Rapid cycling manic depressive patients

Chronic administration of lithium carbonate to bipolar manic depressive patients has been shown to prevent or reduce the frequency and severity of subsequent episodes of depression and particularly those of mania.^1–4 Those patients who continue to have affective attacks in spite of lithium carbonate prophylactic treatment have been studied by our group and others in order to determine if any clinical factors might be predictive of the lithium failure group.^5–6 In a prior report from our clinic we noted that a group of patients with a high frequency of affective attacks predictably had a poor prophylactic outcome with lithium treatment. These patients were termed “rapid cyclers” and were characterized by having four or more episodes of depression and/or mania per year prior to the initiation of lithium prophylactic therapy.The purpose of this paper is to describe such patients in greater clinical detail and to illustrate the effect of lithium prophylactic treatment on their clinical courses. Based on our clinical experience with such patients, an approach to the treatment of rapid cycling manic-depressive patients is presented.     

An electrophysiological study of the effects of D-tubocurarine, atropine, and alpha-bungarotoxin on the cholinergic receptor in innervated and chronically denervated mammalian skeletal muscles

An electrophysiological study of the action of d-tubocurarine (d-TC), atropine, and α-bungarotoxin (BuTX) was made on the innervated and chronically denervated diaphragm and soleus muscles of the rat and mouse. All three drugs were able to block endplate potentials of innervated muscles as well as acetylcholine (ACh) sensitivity of chronically denervated muscles. The effects of atropine and d-TC were fully reversed upon washing with Ringer's solution, white the effects of BuTX were only partially reversed. The reversibility of BuTX was more evident at extrajunctional areas in chronically denervated muscles than at the innervated endplate region, but in both cases only a fraction of the normal response could be detected after intensive washing for at least 2 hr. The blockade of ACh sensitivity in chronically denervated muscles required a concentration of d-TC 10-fold higher than that necessary to block the endplate potentials of innervated muscles. BuTX and d-TC did not affect the ionic permeabilities of the muscle fiber during an action potential while atropine decreased both Na⁺ and K⁺ conductances, the magnitude of the effect being dependent on the frequency of stimulation. At the endplate region, d-TC was much more effective than atropine in protecting against the irreversible effect of BuTX. In the chronically denervated preparation, however, neither of the two drugs effectively protected against BuTX. It is concluded that in terms of their reactivities to cholinolytic agents, the extrajunctional receptors induced by chronic denervation of skeletal muscles are qualitatively similar to those found at endplate regions of normal muscles, but that they exhibit differences in their quantitative interaction with different cholinolytic agents. The data further indicate that atropine interacts with the ionic conductance modulator unit associated with the cholinergic receptor, rather than with the ACh receptor itself.     

Behavior modification with children: An index of reviews

An index is presented to review articles published in the last 10 yr relating to the use of behavioral methods with children. Eighty-nine reviews identified through computer searches of the psychological, educational and social sciences literature are listed under 36 cross-referenced subject categories.     

Efficacy and safety of induced seizures (EST) in man

A review of the EST process finds its efficacy and safety in the treatment of psychotic depressive states and mania to be well-documented. In acute schizophrenia, EST is symptomatic and its usefulness is equivalent to psychotropic drugs. In chronic schizophrenia, the effects of EST and other therapies are equally poor; but the principal studies are faulted by inadequate numbers of EST treatments. In all other conditions, including the use in children and adolescents, the data are insecure and additional studies are needed.The principal risks of EST have been reduced by improved treatment methods. Fracture, panic, spontaneous seizures, and death are no longer prominent. Persistent deficits in memory and the psychologic stigma of having had “shock therapy” are the principal costs of therapy today. Suggestions to reduce these risks are made.For depression, mania, and acute schizophrenia, EST has a risk/benefit ratio equal to or better than other available treatments. Further study of the relative efficacy and safety of these treatments are needed; as are controlled studies for other conditions where its use has been recommended.     

