The effects of anticancer chemotherapeutic drugs on cognitive function and other neuropsychiatric dimensions in breast cancer patients.

This preliminary study aimed to apply a novel computerized measure derived from the content analysis of 5-min speech samples from patients with breast cancer to measure cognitive impairment and other neuropsychiatric dimensions during the course of anticancer chemotherapeutic treatment. Since such patients are often administered other pharmacological agents to alleviate their symptoms in addition to anticancer chemotherapeutic agents, another aim was to try to distinguish the mental effects of the anticancer drugs from the effects of any other drugs administered. Before and during the course of their anticancer chemotherapy, 12 breast cancer patients gave 5-min verbal samples, elicited by purposely ambiguous instructions, to talk about any personal life experiences. The recorded verbal samples were scored by a computer program (PCAD 2000) to measure the magnitude of cognitive impairment and other relevant neuropsychiatric dimensions. All of the pharmacological agents administered to the patients were recorded. The computer program automatically compared the scores derived from each verbal sample to already established norms to determine whether each score was within normal limits or one to three standard deviations from the norms. Significantly elevated Cognitive Impairment Scale scores were found in the verbal samples of 9 of the 12 patients. All patients had instances of elevated Health/Sickness Content Analysis Scale scores as well as frequent significantly elevated scores in shame anxiety and in death anxiety. In the Quality of Life Content Scale, the scores were uniformly low, ranging from +1.64 to -9.11. Further studies are being carried out to determine which patients are especially susceptible to cognitive impairment under these treatment conditions.

The cerebral neurobiology of anxiety, anxiety displacement, and anxiety denial.

BACKGROUND: Previous studies examining the relationship of anxiety scores, derived from the content analysis of speech of normal individuals, have revealed that the anxiety scores occurring in the dreams associated with rapid eye movement (REM) sleep are significantly correlated with localized cerebral glucose metabolic rates assessed by positron emission tomography (PET) scanning. These significant intercorrelations occur in different cerebral areas when the anxiety scores are obtained from mental experiences reported during non-REM sleep or during wakeful silent mentation. OBJECTIVE: The purpose of the present study was to examine the intercorrelations found between anxiety attributed to the self, anxiety-displacement, and anxiety denial measured from computerized content analysis of 5-min verbal reports of subjective thoughts and feelings obtained from wakeful normal subjects and localized cerebral glucose metabolic rates during PET scanning. METHODS: The subjects were 10 wakeful young males. Their anxiety scores were derived from computerized content analysis of 5-min reports they gave of their subjective thoughts, feelings and fantasies during a 30-min period following an intravenous injection of F D-deoxyglucose (FDG). The subjects were moved 32--45 min after this injection to obtain a PET scan, which records all of the localized cerebral glucose metabolic rates during the 30 min following the FDG injection. RESULTS: Significant intercorrelations of localized cerebral glucose metabolic rates with the scores of self-anxiety, anxiety displacement, and anxiety-denial were found in dissimilar cerebral locations depending on the type of anxiety involved. The significant correlations occurred in brain regions known to be associated with the functions of emotions, cognition, memory, and vision. CONCLUSIONS: Specific combinations of cerebral areas, based on glucose metabolic rates, appear to distinguish and be associated with different verbal expressions of anxiety. Replication of this preliminary research will be carried out.

Computerized measurement of cognitive impairment and associated neuropsychiatric dimensions.

This study aimed to cross-validate the capacity of a computer software program to detect and measure, using a measurement method applied to the content and form analysis of 5-minute speech samples, cognitive impairment and associated comorbid neuropsychiatric psychobiological dimensions in drug-abusing patients. At the University of California-Irvine (UCI) Neuropsychiatric Center, 28 drug-abusing inpatients using illegal drugs were clinically evaluated. Their scores for cognitive impairment derived by the computerized content analysis method were compared with scores derived from selected tests from the Halstead-Reitan Neuropsychological Test Battery, the computerized Automated Neuropsychological Assessment Metric Battery (ANAM), the Alzheimer's Disease Assessment Scale-Cognitive Portion, the Stroop Color and Word Test, the Symbol Digit Modalities Test, and the Controlled Oral Word Association Test. The statistical significance (P value) of the correlations of scores from these different measures with scores obtained from the computerized content analysis measures was less than .05 to .001. The comparative "hit rate," detecting cognitive impairment above the norms for each measure administered to these drug-abusing patients, for the computerized content analysis measures and some of the ANAM neuropsychological measures was 75% to 89%, and for the other neuropsychological measures, 25% to 64%. In conclusion, the computerized content analysis methodology applied to 5-minute verbal samples is a valid, rapid, easily administered measurement instrument for assessing the magnitude of cognitive impairment and comorbid neuropsychiatric dimensions.

