Biomedical subjects

M Flaum

Publications and source records attributed to M Flaum.

At least 55 records · Page 3Linked to original sources

PubMed1995

A longitudinal study of symptom dimensions in schizophrenia. Prediction and patterns of change.

BACKGROUND: Factor analytic studies have suggested that the symptoms of schizophrenia may be divided into three uncorrelated dimensions. This study examines the longitudinal course of the symptoms of schizophrenia using this three-dimensional perspective. METHODS: The sample was composed primarily of neuroleptic-naive patients suffering from schizophrenia. Subjects were studied in a prospective longitudinal design, with comprehensive structured assessments at index, discharge, and 6-month intervals after discharge over a 2-year period. RESULTS: Negative symptoms were already relatively prominent at the time of index evaluation; they tended to remain stable throughout the follow-up period. The two dimensions of positive symptoms, psychoticism and disorganization, although prominent at index evaluation, declined over the course of the follow-up period and tended to be less stable. A longitudinal factor analysis was conducted to determine whether the changes in symptoms followed any consistent pattern. We observed that all three groups of symptoms tended to change in unison and independently from one another. CONCLUSIONS: These results suggest that these three dimensions of psychopathology show different patterns of exacerbation and remission during the course of schizophrenia. This independent pattern of evolution suggests that these three dimensions should be studied further with respect to response to treatment, cognitive mechanisms, psychosocial correlates, and neural substrates.

Adult↗

PubMed1995

No difference found between winter- and non-winter-born schizophrenic cases.

The distinction between winter-born (WBS) and non-winter born (NWBS) schizophrenic cases has been proposed as a strategy to identify distinct etiologic subtypes within schizophrenia, the WBS subgroup being a predominantly environmental subtype. The goal of this paper is to empirically test the validity of this strategy by comparing WBS and NWBS groups on a broad array of clinical and biological variables. DSM-III-R schizophrenic, schizoaffective and schizophreniform subjects were comprehensively assessed using (i) the Comprehensive Assessment of Symptoms and History; (ii) a comprehensive neurological exam; (iii) a neuropsychological battery, including IQ and the Continuous Performance Test and (iv) an MRI scanning. The patients were divided into WBS and NWBS, using five alternative sets of definitions of winter birth. These comparisons yielded no differences between the groups on any of the 23 variables. The results suggest that the distinction between winter-born and non-winter-born cases has very limited power to identify distinct schizophrenic subtypes, and that better delineation of the correlates of environmental risk factors in schizophrenia will require a better identification of these factors.

Adult↗

PubMed1995

Abnormalities in midline attentional circuitry in schizophrenia: evidence from magnetic resonance and positron emission tomography.

The syndrome of schizophrenia presents with a complex array of symptoms that are difficult to explain at the neural level. Data collected using magnetic resonance (MR) and positron emission tomography (PET) suggest that this complex array could occur as a consequence of misconnections and mismatches in midline circuitry that is reticular-thalamic-cingulate-cortical. MR studies have shown a variety of abnormalities, including callosal agenesis, cavum septi pellucidi, decreased thalamic size, decreased frontal size, and changes in signal intensity in white matter tracts between the thalamus and the frontal cortex. PET studies using a dichotic listening paradigm suggest that patients suffering from schizophrenia have brain blood flow abnormalities consistent with a difficulty in focusing or shifting attention, which may reflect the functional substrate of the anatomic abnormalities.

Attention↗

PubMed1995

Correlational studies of the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms: an overview and update.

The interrelationships between the various symptoms of schizophrenia may be explored by examining their intercorrelations. Five different factor analytic studies, which examine these interrelationships, are summarized. Three major factors emerge consistently: psychotic, disorganized, and negative. These three factors appear to represent three dimensions of the psychopathology of schizophrenia.

Factor Analysis, Statistical↗

PubMed1995

Brain morphology in first-episode schizophrenia.

