Effect of age on long-term heart rate variability.

OBJECTIVE: Previous studies on short-term time series of heart rage suggest an inverse relationship between age and spectral powers of heart rate variability in various frequency bands. In this study, we examined the relationship between age (6-61 years) and long-term heart rate variability. METHODS: We obtained 24-h Holter ECG in 33 healthy human subjects (11 children and 22 adults). The heart rate data were analyzed by using spectral analysis and fractal dimensions of the time series. RESULTS: We found a significant negative correlation between age and very low frequency (VLF, 0.0033-0.04 Hz), low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) powers and fractal dimensions during awake as well as sleep periods, and a positive correlation between age and LF/HF ratios. Age and ultra-low frequency (ULF, < 0.0033 Hz) were modestly and negatively correlated only during the awake period. CONCLUSIONS: Sleep ULF power is not significantly affected by age, whereas VLF, LF and HF powers and fractal dimensions of heart rate significantly decrease with age during awake as well as sleep periods.

Effects of isoproterenol in panic disorder patients after antidepressant treatment.

Fourteen panic disorder patients were infused with isoproterenol both before and after treatment with tricyclic antidepressants. Thirteen patients had panic attacks before treatment, and only 2 after treatment. There was a significant decrease in anxiety as measured by a Panic Description Scale during posttreatment infusions, and patients were able to tolerate longer infusions posttreatment. Isoproterenol increased systolic blood pressure and decreased diastolic blood pressure in both untreated patients and in 10 normal controls. Tricyclic antidepressant treatment of panic disorder patients abolished isoproterenol-induced increases in systolic blood pressure, but did not affect diastolic blood pressure response. These changes are consistent with a decrease in sensitivity to beta-1 receptor stimulation after treatment with tricyclic antidepressants.

Clinical ratings and plasma HVA during cocaine abstinence.

Six patients were evaluated over a 21-day period during inpatient recovery from chronic repeated cocaine use. Serial evaluations of Hamilton depression rating, cocaine craving, plasma homovanillic acid (pHVA), and plasma 3-methoxy-4-hydroxyphenylethyleneglycol (pMHPG) concentrations were determined. There was a distinct increase in cocaine craving between 1 and 2 weeks after the last cocaine use. Levels of pHVA also increased at the time of heightened craving. The data provide preliminary evidence to suggest that changes in cocaine craving during abstinence are positively correlated with changes in dopamine turnover.

Sodium lactate infusions after treatment with tricyclic antidepressants: behavioral and physiological findings.

Fourteen patients with panic disorder were infused with sodium lactate both before and after treatment with tricyclic antidepressants. All patients had panic attacks before treatment, and only five after treatment. There was a significant decrease in measures of anxiety prior to and during infusions after treatment. The patients were able to tolerate more lactate during reinfusions. The comparison of reinfusion panickers and nonpanickers revealed that the reinfusion panickers had higher levels of anxiety, as measured by psychological symptoms on the Panic Description Scale, during both their pretreatment and posttreatment infusions. Tricyclic antidepressants appear to increase the threshold for lactate-induced panic attacks.

Do higher preinfusion heart rates predict laboratory-induced panic attacks?

Baseline and preinfusion heart rates of 13 panic disorder patients who panicked during a placebo infusion were not significantly different from those of 57 panic disorder patients who did not panic during a placebo infusion. The change in preinfusion heart rates from baseline values also was not significantly different between the two groups.

Isoproterenol-induced panic attacks.

Eighty-six panic disorder patients and 45 nonpsychiatric controls were infused with isoproterenol at a rate of 1 microgram/min for up to 20 min in a placebo-controlled, double-blind study. Sixty-six percent of panic disorder patients experienced panic attacks during isoproterenol infusions, compared to 16% during placebo infusions. Nine percent of control subjects panicked with isoproterenol, but none panicked with placebo. Patients were more sensitive than controls to the anxiogenic effects of isoproterenol, as measured by subject self-ratings on a panic description scale. The frequency of panic attacks induced in patients was related to the dosage of isoproterenol; 79% of the patients who received a mean of 18.5 ng/min/kg of isoproterenol panicked. The panic attacks experienced by patients during isoproterenol infusions were similar to those experienced during placebo infusions.

