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Biomedical subjects

D F Klein

Publications and source records attributed to D F Klein.

At least 37 records · Page 2Linked to original sources
PubMed2000

Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design.

OBJECTIVE: The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium. METHOD: Twenty outpatient children and adolescents (ages 10-18) with a disruptive behavior disorder (oppositional defiant disorder or conduct disorder) met the specific criteria for explosive temper and mood lability. They received 6 weeks of divalproex treatment and 6 weeks of placebo by random assignment. Independent evaluators blind to group assignment assessed response at the end of each phase. RESULTS: At the end of phase 1, eight of 10 subjects had responded to divalproex; zero of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 has superior response taking divalproex. CONCLUSIONS: This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents.

Adolescent↗
PubMed2000

Flawed meta-analyses comparing psychotherapy with pharmacotherapy.

OBJECTIVE: The author sought to illustrate the invalidity of meta-analyses that claim to quantitatively compare the benefits of psychotherapy to pharmacotherapy in patients with psychiatric disorders. METHOD: Studies included in four meta-analyses were retrieved and their study designs evaluated. RESULTS: The meta-analyses compared effect sizes from disparate studies that were not uniformly blind, random, controlled, or of high quality. The studies did not directly address the comparative efficacy question or lacked assay sensitivity. CONCLUSIONS: Numerous types of studies exemplify the need for caution in evaluating meta-analytic conclusions without first critically examining the included studies. Estimates of the relative efficacy of different treatments are not well founded when based almost exclusively on indirect, multiply confounded comparisons. Meta-analyses based on flawed studies or studies that lack demonstrated assay sensitivity are also inadequate for the criticism of treatment guidelines. Some bodies of data are inadequate to support a proper meta-analysis.

Antidepressive Agents↗
PubMed1999

Panic induced by carbon dioxide inhalation and lack of hypothalamic-pituitary-adrenal axis activation.

It has been hypothesized that spontaneous panic is distinct from anticipatory anxiety, which activates the hypothalamic-pituitary-adrenal (HPA) axis. Panic attacks characterized by prominent respiratory symptoms, such as those induced by sodium lactate, are not associated with increases in cortisol. We examined blood cortisol responses to CO2-induced panic. Cortisol levels did not increase and actually decreased significantly in 10 panicking subjects with panic disorder. No reductions were noted after 20 min of CO2 inhalation in either eight normal comparison subjects or six non-panicking panic disorder patients. These results lend support to the hypothesis that the pathophysiological mechanism underlying CO2-induced panic is different from that underlying general or anticipatory anxiety.

Adult↗
PubMed1999

Panic disorder.

Explore the source record for details and available documents.

Humans↗
PubMed1999

Smoking and panic attacks: an epidemiologic investigation.

BACKGROUND: Epidemiologic studies have reported a lifetime association between smoking and panic disorder. In this study, we examine potential explanations for this association. METHODS: Analysis was conducted on data from 2 epidemiologic studies, the Epidemiologic Study of Young Adults in southeast Michigan (N = 1007) and the National Comorbidity Survey Tobacco Supplement (n = 4411). Cox proportional hazards models with time-dependent covariates were used to estimate the risk for onset of panic attacks associated with prior smoking and vice versa, controlling for history of major depression. The role of lung disease in the smoking-panic attacks association was explored. RESULTS: Daily smoking signaled an increased risk for first occurrence of panic attack and disorder; the risk was higher in active than past smokers. No significant risk was detected for onset of daily smoking in persons with prior panic attacks or disorder. Exploratory analyses suggest that lung disease might be one of the mechanisms linking smoking to panic attacks. CONCLUSIONS: The evidence that the association between smoking and panic disorder might result primarily from an influence in one direction (i.e., from prior smoking to first panic attack) and the possibility of a higher risk in active than past smokers suggest a causal hypothesis for the smoking-panic attacks relationship.

Adult↗
PubMed1999

Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of pathophysiologic significance in certain patients with panic disorder. It remains to be demonstrated if the peripheral autoimmunity is representative of CNS 5-HT neuronal alterations. Replication appears warranted.

Adult↗
PubMed1999

Harmful dysfunction, disorder, disease, illness, and evolution.

