Showing papers in "Archives of General Psychiatry in 1976"

The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbance.

Abstract: † The Global Assessment Scale (GAS) is a rating scale for evaluating the overall functioning of a subject during a specified time period on a continuum from psychological or psychiatric sickness to health. In five studies encompassing the range of populations to which measures of overall severity of illness are likely to be applied, the GAS was found to have good reliability. GAS ratings were found to have greater sensitivity to change over time than did other ratings of overall severity or specific symptom dimensions. Former inpatients in the community with a GAS rating below 40 had a higher probability of readmission to the hospital than did patients with higher GAS scores. The relative simplicity, reliability, and validity of the GAS suggests that it would be useful in a wide variety of clinical and research settings.

Assessment of Social Adjustment by Patient Self-Report

Abstract: Current emphasis on early case finding, outpatient care, and on longitudinal studies of asymptomatic patients has focused attention on the community adjustment of psychiatric patients. Thus, simple and inexpensive methods such as self-report scales, which allow the routine assessment of patient adjustment, are potentially useful. The derivation and testing of such a method, the Social Adjustment Scale Self-Report, is described. This scale covers the patient's role performance, interpersonal relationships, friction, feelings and satisfaction in work, and social and leisure activities with the extended family, as a spouse, parent, and member of a family unit. Self-report results based on 76 depressed outpatients were comparable to those obtained from relatives as well as by a rater who interviewed the patient directly.

5-HIAA in the Cerebrospinal Fluid: A Biochemical Suicide Predictor?

Abstract: • The incidence of suicidal acts was studied in 68 depressed patients and related to the level of 5-hydroxyindoleacetic acid (5HIAA) in the cerebrospinal fluid. The distribution of 5-HIAA levels was bimodal. Patients in the low 5-HIAA mode (below 15 ng/ml) attempted suicide significantly more often than those in the high mode, and they used more violent means. Two of the 20 patients in the low mode, and none of the 48 patients in the high mode died from suicide.

Neuroendocrine Regulation in Depression: I. Limbic System-Adrenocortical Dysfunction

Abstract: • The regulation of hypothalamopituitary-adrenal (HPA) function in depressed patients was studied by a midnight dexamethasone suppression test. By using an observation period of 24 hours postadministration of dexamethasone, a graded series of abnormal test responses was identified. Depressed patients show abnormal early escape from suppression rather than absolute resistance to HPA suppression by dexamethasone. With increasing severity of depression, this escape occurs progressively more early on the day after administration of dexamethasone. These abnormalities were strongly related to the presence of HPA hyperactivity before dexamethasone was given. The essential disturbance of neuroendocrine regulation in depression is a failure of the normal brain inhibitory influence on the HPA system. This disinhibition of HPA activity suggests that there is an abnormal limbic system drive on the HPA axis in primary depressive illness.

Neuroendocrine regulation in depression. II. Discrimination of depressed from nondepressed patients.

Abstract: • Forty-two patients with endogenomorphic depression (ED) and 42 patients with other psychiatric disorders received an overnight dexamethasone test of hypothalamopituitary-adrenal (HPA) suppressibility. Plasma and urinary cortisol measures showed that the ED patients had significantly greater HPA activity before dexamethasone and less complete HPA suppression after dexamethasone. High cortisol values after dexamethasone correlated strongly with spontaneous HPA disinhibition, as indicated by high baseline midnight plasma cortisol levels. Criteria for defining normal suppression responses were developed. All patients with depressive neuroses and most patients with other nondepressive disorders had completely normal responses to dexamethasone. About half of the ED patients had abnormal responses, whether or not they were receiving other drugs at the time of the test. Drug-free patients with depressive neuroses or other disorders showed no abnormal responses to dexamethasone. The effects of psychotropic drugs on the test require further study. Patients with two or more abnormal cortisol values after administration of dexamethasone were identified correctly as ED at confidence levels close to100%. dexa-methasone suppression test may be of value as a laboratory aid in the diagnosis of "endogenous" depression.

Comparative doses and costs of antipsychotic medication.

