with panic disorder (PD) collected from six different sites during the conduct of a multicenter clinical trial. This information was obtained utilizing the Health Questionnaire, a 47-item self-report list of medical symptoms, patterned after the Somatization Disorder section of the Diagnostic Interview Schedule. Although the patients in this sample had a wide variety of medically explained and unexplained physical symptoms, none of them qualified for a diagnosis of somatization disorder by DSM-III-R criteria. GAD and PD patients reported remarkably similar numbers of explained and unexplained medical symptoms. The panoply of somatic symptoms presented by these patients presents a formidable diagnostic challenge for clinicians. These findings suggest that the pattern of overutilization of medical services that is well documented for PD patients may also be found for GAD patients.

Adult↗

Normal caudate nucleus in obsessive-compulsive disorder assessed by quantitative neuroimaging.

BACKGROUND: Prior neuroimaging studies have not consistently demonstrated a structural or functional abnormality of the caudate nucleus in patients with obsessive-compulsive disorder (OCD). However, there is theoretical support for some associated dysfunction of the caudate nucleus. METHODS: We examined volumes of the caudate nucleus and putamen with magnetic resonance imaging in 24 patients with adult-onset OCD and 21 control subjects, group-matched on age, race, education, and sex. Patients were relatively free from tics. To evaluate function (metabolism or blood flow) of the caudate nucleus, we performed a quantitative review, including a meta-analysis, of normalized data from functional neuroimaging studies that compared patients who had OCD with normal control subjects. RESULTS: All structural basal ganglia measures failed to exhibit differences between patients with OCD and matched normal control subjects. Patients did not demonstrate evidence of ventricular enlargement. Quantitative meta-analysis of the functional neuroimaging literature did not demonstrate a consistent abnormality of the caudate nucleus. CONCLUSIONS: We did not observe evidence of a structural abnormality of the caudate nucleus in patients with OCD. Prior reports of a structural aberration of the caudate nucleus were mixed. We also did not find strong support for relative caudate metabolic or perfusion dysfunction in the literature, although increased function in the frontal cerebral cortex was identified. The heterogeneous nature of this disorder may account for inconsistencies between studies. For example, ventricular enlargement or reduced caudate volume or blood flow might be evident in patients with soft neurological signs (eg, tics), while patients in the current study were relatively free from tics. Although theories of OCD suggest a dysfunction of the caudate nucleus, the structural and functional neuroimaging literature has not consistently verified this.

Adult↗

Treatment, discontinuation, and psychomotor effects of diazepam in women with generalized anxiety disorder.

Twenty-one women with generalized anxiety disorder (GAD) participated in a 6-week, double-blind, placebo-controlled trial to assess the treatment and abrupt withdrawal effects of diazepam on psychic and somatic symptoms of anxiety. The results confirmed those of previous studies reporting that (1) clinical doses of diazepam are effective in attenuating the symptoms of generalized anxiety to a greater extent than placebo during the first 3 weeks of treatment; (2) somatic symptoms are more responsive to diazepam treatment than psychic symptoms; and (3) patients taking diazepam exhibit increased anxiety upon abrupt withdrawal of medication. This finding, combined with the fact that diazepam discontinuation did not produce withdrawal effects in non-anxious volunteers, suggests that diazepam discontinuation after 6 weeks results in rebound anxiety rather than a physical withdrawal syndrome. Diazepam did not improve psychomotor performance in GAD patients. Psychomotor impairment after 6 weeks of diazepam was similar to that seen in nonanxious volunteers.

Adult↗

Is hyperarousal essential to obsessive-compulsive disorder? Diminished physiologic flexibility, but not hyperarousal, characterizes patients with obsessive-compulsive disorder.

OBJECTIVE: To examine the hypothesis that the pathologic features of obsessive-compulsive disorder (OCD) are facilitated by abnormal levels of arousal, we compared patients with OCD with controls on self-reports and psychophysiologic measures. METHODS: Twenty-three patients with OCD were compared with 21 controls on rating scales and on psychophysiologic measures (ie, heart interbeat interval, skin conductance, respiration, blood pressure, and electromyographic activity) during rest and during two psychologically stressful tasks. RESULTS: Patients rated themselves higher on psychic and somatic anxiety scales. Mean physiologic activities were not elevated at rest. During tasks, changes in electrodermal, cardiovascular (except blood pressure), and muscle activities were smaller in patients with OCD, indicating decreased physiologic flexibility. CONCLUSIONS: Hyperarousal, measured peripherally, is not an essential pathologic feature of OCD. Decreased physiologic flexibility indicates an anxiety-related, but not OCD-specific, impairment of psychophysiologic reactivity to one's environment.

Adult↗