Allergy to tartrazine in antidepressants.

The authors describe five cases of apparent allergy to tartrazine (FD&C yellow dye number 5) in 170 patients exposed to the dye in antidepressants. The frequency of tartrazine sensitivity was much higher than the reported frequency of six in 1,000 persons.

Lactate sensitivity and cardiac cholinergic function in panic disorder.

Using spectral analysis of the continuous time series signal before and during lactate and placebo infusions, the authors studied heart rate variability in six patients with panic disorder and nine normal comparison subjects. The decrease in high-frequency (0.20-0.50 Hz) power and the increase in sympathovagal ratios (mid-frequency [0.07-0.15 Hz] to high-frequency powers) after the administration of intravenous sodium lactate were significantly greater in the patients than in the normal subjects after correction of the values for the amount of lactate infused. This result suggests an exaggerated cardiac vagal withdrawal in patients with panic disorder during lactate infusions.

Family history of anxiety disorders in control subjects with lactate-induced panic attacks.

The authors infused 45 control subjects with sodium lactate. Eight of 10 subjects with lactate-induced panic attacks and 26 of 35 without panic attacks were interviewed. An investigator, blind to the outcome of the infusion study, obtained family histories of 160 relatives. There was a high prevalence of anxiety disorders among first-degree relatives of subjects with panic attacks. There was no significant difference in the prevalence of mood disorders and substance abuse between first-degree relatives of subjects with (N = 45) and without (N = 115) panic attacks. The results suggest that individuals with a family history of anxiety disorders may be vulnerable to lactate-induced panic attacks.

Follow-up study of control subjects with lactate- and isoproterenol-induced panic attacks.

Eleven of 45 normal control subjects experienced panic attacks during lactate and/or isoproterenol infusions. Ten of the 11 subjects were followed up for a mean period of 32.5 months. Two subjects reported the development of spontaneous panic attacks during the follow-up period; one related the development of these attacks to the infusion experience. Neither subject met DSM-III criteria for panic disorder either before or after the infusions. Twenty-six healthy control subjects who did not experience panic attacks during the infusion experience did not report any attacks during a follow-up period of 31.1 months.

Improvement of phencyclidine-associated psychosis with ECT.

Phencyclidine-associated psychosis may mimic classic forms of both schizophrenia and affective psychosis. Treatment of phencyclidine-associated psychosis may prove very difficult for some patients. A patient who developed a severe phencyclidine-associated psychosis and failed to respond to high doses of antipsychotics is described. The patient responded dramatically to electroconvulsive therapy.

Biological and psychological aspects of a case of Gilles de la Tourette's syndrome.

The case of a 12-year-old girl with Gilles de la Tourette's syndrome is presented, and the following factors are discussed: psychological aspects, urinary excretion of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and unconjugated amines, and CT scan findings. The most noticeable differences from normal controls seen in the urine studies were elevated levels of beta-phenylethylamine and the catecholamine metabolites normetanephrine, MHPG, and 3-methoxytyramine, and a decrease in 5-hydroxytryptamine. A CT scan revealed a slight increase in density in the caudate nuclei bilaterally; this was thought to be due to calcification.

The jitteriness syndrome in panic disorder patients treated with antidepressants.

The jitteriness syndrome (jitteriness, shakiness, increased anxiety, and insomnia) can develop with low doses of tricyclic antidepressants in patients who are sensitive to these drugs. The authors review the antidepressant treatment of 180 patients. Only those with panic attacks had jitteriness, usually during the first week of treatment. Desipramine was associated with a much higher frequency of jitteriness than was imipramine. Tolerance to jitteriness occurred with continued treatment, but fewer patients with jitteriness responded to treatment, apparently because of difficulties in increasing the dose. Characteristics of the jitteriness syndrome in panic disorder patients are consistent with noradrenergic hypotheses of panic anxiety. The clinical and theoretical implications of these findings are discussed.

Buspirone-induced jitteriness in three patients with panic disorder and one patient with generalized anxiety disorder.