Binding of D-tubocurarine and alpha-bungarotoxin in normal and denervated mouse muscles

The action of native and mono-³H-acetylated-α-bungarotoxin (³H-BuTX) was studied at the acetylcholine (ACh) receptors of innervated and of chronically denervated diaphragm and soleus muscles of the mouse. The ³H-BuTX was similar in potency to the native toxin, and both toxins produced complete blockade of endplate potentials of innervated muscles and of ACh sensitivity of chronically denervated muscles. When the innervated muscles were washed for 4–7 hr after exposure to either toxin (at 1–5 μg/ml), recovery to an endplate potential value of 0.5–1 mV was recorded in most of the endplate regions of the surface fibers. Parallel experiments on the chronically denervated muscle after a 4–7 hr wash showed a much larger fraction of reversibility; i.e., while in control denervated preparations the ACh sensitivity was 50–75 mV/nC, after the toxin treatment and washing the values were 5–10 mV/nC. When d-tubocurarine (d-TC, 28 × 10^?6m) was present to protect against the blockade of the toxin at the endplates, a complete recovery of neuromuscular transmission could always be obtained upon washing. In the chronically denervated muscles, however, much less protection from the ³H-BuTX blockade was observed. Uptake of ³H-BuTX at the endplates was measured by radioactivity analyses; these revealed that only about 60% of the endplate ACh receptors are protected at saturating d-TC levels. Kinetic analyses of the uptake confirmed this. The observations can be interpreted in terms of two types of sites at the endplate; the two are equally reactive with α-bungarotoxin, but only one of them binds d-TC firmly. Similar observations were made with d-TC protection in the denervated muscles; the results showed much lower affinity of d-TC in these muscles. The changes in d-TC effectiveness in the receptors after denervation are all parallel, when measured in several muscles by three approaches—blockade of ACh sensitivity, prevention of α-bungarotoxin blockade of ACh sensitivity, and inhibition of uptake of ³H-BuTX. We conclude that the ACh receptor molecules themselves, when induced by denervation, are different from normal receptors in that they interact much less strongly with d-TC.     

Use of the Hamilton rating scale for classification of depressive disorders

The Hamilton Depression Scale (HAM-D) is an instrument for recording ratings of severity for some 21 symptoms that are often present in depressive disorders. Each patient does not have all symptoms. Empirical cluster analysis methods applied to a sample of 420 HAM-D profile patterns revealed five distinct subtypes within the population of patients treated with antidepressant drugs. The empirically-identified syndromes are designated anxious depression, suicidal depression, somatizing depression, vegetative depression, and paranoid depression. Discriminant functions that can be used to assign new patients among the five classification categories are presented.     

Assertion training for couples

Changes in behavioral and self-report measures for 20 couples receiving conjoint assertion training were compared with those for 10 couples receiving minimal treatment. As hypothesized, univariate tests indicated a significant increase in verbal assertion and a significant decrease in verbal aggression for trained couples, relative to controls. The hypothesized decrease in verbal avoidance following treatment was not found. As hypothesized, significant increases in self-reported clarity by self and spouse, and positive interaction by spouse were found, while positive interaction by self tended to increase. In a multivariate analysis, verbal aggression and self-report of spouse's clarity produced no increments in group differentiation over the other variables.     

Effeminate behavior present in boys from childhood: Ten additional years of follow-up

This is a 10-year further follow-up of 16 boys with early effeminate behavior, a group of cases first reported in 1966. The average age at this follow-up was 22 years, and the average number of years elapsed since first seen was 14 years. Twelve of the 16 cases developed some form of deviant behavior—homosexuality in 10, transvestism in 1, and transsexualism in 1. Two of the cases were heterosexually oriented, and in the remaining two, no decision could be reached as to their sexual orientation.     

Life events, psychological distress and the Type A coronary-prone behavior pattern

The relationship between life events and psychological distress was examined in Type A and Type B coronary-prone college students. The results indicated that Type A's report the occurrence of more life events than Type B's. In addition, examination of the perceived characteristics of the life events revealed different patterns for A's vs B's. Life events seen as undesirable, unexpected, and ambiguous in terms of perceived control were positively correlated with increased distress for Type A's. Type B's, on the other hand, were less distressed the more the event was perceived to be beyond their control. The results are discussed in terms of the differences in the Type A/B personality styles.     