OBJECTIVE: Neuroimaging studies have provided robust evidence that schizophrenia is associated with structural brain abnormalities. However, the underlying pathophysiology of these changes is still unknown. By evaluating brain morphology early in the course of illness, confounding effects of treatment and duration of illness are minimized. The goal of this study was to evaluate brain structure in patients early in the course of schizophrenia who had received no or minimal neuroleptics. METHOD: Magnetic resonance imaging was used to evaluate 12 male and 12 female patients experiencing their first episode of schizophrenia (mean duration of psychotic episode = 14 weeks) and 12 male and 12 female normal volunteers equivalent in age, height, and parents' socioeconomic status. A totally automated method was used to analyze scans, yielding volumes of brain tissue and CSF, divided into lobes. RESULTS: The patient group had significantly more total CSF than the comparison subjects. This was accounted for by higher levels of intersulcal CSF as well as ventricular CSF. There were no differences in total volume of brain tissue between the two groups, but patients had a significant regionally specific decrement in frontal lobe tissue compared with the normal subjects. CONCLUSIONS: These findings indicate that structural brain abnormalities are present very early in schizophrenia and may not be due to factors such as treatment or chronicity of illness. Rather, since the abnormalities are present near the onset of the illness, a neurodevelopmental mechanism may be suggested.

Adult↗

PubMed1995

Neurological soft signs in neuroleptic-naive and neuroleptic-treated schizophrenic patients and in normal comparison subjects.

OBJECTIVE: The goal of this study was to assess neurological soft signs and developmental reflexes in schizophrenic patients who had never received neuroleptic medication and those who were receiving neuroleptic medication. METHOD: Neurological soft signs and developmental reflexes were examined in 26 schizophrenic patients who had never received a neuroleptic, 126 schizophrenic patients who were currently receiving neuroleptics, and 117 normal subjects. RESULTS: Soft signs were present in 23% of the neuroleptic-naive and 46% of the medicated schizophrenic patients. Developmental reflexes were present in 19% of the neuroleptic-naive and 12% of the medicated patients. Both soft signs and developmental reflexes were absent in the normal subjects. There were significant differences between patients and normal subjects in neurological soft signs and developmental reflexes. The possibly confounding variables of age, age at onset, duration of illness, number of hospitalizations, Abnormal Involuntary Movement Scale (AIMS) scores, and Simpson-Angus Scale extrapyramidal symptom scores were assessed by using logistic regression in the patients who were receiving neuroleptics. AIMS scores and Simpson-Angus Scale scores correlated with soft signs in these patients. CONCLUSIONS: The presence of neurological soft signs in schizophrenic patients who had never received neuroleptics indicates that these signs are present independent of medication effects, but it is possible that neuroleptics contribute to the prevalence of these abnormalities, as demonstrated by the patients who were receiving neuroleptics.

Adult↗

PubMed1995

Spurious precision: procedural validity of diagnostic assessment in psychotic disorders.

OBJECTIVE: Very few studies have quantified the level of agreement among alternative diagnostic procedures that use a common set of fixed operational criteria. The authors examined the procedural validity of four independent methods of assigning DSM-III-R diagnoses of psychotic disorders. METHOD: The research was conducted as a satellite study to the DSM-IV Field Trial for Schizophrenia and Related Psychotic Disorders. The setting was the National Health and Medical Research Council Schizophrenia Research Unit's Early Psychosis Prevention and Intervention Centre, which focuses on first-episode psychosis. Consecutively admitted patients (N = 50) were assessed by independent raters who used four different procedures to determine a DSM-III-R diagnosis. These procedures were 1) the diagnostic instrument developed for the DSM-IV field trial, 2) the Royal Park Multidiagnostic Instrument for Psychosis, 3) the Munich Diagnostic Checklists, and 4) a consensus DSM-III-R diagnosis assigned by a team of clinician researchers who were expert in the use of diagnostic criteria. RESULTS: Concordance between pairs of diagnostic procedures was only moderate. Corresponding levels of percent agreement, however, ranged from 66% to 76%, with converse misclassification rates of 24%-34% (assuming one procedure to be "correct"). CONCLUSIONS: These findings have significant research and clinical implications. Despite the introduction of operationally defined diagnoses, there remained an appreciable level of differential classification or misclassification arising from variability in the method of assigning the diagnostic criteria rather than the criteria themselves. Such misclassification may impede neurobiological research and have harmful clinical effects on patients with first-episode psychosis.

Adolescent↗

PubMed1995

Effects of diagnosis, laterality, and gender on brain morphology in schizophrenia.