Can psychiatric disorders be conceptualized as "harmful dysfunctions" (J. C. Wakefield, 1992a, 1992b, 1999; S. O. Lilienfeld & L. Marino, 1995)? Wakefield's (1992a) central concept of disorder as "harmful dysfunction" is discussed by placing it in the context of a complementary discussion of disease, illness, the sick role, and evolution (D. F. Klein, 1978). S. O. Lilienfeld and L. Marino (1995) contended that proper biological function cannot be determined. This argument obscures the key significance of involuntary impairment of evolved functions. The claim that the Roschian concept has no counterpart in reality is incorrect and does not support the conclusion that dysfunctions are irreducibly evaluative and therefore arbitrary. J. C. Wakefield's (1999) views in this area are supplemented. The role of monothetic and polythetic categorization, extremal terms, and the concept of normality in nosology is considered. This analysis refutes the implication that deviance and illness are equivalent. The resolution of this debate is practically relevant to emphasizing areas of research investment, such as therapeutics.

Biological Evolution↗
PubMed1999

Lack of genetic linkage or association between a functional serotonin transporter polymorphism and panic disorder.

Given the efficacy of medications that interact with the serotonin transporter (5-HTT) in the treatment of panic disorder, we have used a family-based design to test for genetic association and linkage between panic disorder and a functional polymorphism in the promoter of the gene for 5-HTT. In this study, 340 individuals in 45 families, as well as 74 haplotype relative risk 'trios' were genotyped at the polymorphic locus, which consists of a 44 base pair deletion/insertion. There were no significant differences in allele frequencies or occurrence of genotypes within the triads. No linkage between the 5-HTT polymorphism and panic disorder was observed in the multiplex families, using a variety of simulations for dominant and recessive models of inheritance. Recent reports suggest an association between the 5-HTT polymorphism and anxiety-related traits, as measured with personality assessment. The results reported here provide evidence that the genetic basis of panic disorder may be distinct from anxiety-related traits assessed by personality inventories in normal populations.

Alleles↗
PubMed1999

Cognitive-behavioral group therapy versus phenelzine in social phobia: long-term outcome.

UNLABELLED: To evaluate the effects of maintenance treatment and durability of gains after treatment discontinuation, responders to either phenelzine (PZ) or cognitive-behavioral group therapy (CBGT) from an acute trial comparing these two treatments as well as pill placebo and a psychotherapy control (educational supportive group therapy) were enrolled into maintenance and treatment-free follow-up phases. EXPERIMENTAL DESIGN: Responders to an acute trial contrasting PZ and CBGT entered a six-month maintenance phase. Patients who continued to respond through the maintenance phase entered a six-month treatment free phase. Patients receiving pill placebo or educational supportive group therapy in the acute trial did not enter the long term study. PRINCIPAL OBSERVATIONS: PZ patients entered maintenance more improved than CBGT patients, and nonrelapsing PZ patients maintained their superior gains throughout the study. Relapse during maintenance did not differ between treatments. However, PZ patients showed a trend toward greater relapse during treatment-free follow-up. There was a greater relapse among patients with generalized social phobia with phenelzine. CONCLUSIONS: PZ and cognitive-behavioral group therapy may differ in their long term effects. The superiority seen with PZ on some measures in the acute study persisted in patients who maintained their gains over the course of maintenance and treatment-free follow-up. However, CBGT may lead to a greater likelihood of maintaining response after treatment has terminated. Replication with larger samples is needed, as is a study of the acute and long-term efficacy of combined PZ and CBGT.

Adult↗
PubMed1999

Specific phobia 10-16 years after treatment.

Twenty eight participants, initially treated for specific phobia as part of a comparative treatment study, were evaluated 10 to 16 years (X = 12 years) later. A comprehensive, in-person, semi-structured diagnostic interview was utilized, which also assessed comorbid disorders. Of 21 patients who had been rated as responders (much improved or very much improved) at treatment termination, 13 (62%) had clinically significant avoidance or endurance with dread subsequent to treatment. Among a subgroup of these responders who had been considered completely recovered (n = 11), 5 (45%) had clinically significant symptoms following treatment. None of the seven subjects who had been considered unimproved at treatment termination recovered from phobia symptoms in the intervening years. Positive response to treatment was associated with better long term outcome. Clinical characteristics, such as phobia subtype, age of onset, baseline severity, and lifetime comorbidity of other psychiatric disorders were not associated with long term outcome in this sample. Type of treatment was not associated with long term outcome. Results challenge the notion that recovery from specific phobia following treatment is characterized by complete and enduring cessation of symptoms.

