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Biomedical subjects

D S Cowley

Publications and source records attributed to D S Cowley.

At least 37 records · Page 2Linked to original sources
PubMed1995

Human oculomotor function: reliability and diurnal variation.

To provide information on test-retest reliability for seven oculomotor paradigms currently used in studies of schizophrenia and other neuropsychiatric conditions, we tested eight controls at four weekly intervals, twice in the morning (8-10 AM) and twice in the afternoon (3-5 PM). Intraclass correlation coefficients were significant (p < .05) for both AM and PM pairs of measures as well as for mean AM and PM pairs for closed-loop pursuit gain, open-loop pursuit gain (using velocity as the measure), saccadic frequency during pursuit and fixation, visually and nonvisually guided saccadic latency and velocity, antisaccadic latency, and premature reflexive saccades during the memory-guided saccade task. Acceleration as a measure of open-loop gain (for slower targets) and accuracy of saccades to a moving target were only reliable at PM testing time. Nonvisually guided saccadic accuracy and inappropriate reflexive saccades during the antisaccade task were not reliable, possibly due to the narrow range of values for these measures. Except for approximately 10% fewer saccades during pursuit and fixation in the morning, there were no consistent diurnal differences. These findings suggest that, in a small sample of subjects, most measures of oculomotor function are stable across time and may reflect underlying neurophysiologic traits.

Adolescent↗
PubMed1995

Effects of diphenhydramine on human eye movements.

Peak saccadic eye movement velocity (SEV) and average smooth pursuit gain (SP) are reduced in a dose-dependent manner by diazepam and provide reliable, quantitative measures of benzodiazepine agonist effects. To evaluate the specificity of these eye movement effects for agents acting at the central GABA-benzodiazepine receptor complex and the role of sedation in benzodiazepine effects, we studied eye movement effects of diphenhydramine, a sedating drug which does not act at the GABA-benzodiazepine receptor complex. Ten healthy males, aged 19-28 years, with no history of axis I psychiatric disorders or substance abuse, received 50 mg/70 kg intravenous diphenhydramine or a similar volume of saline on separate days 1 week apart. SEV, saccade latency and accuracy, SP, self-rated sedation, and short-term memory were assessed at baseline and at 5, 15, 30, 45, 60, 90 and 120 min after drug administration. Compared with placebo, diphenhydramine produced significant SEV slowing, and increases in saccade latency and self-rated sedation. There was no significant effect of diphenhydramine on smooth pursuit gain, saccade accuracy, or short-term memory. These results suggest that, like diazepam, diphenhydramine causes sedation, SEV slowing, and an increase in saccade latency. Since the degree of diphenhydramine-induced sedation was not correlated with changes in SEV or saccade latency, slowing of saccadic eye movements is unlikely to be attributable to sedation alone. Unlike diazepam, diphenhydramine does not impair smooth pursuit gain, saccadic accuracy, or memory. Different neurotransmitter systems may influence the neural pathways involved in SEV and smooth pursuit again.

Adult↗
PubMed1995

Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment.

The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment.

Adult↗
PubMed1995

Assessment of family history of alcoholism in sons of alcoholic fathers.

Results of studies of sons of alcoholics (SOAs) may vary depending on the density of the family history of alcoholism of the SOA subjects selected. To assess how reliably SOA subjects report a history of alcoholism in first- and second-degree relatives, we compared family histories obtained from 20 SOAs with those provided by their fathers. In all 20 cases, SOAs and their fathers agreed that the father met criteria for alcohol dependence but for no other primary Axis I psychiatric disorder. However, agreement was not as good for whether other paternal relatives in addition to the father were affected (kappa = 0.36) or for whether the family history was unigenerational or multigenerational for alcoholism (kappa = 0.44). Whether this discrepancy was due to under-reporting by the son or over-reporting by the father is unclear. These results suggest that 18-25 year old SOAs are reliable sources regarding alcohol dependence in their fathers, but that for determination of density of the family history of alcoholism, other relatives should also be interviewed directly.

