Biomedical subjects

N C Andreasen

Publications and source records attributed to N C Andreasen.

At least 19 recordsLinked to original sources

PubMed1992

Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study.

Volumetric measurements of subcortical and temporal structures were done on a sample of 54 schizophrenic patients, who were compared with 48 bipolar patients and 47 normal controls. We observed the male schizophrenic patients to have significant enlargement in the putamen and lesser enlargement in the caudate. We found the right temporal lobe to be larger than the left across all diagnostic groups, although bipolar females failed to have this asymmetry. We did not replicate the finding of decreased hippocampal, amygdala, or temporal lobe volume in our schizophrenic patients. Nor did we find significant differences between our bipolar patients and controls in the structures measured, with the exception of the right hippocampus. Our findings are consistent with a developmental defect in pruning of subcortical brain regions or with a compensatory synaptic increase secondary to decreased input from other brain regions such as the prefrontal cortex or anterior temporal lobe structures. Coupled with the lack of temporal lobe asymmetry in bipolar females, these findings suggest that different types of gender-specific neurodevelopmental abnormalities may occur in affective versus schizophrenic psychosis, which may reflect the effects of hormonal influences on brain development in predisposed individuals.

Adult↗

PubMed1992

The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology.

The Comprehensive Assessment of Symptoms and History was developed for research studies of schizophrenia spectrum conditions and affective spectrum conditions. It is designed to provide a comprehensive information base concerning current and past signs and symptoms, premorbid functioning, cognitive functioning, sociodemographic status, treatment, and course of illness. Because the information base is broad, it is not wedded to a specific diagnostic system but rather permits clinicians and investigators to make diagnoses using a wide range of systems, including Research Diagnostic Criteria, DSM-III, DSM-III-R, and the International Classification of Diseases. Given the fact that disorders in psychiatry are not defined at the etiological or pathophysiological level, diagnostic criteria are prone to ongoing revision as our knowledge base changes. Research strategies suggest that investigators should maintain a flexible database to permit them to adapt to changes in diagnostic systems, to do comparative nosological studies, and, ultimately, to develop new diagnostic systems based on knowledge concerning the underlying neurobiological nature of disorders. Because it provides a comprehensive information base, the Comprehensive Assessment of Symptoms and History facilitates research of this type. Extensive developmental work has been done with the Comprehensive Assessment of Symptoms and History, including interrater and test-retest reliability studies, validity studies, training programs, and data entry programs.

Databases, Factual↗

PubMed1992

Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London.

The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.

Adult↗

PubMed1992

Segmentation techniques for the classification of brain tissue using magnetic resonance imaging.

A technique is described for classifying brain tissue into three components: gray matter, white matter, and cerebrospinal fluid. This technique uses simultaneously registered proton density and T2-weighted images. Samples of each of the three types of tissue are identified on both image sets and used as "training classes"; these tissue samples are then used to generate a linear discriminant function, which is used to classify the remaining pixels in the image data set. Effects of varying the location and number of training classes have been explored; six pairs of training classes have been found to yield a suitable classification. Interrater and test-retest reliability have been examined and found to be good. Intrascanner and interscanner reproducibility has also been evaluated; classification rates are reproducible within the same individual when the same scanner is used, but in this study poor reproducibility occurs when the same individual is scanned on two different scanners. The validity of the technique has been tested by examining correlations between traced and segmented regions of interest, evaluating correlations with age, and conducting phantom studies, in addition to using visual inspection of the classified images as an indication of face validity. From all four perspectives, the method has been found to have good validity. Additional applications, strengths, and limitations are discussed.

Age Factors↗

PubMed1992

Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment.

Co-morbid substance use and abuse is common in schizophrenic patients, and the role of substance abuse in initiating and maintaining psychosis has important definitional and aetiological implications. We investigated the issue in a cohort of 131 schizophrenic patients. We found non-users (N = 67) were similar to pathological users (N = 64) in current symptomatology and clinical history. The pathological users did, however, have better pre-morbid adjustment levels. Only alcohol use and to some extent cannabis use contributed to this effect; use of stimulants or hallucinogens did not. These results indicate the importance of evaluating the various types of substance used when attempting to explore the significance of co-morbidity. The results also suggest that co-morbidity of substance abuse and schizophrenia may be explained by a common factor antecedent to both: better pre-morbid adjustment. A two-stage model is proposed to explain these findings: increased sociability increases exposure to opportunities of substance use in a subset of patients; subsequent onset of psychotic illness accelerates the use to a pathological level as the individual attempts to cope with the stress of the developing mental illness.

Adaptation, Psychological↗

PubMed1992

The Iowa prospective longitudinal study of recent-onset psychoses.

In this article, the methods of a prospective longitudinal study of recent-onset psychoses are described. Methodological issues that may be common to studies employing a similar design are discussed in the context of the rationale behind this study's strategies. Particular attention is paid to statistical strategies that maximally exploit longitudinal data.