Three patients with a history of panic disorder and one patient with a history of generalized anxiety disorder were treated with buspirone and experienced an increase in their anxiety levels, agitation, and restlessness and also developed pressured speech and racing thoughts. These symptoms completely resolved after buspirone was discontinued. Jitteriness may have been due to an unusual adrenergic sensitivity in these patients.

Sexual dysfunction during antidepressant treatment.

BACKGROUND: The reported incidence of sexual dysfunction associated with antidepressant medication varies from 1.9% to 92%. The majority of studies reporting incidences were not systematically conducted. METHOD: We interviewed 60 patients (22 men and 38 women, with anxiety and mood disorders) who were being treated with various antidepressants. We used a questionnaire focused on sexual side effects and other side effects. RESULTS: The incidence of sexual dysfunction during antidepressant use in our study is 43.3%. The sexual dysfunction was not limited to any particular diagnostic group nor to any particular antidepressant. There was no significant correlation between sexual dysfunction and anticholinergic side effects. The incidence of painful orgasm with antidepressants was 18% among males in our study. CONCLUSION: The relatively high incidence of sexual dysfunction associated with antidepressant treatment in this systematic study emphasizes the importance of a detailed inquiry about sexual side effects as this interferes with treatment compliance.

Monosodium glutamate and tranylcypromine administration in healthy subjects.

The authors administered 400 to 1600 mg of monosodium glutamate and placebo to five healthy males while they were medication-free and again while they were receiving the monoamine oxidase inhibitor tranylcypromine, after having received the drug daily for at least 2 weeks. Monosodium glutamate produced no consistent changes in either blood pressure or heart rate in subjects receiving tranylcypromine. Spontaneous hypertensive episodes were observed in two subjects. These blood pressure increases also occurred with tranylcypromine alone and were unrelated to monosodium glutamate administration. Diet was not violated during these episodes.

Preinfusion anxiety and laboratory-induced panic attacks in panic disorder patients.

Seventy panic disorder patients participated in a double-blind, placebo-controlled, randomized infusion study in which sodium lactate and isoproterenol were used to induce panic anxiety. Patients who panicked during lactate, isoproterenol, and placebo infusions generally had higher preinfusion anxiety scores. These findings held true irrespective of the order the infusions were given. Stepwise multiple regression analyses comparing panickers with nonpanickers as the criterion variable revealed that the items "afraid of going crazy," "feeling unsteady," and "feeling paralyzed" on the Panic Description Scale had the highest predicting values.

Response of tricyclic-induced jitteriness to a phenothiazine in two patients.

Some patients with panic attacks are extremely sensitive to tricyclic antidepressants and develop jitteriness, shakiness, and insomnia when given very low doses. Two patients who developed this "jitteriness syndrome" while taking tricyclic antidepressants are described. The side effects in these patients were markedly relieved by the addition of perphenazine.

Intravenous sodium lactate decreases plasma GABA levels in man.

Gamma aminobutyric acid (GABA), an inhibitory neurotransmitter, may play an important role in anxiety. We studied changes in plasma GABA levels in nine healthy subjects before and after infusions of sodium lactate and dextrose. Plasma GABA significantly decreased during infusions of sodium lactate (109.3 +/- 4.4 versus 91.6 +/- 5.1 pmol/ml; P = 0.0001) but not during infusions of dextrose.

Beta-receptor responsiveness after desipramine treatment.

To examine whether a tricyclic antidepressant affects the functional response to a beta-receptor agonist in man, the response of heart rate, blood pressure, and plasma cAMP to isoproterenol was measured in 14 normal controls taking 75 mg desipramine daily. Desipramine significantly increased the bolus dose of isoproterenol needed to increase heart rate by 25 bpm at 14-30 days but not at 3-8 days. During infusions of isoproterenol, the increase in systolic blood pressure was blunted at both 3-8 days and 14-30 days, while the decrease in diastolic blood pressure was unaffected. Blood pressure findings were not affected by preadministration of bethanechol. In ten controls, isoproterenol infusions increased plasma cAMP, but this was unaffected by desipramine treatment. These findings suggest a decrease in the functional response of beta 1, but not beta 2, receptors after treatment with desipramine.