Adolescent↗
PubMed1994

Eye movement effects of diazepam in sons of alcoholic fathers and male control subjects.

Both animal and human studies suggest that the GABA-benzodiazepine receptor complex may be involved in the acute effects of ethanol, as well as the development of tolerance and dependence with chronic ethanol use. The current study was performed to assess sensitivity to benzodiazepines, and thus the functional sensitivity of the GABA-benzodiazepine receptor system, in subjects at high risk for alcoholism. Sons of alcoholic fathers (SOAs; n = 27) were compared with male controls without a family history of alcoholism (n = 23) in response to diazepam versus placebo. SOAs and controls received four logarithmically increasing doses of intravenous diazepam or placebo in randomized order on 2 days at least 1 week apart. Effects of diazepam were assessed using two eye movement tasks, peak saccadic eye movement velocity, and average smooth pursuit eye movement gain, which provide reliable, quantitative measures of benzodiazepine effects. In addition, memory, self-rated sedation, and pleasurable drug effects were measured. In comparison with control subjects, SOAs displayed significantly less diazepam effects on peak saccade velocity, average smooth pursuit gain, memory, and self-rated sedation, but significantly greater pleasurable drug effects. Differences in response to diazepam between SOAs and male controls may reflect altered functional sensitivity of the central GABA-benzodiazepine receptor system or a more general difference between groups in the effects of CNS active or sedating drugs.

Adult↗
PubMed1993

Benzodiazepine pharmacodynamics: utility of eye movement measures.

The utility of several measures of saccadic and smooth pursuit eye movements as benzodiazepine pharmacodynamic measures was explored in 24 psychiatrically and medically health control subjects. Measures of sedation and memory impairment were also included. Subjects received four logarithmically increasing doses of intravenous diazepam at 15-min intervals on 1 day resulting in monotonically increasing plasma diazepam levels, and placebo on another day in random order 1 week apart. Measures were collected twice at baseline, once after each dose of diazepam/placebo and twice more, 15 and 30 min after the last dose. Peak saccadic velocity and smooth pursuit gain showed the greatest overall and dose-dependent drug effect among eye movement measures. Although effect sizes at the highest dose for memory impairment and self-rated sedation were comparable to these two measures, reliability (i.e., placebo-day fluctuation) with these measures was considerably poorer. Log-linear pharmacodynamic modeling was used to calculate the effective dose (ED30) or concentration (EC30) required to reduce saccadic velocity or pursuit gain by 30%. Almost all (23/24) subjects had linear and easily interpretable plots for saccadic velocity, while a majority (19/24) of subjects had interpretable plots for smooth pursuit gain. The distribution of ED30 and EC30 values showed a wide range of sensitivities to diazepam. These findings suggest that saccadic velocity and smooth pursuit gain are sensitive, reliable, quantitative benzodiazepine pharmacodynamic measures.

Adolescent↗
PubMed1993

Adjunctive treatment of benzodiazepine discontinuation syndromes: a review.

The variety of pharmacologic and psychotherapeutic approaches to facilitate benzodiazepine discontinuation are reviewed. Strategies to attenuate physiologic withdrawal with clonidine, propranolol and carbamazepine have been inconsistently effective. Strategies to prevent relapse by substituting medications that could later be discontinued more easily (i.e., antidepressants and azapirones) appear more useful but have been less well studied. Psychotherapeutic approaches appear to work, but specific therapeutic components are unclear and non-specific "placebo" effects may play an important role.

Anti-Anxiety Agents↗
PubMed1993

DSM-III-R personality disorders in a mood and anxiety disorders clinic: prevalence, comorbidity, and clinical correlates.