Adult↗
PubMed1998

Results of a genome-wide genetic screen for panic disorder.

Panic disorder is characterized by spontaneous and recurrent panic attacks, often accompanied by agoraphobia. The results of family, twin, and segregation studies suggest a genetic role in the etiology of the illness. We have genotyped up to 23 families that have a high density of panic disorder with 540 microsatellite DNA markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing all the autosomes, at an average marker density of 11 cM. Over 110,000 genotypes have been generated on the whole set of families, and the data have been analyzed under both a dominant and a recessive model, and with the program SIBPAIR. No lod scores exceed 2.0 for either parametric model. Two markers give lod scores over 1.0 under the dominant model (chromosomes 1p and 20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these (20p) may be particularly promising. Analysis with SIBPAIR yielded P values equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided, uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q, 16p, 20p and 20q).

Adolescent↗
PubMed1998

Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study.

BACKGROUND: Uncontrolled reports suggest that intravenous clomipramine hydrochloride may be effective for patients with obsessive-compulsive disorder (OCD) who are nonresponsive to oral clomipramine. METHODS: Fifty-four patients with oral clomipramine-refractory OCD were randomized to receive 14 infusions of either placebo or clomipramine hydrochloride, starting at 25 mg/d and increasing to 250 mg/d. Ratings were conducted double-blind after infusion 14 among 54 patients, single-blind 1 week later among 39 patients, and nonblind 1 month later among 31 patients. Response was based on a Clinical Global Impressions rating of at least "much improved." RESULTS: Six (21%) of 29 patients randomized to receive intravenous (i.v.) clomipramine vs 0 of 25 patients given i.v. placebo were responders after 14 infusions (df = 1, P<.02). Dimensional ratings after infusion 14 revealed significant (P = .007) improvement on the National Institute of Mental Health-Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (P = .03), but not the Yale-Brown Obsessive Compulsive Scale. One week later, all dimensional measures of OCD showed significant improvement. At 1 week post-i.v., 9 (43%) of 21 patients initially randomized to i.v. clomipramine and treated subsequently with oral clomipramine were responders, whereas 0 of 18 patients initially randomized to receive i.v. placebo and treated subsequently with several days of open-label i.v. clomipramine responded (df = 1, P<.002). Of the 31 patients assessed 1 month after i.v. infusion (treatment not controlled), 18 (58.1%) were responders. Intravenous clomipramine treatment was safe with no serious adverse consequences. CONCLUSIONS: Intravenous clomipramine is more effective than i.v. placebo for patients with OCD with a history of inadequate response or intolerance to oral clomipramine. Further study of this promising treatment for refractory OCD is needed.

Administration, Oral↗
PubMed1998

Cognitive behavioral group therapy vs phenelzine therapy for social phobia: 12-week outcome.

BACKGROUND: This article presents results of the acute treatment phase of a 2-site study comparing cognitive behavioral group therapy (CBGT) and treatment with the monoamine oxidase inhibitor phenelzine sulfate for social phobia. METHODS: One hundred thirty-three patients from 2 sites received 12 weeks of CBGT, phenelzine therapy, pill placebo administration, or educational-supportive group therapy (an attention-placebo treatment of equal credibility to CBGT). The "allegiance effect," ie, the tendency for treatments to seem most efficacious in settings of similar theoretical orientation and less efficacious in theoretically divergent settings, was also examined by comparing responses to the treatment conditions at both sites: 1 known for pharmacological treatment of anxiety disorders and the other for cognitive behavioral treatment. RESULTS: After 12 weeks, phenelzine therapy and CBGT led to superior response rates and greater change on dimensional measures than did either control condition. However, response to phenelzine therapy was more evident after 6 weeks, and phenelzine therapy was also superior to CBGT after 12 weeks on some measures. There were few differences between sites, suggesting that these treatments can be efficacious at facilities with differing theoretical allegiances. CONCLUSIONS: After 12 weeks, both phenelzine therapy and CBGT were associated with marked positive response. Although phenelzine therapy was superior to CBGT on some measures, both were more efficacious than the control conditions. More extended cognitive behavioral treatment and the combination of modalities may enhance treatment effect.

