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Biomedical subjects

M Flaum

Publications and source records attributed to M Flaum.

At least 19 recordsLinked to original sources
PubMed1999

Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms.

All research on schizophrenia depends on selecting the correct phenotype to define the sample to be studied. Definition of the phenotype is complicated by the fact that there are no objective markers for the disorder. Further, the symptoms are diverse, leading some to propose that the disorder is heterogeneous and not a single disorder or syndrome. This article explores an alternative possibility. It proposes that schizophrenia may be a single disorder linked by a common pathophysiology (a neurodevelopmental mechanism), which leads to a misconnection syndrome of neural circuitry. Evidence for disruption in a specific circuit is explored: the cortical-thalamic-cerebellar-cortical circuit (CCTCC). It is suggested that a disruption in this circuit leads to an impairment in synchrony, or the smooth coordination of mental processes. When synchrony is impaired, the patient suffers from a cognitive dysmetria, and the impairment in this basic cognitive process defines the phenotype of schizophrenia and produces its diversity of symptoms.

Brain Mapping↗
PubMed1999

Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia.

BACKGROUND: In this study, we examined whether brain morphology assessed early in the course of schizophrenia predicted psychosocial or symptomatic outcome. METHODS: We acquired magnetic resonance images on 63 subjects with schizophrenia spectrum disorders and manually traced regions of interest, including the cerebrum, temporal lobes, ventricles, and cerebellum. Subjects were then prospectively assessed every 6 months for an average of 7 years. Outcome symptom measures were longitudinal rather than cross-sectional, and included average number of weeks per year spent in a psychotic negative, or disorganized symptom syndrome, and average number of weeks of inpatient treatment per year. A psychosocial outcome measure summed ratings of impairment in employment, recreation, sexual activity, and interpersonal relationships. RESULTS: Negative associations were found between cerebellar volume and three outcome measures: negative and psychotic symptom duration, and psychosocial impairment. CONCLUSIONS: These results underscore the potential role of cerebellar abnormalities in the etiology and pathophysiology of schizophrenia.

Adult↗
PubMed1999

Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging.

Clinical observation suggests that the aging process affects gyrification, with the brain appearing more 'atrophic' with increasing age. Empirical studies of tissue type indicate that gray matter volume decreases with age while cerebrospinal fluid increases. Quantitative changes in cortical surface characteristics such as sulcal and gyral shape have not been measured, however, due to difficulties in developing a method that separates abutting gyral crowns and opens up the sulci -- the 'problem of buried cortex'. We describe a quantitative method for measuring brain surface characteristics that is reliable and valid. This method is used to define the gyral and sulcal characteristics of atrophic and non-atrophic brains and to examine changes that occur with aging in a sample of 148 normal individuals from a broad age range. The shape of gyri and sulci change significantly over time, with the gyri becoming more sharply and steeply curved, while the sulci become more flattened and less curved. Cortical thickness also decreases over time. Cortical thinning progresses more rapidly in males than in females. The progression of these changes appears to be relatively stable during midlife and to begin to progress some time during the fourth decade. Measurements of sulcal and gyral shape may be useful in studying the mechanisms of both neurodevelopmental and neurodegenerative changes that occur during brain maturation and aging.

Adolescent↗
PubMed1999

Prevalence of depressive symptoms early in the course of schizophrenia.

OBJECTIVE: The rate of depressive symptoms early in the course of schizophrenia was determined. METHOD: Seventy subjects with recent-onset schizophrenia were followed for 5 years by using semistructured interview instruments. The initial assessment included ratings of each criterion A symptom of a DSM-III-R major depressive episode. The rates of symptoms experienced with at least moderate severity were calculated, and an algorithm based on DSM identified subjects meeting the criteria for a major depressive episode. RESULTS: Four symptoms were present to at least a moderate degree in a majority of subjects, while no symptom was present in fewer than 12% of subjects. More than one-third of the subjects met the algorithmic criteria for a major depressive episode at the time of intake. CONCLUSIONS: Depressive symptoms are common early in the course of schizophrenia. This finding is consistent with other recent data and has potential implications for current diagnostic and treatment practices.

Adult↗
PubMed1998

Morphometry in schizophrenia revisited: height and its relationship to pre-morbid function.