Rating the severity of depressive symptoms in adolescents and young adults

Recent investigations of affective disorders have revealed an earlier age of onset for many of them than is generally recognized. Studies of depressive symptomatology in older adult samples have commonly employed such measures as the Hamilton Depression Rating Scale (HDRS) or, more recently, the Schedule for Affective Disorders and Schizophrenia (SADS). The current study attempts to replicate and extend a procedure developed for extracting the HDRS score from the SADS. Its performance characteristics in samples of adolescents and young adults are compared. Its good reliability and construct validity in both samples made it possible to identify differences in phenomenology that may be age-related. These differences and their implication for rating the severity of depressive symptoms in adolescents are discussed.     

Food intake and amphetamine anorexia after selective forebrain norepinephrine loss

Hyperphagia leading to obesity followed selective electrolytic destruction of the ventral noradrenergic bundle (ventral NAB; the main norepinephrine-containing pathway to the rat hypothalamus). Midbrain injection of 8.0 μg 6-hydroxydopamine (6-OH-DA) near this tract, which destroyed all ascending noradrenergic paths to the forebrain, produced a similar result. Male as well as female rats became hyperphagic. Fluorescence histochemistry revealed nearly complete losses of norepinephrine-containing varicosities in almost all known noradrenergically innervated forebrain areas after 6-OH_DA; forebrain assays indicated that norepinephrine levels were lowered to less than 10% of normal. Dopamine was only slightly reduced by the 6-OH-DA while serotonin was unchanged.Pretreatment of 6-OH-DA-injected animals with 50 mg/kg desmethylimipramine, a specific uptake blocker in norepinephrine neurons, blocked the loss of noradrenergic varicosities and prevented overeating. Animals which were injected with 6-OH-DA near the dorsal NAB, sparing the ventral system, did not become hyperphagic. In additional rats, electrolytic lesions or 6-OH-DA in the vicinity of the ventral NAB antagonized amphthamine-induced anorexia. This suggests that in normal animals, the ventral NAB may serve as a substrate for amphthamine in producing appetite loss. These results indicate that the role of forebrain norepinephrine in the control of food intake is predominantly inhibitory.     

Neuroendocrinology and ECT: A review of recent developments

The experience of more than four decades finds that the repeated and spaced induction of seizures (convulsive therapy) relieves the symptoms of severe depressive mood disorders, particularly those accompanied by vegetative symptoms. Neuroendocrine abnormalities characterize patients with primary depression (melancholia) and these abnormalities are reversed by convulsive therapy. Tests of neuroendocrine functions provide criteria for the classification of such cases, and probably will become useful in identifying patients suitable for convulsive therapy.We postulate that the antidepressant efficacy of convulsive therapy results from the increased release and more widespread cerebral distribution of hypothalamic peptides with behavioral effects. Such a hypothesis provides a basis for clinical trials of centrally active peptides in cases of primary depression; for the study of neuroendocrine functions as predictors of outcome and of the duration of a course of convulsive therapy; and for the search for a biochemical substitute for convulsive therapy.     

Differential contributions of the two cerebral hemispheres to the perception of happy and sad faces

Emotional and neutral facial expressions of the same individual were presented simultaneously, one to each visual field, and subjects were required to identify the side containing the affective face. Reaction time was faster to right vs left visual field presentations when the expression was happy and vice versa when it was sad. The data support the hypothesis of differential hemispheric specialization for positive and negative emotion.     

Observations on the effects of four weeks of heavy marihuana smoking on group interaction and individual behavior

The clinical effects of intensive marihuana smoking on physically and mentally healthy male volunteers were studied in group sessions during a marihuana research project. The study was divided into three periods: presmoking, “wash-out” (4 weeks); smoking (4 weeks); and postsmoking, “wash-out” (4 weeks).Subjects exhibited mild referentiality because of confinement and observation even before smoking began. With light smoking, subjects reported pleasurable effects and enhanced sensitivity. group cohesiveness increased. With heavy smoking subjects became apathetic and withdrawn and markedly referential. This disappeared completely when smoking ceased. Subjects were felt to be clinically hyperirritable during the first week of withdrawal. This disappeared completely after the first withdrawal week. Because of conflicting opinions about the effects of abstinence after chronic heavy use, it is felt that improved design of mood rating scales is needed.