Anxiety levels in dreams: relation to changes in plasma free fatty acids.

Blood samples for determination of plasma free fatty acids were obtained throughout the night by means of an indwelling catheter. The first sample was drawn at the onset of rapid eye movements and a second after 15 minutes of these movements. Subjects were then awakened and asked to relate their dreams; a third sample was drawn 15 to 25 minutes later. Anxiety scores derived from 20 dreams of nine subjects had significant positive correlations with changes in free fatty acids occurring during REM sleep. No statistically significant relation was found between anxiety and the changes in free fatty acids occurring from the time just before awakening to 15 to 25 minutes later. Presumably, anxiety in dreams triggers the release of catecholamines into the circulation, and these catecholamines mobilize proportional amounts of free fatty acids from body fat.

Striatal metabolic rate and clinical response to neuroleptics in schizophrenia.

A low metabolic rate in the caudate nucleus and putamen in schizophrenic patients while they were not receiving medication was found to predict a favorable clinical response to haloperidol. Twenty-five patients (21 men and four women) entered a double-blind crossover trial of haloperidol and placebo; to our knowledge, this is the first such trial with positron emission tomography to be reported. Patients received either placebo or medication for the first 5 weeks, and they received the other treatment for the second 5 weeks. Positron emission tomographic scans were obtained at weeks 5 and 10. Patients with low relative metabolic rates in the caudate nucleus and putamen while they were receiving placebo were more likely to show decreases in their Brief Psychiatric Rating Scale scores with haloperidol treatment than individuals with normal or high metabolic rates. Among responders, haloperidol treatment had a "normalizing" effect on metabolic activity in the striatum, with the metabolic rate while they were receiving haloperidol being higher than that while they were receiving placebo. Nonresponders were more likely to show a worsening of hypofrontality while they were receiving medication and an absence of change in the striatum.

Effect of marijuana and placebo-marijuana smoking on psychological state and on psychophysiological cardiovascular functioning in anginal patients.

Ten male anginal patients with angiographically documented coronary artery disease, in a randomized double-blind crossover study, smoked one marijuana cigarette (containing 18 mg of delta-9-THC) on one morning and one placebo marijuana cigarette (containing 0.05 mg of delta-9-THC) on a successive morning. Significant increases occurred in average cognitive and intellectual impairment scores, derived from the objective content analysis of 5 min of speech, 30 mins after smoking the marijuana cigarette as compared to the placebo marijuana cigarette, and these scores decreased to near presmoking levels 60 min after smoking. No significant average changes occurred in anxiety or three hostility scale scores following smoking marijuana. Sizable individual differences were noted in the psychological responses to marijuana smoking due, presumably, to personality differences and/or differences in THC pharmacokinetics. Significant psychocardiovascular hemodynamic correlations, as measured by echocardiography, were observed during placebo-marijuana smoking between hostility inward scores and systolic blood pressure and ejection fraction, overt hostility outward scores and diastolic blood pressure, as well as between anxiety scores and stroke volume and left ventricular end-diastolic dimension and left ventricular diastolic volume. These significant psychophysiologic correlations were all eliminated during marijuana smoking. In view of associated findings that marijuana smoking decreased myocardial oxygen delivery, decreased exercise time until the onset of anginal pain, and increased myocardial oxygen demand in anginal patients, the use of marijuana by such patients is clearly inadvisable.

Relationship between neuropsychological performance and alcohol consumption in alcoholics.

Cognitive performance in drug-free alcoholic patients (n = 95) within 7 days of their last drink was significantly predicted by chronic and recent drinking practices. Conceptually distinct cognitive functions were differentially influenced by various combinations of drinking variables. Consideration of curvilinear relationships enhanced the amount of variance explained, and it is suggested that certain patterns of consumption may accelerate the alcohol-induced decline of brain function.

Changes in neuropsychological performance during treatment for alcoholism.

A battery of 24 neuropsychological tests was administered to drug-free alcoholic inpatients (n = 91) within 7 days of their last drink and again 17 days later. Comparisons between this group and a nonalcoholic group of medical inpatients (n = 20) also given the same test battery twice indicated very little improvement due to abstinence (short-term improvement) in the alcoholics after controlling for practice effects. Similarly, when early postwithdrawal performance of the alcoholics was compared to an alcoholic control group (n = 32), which took the test battery only once 21 days after their last drink, little evidence for short-term recovery of cognitive functions was obtained. Insofar as decisions about the initiation of therapeutic treatments which rely on cognitive processes are based on neuropsychological performance, we conclude that such treatments may commence as soon as the clinical symptoms associated with acute withdrawal have subsided.

Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients.

OBJECTIVE: The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in schizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its main symptoms. METHOD: Seventy male schizophrenic patients underwent [18F]-fluorodeoxyglucose positron emission tomography after a period of at least 4 weeks during which they had not received neuroleptic medication and were compared to 30 age-matched male normal comparison subjects. RESULTS: Analyses revealed decreased metabolism in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ventral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previous studies, the schizophrenic group had lower hypofrontality scores (ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic patients did not differ from that of comparison subjects, while occipital cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal activity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for each schizophrenic patient on the scan day, were correlated with regional brain glucose metabolic rate. Medial frontal cortical and thalamic activity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and hypofrontality scores did not significantly correlate with negative symptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions. CONCLUSIONS: Low metabolic rates were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striatal-thalamic pathways in schizophrenia. Loss of normal lateralization patterns was also observed on an exploratory basis. Correlations with negative symptoms and group differences were more prominent in medial than lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology.

D2 dopamine receptor polymorphism and brain regional glucose metabolism.

Positron emission tomography (PET) studies have shown decreased glucose metabolism in brain regions of detoxified alcoholics and cocaine abusers. However, it is not clear whether this decrease is due to chronic drug abuse or a pre-existing condition. Molecular genetic studies have found an association of the D2 dopamine receptor (DRD2) A1 allele with alcoholism and drug abuse. Moreover, reduced central dopaminergic function has been suggested in subjects who carry the A1 allele (A1+) compared with those who do not (A1-). In the present study, using 18F-deoxyglucose, regional glucose metabolism was determined in healthy nonalcohol/nondrug-abusing subjects with the A1+ or A1- allele. The mean relative glucose metabolic rate (GMR) was significantly lower in the A1+ than the A1- group in many brain regions, including the putamen, nucleus accumbens, frontal and temporal gyri and medial prefrontal, occipito-temporal and orbital cortices. Decreased relative GMR in the A1+ group was also found in Broca's area, anterior insula, hippocampus, and substantia nigra. A few brain areas, however, showed increased relative GMR in the A1+ group. Since polymorphism of the DRD2 gene is commonly observed in humans, the importance of differentiating A1+ and A1- alleles subjects in PET studies is suggested.

Clinical relevance of the bioavailability/bioequivalence controversy.

A generic drug containing the same active ingredient as a brand name drug may not show identical clinical efficacy. There is increasing evidence that substitution of a generic for a brand name (or vice versa) drug with the expectation of similar results is problematic and that improper treatment may result. Clinical trials are needed to test generic psychoactive drugs. This paper provides guidelines for clinical situations in which problems relating to bioavailability and bioequivalence may arise, for example, in patients taking concomitant medication(s) or in chronically ill or elderly patients. In addition, the importance of knowing which assay methods are used to measure psychoactive drug blood levels in considering drug efficacy is stressed.

Effects of abstinence on the ability of clinical laboratory tests to identify male alcoholics.

Quadratic discriminant analysis of 25 commonly ordered clinical laboratory tests resulted in correct classification of 100% of nonalcoholic inpatients (n = 41), 100% of medical ward alcoholics as alcoholic (n = 63), and 95% of alcoholism treatment program participants as alcoholic (n = 274). Admission laboratory values for a random sample of 138 additional alcoholism treatment program participants were used to correctly classify 96% of them as alcoholics. Repeat analysis of these same laboratory tests after some 27 days of hospitalization resulted in 94% of the 138 patients still being classified as alcoholic, even though significant improvements in individual hepatic and hematologic laboratory values were noted. Classification was not changed with reanalysis after long-term abstinence (7 or 24 months), suggesting widespread and persistent alcohol-related alterations in organ system functioning with chronic alcohol abuse. Quadratic discriminant analysis of laboratory tests is an effective means of identifying people with present or past alcohol abuse but is not yet of value in detecting compliance with a treatment goal of abstinence.

Platelet monoamine oxidase activity and evoked response as predictors of anxiety and depression derived from the content analysis of speech.