OBJECTIVE: Structural neuroimaging and neuropathological studies have demonstrated a variety of aspects of brain morphology that appear to distinguish schizophrenic patients from comparison subjects (diagnostic effects), a predominance of left-sided pathology (laterality effects), and a greater likelihood of brain abnormality among males (gender effects). However, findings have been inconsistent across studies, perhaps reflecting limited power due to small study group sizes. The goal of this study was to examine diagnostic, laterality, and gender effects of brain morphology as assessed by magnetic resonance imaging in a large, carefully evaluated group of schizophrenic and comparison subjects. METHOD: One hundred two patients with schizophrenia (DSM-III-R) (70 men and 32 women) and 87 normal comparison subjects, chosen to be equivalent to the patients in terms of familial socioeconomic background, underwent magnetic resonance imaging with a 1.5-tesla scanner. All regions of interest were outlined manually by an experienced technician on all slices in which they were visualized. Region of interest volumes were compared across groups, and age, sex, and stature were controlled. RESULTS: Schizophrenic patients were found to have larger lateral and third ventricles and smaller thalamic, hippocampal, and superior temporal volumes than comparison subjects. No significant differences were demonstrated for intracranial, cerebral, cerebellar, temporal lobe, caudate nuclei, or temporal horn volumes. There were no significant Laterality by Diagnosis effects and no significant Gender by Diagnosis effects for any of the regions of interest. CONCLUSIONS: Many, but not all, of the hypotheses informed by earlier studies regarding diagnostic effects were confirmed, while hypotheses regarding gender and laterality interactions with diagnosis were not supported.

Adult↗

PubMed1994

Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging.

OBJECTIVE: To determine general and regional indices of structural brain abnormality in schizophrenia. DESIGN: Case-control comparison study. SUBJECTS: Fifty-two patients diagnosed as having schizophrenia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, were compared with 90 healthy volunteers recruited from the community. MEASUREMENTS: Structural brain images were acquired using magnetic resonance; measurements were obtained using three-dimensional visualization of volume-rendered brains and an automated atlas-based dissection of specific regions. General measures included the volume of total brain tissue, total cerebrospinal fluid (CSF), and CSF within the ventricular system. Regional measures included the volume of tissue and CSF in the frontal, temporal, parietal, and occipital lobes and the cerebellum. RESULTS: Compared with the controls, the patients had a smaller average volume of total brain tissue and a greater average volume of total and ventricular CSF. A specific relative decrease in brain tissue was found only in the frontal lobes, although the volume of CSF was greater in patients than in controls in all brain regions. CONCLUSION: In addition to the generalized brain abnormalities observed in schizophrenia, a regional abnormality may be present in frontal regions. Since the frontal lobes integrate multimodality information and perform a variety of "higher" cognitive and emotional functions that are impaired in schizophrenia, the frontal abnormality noted is consistent with the clinical presentation of the illness. Impaired frontal function and a disruption in its complex circuitry (including thalamocortical projections) may explain why patients with schizophrenia often have significant deficits in formulating concepts and organizing their thinking and behavior.

Adult↗

PubMed1994

Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging.

Schizophrenia is a complex illness characterized by multiple types of symptoms involving many aspects of cognition and emotion. Most efforts to identify its underlying neural substrates have focused on a strategy that relates a single symptom to a single brain region. An alternative hypothesis, that the variety of symptoms could be explained by a lesion in midline neural circuits mediating attention and information processing, is explored. Magnetic resonance images from patients and controls were transformed with a "bounding box" to produce an "average schizophrenic brain" and an "average normal brain." After image subtraction of the two averages, the areas of difference were displayed as an effect size map. Specific regional abnormalities were observed in the thalamus and adjacent white matter. An abnormality in the thalamus and related circuitry explains the diverse symptoms of schizophrenia parsimoniously because they could all result from a defect in filtering or gating sensory input, which is one of the primary functions of the thalamus in the human brain.

Brain↗

PubMed1994

Techniques for measuring sulcal/gyral patterns in the brain as visualized through magnetic resonance scanning: BRAINPLOT and BRAINMAP.

