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Biomedical subjects

A C Swann

Publications and source records attributed to A C Swann.

At least 19 recordsLinked to original sources
PubMed1992

Noradrenergic receptor mechanisms in neophobia.

We have previously demonstrated that depletion of forebrain norepinephrine (NE) led to an attenuation of neophobia in a novel environment, as defined by a greater preference for novel food over familiar food. To study further the role of forebrain NE in neophobia we chronically infused noradrenergic receptor ligands or forskolin into the lateral ventricles of sham and 6-hydroxydopamine dorsal bundle lesioned rats. Chronic NE infusions into lesioned animals reversed the lesion-induced shift in relative food preference. The beta receptor agonist isoproterenol had moderate effects similar to those of NE in lesioned and sham animals. Phenylephrine, an alpha-1 agonist, was without effect. Forskolin, an adenylate cyclase activator, mimicked the effects of NE infusions. These data suggest a role for noradrenergic stimulation of adenylate cyclase in neophobia.

Adenylyl Cyclases↗
PubMed1992

A comparison of clinical features in trichotillomania and obsessive-compulsive disorder.

Trichotillomania (TM) recently has been conceptualized as a variant of obsessive-compulsive disorder (OCD). However, no systematic data have compared the clinical features of these two disorders. Here we report data from 8 TM and 13 OCD patients which suggest important clinical differences between groups. First, TM patients reported a significantly greater degree of pleasure during hair-pulling than OCD patients reported during performance of ritualistic behaviors. Second, TM was accompanied by significantly fewer associated obsessive-compulsive symptoms. Third, the groups differed with regard to other clinical features including anxiety, depression, and personality characteristics. We conclude that TM is not conceptualized best as a variant of OCD.

Adult↗
PubMed1992

Dysphoric mania.

Lithium remains the mainstay of therapy for most patients with bipolar disorder. Patients with syndromal variations of bipolar disorder, such as those experiencing mixed states or dysphoria have generally had a rather poor therapeutic response to lithium. Our group conducted a double-blind, parallel-group comparison of lithium and valproate for the control of mania in 27 patients with bipolar disorder. The study addressed the question of whether certain illness characteristics might be predictive of a positive response to a particular pharmacologic agent. There were significant differences in the cohort of patients who responded favorably to valproate compared with those who did not. Pretreatment depression scores were higher in the patients responding to valproate than in nonresponders. Patients with depressed mood or anxiety associated with mixed states responded equally to lithium and valproate. Studies are needed to clarify the clinical and pathophysiologic status of mixed or dysphoric manic states and to validate predictors of response to therapeutic agents.

Bipolar Disorder↗
PubMed1992

Hypothalamic-pituitary-adrenocortical function in mixed and pure mania.

There is little information about hypothalamic-pituitary-adrenocortical (HPA) axis function in mania, particularly in mixed states. We therefore investigated HPA function and its relationship to clinical state in 19 hospitalized manic patients meeting Schedule for Affective Disorders and Schizophrenia - Research Diagnostic Criteria for acute manic episodes, compared patients with and without a mixed presentation, and examined correlations between HPA activity and behavior. Data were available from 13-16 patients. Behavioral and biochemical analyses were conducted during a 15-d placebo period. Patients with mania had elevated cerebrospinal fluid (CSF) and urinary free cortisol excretion compared with healthy subjects, and did not differ from depressed patients in any cortisol measures. Mixed manics had significantly higher morning plasma cortisol, postdexamethasone plasma cortisol and CSF cortisol than pure manics. Five of 7 mixed manics and 3 of 9 pure manics were dexamethasone suppression test (DST) nonsuppressors. Afternoon plasma cortisol and CSF cortisol correlated significantly with depressed mood; urinary free cortisol correlated with anxiety. None of the cortisol measures correlated with mania or agitation scores. These data suggest that increased cortisol secretion is a characteristic of the depressed state in mixed manics, although pure manics may also have increased DST nonsuppression.

Adult↗
PubMed1992

A double-blind comparison of valproate and lithium in the treatment of acute mania.