Platelet MAO activity has been reported by several investigators to differentiate schizophrenia, schizophrenia related depressive disorders, alcoholism, unipolar and bipolar depression from normal controls. Evoked potentials likewise have differentiated schizophrenic and affective patients. However, the precise relationship between MAO activity, evoked potentials (EP), and psychiatric illness has not been clarified. A possible association between psychopathology and high MAO activity/EP reducing and low MAO activity/EP augmenting has been reported. Such a bidirectionality further confounds results. This study was undertaken to determine the association of psychopathological dimensions found in a group of subjects whose platelet MAO activity and evoked responses were obtained two years earlier. Utilizing the Gottschalk-Gleser verbal behavior scales of Anxiety, Depression, Social Alienation-Personal Disorganization and Cognitive Impairment a significant correlation was revealed between low platelet MAO activity and high Total Anxiety scale and Shame Anxiety subscale scores. Additionally, a significant correlation was demonstrated between reducing evoked potentials and elevated Death Anxiety, Somatic Concerns, and Total Death and Mutilation Depression subscales scores, combined and separately. Furthermore, a significant positive correlation was found between augmenting evoked potentials and Overt Hostility Outward scores. No significant correlations were demonstrated between platelet MAO activity or evoked potentials and Social Alienation-Personal Disorganization or Cognitive Impairment scores. These findings lend support to the position that biological markers may predict predispositions to anxiety and depression.

Anxiety levels in dreams: relation to localized cerebral glucose metabolic rate.

Ten normal male subjects were injected with D-[18F]deoxyglucose during REM sleep, and 32-45 min later they were aroused and reported their dreams as well as free associations to these dreams. Nonparametric correlations between the anxiety scores derived from the typescripts of these verbal reports by the Gottschalk-Gleser content analysis method and localized cerebral glucose metabolic rates obtained from PET scans revealed significant positive correlations in lateral parietal and medial frontal cortex and negative correlations in adjacent white matter.

Cognitive impairment associated with acute or chronic disease.

Cognitive impairment in connection with acute or chronic disease may complicate the disgnosis, management and treatment of general hospital inpatients. Consulting psychiatrists may be called upon to evaluate cognitive and intellectual impairment associated with organic brain syndromes versus psychiatric disorders due to other causes. To assist the psychiatrist in formulating a differential diagnosis, the standard mental status examination and various objective neuropsychologic tests can be used. In addition, the author suggests a method of cognitive measurement using content and form analysis of five-minute speech samples. Impaired cognitive function may be caused or exacerbated by conditions such as alcohol abuse or psychoactive drug abuse which may not be revealed by the patient during the history taking.

A depression scale applicable to verbal samples.

A depression scale scored through the content analysis of verbal samples is described. A classification is provided of the type of content analysis used in the development of this scale. The rationale for various mathematical transformations used in deriving the scores is given. The construct of depression is discussed, and measurement problems occurring in its assessment are outlined. The content analysis approach to measurement of psychological and behavioral dimensions is seen as a combination of self-report and independent observer rating scale methods. The place of normative scores with such measurement tools is explained. Reliability of scoring and construct validation data using the depression scale are presented.

The emotional impact of mastectomy.

To learn about the effects of unilateral mastectomy, the emotional responses of four groups of women were compared 1-3 and 10-12 months after surgery: (1) mastectomy group (n = 125)--women who had a unilateral mastectomy for stage I or II breast cancer; (2) biopsy group (n = 65)--women who had a biopsy revealing benign breast disease; (3) cholecystectomy group (n = 75)--women who had a cholecystectomy; (4) healthy group (n = 84)--women who had not had a major surgical intervention. Measures of emotions were: (1) the SCL-90 Analogue; (2) the Global Assessment Scale (GAS); and (3) the Gottschalk-Gleser Content Analysis Scale. The mastectomy group had significantly higher mean Gottschalk-Gleser scores for total anxiety, death and mutilation anxiety, ambivalent hostility, total denial and anxiety denial, and hopefulness. Significant reductions were found in mean total anxiety, mutilation, and shame anxiety in the mastectomy group and in total, death, and mutilation anxiety in the cholecystectomy group between the two postsurgical assessments. The mastectomy group had a significantly higher mean anxiety and depression score than the healthy group on the SCL-90 at both time points. The mastectomy and cholecystectomy groups had lower emotional well-being scores on the GAS than the healthy group over both testing periods. The groups also differed in their amount of change on the GAS over time. All measures, especially the Gottschalk-Gleser scales, showed significantly more psychopathological emotional responses in the mastectomy group, somewhat less in the cholecystectomy group, and the least in the biopsy group.