A method for measuring sulcal and gyral patterns, using data derived from magnetic resonance (MR) scanning, is described. This method can be applied through two newly developed computer programs, BRAINPLOT and BRAINMAP. These programs provide quantitative measures of brain surface pattern. The method has been validated with postmortem brains, phantoms, and human MR data. The method is robust to detecting differences in brain surface anatomy between atrophic and nonatrophic brains. It appears to offer an efficient, fully automated, and accurate method for analyzing the large amounts of information generated through in vivo neuroimaging techniques.

Autopsy↗

PubMed1994

Awareness of illness in schizophrenia and schizoaffective and mood disorders.

BACKGROUND: The literature on insight, or self-awareness, in schizophrenia suggests that this cognitive dimension may be of nosological value. Poor insight has descriptive validity at the phenomenological and neuropsychological levels of schizophrenia and has prognostic validity in terms of the prediction of the course of illness. The lack of empirical data on the diagnostic specificity of poor insight to schizophrenia and the previous use of insight measures with questionable reliability and validity have limited this interpretation. METHODS: In the present study, we assessed insight into multiple aspects of mental disorder using a measure with demonstrated reliability and validity. A sample of 412 patients with psychotic and mood disorders coming from geographically diverse regions of the United States and one international site was studied. The main aims were to determine the prevalence of self-awareness deficits in patients in whom schizophrenia was diagnosed, to examine the relative severity of self-awareness deficits associated with schizophrenia compared with that of schizoaffective and mood disorders with and without psychosis, and to evaluate the clinical correlates of self-awareness in patients with schizophrenia. RESULTS: The results indicated that poor insight is a prevalent feature of schizophrenia. A variety of self-awareness deficits are more severe and pervasive in patients with schizophrenia than in patients with schizoaffective or major depressive disorders with or without psychosis and are associated with poorer psychosocial functioning. CONCLUSIONS: The results suggest that severe self-awareness deficits are a prevalent feature of schizophrenia, perhaps stemming from the neuropsychological dysfunction associated with the disorder, and are more common in schizophrenia than in other psychotic disorders.

Adaptation, Psychological↗

PubMed1994

IQ and brain size in schizophrenia.

In a previous study of normal control subjects, positive correlations were demonstrated between intelligence, as measured by the Wechsler Adult Intelligence Scale-Revised, and various measures of brain size, as assessed by magnetic resonance imaging (Andreasen et al., 1993). The goal of this study was to see if these findings generalized to schizophrenia. Corresponding analyses were performed in a group of DSM-III-R schizophrenic patients (50 men and 22 women) and compared with a subset of those normal control subjects (32 men and 27 women) who were equivalent to the patient group in their age and the educational and socioeconomic background of their families of origin. Full Scale IQ score was found to be uncorrelated with any of the regions of interest for the patient group as a whole. When subjects were divided by sex, the female patients were found to have a pattern of correlations similar to that of normal control subjects, while no such relationship was apparent among the male patients. These differences did not appear to be attributable to variability in symptom severity. Thus, there appear to be gender-related differences in brain structure/function relationships in schizophrenic patients versus normal control subjects.

Adult↗

PubMed1994

Stability of cognitive functioning early in the course of schizophrenia.

This study evaluated the longitudinal course of neuropsychological deficits in a group of patients with new or recent onset schizophrenia. Thirty-five inpatients with DSM-III-R diagnoses of schizophrenia were administered a comprehensive battery of neuropsychological tests during their index hospitalization, and either 1 or 2 years after intake. Cognitive function remained stable in most domains, including motor speed, verbal and nonverbal memory, and verbal learning. Significant improvement in neuropsychological performance was observed on a task of complex attention (Trails B) and a set response shifting task (Stroop). These improvements were correlated with changes in clinical symptoms, but not with changes in medication dose. These findings suggest that most of the neuropsychological functioning in schizophrenia is stable over the first few years of the illness. Moreover, those neuropsychological deficits that remain unchanging appear to be independent of significant change in clinical symptoms, suggesting they may be a trait of the illness. However, a small subset of functions such as complex attention and response inhibition appear to fluctuate with time, and in particular, with clinical symptomatology, and may be considered 'state' dependent.

Adult↗

PubMed1994

Substance abuse in psychotic disorders: associations with affective syndromes. DSM-IV Field Trial Work Group.