OBJECTIVE: This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs. METHOD: Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA). RESULTS: At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response. CONCLUSIONS: Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states.

Analysis of Variance↗
PubMed1992

Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania.

OBJECTIVE: The authors reviewed available evidence regarding the status of dysphoric or mixed mania as a distinct clinical state and formulated operational criteria for its diagnosis. METHOD: Studies of dysphoric mania or hypomania in patients with bipolar disorder were analyzed with regard to clinical characteristics, prevalence, demographic features, course of illness, outcome, family history, associated conditions, biological tests, and response to biological treatment. RESULTS: Although some studies suggest that dysphoric and nondysphoric mania are similar conditions, others suggest that, compared with nondysphoric mania, dysphoric mania may be more severe; more likely to occur in women; more likely to be associated with suicidality, a younger age at onset, a longer duration of illness, higher rates of personal and familial depression, concomitant alcohol or sedative-hypnotic abuse, neuropsychiatric abnormalities, and poorer outcome; more frequently associated with cortisol nonsuppression; and less likely to respond adequately to lithium but perhaps more likely to respond to ECT or anticonvulsants. CONCLUSIONS: Substantial evidence suggests that dysphoric mania may be a distinct affective state. Contrary evidence, however, suggests that dysphoric mania may be a form of typical mania, a stage-related or severe form of mania, or a transitional state between mania and depression. Because the evidence may be inconsistent because of varying definitions of dysphoric mania among studies, the authors propose preliminary operational diagnostic criteria for the future study of dysphoric mania.

Adolescent↗
PubMed1991

Brain Na+,K(+)-ATPase regulation in vivo: reduction in activity and response to sodium by intracerebroventricular tetrodotoxin.

We investigated the effects of intracerebroventricular infusion of tetrodotoxin on activity and function of brain Na+,K(+)-ATPase. Infusion of 1 or 3 micrograms/h for 2, 4 or 7 days by osmotic minipump reduced the number of Na+,K(+)-ATPase sites as measured by ouabain binding in cerebral cortex. Tetrodotoxin infusions substantially reduced the functional transport capacity of Na+,K(+)-ATPase, measured by the maximal increase in synaptoneurosomal 86Rb+ uptake in the presence of monensin. The effects were maximal at 4 days, with a possible partial recovery of activity at 7 days. Results of ouabain inhibition curves suggested that the effect of tetrodotoxin was not specific for enzyme with high or low affinity for ouabain.

Animals↗
PubMed1991

Mania: sympathoadrenal function and clinical state.

We investigated sympathoadrenal and sympathetic nervous system activity, catecholamine disposition, and clinical state in 19 hospitalized manic patients. Severity of the core manic syndrome, anxiety, and hostility correlated with 24-hour urinary excretion of epinephrine relative to its metabolites, but only weakly with norepinephrine. Agitation, however, correlated most strongly and significantly with norepinephrine. Eight of the patients had mixed states: concurrent manic and depressive syndromes. There were no differences between mixed and pure manic patients with respect to catecholamine or metabolite excretion or precursor/product ratios, but mixed manic patients tended to have higher excretion of norepinephrine and had increased variance with respect to catecholamine measures. These data suggest that the function of the adrenal medulla, whether directly or indirectly, is important in the symptoms of both mixed and pure mania.

Adrenal Medulla↗
PubMed1990

Lithium distribution in mania: single-dose pharmacokinetics and sympathoadrenal function.

We examined lithium distribution after a single dose of 25 mEq in 14 drug-free manic patients. Lithium concentrations were measured in plasma, red blood cells, and urine. Maximum concentrations of lithium, times at which they were attained, and influx and efflux rate constants for extracellular fluid, red blood cell, and muscle-like compartments were estimated using a three-compartment pharmacokinetic model. Tissue lithium concentrations may continue to increase for hours after plasma lithium concentrations have peaked. Rate constants for absorption, excretion, and influx and efflux for the tissue compartments were similar to those previously reported for normal subjects. Rate constants for transport into and out of the tissue compartments correlated negatively with norepinephrine or epinephrine excretion and positively with the plasma/red cell Na+ gradient. Rate constants for efflux from red blood cell and muscle compartments correlated with measures of adrenocortical function and were higher in dexamethasone nonsuppressors than in suppressors. These data show that distribution of lithium may be related to sympathodrenal activity and Na+ distribution in manic patients.