Abstract: • It is clinically useful to have a table listing the equivalent doses of the various neuroleptics to a standard, such as chlorpromazine. This article derives such data by reviewing doubleblind controlled studies that used a flexible dosage schedule of neuroleptics in treating schizophrenic patients. Each neuroleptic is then converted to 100-mg chlorpromazine equivalents. This empirically derived dosage comparability table is compared with a similar table derived from the opinions of experts. Since these comparable doses produce equivalent amounts of antipsychotic activity, the cost to provide such medication was then calculated, and a table comparing the costs of the different neuroleptics was constructed. In absolute amounts, the cost differences between drugs are small. However, for any drug, large savings accrue when the largest possible capsule or tablet to achieve the desired dose is prescribed.

Neurologic Soft Signs in Schizophrenia and Character Disorders: Organicity in Schizophrenia With Premorbid Asociality and Emotionally Unstable Character Disorders

Abstract: • Previous studies indicated that for two subgroups of patients, schizophrenics with premorbid asociality (SPA) and individuals with emotionally unstable character disorders (EUCD), central nervous system damage may have etiologic significance. It was hypothesized that these two patient groups would also have an increased number of neurologic soft signs. The relationship of neurologic examination, tests of auditoryvisual integration, and intelligence quotient, and diagnoses was studied for 350 patients. Tests of reliability and persistence for all observed signs were performed. The EUCD and SPA groups had increased evidence of neurologic soft signs. Differences in patterns of IQ scores also suggest that different forms of brain damage may be present in these two groups. When the two groups were removed from the larger patient sample, those patients with other types of schizophrenia and character disorder did not exhibit evidence of neurologic impairment. This study of neurologic soft signs adds to the validity of considering SPA and EUCD as separate diagnostic entities.

Cardiovascular and Subjective Effects of Intravenous Cocaine Administration in Humans

Abstract: Nine volunteer subjects were tested with intravenously administered cocaine hydrochloride in doses ranging from 4 to 32 mg, as well as 10 mg of dextroamphetamine sulfate. Measures of cardiovascular and subjective effects were made. Generally parallel dose-effect functions were obtained for heart rate, blood pressure, Addiction Research Center Inventory scores, Profile of Mood Scales, and subject ratings. A substantial effect on each of these variables was recorded after 8 mg of cocaine. The increase continued and peaked at approximately 16 mg after which it usually leveled off. Ten milligrams of dextroamphetamine generally had an effect comparable to 8 to 16 mg of cocaine.

Mortality in depressed patients treated with electroconvulsive therapy and antidepressants.

Abstract: The treatments of 519 depressed patients hospitalized from 1959 to 1969 were compared in a three-year follow-up study with particular reference to mortality. The electroconvulsive therapy (ECT) group had a significantly lower mortality than the inadequate antidepressant treatment group (P less than .05) and the group that received neither ECT nor antidepressants (P less than .025). Although the adequate antidepressant treatment group had a low mortality, statistically significant differences between this and other treatment groups could not be documented. Nonsuicidal deaths (P less than .005), and particularly myocardial infarctions (P less than .01), were significantly more frequent in the inadequately treated group compared to the adequately treated group. The superiority of adequate treatment is especially striking among men and among the older age groups. The results underscore the importance of adequate treatment of depression, especially in the older man.

Diagnosis and treatment of minimal brain dysfunction in adults: a preliminary report.

Abstract: • Minimal brain dysfunction (MBD) has long been considered a disorder limited to childhood. A number of longitudinal and adoption studies suggest that MBD may persist into adult life where its existence is concealed by the application of a variety of diagnostic labels. In order to test the hypothesis that MBD does persist into adulthood, 15 putative MBD adults were identified on the basis of current MBD-like complaints, self-description of MBD characteristics in childhood, and a parental rating (on a standardized form) of "hyperactivity" in childhood. Eleven of the 15 subjects were given a double-blind trial of methylphenidate hydrochloride, and all 15 were given an open trial of pemoline, imipramine hydrochloride, or amitryptiline hydrochloride. Eight of the 11 showed a significant response to the double-blind trial of methylphenidate. Of the 15, eight showed a good response to stimulants or tricyclic antidepressants, two showed a moderately favorable response, and five were unresponsive to drug therapy.