Adult↗
PubMed1998

Ventilatory physiology of children and adolescents with anxiety disorders.

BACKGROUND: Abnormalities in ventilatory physiology have been noted in adults with panic disorder. We tested the hypothesis that abnormalities in ventilatory physiology differentiate children and adolescents with anxiety disorders from psychiatrically healthy children. METHODS: Ventilatory physiology was monitored with a canopy apparatus during room-air breathing and 15 minutes of carbon dioxide exposure in 33 children and adolescents comprising 18 probands with an anxiety disorder and 15 psychiatrically healthy children. RESULTS: During room-air breathing, probands had significantly larger minute ventilation, larger tidal volumes, and more variable breathing patterns than healthy comparisons, but the groups did not differ in end-tidal carbon dioxide or respiratory rate. During carbon dioxide challenge, probands exhibited larger minute ventilation and respiratory rate responses relative to comparisons. CONCLUSION: These findings on the association between ventilatory physiology and anxiety disorders in children and adolescents are consistent with results from studies of adults with panic disorder.

Adolescent↗
PubMed1998

Plasma cortisol concentrations preceding lactate-induced panic. Psychological, biochemical, and physiological correlates.

BACKGROUND: We evaluated the role of plasma cortisol levels in determining sodium lactate-induced panic by reporting psychological, physiological, and biochemical data collected from an extended sample of 214 subjects during the "placebo" infusion (isotonic saline solution) immediately preceding the lactate infusion procedure. METHODS: One hundred seventy patients with panic disorder, 101 (59%) of whom were assessed to have panicked (P group), and 69 (41%) who were assessed not to have panicked (NP group) with lactate infusion; and 44 normal healthy volunteer controls (1 of whom panicked with lactate infusion) were studied. RESULTS: Before the lactate infusion, the P group exhibited hypothalamic-pituitary-adrenal (HPA) axis activation (high plasma cortisol levels) and evidence of hyperventilation (low PCO2 levels) in comparison with NP and control groups. Self-reported fear, dyspnea, and diastolic blood pressure were highest in the P group, intermediate in the NP group, and lowest in the control group. Within the P group, baseline fear scores correlated inversely with PCO2 levels and positively with cortisol levels while PCO2 levels correlated negatively with cortisol levels. Significant predictors of lactate-induced panic were prelactate infusion fear and the interaction of high cortisol levels and low PCO2 levels. CONCLUSION: Combined data suggest that synchronized elevations of HPA axis activity, self-reported fear, and hyperventilation during the period before lactate infusion predisposes to lactate-induced panic.

Acute Disease↗
PubMed1998

Hemodynamic response to respiratory challenges in panic disorder.

This study compares the hemodynamic response to panic disorder subjects with that of normal controls during respiratory challenges. Panic patients meeting DSM-IIIR criteria for panic disorder and normal controls were challenged with room air hyperventilation, 5% CO2 breathing, and 7% CO2 breathing. Measurements of pulse and blood pressure were taken at resting baseline and before and at the end of each respiratory challenge. Panic attack to each challenge was determined by using raters blinded to subject diagnosis and each subject's self-rating of panic. Significantly larger systolic and diastolic blood pressure increases were found in patients who panicked with room air hyperventilation than nonpanicking patients or normal controls. No significant blood pressure differences were found with 7% or 5% CO2 challenges, but higher pulse rates were found in the patient group. It may be possible that panic with room air hyperventilation causes a significant increase in systolic and diastolic blood pressure, or that a subgroup of panic disorder patients has a hyperactive vascular response to hypocapnia. These patients panic with room air hyperventilation and develop greater vasoconstriction and/or increased blood pressure response.

Administration, Inhalation↗