This study examined the prevalence, comorbidity, and clinical correlates of personality disorders in an outpatient sample (N = 352) with anxiety and depression. Subjects were diagnosed using the Structured Clinical Interview for DSM-III-R (SCID) on Axes I and II, and they also completed interview and self-report measures of symptoms. Subjects with a personality disorder were less likely to be married, more likely to be single or divorced, had lower family incomes, had more severe symptoms of both anxiety and depression, and had a greater number of lifetime Axis I diagnoses. Subjects with dysthymic and bipolar disorders were more likely, and subjects with panic disorder uncomplicated by agoraphobia were less likely to have a personality disorder compared to the rest of the sample. The most prevalent personality disorders were Avoidant, Obsessive-Compulsive, Paranoid, and Borderline. Paranoid co-occurred with Narcissistic, and Borderline co-occurred with Histrionic personality disorder significantly more often than chance and base rates would predict.

Adolescent↗
PubMed1993

Personality and benzodiazepine sensitivity in anxious patients and control subjects.

Cloninger has recently proposed a model of personality variability that is based on three independent heritable traits of harm avoidance, novelty seeking, and reward dependence, each of which is thought to be mediated by a separate neurochemical and neuroanatomic mechanism. The current study tested hypotheses generated on the basis of this theory in anxious patients and control subjects. Eighteen patients with panic disorder, 12 patients with generalized anxiety disorder, and 21 control subjects underwent both personality testing and assessment of their sensitivity to diazepam, as measured by slowing of saccadic eye movement velocity. As expected, anxious patients displayed higher harm avoidance scores than controls. Although an inverse correlation between harm avoidance and benzodiazepine sensitivity was predicted, no relationship between these variables was found in any diagnostic group. However, a significant correlation was found between novelty-seeking scores and sensitivity to diazepam. This finding, although not predicted by Cloninger's theory, is consistent with prior preclinical and human studies.

Adult↗
PubMed1992

Alcohol abuse, substance abuse, and panic disorder.

The purpose of this article is to review the literature concerning the interaction of alcohol and/or substance abuse with panic disorder, the comorbidity of these disorders, possible causal relationships, biologic relationships, and the recognition and treatment of dually disordered patients. A number of studies suggest significant comorbidity between panic disorder and alcoholism or abuse of drugs, especially cocaine and sedatives. Panic may lead to drinking or sedative use and also result from prolonged use or withdrawal of alcohol or other drugs. Possible biologic relationships involve the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex and the central noradrenergic system. Although treatment of panic in substance abusers has not been studied specifically, guidelines for recognition and management of these patients, including use of antipanic medication, are discussed.

Alcoholism↗
PubMed1992

Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls.

The acute effects of diazepam on plasma GABA were determined in 18 patients with panic disorder, 13 patients with generalized anxiety disorder and 20 healthy controls. All subjects were benzodiazepine-naive. Four logarithmically increasing doses of diazepam/placebo were administered intravenously at 15-min intervals on 2 separate days. Plasma GABA was measured at baseline and 3 min after the highest dose of diazepam/placebo. There was an overall decrease in plasma GABA that was significantly greater following diazepam compared with placebo, but no group differences in response. In a separate group of 18 panic disorder patients receiving chronic benzodiazepine treatment with alprazolam, the same diazepam infusion procedure (no placebo day) produced decreases in plasma GABA similar to those seen in the untreated panic disorder patients. The clinical and physiologic implications of these findings are discussed.

Adult↗
PubMed1992

Coping in panic and major depressive disorder. Relative effects of symptom severity and diagnostic comorbidity.

This study used the Ways of Coping Checklist to examine coping style in patients with panic and major depressive disorders. The relative contribution of distress (symptom severity) and diagnostic comorbidity was determined in three sets of diagnostic subgroups: patients suffering from both panic and major depressive disorders (compared with either disorder alone); panic patients with and without agoraphobia (regardless of concurrent depression); and patients with versus without a concurrent axis II personality disorder. Use of less problem-focused and more emotion-focused coping was strongly correlated with level of distress and was associated with all three examples of diagnostic comorbidity when level of distress was used as a covariate. Regression analyses showed that, except for the presence of a personality disorder, distress was a much stronger predictor of coping than diagnostic subtype.

Adaptation, Psychological↗
PubMed1992

Response to diazepam in sons of alcoholics.