Memory Functions in Depression: Improvement With Antidepressant Medication

Abstract: •In an attempt to elucidate the memory deficit in depression, short-term memory and long-term memory were examined by means of a memory test battery in 26 hospitalized depressed patients. Their performance was compared with a matched control group and with the performance of those 20 patients who improved after 26 days of treatment with antidepressants. Results Indicate that depressed patients show marked impairment in short-term memory without an impairment in long-term memory. The greater the improvement of the clinical state, the greater the Improvement In short-term memory, whereas long-term memory was not influenced by the therapeutic success.

Hopelessness, Depression, and Suicide Intent

Abstract: • One hundred fifty-four suicide attempters, threateners, and psychiatric controls were rated on suicide intent scales and given tests to assess hopelessness, depression, and self-rated suicide risk. Ninety-four subjects were retested one month later. Both hopelessness and depression were significantly greater in suicidal subjects. In threateners, hopelessness and depression scores differed significantly between high and low suicide intent subjects. In attempters ranked by suicide intent at time of testing, more and less suicidal subjects differed significantly in hopelessness and depression scores. Both depression and hopelessness were sensitive to changes in suicide risk during the one-month follow-up. In all analyses, hopelessness correlated more highly with suicide intent than did depression. The data were regarded as supporting the hypothesis that hopelessness is more closely related to suicide intent than is depression.

Prediction of tricyclic antidepressant response: a critical review.

Abstract: • This article reviews all the prospective, double-blind controlled studies that have evaluated the prediction of response to imipramine hydrochloride and amitriptyline hydrochloride in depressed patients. Despite widely divergent methodologies, an attempt is made to extract clinically useful conclusions from these data. Critiques of each study and the criteria used in their evaluation are presented, with suggestions for future research included. The predictors of positive response to imipramine and amitriptyline are as follows: upper socioeconomic class, insidious onset, anorexia, weight loss, middle and late insomnia, and psychomotor disturbance. The predictors of poor response are the following: neurotic, hypochondriacal, and hysterical traits, multiple prior episodes, and delusions. Pretreatment urinary 3methoxy-4-hydroxyphenylglycol (MHPG) levels may some day be useful in predicting to which of these two tricyclic antidepressants a patient will respond.

Postpsychotic Depression in Schizophrenia

Abstract: • Several authors have described a severe depression in patients emerging from psychotic states. The clinical picture usually resembles that of a retarded depression with strong neurasthenic and schizoid components. It frequently emerges after a patient has been discharged from the hospital and may often go unnoticed. When manifest, the syndrome is usually stable phenomenologically, is often lengthy, and may be resistant to all modalities of treatment. Postpsychotic depression is a relatively neglected clinical area despite the risk of suicide and prolonged suffering. Therapeutic perseverence purportedly can improve the patient's long-term prognosis, and the phenomenon itself may be a favorable prognostic sign. We present here a review and reformulation of this syndrome.

Catatonia: A Prospective Clinical Study

Abstract: • We studied 55 patients admitted during 14 months to two inpatient psychiatric units of a municipal hospital who exhibited one or more of the catatonic signs of mutism, stereotypy, posturing, catalepsy, automatic obedience, negativism, echolalia/ echopraxia, or stupor. Only four of the 55 patients satisfied our research criteria for schizophrenia, whereas over two thirds had diagnosable affective disorders, usually mania. The eight catatonic motor signs were nonspecific and homogeneously distributed among the various research diagnostic groups, with the number and type of individual signs unrelated to short-term treatment outcome. A favorable treatment response was shown for the entire catatonic sample, with two thirds markedly improved or in remission at the time of discharge. These findings are consistent with those of other investigators of the catatonic syndrome for the past 100 years.

Recorded and reported sleep in chronic primary insomnia.

Abstract: • Sleep polygraph and questionnaire data of 18 chronic primary insomniacs were compared with those of 18 age- and sex-matched controls. The insomniacs had significantly longer sleep latencies, less total sleep, less sleep efficiency, more terminal wake time, and less delta sleep. There were significant discrepancies between the insomniacs' and controls' subjective assessments of their sleep and the sleep-polygraph data, but in opposite directions. The insomniacs' recorded sleep also showed more night-to-night variability than that of the controls. However, the controls, in contrast to the insomniacs, reported sleeping worse in the laboratory than at home. Significant differences between insomnia subtypes validly reflected the insomniacs' subjective complaints and were generally in accord with expectations based on them.