The application of computerized content analysis of natural language in psychotherapy research now and in the future.

For many years the author and his colleagues have been involved in studying the roots and processes of the conveyance of semantic messages via spoken language and verbal texts. After establishing that reliable and valid measurements of highly relevant neuropsychiatric categories, such as anxiety, depression, and cognitive impairment, can be made by identifying and counting the occurrence per grammatical clause of language content and form categories typifying specific content-analysis scales, the research focus has turned towards computerizing this process of content analysis. This report summarizes the achievements and applications of the current empirical status of this method of computerized content analysis of natural language to psychotherapy research, and it speculates on possible future applications in the millennium.

Risperidone for the treatment of stuttering.

A randomized, double-blind, placebo-controlled study was conducted to assess the efficacy of risperidone in the treatment of developmental stuttering in 16 adults. Eight subjects received placebo and eight received risperidone at 0.5 mg once daily at night, increased to a maximum of 2 mg/day. After 6 weeks of treatment, decreases in all measures of stuttering severity were greater in the risperidone group than in the placebo group; the between-treatment difference was significant (p < 0.05) on the most important measure, the percentage of syllables stuttered. In the risperidone group, reductions from baseline in scores for the percentage of syllables stuttered, time stuttering as a percentage of total time speaking, and overall stuttering severity were significant (p < 0.01); changes in scores on the fourth measure of stuttering, duration, were not significant. No significant decreases occurred in the placebo group. Among the eight patients in the risperidone group, five responded best to 0.5 mg/day, with stuttering recurring at higher doses. The remaining three patients responded better with increasing doses of risperidone. Risperidone was generally well tolerated. The results of this small study indicate that risperidone may be effective in the treatment of developmental stuttering. This finding needs to be confirmed in a larger trial.

Anxiety and hope during the course of three different medical illnesses: a longitudinal study.

BACKGROUND: Somatic illness and its consequences evoke strong emotions of various kinds. They may affect the course of illness and the treatment results through their physiological components. The purpose of the study was to explore emotional reactions to different kinds of illnesses and changes of these emotions over time. METHODS: Subjects were 259 medical patients suffering from: primary hypertension, myocardial infarction and cancer of the lungs or pharynx. The study was longitudinal and consisted of three phases. The first was performed immediately after the patient was diagnosed, the second was done 5 weeks later and the third about half a year after the onset of illness. The patients' emotional state was evaluated with the Gottschalk-Gleser Content Analysis Scales: the Anxiety and the Hope Scales. RESULTS: Significant effects of the kind of illness and of its interaction with the phase of the study were found. In the hypertension group, both anxiety and hope were slightly elevated immediately after diagnosis, then slightly lowered. The myocardial infarction group exhibited a low level of these emotions in the first phase, an increase in the second and then a little decrease. Cancer patients manifested high anxiety and relatively low hope in the initial phase, then a decrease in anxiety and an increase in hope. CONCLUSIONS: Both anxiety and hope accompany the illness in its consecutive phases, reflecting properties of illness as a source of psychological stress and the coping process.

Stuttering: neuropsychiatric features measured by content analysis of speech and the effect of risperidone on stuttering severity.