In a sample of 412 patients with psychotic disorders, the authors examined whether comorbid substance use can be reliably diagnosed, is associated with increased rates of affective symptoms and syndromes and specific psychotic symptoms, and is associated with lowered reliability of the DSM-III-R principal diagnosis. Data from the DSM-IV Field Trial for Schizophrenia and Other Psychotic Disorders was analyzed. In this dataset, substance use was scored on a 4-point ordinal scale and reliability was determined using weighted kappa scores. The associations of significant substance use with affective syndromes and symptoms, and psychotic symptoms were analyzed. Kappa statistics were calculated for principal psychotic disorder diagnoses for patients with and without significant substance use. Weighted kappa scores for substance use ratings ranged from 0.27 to 0.96 (median = 0.85). Syndromal depression was significantly associated with current alcohol use in the entire sample and in the subgroup with schizophrenia alone. Grandiose delusions were also associated with substance use. Significant comorbid substance use was not associated with lowered reliability of diagnosing the principal psychotic disorder. These findings support the hypothesis that comorbid substance abuse can be reliably diagnosed and that alcohol abuse is associated with depressive syndromes in patients with psychotic disorders.

Adult↗

PubMed1994

Further evidence for olfactory identification deficits in schizophrenia.

Forty-seven schizophrenic patients and 36 normal controls, matched for smoking history, were administered the University of Pennsylvania Smell Identification Test (UPSIT) and the Picture Identification Test (PIT). Amongst subjects successfully completing the PIT, non-smoking schizophrenic patients had significantly lower UPSIT scores than non-smoking controls. Smoking history and diagnosis did not interact to produce any pronounced effect. No significant gender difference was found. These results suggest schizophrenics display decreased olfactory identification even if likely confounders are adequately controlled.

Adolescent↗

PubMed1994

Effect of antipsychotic withdrawal on negative symptoms in schizophrenia.

Although it is generally accepted that antipsychotic treatment improves the negative symptoms of schizophrenia in the context of improvement of positive symptoms, exactly how and to what extent they effect "primary" negative symptoms remains controversial. Antipsychotic treatment may reduce only those negative symptoms secondary to positive or depressive symptoms, and may have minimal, if any effect, on negative symptoms that represent a primary psychopathological trait manifestation of schizophrenia. In an effort to further examine this issue, we prospectively assessed negative, positive, depressive, and extrapyramidal symptoms following the discontinuation of antipsychotic medication. Fifty-nine DSM III-R schizophrenic patients underwent a three-week drug wash as part of our neuroimaging protocols. We assessed psychopathological status and adverse effects utilizing various rating instruments (i.e., Scale for Assessment of Positive Symptoms [SAPS], Scale for Assessment of Negative Symptoms [SANS], Hamilton Rating Scale for Depression, and Simpson-Angus Extrapyramidal) at baseline and weekly during this three-week period. Negative symptoms, as measured by the SANS, worsened significantly during the three-week drug wash. Positive symptoms showed a less consistent change with symptoms of disorganization worsening and with psychotic symptoms remaining the same. The changes in negative symptoms during the drug-free period were correlated with the changes in psychosis and disorganization, but not with changes in depression or extrapyramidal side effects. We were not able to substantiate if the worsening in negative symptoms was a direct result of the worsening of positive symptoms or if they were changing simultaneously, but independent of each other.

Adult↗

PubMed1994

Positive and negative symptoms of schizophrenia: past, present, and future.

The "group of schizophrenias," normally referred to with a single nominative, is phenomenologically heterogeneous. Its symptoms represent multiple psychological domains, including perception, inferential thinking, language, attention, social interaction, emotion expression, and volition. Studies of psychopathology have simplified this complex array in several ways; one has been a subdivision into positive and negative symptoms. Reports by our group and others suggest that the symptoms of schizophrenia fall into three natural dimensions: positive symptoms subdivided into psychotic and disorganized dimensions, while a third negative dimension also emerges. Since these dimensions have impressive consistency across studies, future work must examine their relationship to clinically relevant concepts such as prognosis or etiology and examine four different aspects: longitudinal course, neural mechanisms, relationship to treatment, and interrelationships in other pathological conditions.

Brain↗