The effect of neuroleptics on serum prolactin in schizophrenic patients.

Abstract: • Serum prolactin levels were studied before and during longterm administration of phenothiazines on a twice daily schedule to 27 newly admitted schizophrenic patients. An increase in serum prolactin is believed to be a reflection of inhibition of dopamine receptors in the hypothalamopituitary axis. By 72 hours after the initiation of treatment, all 27 patients had persistently elevated serum prolactin levels averaging 3.2-fold and 3.8-fold in men and women, respectively. There was a lag between clinical response and dopamine blockade, as indicated by serum prolactin levels in most patients. Serum prolactin levels remained elevated during the one- to three-month period subjects were studied, suggesting there was no tolerance to this effect of phenothiazines. Serum prolactin levels tended to be higher with thioridazine than on equivalent doses of chlorpromazine or trifluoperazine hydrochloride. There was some evidence that the magnitude of the serum prolactin elevation correlated with clinical response. After cessation of phenothiazines, serum prolactin levels rapidly reverted to normal within 48 to 96 hours.

Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients.

Abstract: • Hospitalized bipolar and unipolar endogenously depressed patients who showed an antidepressant response to the monoamine oxidase (MAO) inhibitor, tranylcypromine sulfate, relapsed (ie, depression returned) when relatively small doses of parachlorophenylalanine (PCPA) were added for brief periods. Considered together with our findings that PCPA similarly reversed the antidepressant effects of the tricyclic drug, imipramine hydrochloride, implications are (1) serotonergic mechanisms are likely involved in the antidepressant effects of both the tricyclic drugs and MAO inhibitors in man and (2) this indolamine may also play a role in the endogenous clinical state of depression.

Drug refusal in schizophrenia and the wish to be crazy.

Abstract: • The extremes of drug compliance were studied in two groups of schizophrenics: 29 habitual drug-refusers who invariably discontinued medication only to be readmitted several months later, and 30 drug-complier patients who habitually came in for their refills or injections of antipsychotic medication. The drug-refusers experienced the resurgence of an ego-syntonic grandiose psychosis after they discontinued medication. The habitual compliers, in contrast, developed decompensations characterized by such dysphoric affects as depression, anxiety, virtual absence of grandiosity, and some awareness of illness. The refusal of these chronic schizophrenics to take their medication could not be attributed to social isolation, paranoid diagnosis, or secondary gain. A discriminant function analysis showed grandiosity to be the most powerful discriminating variable between the two groups. We interpret these findings to mean that some schizophrenics may prefer an ego-syntonic grandiose psychosis to a relative drug-induced normality.

Incidence and Significance of Mixed Affective States in a Bipolar Population

Abstract: The simultaneous existence of manic and depressive symptoms in a manic-depressive patient was first described by Kraepelin. This so-called mixed state has come to have much theoretical significance in recent hypotheses about the nature of bipolar affective disorders. In this investigation a mixed state is shown to be the initial episode in 31% of 84 manic-depressive outpatients. Moreover, the presence of "mixed" features does not correlate with severity of illness or mood circularity, but does correlate with sedative abuse and poor response to psychopharmacologic treatment. These results suggest that the "continuum hypothesis" and its satellite theories represent viable conceptualizations of the nature of manic-depressive illness.

Natural history of male psychological health. V. The relation of choice of ego mechanisms of defense to adult adjustment.

Abstract: • Ninety-five men, selected in college on the basis of health, have been prospectively followed up for 30 years. Their adaptive styles have been isolated, labeled by the ego mechanisms of defense that their behavior reflects, and studied by semiquantitative techniques. A hierarchy of ego mechanisms was devised that ordered defenses along a continuum that reflected the following two dimensions: (1) immaturity-maturity and (2) psychopathology-mental health. The most important finding was that despite blind assessment, a scale reflecting the maturity of a subject's defenses correlated with scales measuring his objective psychopathology ( r = —.35) and his objective adaptation to the external environment ( r =.65). Highly significant shifts in defensive style occurred as individuals matured. In order to conceptualize the continuum that underlies mental health, identification of a person's dominant defensive styles may be superior to our current scheme of static unitary diagnoses.