Positron-emission tomographic (PET) studies and genetic research of stuttering have recently revealed underlying cerebral neurobiologic contributing factors in this disorder. We aimed to assess whether cognitive impairment and other neuropsychiatric dimensions could be detected through computerized content analysis of short samples of speech from stutterers, and whether administration of risperidone in a double-blind placebo-controlled study could decrease the severity of stuttering, as well as any of the neuropsychiatric features of these stutterers. A group of 21 stutterers with the developmental form of stuttering, an onset before age of 6 years, aged 20 to 74 years, and who were otherwise free of major medical or psychiatric problems, initially gave a 5-minute tape-recorded speech sample in response to purposely ambiguous instructions to talk about any interesting or dramatic life experiences. Then, half of these subjects (n = 10) were randomly selected to receive 6 weeks of risperidone treatment up to 2.0 mg/d and the other half (n = 11) were administered a placebo. Both groups of subjects gave a second verbal sample after 6 weeks of treatment. Significantly elevated cognitive impairment and social alienation-personal disorganization scores, derived from the computerized content of the initial 5-minute speech samples, were found. After 6 weeks, the risperidone group improved significantly on a measure of severity of stuttering but did not improve on the percentage of time spent stuttering. The placebo group did not improve on either measure of stuttering. The psychopathological processes of subjects who received risperidone treatment, including those with elevated cognitive impairment and social alienation-personal disorganization, did not change significantly. However, stutterers who had lower scores on verbal content analysis-derived shame anxiety, guilt anxiety, or hostility inward measures improved significantly more with risperidone than stutterers with higher scores on these measures. The findings of elevated cognitive impairment and social alienation-personal disorganization scores of adult stutterers with the early developmental form of stuttering are consistent with the neurobiologic abnormalities found in PET-scan and genetic research involving stutterers. Risperidone (< or =2.0 mg/d) can reduce the severity of stuttering while not significantly affecting the magnitude of neuropsychiatric dimensions such as cognitive impairment or social alienation-personal disorganization. The less the inward shame, guilt, or hostility of the stutterers, the better the beneficial effect of risperidone on the severity of stuttering.

The application of a computerized measurement of the content analysis of natural language to the assessment of the effects of psychoactive drugs.

This article aims to answer the question whether developing technology is now capable of measuring objectively and accurately the effects of psychoactive pharmacological agents by means of computerized assessments of psychological states and traits through the analysis of content and form of people's speech. At the present time, psychopharmacological researchers involved in clinical trials rely on DSM-IV criteria and standardized self-report measures and observer rating scales to assess psychoactive drug effects. Attention is drawn to the potentially unrecognized measurement errors and relatively low interrater reliability by these methods--for example, all raters are not free of observer bias and every subject administered a drug is not equally and accurately well-informed about the self. The computerized content analysis methods tend to avoid these biases and measurement errors. A review is provided describing the Gottschalk-Gleser method of measuring psychobiological dimensions from the form and content of short (usually five-minute) speech samples of verbal behavior, generally elicited by standardized and purposely ambiguous instructions to talk about any interesting or dramatic personal life experiences. Norms have been obtained by this method of speech elicitation, adjusted for age, sex and educational level. Sections are provided covering cross-cultural and language validation research on the Gottschalk-Gleser content analysis method, the influence of medical or psychiatric illness as well as psychoactive drugs on verbal content analysis-derived scores, and the research carried out for more than 20 years computerizing this content analysis procedure through the development of artificial intelligence software enabling these measurements to be done from typescripts of speech samples on computer diskettes. A brief review deals with the general applications of this method of measurement to basic and clinical psychiatry, psychosomatic medicine, neuropsychology, the diagnostic process in a psychiatry outpatient clinic, children's mental health problems, dream research, and assessment of mental processes during PET scanning of the brain. This is followed by a review of the applications of this method of content analysis of speech to neuropsychopharmacological testing of antianxiety, antidepressive, antipsychotic, and other psychoactive drugs, as well as to pharmacokinetic variables and clinical response. This method is now in the process of being used in clinical trials in psychopharmacology and is recommended for more extensive use in this research area.

The application of computerized content analysis of speech to the diagnostic process in a psychiatric outpatient clinic.

Twenty-five new psychiatric outpatient were clinically evaluated and were routinely administered a brief psychological screening battery which included measures of symptoms, personality, and cognitive function. Included in this assessment procedure were the Gottschalk-Gleser Content Analysis Scales on which scores were derived from five-minute speech samples by means of an artificial intelligence-based computer program. Intercorrelations of these content analysis measures with scores obtained from the MMPI-2, SCL90, and other measures confirmed previously published construct validation findings. The use of this computerized content analysis procedure for initial, rapid diagnostic neuropsychiatric appraisal is supported by this research.

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.

Computerized measurement of the content analysis of natural language for use in biomedical and neuropsychiatric research.