Humans↗

PubMed1992

Image processing for the study of brain structure and function: problems and programs.

Fundamental problems in the analysis of functional and structural imaging data include data transport, boundary identification (including manual tracing, edge detection, and tissue segmentation), volume estimation, three-dimensional reconstruction and display, surface and volume rendering, shape analysis, and image overlay. These problems require that research investigators have access to suitable methods of image analysis, implemented on a set of software programs, in order to conduct neuroimaging research. The authors describe a group of software programs designed to provide a comprehensive solution for these problems.

Brain↗

PubMed1992

[Positive and negative symptoms of schizophrenia].

Aim of the present study is to draw conclusions from published research regarding the positive-negative schizophrenia concept, and to try to present the opinion of supporters and critics of the concept in a balanced way. The historical background of the concept, from Reynolds and Jackson during the last century until today, is reviewed. After giving the definitions and presenting various instruments of evaluation, the question is discussed, how stable "negative" und "positive" psychopathological constellations are. Consideration of the results of research on the long-term time course of schizophrenia, as well as in genetics, biology und psychopharmacology, leads one to conclude, on the one hand that the positive-negative concept is relevant for clinical practice and research, but on the other hand that many of the present studies were not able to confirm a clear cut positive-negative dichotomy.

Delusions↗

PubMed1991

Lack of linkage to chromosome 5q11-q13 markers in six schizophrenia pedigrees.

We examined linkage between schizophrenia and five genetic markers on chromosome 5 in six pedigrees. Analyses were run considering the affected phenotype to be schizophrenia, schizophrenia plus a spectrum of related disorders, and these disorders plus any axis I diagnosis. None of the analyses were suggestive of linkage at any of the markers, either considering the pedigrees individually or in the aggregate. In our pedigrees, multipoint linkage analyses excluded much of the region that had supported linkage in an earlier study. These findings are consistent with other attempts to replicate the chromosome 5 linkage finding.

Chromosome Mapping↗

PubMed1991

T1 and T2 relaxation times in schizophrenia as measured with magnetic resonance imaging.

T1 and T2 relaxation times were measured in ten brain regions on the right and left side in a sample of 27 schizophrenic patients and 37 normal controls. The schizophrenic patients showed a prolongation of T2 relaxation time, and to a lesser extent of T1 relaxation time, which was more predominantly localized in the right hemisphere and in gray matter structures. These results may indicate that metabolic, physiological, or neurochemical brain function in schizophrenia is related in some way to a change in tissue fluid in neuronal cell bodies or interstitial gray matter.

Adult↗

PubMed1991

MRI abnormalities in tardive dyskinesia.

Most investigators studying tardive dyskinesia (TD) hypothesize that the condition is due to a neurochemical abnormality of the striatum. Recently, numerous CT studies have been done to verify brain abnormalities in patients with TD; the findings have, however, been conflicting. The present study was designed to detect possible neuropathological abnormalities in the basal ganglia in a young sample of schizophrenic patients with TD as compared with schizophrenic patients without TD and normal controls. Magnetic resonance imaging (MRI) was used to measure the volumes of the caudate, putamen, globus pallidus, lateral ventricle, and intracranium. The volumes of the caudate nuclei of the patients with TD were significantly smaller than the volumes of the caudate nuclei of the patients without TD and normal controls. This abnormality in the caudate may be related to some previous conditions, which may prove a substrate that is necessary for TD to establish itself in association with neuroleptic use. Further studies are necessary to confirm our findings and to determine the pathophysiologic nature of these structural alterations and the role played by neuroleptics, whether primary or secondary.

Adult↗

PubMed1991

Problems with ratio and proportion measures of imaged cerebral structures.

Ratio measures, such as the ventricle-brain ratio (VBR) based on computed tomography or magnetic resonance imaging, are widely used in psychiatric research in studies of brain function and morphology. While imaging techniques have advanced considerably, the form of the index of a structure's size has remained the same--a proportion based on an estimate of the structure's size divided by a like estimate of the whole brain size. We demonstrate that ratio and similar indices can suffer greatly in reliability when compared with simple volume measures. This loss of reliability is related to the relation of a structure's size and whole brain size. We review various methods for measuring the size of structures and discuss their strengths and limitations in terms of reliability and validity. In many instances, other methods of "correcting" for brain size (e.g., regression or covariance) may yield measurements that are more appropriate than ratios.

Adult↗

PubMed1991

Diagnostic criteria for schizophrenia and related disorders: options for DSM-IV.

Five alternative sets of diagnostic criteria for schizophrenia and related psychotic disorders are presented in the appendix following this report. They include the DSM-III-R criteria, the most recent version of the ICD-10 research criteria, and three new sets that have been proposed as options for DSM-IV. A multicenter field trial is currently gathering data that will allow researchers to compare the performance characteristics of each set of criteria, including dimensions such as classification rates, reliability, and user-friendliness. In this report, the rationale behind the proposed modifications and the methods and goals of the field trials are summarized.