Personality Patterns in Insomnia: Theoretical Implications

Abstract: • Subjects with a primary complaint of insomnia (N = 124) were evaluated with Minnesota Multiphasic Personality Inventories (MMPIs). A high percentage of subjects (85%) had one or more MMPI scales elevated to a pathological degree. The scales most elevated were, in order, 2 (depression), 7 (psychasthenia), and 3 (conversion hysteria). A striking finding was the preponderance of depression. This was indicated by the frequency in which scale 2 was elevated above 70, the frequency in which this scale had the highest elevation, and the frequency of MMPI code types that included scale 2. Four common MMPI code types representing various types of depression were noted, indicating considerable homogeneity for code types in this sample. The predominant personality styles in this sample were characterized by the internalization of psychological disturbances rather than by acting out or aggression. We propose that this internalization produces a state of constant emotional arousal and resultant physiological activation and that this process is a psychophysiological mechanism underlying insomnia.

Hyperactive Boys and Their Brothers: A 25-Year Follow-Up Study

Abstract: • Twenty men, who had conformed to diagnostic criteria for the hyperactive child syndrome 20 to 25 years ago, and their brothers were interviewed. A large majority of men who were hyperactive had completed high school, and each was steadily employed and self-supporting. Half of the men who were hyperactive continued to show a number of symptoms of hyperactivity. Nearly half had problems of a psychiatric nature and, despite normal intelligence quota scores and levels of education, these men had not achieved a socioeconomic status equal to that of their brothers or their fathers. Our findings suggest that emotional problems in everyday living may result from the persistence of symptoms of hyperactivity and that most social and psychiatric consequences of the disorder relate to its presence in childhood as well as to its persistence in adulthood.

Methylphenidate, Dextroamphetamine, and Levamfetamine: Effects on Schizophrenic Symptoms

Abstract: • Methylphenidate hydrochloride dextroamphetamine sulfate, and levamfetamine succinate have potential as pharmacologic tools for the indirect evaluation of the role of neurotransmitters in schizophrenia. In actively ill schizophrenic patients, methylphenidate administered intravenously causes a brief but clear intensification of preexisting psychotic symptoms, such as hallucinations and delusions. In our study, methylphenidate, dextroamphetamine, and levamfetamine were administered in equimolar doses to schizophrenic patients. Methylphenidate was a more effective activator of symptoms than dextroamphetamine, which in turn was more effective than levamfetamine. Levodopa (L-dopa) given orally also reportedly produces a temporary worsening of schizophrenic symptoms. While these findings augment a body of information suggesting that dopamine and norepinephrine may play a role in the activation of schizophrenic symptoms, our findings with methylphenidate (reportedly weak in eliciting sterotyped behaviour in rat) and our review of the literature indicate complexities that remain to be resolved. There is some utility of the procedure for differential diagnosis and selective therapy, but this is still of occasional and limited potential.

Methadyl Acetate and Methadone as Maintenance Treatments for Heroin Addicts: A Veterans Administration Cooperative Study

Abstract: • This was a double-blind comparison of methadyl acetate and two dose levels of methadone hydrochloride in the maintenance of 430 street heroin addicts from 12 Veterans Administration hospitals. The starting sample consisted of 146 patients receiving low-dose methadone, 142 patients receiving high-dose methadone, and 142 patients receiving methadyl acetate. Patients were first given 30 mg of both drugs, and doses were incremented by 10 mg/week until they stabilized at methadyl acetate, 80 mg three times a week, and methadone hydrochloride, 50 mg daily or 100 mg daily. Dosage was fixed for the balance of the 40-week treatment period. Safety was evaluated by clinical and laboratory observations conducted at frequent intervals throughout the study. Relative efficacy was evaluated by illicit drug use, program retention and attendance, and global staff judgments. It is concluded that methadyl acetate is as safe a drug as methadone and that it compares favorably with highdose methadone in terms of efficacy. Both methadyl acetate and high-dose methadone appear to be better maintenance regimens than low-dose methadone under the conditions of this study.