Biochemical and hematological consequences of posttreatment drinking behavior in male alcoholics.

A prospective study was designed to determine the effects of posttreatment alcohol consumption by alcoholics on 25 commonly ordered clinical laboratory tests. Laboratory values were determined on 56 male alcoholics on admission to an alcoholism treatment program and again some 7 months later. Although there was a significant decrease in posttreatment alcohol consumption, frequency of drinking and quantity per occasion were predictive of approximately half of the laboratory tests. Increased frequency or quantity per occasion predicted more impaired hepatic and hematologic functioning. Additional analyses revealed that abstainers showed significant improvement in hepatic and hematologic parameters, whereas drinkers had levels similar to those observed at admission. Continued alcohol consumption by alcoholics increases the risk of adverse medical consequences as measured by clinical laboratory tests.

Preliminary validation of a set of content analysis scales applicable to verbal samples for measuring the magnitude of psychological states in children.

Scores on 17 psychological dimensions of the Gottschalk-Gleser content analysis scales were obtained from 5-minute speech samples of 37 white children hospitalized on the psychiatric service of a general hospital. These content analysis scores were compared to identical scores obtained from a normative sample of 109 white children. Groups of children were classified by the Group for the Advancement of Psychiatry (GAP) system as having Healthy Responses (N = 2), Personality Disorders (N = 17), Reactive Disorders (N = 9), Psychoneurotic Disorders (N = 7), and Developmental Deviations (N = 2), and by DSM-III as having Parent-Child Problems (N = 2), Conduct Disorders (N = 26), Anxiety Disorders (N = 7), and Special Developmental Disorders (N = 2). By either classification, these groups of children showed salient differences in their scores in certain psychological dimensions from the same types of scores occurring with the normative group. These findings provide initial construct validation of the Gottshalk-Gleser content analysis scales when applied to speech samples obtained for children. Moreover, the profiles of children's psychological characteristics obtained by this method provide, in themselves, an objective descriptive and dynamic classification.

Plasma concentrations of thioridazine metabolites and ECG abnormalities.

Five acute schizophrenic patients were given a standard thioridazine dose (4 mg/kg/day po). Their plasma concentrations of thioridazine and its metabolites were determined by GLC, and their ECG's were recorded routinely. In four of the five patients, abnormal ECG's (malformation of the T-wave or lengthening of the repolarization time) were found whenever plasma concentrations of the thioridazine ring sulfoxide were elevated. No relationship could be detected between the appearance of ECG abnormalities and the concentrations of thioridazine and its other metabolites.

Pretreatment consumption as a predictor of posttreatment consumption in male alcoholics.

Pretreatment levels of alcohol consumption for 72 male alcoholics were found to be related statistically to posttreatment levels of consumption determined approximately 8 months after completion of an inpatient alcoholism treatment program. Multiple logistic regression analysis was used successfully to determine the risk of relapse. Increased risk was associated with excessive drinkers who were relatively early in their alcoholic careers as assessed by years of abusive drinking and lifetime gallons consumed. Logistic regression appears to be a clinically useful procedure that would allow individual treatment programs to set their own criteria of success and increase their treatment effectiveness.

Neuropsychological consequences of posttreatment drinking behavior in male alcoholics.

A prospective study was designed to determine the neuropsychological consequences of continued alcohol consumption after treatment for alcoholism. Performance on 24 commonly used clinical neuropsychological tests was examined in 56 male alcoholics approximately 7 months after completion of an inpatient alcoholism treatment program. Abstainers (n = 17) performed better than those who resumed alcohol consumption. Although there was a significant decrease in alcohol consumption, posttreatment drinking behavior still predicted cognitive performance, with increased frequency and quantity per occasion having more deleterious consequences even at consumption levels that are deemed by some to be socially acceptable. It is concluded that alcohol consumption by former alcoholics might serve to maintain cognitive performance at reduced levels, and that this possibility should be considered in determining appropriate treatment goals for alcoholic patients.

GLC analysis of thioridazine, mesoridazine, and their metabolites.

A GLC method for measuring thioridazine, mesoridazine, their metabolites, and possibly other phenothiazines was developed. By using this method, seven different phenothiazine derivatives, thioridazine, and six known thioridazine metabolites were extracted and separated. This method was tested by assaying plasma samples from 30 hospitalized psychiatric patients receiving thioridazine or mesoridazine.