Adrenal Cortex↗
PubMed1990

Ethanol and (Na+,K+)-ATPase: alteration of Na(+)-K+ selectivity.

Relative internal concentrations of Na+ and K+ are important in regulating (Na+,K+)-ATPase in situ. Ethanol is known to inhibit (Na+,K+)-ATPase and to reduce K+ affinity, but the concentrations required for these effects in vitro are large compared with those probably attainable in vivo. Yet, there is evidence suggesting that ethanol has physiologically relevant effects on (Na+,K+)-ATPase. We have investigated the effects of ethanol on selectivity for Na+ versus K+. At 150 mM, ethanol had little effect on (Na+,K+)-ATPase activity under the usual assay conditions, slightly (but nonsignificantly) reduced K+ affinity, and had no effect on extrapolated Na+ affinity in the absence of K+. However, ethanol had marked effects on cation selectivity, doubling the Ki for K+ on Na+ affinity and halving the Ki for Na+ on K+ affinity. These data show that ethanol, at concentrations too small for effects on (Na+,K+)-ATPase activity under optimal assay conditions, can alter its responses to changes in Na+ or K+.

Adenosine Triphosphate↗
PubMed1990

Stress, depression, and mania: relationship between perceived role of stressful events and clinical and biochemical characteristics.

We investigated the perceived role of stressful events in episodes of major affective disorder in patients studied in the NIMH Clinical Research Branch Collaborative Program on the Psychobiology of Depression (Biological Studies). Using items from the Schedule for Affective Disorders and Schizophrenia (SADS), episodes were divided into environment-sensitive (high perceived role of stressful events) and autonomous (minimal or no perceived role of stressful events). Patients with environment-sensitive episodes had fewer previous episodes and a longer index episode. The groups did not differ with respect to age, gender, education, socioeconomic group, diagnosis, severity of illness, or eventual response to treatment. Unipolar depressed patients with environment-sensitive episodes had lower CSF 5-HIAA than those with autonomous episodes. Among bipolar depressed patients, those with autonomous episodes had elevated excretion of O-methylated catecholamine metabolites and of epinephrine, while those with environment-sensitive episodes had normal excretion of catecholamines and metabolites. Manic subjects with environment-sensitive episodes had elevated norepinephrine excretion, while this was normal in manics with autonomous episodes. Relationships between environmental sensitivity of affective episodes and neurotransmitter function therefore appear to be related to the type of episode.

Adaptation, Psychological↗
PubMed1990

Ethanol inhibition of active 86Rb(+)-transport: evidence for enhancement by sodium or calcium influx.

We investigated interactions between ethanol and active cation transport mediated by Na,K-ATPase in rat brain synaptoneurosomes. Conditions that increased internal sodium also increased sensitivity of transport to ethanol, whereas low-sodium medium had the opposite effect. Ethanol also blocked the stimulation of ouabain-sensitive transport, glucose uptake and hyperpolarization associated with sodium influx. Low calcium decreased, while the calcium ionophore A23187 increased, sensitivity to ethanol. Inhibition of mitochondrial respiration or incubation under anaerobic conditions increased sensitivity of transport to inhibition by ethanol, but did not prevent the effect of A23187. Consistent with increased sensitivity to ethanol by cell calcium, ethanol potentiated the inhibition of transport by A23187. Although transport under basal conditions does not appear very sensitive to ethanol, these data suggest that sensitivity to ethanol may be increased under conditions associated with increased neural activity, and that ethanol may reduce the transport response to electrical activity.

Animals↗
PubMed1989

Noradrenaline and thyroid function regulate (Na+,K+)-adenosine triphosphatase independently in vivo.