Another View of Schizophrenia Subtypes: A Report From the International Pilot Study of Schizophrenia

Abstract: • Schizophrenia subtypes are defined predominantly by manifest symptoms and behavior. This report, based on sign and symptom data from the International Pilot Study of Schizophrenia, addresses three questions: (1) Are traditional subtype diagnoses applied similarly across cultures? (2) Are the various traditional subtypes symptomatically distinguishable from one another? (3) Can cluster analytic techniques define a more distinctive set of schizophrenic subgroups? Present State Examination data were reduced to 27 psychopathologic signs and symptoms. Profile analysis of variance results indicate that each subtype appears similar, regardless of center of origin. However, this is based on a lack of distinguishing features between different subtypes. On the other hand, when a cluster analytic technique was used, it showed one large and three small subgroups, each readily distinguishable from the others. These subgroups, labeled "usual," "flagrant," "insightful," and "hypochondriacal," are described clinically. If replicated or validated, such subgroups may prove meaningful in future considerations of subdivisions of the schizophrenia syndrome.

Smooth pursuit eye movements, attention, and schizophrenia.

Abstract: • In previous studies, smooth pursuit eye movements (SPEM) have been shown to be disordered in about 70% of schizophrenics and about 45% of their first-degree relatives. In this report, the role of attention in these eye movements is addressed in three experiments (using as subjects schizophrenics, their firstdegree relatives, and normals administered chloral hydrate) that recruit focused attention to the task. These studies show that voluntary attention in the form of inattention, "heedless negligence," or failure to cooperate, is not the specific attentional quality that is disordered in SPEM of schizophrenics and their relatives. Rather, the data both indicate that nonvoluntary attending is specifically disordered in these persons, and implicate a neurophysiological substrate that can be described as a failure of inhibitory, synchronizing or integrating systems which may be located in the brain stem.

Eye-tracking performance and engagement of attention.

Abstract: Eye-tracking dysfunction has previously been demonstrated in psychotic patients. To investigate possible influences on this finding of factors related to attention, subjects were required to read numbers while tracking an oscillating pendulum or a pendulum-like target displayed on an oscilloscope tube. Subjects for the pendulum task were 16 nonpatients and 21 patients; 10 nonpatients and 14 patients performed the other task. Introduction of the number-reading maneuver greatly improved tracking performance in both tasks in patients and nonpatients. The results indicate that poor eye-tracking can be improved by facilitating attentional effort; it is suggested that the number-reading maneuver improved tracking by providing extra feedback cues. The poorer the base line performance, the greater the improvement. However, differences between patients and nonpatients were not abolished with number reading.

Comparative Effects of Methylphenidate and Thioridazine in Hyperkinetic Children: I. Clinical Results

Abstract: • The effects of three pharmacological treatments, methylphenidate hydrochloride, thioridazine hydrochloride, a methylphenidate/thioridazine combination, and placebo were studied in outpatient hyperkinetic children rated hyperactive both in school and at home or clinic. Active treatment lasted 12 weeks; placebo lasted four weeks. Significant clinical improvement was obtained in a variety of settings–all treatments were superior to placebo on ratings filled out by parents, teachers, and clinic staff. Though initially the combination of methylphenidate and thioridazine tended to produce greater clinical improvement, it was not superior to methylphenidate alone after 12 weeks of treatment. Methylphenidate alone and the methylphenidate/ thioridazine combination were more effective than thioridazine alone. The salient side effects with methylphenidate treatment were decrease in appetite, difficulty in falling asleep, and increased mood sensitivity. In contrast, thioridazine administration was associated with appetite increase and enuresis.

Schizophrenia—A Follow-up Study of Results of Treatment: II. Hospital Stay Over Two to Five Years

Abstract: • This is the second article from a study of the outcome of five different methods of treatment for schizophrenia; patients were followed up over a period of two to five years after first admission and the first release. Patients who had been originally treated in hospital with psychotherapy alone stayed longer in hospital over the follow-up period than those who had received electroconvulsive therapy (ECT), drug alone, or drug plus psychotherapy. Those who had been treated with milieu therapy also had a longer stay dated from the time of admission. Patients treated initially with drugs or ECT showed a trend toward spending less time in hospitalafter their release.