Effects of psychoeducational intervention for married patients with bipolar disorder and their spouses.

The relative benefit of adding a structured psychoeducational intervention to standard medication treatment for married patients with bipolar disorder and their spouses was assessed. Patients were randomly assigned to receive either medication management or medication management plus a marital intervention with their spouses for an 11-month period. Patients' symptoms, functioning, and adherence to their medication regimens were measured at study entry and at 11 months. Significant effects favoring the combined treatments were observed for overall patient functioning but not for symptom levels. The marital intervention was associated with improved medication adherence. Combined psychosocial and medication treatment does not affect patients' symptom levels beyond the effects of medication alone, but it does result in significant incremental gains in overall patient functioning.

Subsensitivity of adenylyl cyclase-coupled receptors on mononuclear leukocytes from drug-free inpatients with a major depressive episode.

Previous studies have demonstrated blunted beta-adrenergic responsivity in leukocytes from depressed patients. We sought to determine if this blunted cyclic adenosine monophosphate (AMP) response is specific for beta-adrenergic receptors (homologous), or whether other adenylyl cyclase-coupled receptors are also involved (heterologous), in order to localize this effect at the level of the receptor versus the coupling protein or the transducer, adenylyl cyclase. We studied adenylyl cyclase-mediated responses in peripheral blood mononuclear cells from 95 drug-free patients with a major depressive episode and 69 healthy controls. We found a similar degree of decrease in the peak cyclic AMP response to activation of the beta-adrenergic receptor (28%) and the prostaglandin receptor (34%) in the depressed patients, which indicated heterologous desensitization. Forskolin cyclic AMP responses were not blunted. Blunting of cyclic AMP responses to isoproterenol did not appear to correlate with levels of plasma norepinephrine and epinephrine or hypothalamic-pituitary-adrenocortical function. The absence of a decrease in the peak forskolin-generated cyclic AMP response, which involves direct activation of adenylyl cyclase, suggests an abnormality at the level of the coupling protein in these adenylyl-coupled receptors in depressed patients. Future studies need to determine whether this leukocyte signal transduction defect in depression also involves brain adenylyl cyclase-coupled receptors.

Personality pathology among married adults with bipolar disorder.

The comorbidity of DSM-III-R axis II personality disorders in patients with bipolar disorder has received less attention than for unipolar depression perhaps because of the potential confounding of state vs. trait qualities. The current study took steps to separate pathological traits of personality from behaviors evidenced during discrete affective episodes in a sample of married, outpatient bipolar patients. Data indicated that 22% of our patients met criteria for a categorical diagnosis of personality disorder. Axis II pathology as represented by both categorical and dimensional scores was associated with increased psychiatric symptoms during subsequent treatment and poorer social adjustment.

Neuropsychologic effects of lithium discontinuation.

This study investigated the effects of blind lithium discontinuation and resumption on measures of cognition, creativity, and fine motor performance in 46 lithium-maintained euthymic outpatients. Scores on memory measures, tests of tapping speed, and associative productivity all improved significantly during the time off of lithium. In an effort to further explain these results, analyses were undertaken with six possible intervening variables: age, sex, lithium concentration in plasma, thyroid function, duration of lithium maintenance, and depressive symptoms. Significant group and interactive effects are reported and discussed. A multiple regression analysis suggested that lithium has a greater neuropsychologic effect in younger, less-depressed patients having higher lithium concentrations in plasma.

Acute effects of single and repeated electroconvulsive therapy on plasma catecholamines and blood pressure in major depressive disorder.

The role of activation of adrenergic neurons by electroconvulsive therapy (ECT) in its antidepressant action was studied by examining acute sympathetic nervous system (SNS) responses to ECT during a course of treatment in patients with melancholia. ECT had an acute dose-dependent effect on plasma norepinephrine (NE) level and blood pressure. The postictal increase in plasma NE and blood pressure was independent of electrical seizure duration. Acute levels of NE and epinephrine after ECT correlated positively with ECT dosage. No cumulative effect of repeated ECT was found on the SNS responses. ECT does activate the SNS in a dose-dependent fashion. However, alternative strategies seem necessary for studying the action of ECT on noradrenergic neurons to identify effects that are cumulative, correspond more closely to the time course of its antidepressant action, and correlate with clinical outcome.

Normalization of blunted lymphocyte beta-adrenergic responsivity in melancholic inpatients by a course of electroconvulsive therapy.

Electroconvulsive therapy has been reported to desensitize brain beta-adrenergic receptors in rodents, but this effect has not been studied in man. We examined the effect of a course of electroconvulsive therapy on lymphocyte beta-adrenergic responsivity in 19 inpatients with melancholia. Before treatment, beta-adrenergic cyclic adenosine monophosphate response to isoproterenol was significantly blunted in the patients compared with controls. Following a course of electroconvulsive therapy, beta-adrenergic responsivity increased such that patients no longer differed from controls. Thus, blunted lymphocyte beta-adrenergic responsivity is a state-dependent effect of melancholia that can be corrected by a therapeutic course of electroconvulsive therapy. The effect of electroconvulsive therapy on this beta-adrenergic system is in the opposite direction to that reported for rodent forebrain, where electroconvulsive therapy causes desensitization, and may reflect differences between peripheral and central effects, species differences, or disease effects.

A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor.

Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is limited because of unwanted side effects and the possibility of a tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the official nonproprietary name for this substance is selegiline), a selective MAO type B inhibitor, may be safer and have fewer side effects, but its antidepressant efficacy is uncertain. A double-blind placebo-controlled study was carried out in depressed outpatients who were treated with (-)-deprenyl in an MAO type B selective dose range and at a higher nonselective dose range. (-)-Deprenyl did not have a statistically significant antidepressant effect after three weeks of treatment at doses of 10 mg/d. However, after six weeks and at higher doses (averaging about 30 mg/d for the second three weeks), (-)-deprenyl was superior to placebo in antidepressant effect with a positive response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton Depression Rating Scale mean score vs 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with (-)-deprenyl was no greater than with placebo. It was concluded that (-)-deprenyl is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of nonselective MAO inhibitors.