Over several decades, the senior author, with various colleagues, has developed an objective method of measuring the magnitude of commonly useful and pertinent neuropsychiatric and neuropsychological dimensions from the content and form analysis of verbal behavior and natural language. Extensive reliability and validation studies using this method have been published involving English, German, Spanish and many other languages, and which confirm that these Content Analysis Scales can be reliably scored cross-culturally and have construct validity. The validated measures include the Anxiety Scale (and six subscales), the Hostility Outward Scale (and two subscales), the Hostility In Scale, the Ambivalent Hostility Scale, the Social Alienation-Personal Disorganization Scale, the Cognitive Impairment Scale, the Depression Scale (and seven subscales), and the Hope Scale. Here, the authors report the development of artificial intelligence (LISP based) software that can reliably score these Content Analysis Scales, whose achievement facilitates the application of these measures to biomedical and neuropsychiatric research.

The development, validation, and applications of a computerized measurement of cognitive impairment from the content analysis of verbal behavior.

This is a report of the development, validation, and computerized applications of a method of measuring cognitive and intellectual impairment through the content analysis of verbal behavior. The content analysis procedure utilized is based on the method developed by Gottschalk and Gleser for the measurement of the magnitude of many other psychological states and traits, in addition to cognitive dysfunction. Verbal behavior studies are reviewed that examine the cognitive effects of age, certain psychoactive drugs, alcohol, total body irradiation, sensory overload, and dementia. Finally, the availability of a recently developed artificial intelligence software program is reported that will reliably, rapidly, and objectively score speech samples (on Gottschalk-Gleser Scales) transcribed according to specific directions from IBM-compatible computer diskettes.

Influence of patient caregivers on course of patient illness: "expressed emotion" and alternative measures.

The influence of the quality of care that patients receive during the course of their illness has been the subject of special scrutiny in the area of mental health. The concept of "expressed emotion" (EE) evolved in an effort to understand the impact of family and social environment on the vulnerability to relapse of schizophrenic patients. A semistructured interview, the Camberwell Family Interview, was developed to assess expressed emotion. This article examines the historical context, generalizability, methodological strengths and limitations of the construct of EE and the Camberwell Family Interview, as well as the nature and effects of treatment intervention programs designed to neutralize adverse effects of patient caretaker attitudes.

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.

The cerebral neurobiology of hope and hopelessness.

Hope and hopelessness are useful constructs that have been employed by clinicians in theory making regarding the pathogenesis and course of disease and in the application of various psychological and medical treatments to illness. French (1952) and Frank (1968) viewed hope as a necessary motivating force in influencing an individual to try to overcome inner psychological conflicts and seek to resolve a psychoneurosis. Melges and Bowlby (1969) classified the types of hopelessness in psychopathological processes. Perley et al. (1971), using an objective method for content analysis of small samples of speech (Gottschalk 1974), found that elevated hope scores predicted continuation of psychiatric treatment rather than dropping out. Gottschalk et al. (1967, 1969) found that hope scores derived from verbal samples predicted the duration of survival of patients with terminal cancer receiving irradiation treatment (1969) and predicted relatively favorable outcome in psychotherapy (1967).

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.

The relationship between social alienation and disorganized thinking in normal subjects and localized cerebral glucose metabolic rates assessed by positron emission tomography.

This study investigated the relationships between the relatively mild manifestations in verbal behavior of social alienation and disorganized thinking in normal subjects and cerebral glucose metabolic rates measured by positron emission tomography (PET). Three groups of 10 young normal male subjects were injected with D-[18F]deoxyglucose (FDG) during either wakefulness, rapid eye movement (REM), or non-REM (NONREM) sleep, and 32 to 45 minutes later they were asked to report their thoughts, emotions, or dreams and free-associations to these mental events. Nonparametric correlations were obtained between measures of interpersonal social alienation, intrapsychic conflicts, and thought disorder derived from the typescripts of these reports by content analysis--using the Gottschalk-Gleser Social Alienation-Personal Disorganization Scale--and regional cerebral glucose metabolic rates obtained from PET scans. Total social alienation-personal disorganization scores obtained from the reports of wakeful, silent mentations showed significant positive correlations with glucose metabolic rates in the left temporal lobe. The patterns of significant correlations involving these verbal behavior measures derived from the content analysis of verbal reports of dreams or other mental events occurring during REM and non-REM sleep were in different cerebral locations from those found with these variables during silent, waking mentation. Previous observations suggesting that increased left temporal lobe glucose may typify chronic schizophrenia may instead be indicative of a wide range of thought disorder and/or social alienation manifestations occurring, at times transiently and minimally, in normal people.