Alcohol exerts several of its actions via the chloride channel associated with the central GABA-benzodiazepine receptor complex. To explore a possible role for this receptor complex in risk for alcoholism, and to determine whether risk for alcoholism is associated with risk for benzodiazepine abuse, the authors administered intravenous diazepam to 18 sons of male alcoholics (SOAs) and 18 control subjects. Four logarithmically increasing doses of diazepam and matched volumes of placebo were given in randomized order on separate days about 1 week apart. SOAs were significantly more likely than controls to report euphoric responses to diazepam. At some diazepam doses, SOAs were more likely to report feeling "high" and "intoxicated." SOAs and controls did not differ in feeling "drugged." SOAs and controls may differ in expectations regarding the subjective effects of drugs and/or in the function of the central GABA-benzodiazepine receptor complex. These findings also add further evidence for increased pleasurable effects, and thus possibly increased risk for benzodiazepine abuse, in a subgroup of SOAs.

Adolescent↗
PubMed1991

Lactate vulnerability after alprazolam versus placebo treatment of panic disorder.

Thirty-six patients with panic disorder underwent sodium lactate infusion before and after 8 weeks of treatment with alprazolam or placebo. With reinfusion, those patients panic-free with chronic alprazolam treatment displayed significantly decreased reactivity to lactate, as measured by subjective symptom ratings, duration of infusion before developing peak lactate-induced symptoms, and the proportion of patients experiencing lactate-induced anxiety or panic. Patients panic-free on placebo, as well as nonresponders to alprazolam treatment, displayed some, although less striking, decreases in reactivity to lactate with reinfusion. As a group, patients clinically unchanged with placebo treatment showed no systematic change in lactate response with reinfusion. Although the small numbers of patients in each treatment outcome group prohibit drawing definitive conclusions, these findings suggest that decreases in lactate-induced panic after successful alprazolam treatment of panic may result from a combination of changes in clinical state and direct effects of the medication.

Adult↗
PubMed1991

Neuroendocrine effects of diazepam in panic and generalized anxiety disorders.

The adrenocorticotropic hormone (ACTH), cortisol, and growth hormone responses to four consecutive, logarithmically increasing doses of intravenous diazepam compared with placebo given at 15-min intervals were examined in patients with panic disorder (n = 13), generalized anxiety disorder (n = 8), and healthy controls (n = 13). Diazepam caused dose-dependent decreases in cortisol and increases in GH and dose-independent decreases in ACTH. There were no patient-control differences, possibly due to either the small sample size of the experimental paradigm, which tested subjects in an upright, sitting position in mildly arousing circumstances.

Adrenocorticotropic Hormone↗
PubMed1990

The diagnostic utility of lactate sensitivity in panic disorder.

Lactate infusion is the most extensively studied of the pharmacological challenge tests in panic disorder. We assessed the value of this test in the diagnosis and subtyping of panic in clinical and research settings. Analysis of lactate infusion studies to date suggests that patients with panic attacks are significantly more sensitive to lactate than are healthy controls or patients with other psychiatric disorders without panic attacks. However, the usefulness of lactate infusion is limited by the lack of standardized, objective criteria for lactate-induced panic and uncertainty as to the sensitivity and specificity of the test for current, clinically significant panic attacks. Except in rare cases, the clinical history is likely to be of more value than lactate response in diagnosing panic disorder. Determination of the role of the test in subtyping patients with panic disorder awaits further study of the diagnostic, prognostic, genetic, and pathophysiologic significance of lactate sensitivity.

Anxiety Disorders↗
PubMed1990

Reduced benzodiazepine sensitivity in panic disorder.

We evaluated the functional sensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in 9 patients with panic disorder and 10 psychiatrically healthy control subjects by comparing the effects of four logarithmically increasing doses of intravenous diazepam on saccadic eye movement velocity, memory, and self-rated sedation. Patients with panic disorder were less sensitive than controls to diazepam using eye velocity as the dependent measure. Sedation and memory effects did not distinguish the two groups. These findings suggest that panic disorder is associated with functional subsensitivity of the gamma-aminobutyric acid-benzodiazepine supramolecular complex in brain-stem areas controlling saccadic eye movements.

Adult↗