We investigated interactions between noradrenaline and thyroid hormone status in the regulation of (Na+,K+)-ATPase in vivo. Treatment with the beta-adrenoceptor antagonist propranolol or with the neurotoxin 6-hydroxydopamine did not prevent the increases in heart (Na+,K+)-ATPase associated with triiodothyronine treatment. Administration of methimazole did not prevent the increase in (Na+,K+)-ATPase indices in cerebral cortex and heart associated with subacute noradrenergic stimulation by yohimbine. There was no evidence for synergistic effects between thyroid hormone administration and noradrenergic stimulation by yohimbine. Thyroid hormone, unlike noradrenaline, mainly increased (Na+,K+)-ATPase activity with low affinity for ouabain. These results show that noradrenaline and thyroid hormone regulate (Na+,K+)-ATPase by largely independent mechanisms, and may regulate different populations of enzyme molecules.

4-Nitrophenylphosphatase↗
PubMed1989

Forskolin infusion in vivo increases ouabain binding in brain.

In order to investigate the possible regulation of brain Na,K-ATPase by cyclic AMP, we measured Na,K-ATPase activity and ouabain binding in cerebral cortex after intraventricular infusion of forskolin for 7 days. There was a dose-related increase in high-affinity ouabain binding, with a 75% increase at 12.5 micrograms/h forskolin. The effect on total enzyme activity was smaller but enzyme activity with high affinity for ouabain was increased by 65%, suggesting a selective effect on enzyme with high affinity for ouabain. Forskolin appeared not to interact directly with Na,K-ATPase in vitro.

Animals↗
PubMed1989

Forebrain norepinephrine involvement in selective attention and neophobia.

It has been reported that depletion of forebrain norepinephrine via 6-hydroxydopamine infusion into the dorsal bundle decreases the rat's ability to selectively attend to relevant stimuli and thus increases the rat's responsiveness to novelty. In this study we measured 6-hydroxydopamine lesion effects on 1) selective attention via the nonreversal shift task and extinction of continuous reinforcement bar pressing and on 2) neophobia via consumption of a novel solution in a familiar environment; exploratory behaviors and consumption of a familiar food in a novel environment; and consumption of familiar and novel foods in a novel environment. Our data do not support a role for the dorsal bundle in selective attention. Our data do support a role for forebrain norepinephrine in neophobia and suggest that the lesion effects on neophobia result from an interaction between novelty of environment and novelty of food.

Animals↗
PubMed1989

Development of ethanol tolerance not altered by 6-OHDA lesions of dorsal bundle.

It has been demonstrated via intraventricular (IVT) 6-OHDA infusions that central nervous system norepinephrine is necessary for the development of tolerance to ethanol (ETOH) in the mouse. Because 6-OHDA IVT infusions are not specific, we tested the effects of destruction of a specific NE pathway on development of ETOH tolerance. Rats received 6-OHDA lesions of the dorsal noradrenergic bundle (DB) and the development of ethanol tolerance was measured using the sleeptime test. The time between loss and recovery of the righting reflex was determined after an acute challenge dose of ETOH. Rats were than placed on ETOH diet for 13 days followed by a repeat of the sleeptime test. Sham and 6-OHDA-DB-lesioned rats exhibited the same sleeptime prior to ETOH diet, consumed similar amounts of ETOH diet over the course of 13 days, and exhibited similar significantly (p less than 0.0005) shorter sleeptimes after ETOH diet. Our data suggest that destruction of the DB does not alter development of ETOH tolerance as measured by the sleeptime test.

Animals↗
PubMed1989

Low MHPG and continuing treatment in panic disorder.

1. The paper presents a naturalistic study of 3-Methoxy-4-hydroxyphenylglycol and treatment response in panic disorder. 2. Twenty-eight patients unmedicated for at least one month were entered in a study of MHPG in panic disorder, and given the option of continuing or not continuing treatment. 3. At baseline and on average follow-up 6.8 months later, patients continuing in treatment had significantly lower MHPG than those who did not. 4. At baseline, the two groups of patients did not differ significantly as to number of panic attacks, Zung anxiety scale, and Beck and Hamilton Depression scales. 5. Treated patients did better on all clinical measures at follow-up. 6. Low MHPG may be related to persistence in seeking treatment for panic disorder, and perhaps to treatment response.

Adult↗