Affective Symptoms↗

PubMed1991

Schizophrenia: the characteristic symptoms.

The specific symptoms that have been felt to characterize schizophrenia have varied widely over time and across cultures, as has the diagnostic and prognostic importance placed on these symptoms. In this report, the historical concepts of what constitutes the "characteristic symptoms" of schizophrenia are reviewed in the context of the development of DSM-IV. Through the existing literatures as well as through previously unpublished data sets, the dimensions of reliability, specificity, validity, and descriptive value of the various signs and symptoms used to classify schizophrenia are explored. In addition, the structure of the DSM-III-R definition of schizophrenia with that of the proposed revisions of the International Classification of Diseases (ICD-10) are contrasted, demonstrating several potentially meaningful differences. It is concluded that a comprehensive description of the signs and symptoms of schizophrenia should place a strong emphasis on both positive and negative symptoms. Principles and approaches to guide the development of DSM-IV are suggested.

Humans↗

PubMed1991

Assessment issues and the cost of schizophrenia.

A variety of factors must be considered in developing assessment procedures to evaluate the cost of schizophrenia. One is the definitional problem: definitions of schizophrenia have varied over time and space, with a tendency in recent years to narrow the concept substantially. These changes in definition, which reflect the increasing scientific rigor in psychiatry, make the task of establishing base rates, assessing morbidity and mortality, and ultimately determining the cost of schizophrenia more difficult. Efforts to assess the cost of schizophrenia must also take into account the fact that its cost is not simply monetary, nor can it be conceptualized using only the cost of treatment. The overall cost of schizophrenia also includes social and psychological costs experienced by patients and family members. The concept of "the overall cost" is discussed--the sum of costs to the patient (including suffering, loss of productivity, and mortality), the cost to the family (including suffering and loss of productivity), and cost of treatment (including medications, rehabilitation services, day hospitals, inpatient facilities, etc.). At present, standardized techniques are available only for assessing some aspects of patient costs, while assessments of family and treatment costs are relatively underdeveloped. Over the long run, reduction of the overall cost of schizophrenia is most likely to come from investment in research. The most effective way to reduce the overall cost is to develop improved treatments, to identify the pathophysiology and etiology of schizophrenia, and ultimately to identify ways to prevent it from occurring.

Comprehensive Health Care↗

PubMed1991

The distinction of positive and negative symptoms. The failure of a two-dimensional model.

The distinction of positive and negative symptoms in describing schizophrenic patients has become popular. It presupposes that symptoms cluster in two dimensions, fitting together not only theoretically but empirically. Factor analysis of three published studies of 93, 62 and 52 schizophrenic patients and a large pooled sample showed that more than two distinct dimensions are required to categorise symptoms in schizophrenia. This result is consistent across methods and samples, and with previous literature. The added dimensionality resulted from a splitting of the positive symptom domain into more distinct factors.

Adult↗

PubMed1990

Developmental abnormalities of the corpus callosum in schizophrenia.

Magnetic resonance imaging was used to evaluate neuroanatomical and neuropathologic abnormalities in a consecutive series of 140 patients with schizophrenia for comparison with normal controls. Partial agenesis of the corpus callosum, a rare neurodevelopmental abnormality, was found in two patients, one of whom also had a callosal lipoma. Evidence is presented suggesting that this finding represents an increased prevalence of partial agenesis in schizophrenia. The corpus callosum develops embryologically in intimate relationship to the hippocampal formation, fornix, septum pellucidum, and cingulate gyrus. In individuals with callosal agenesis, abnormalities also occur in the development of these limbic structures. Recent neuropathologic studies have suggested the occurrence of abnormal neurogenesis in the hippocampal formation and in the cingulate gyrus in schizophrenic patients. An increased prevalence of callosal agenesis and its related limbic abnormalities would further support investigation into neurodevelopmental abnormalities of these anatomical regions in schizophrenia.

Adult↗

PubMed1990

Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities.

In a second large series of schizophrenic patients studied with magnetic resonance imaging at the University of Iowa, Iowa City, earlier findings of decreased frontal, cerebral, and cranial size were not replicated. In this second series, control subjects were selected to be educationally equivalent to the schizophrenic patients, a modification in design that may partially account for the failure to replicate. By means of coronal images, ventricular volume was compared in patients and controls and found to differ to a highly significant degree, with the frontal horns being possibly slightly more enlarged than the rest of the ventricular system. A prominent sex effect was also observed, with most of the increased ventricular size occurring in the male patients. Within the male patients, the thalamus was also observed to be significantly smaller, a finding that could be consistent with periventricular injury. Patients with prominent negative symptoms had significantly larger ventricular size than did those with the mixed or positive subtypes. Because of its superior resolution, magnetic resonance imaging appears to offer a more sensitive index of ventricular enlargement than that provided by computed tomography.

Adult↗