BACKGROUND: Morphometry, the measurement of forms, is an ancient practice. In particular, schizophrenic somatology was popular early in this century, but has been essentially absent from the literature for over 30 years. More recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of schizophrenia. Is the body, like the brain, affected by abnormal development in these patients? METHODS: To evaluate global deficit in development and its relationship to pre-morbid function, height was compared in a large group (N = 226) of male schizophrenics and a group of healthy male controls (N = 142) equivalent in parental socio-economic status. Patients in the lower quartile of height were compared to those in the upper quartile of height. RESULTS: The patient group had a mean height of 177.1 cm, which was significantly shorter than the mean height of the control group of 179.4 (P < 0.003). Those in the lower quartile had significantly poorer pre-morbid function as measured by: (1) psychosocial adjustment using the pre-morbid adjustment scales for childhood and adolescence/young adulthood, and (2) cognitive function using measures of school performance such as grades and need for special education. In addition, these measures of pre-morbid function correlated significantly with height when analysed using the entire sample. CONCLUSIONS: These findings provide further support to the idea that abnormal development may play a key role in the pathophysiology of schizophrenia. Furthermore, this is manifested as a global deficit in growth and function resulting in smaller stature, poorer social skills, and deficits in cognitive abilities.

Adolescent↗
PubMed1998

Two-year outcome in first-episode schizophrenia: predictive value of symptoms for quality of life.

OBJECTIVE: Many studies have validated the grouping of schizophrenic symptoms into three independent dimensions: negative, psychotic, and disorganized. Negative symptoms are considered to be an important prognostic indicator, but this clinical observation requires further empirical study, especially with respect to psychosocial functioning. When present at the onset of the first episode, negative symptoms suggest that the patient will develop significant psychosocial impairment. The predictive values of the psychotic and disorganized symptom dimensions, on the other hand, have been less certain. METHOD: In this study of 50 first-episode schizophrenic patients, who were mostly neuroleptic-naive at intake, the authors examined the relationship between the severity of these three symptom dimensions (measured by using the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms) at index hospitalization and quality of life at 2-year follow-up. RESULTS: Negative symptom severity was positively and significantly correlated with later occupational impairment, financial dependence on others, impaired relationships with friends, impaired ability to enjoy recreational activities, and global assessment of functioning. The magnitudes of correlation between the levels of psychotic symptoms or disorganized symptoms and 2-year quality of life measures were comparatively lower. Analyses using multivariate regression statistics also revealed similar findings. CONCLUSIONS: Severity of negative symptoms at index hospitalization may be a portent of poor outcome. In general, severity of psychotic or disorganized symptoms at intake does not appear to predict subsequent quality of life.

Adult↗
PubMed1998

Functional MRI statistical software packages: a comparative analysis.

Currently, there are many choices of software packages for the analysis of fMRI data, each offering many options. Since no one package can meet the needs of all fMRI laboratories, it is helpful to know what each package offers. Several software programs were evaluated for comparison of their documentation, ease of learning and use, referencing, data input steps required, types of statistical methods offered, and output choices. The functionality of each package was detailed and discussed. AFNI 2.01, SPM96, Stimulate 5.0, MEDIMAX 2.01, and FIT were tested. FIASCO, Yale, and MEDx 2.0 were described but not tested. A description of each package is provided.

Algorithms↗
PubMed1997

A method to determine activation thresholds in fMRI paradigms.

Determining meaningful activation thresholds in functional magnetic resonance imaging (fMRI) paradigms is complicated by several factors. These include the time-series nature of the data, the influence of physiological rhythms (e.g. respiration) and vacillations introduced by the experimental design (e.g. cueing). We present an empirical threshold for each subject and each fMRI experiment that takes these factors into account. The method requires an additional fMRI data set as similar to the experimental paradigm as possible without dichotomously varying the experimental task of interest. A letter fluency task was used to illustrate this method. This technique differs from classical methods since the Pearson correlation probability values tabulated from statistical theory are not used. Rather each subject defines his or her own set of threshold probability values for correlations. It is against these empirical thresholds, not Pearson's, that an experimental fMRI correlation is assessed.

Adult↗
PubMed1997

Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naïve patients.

BACKGROUND: There have been reports that patients with schizophrenia have decreased metabolic activity in prefrontal cortex. However, findings have been confounded by medication effects, chronic illness, and difficulties of measurement. We aimed to address these problems by examination of cerebral blood flow with positron emission tomography (PET). METHODS: We studied 17 neuroleptic-naïve patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level. FINDINGS: An initial omnibus test with a randomisation analysis indicated that patients differed from normal controls at the 0.06 level. In the follow-up analysis, three separate prefrontal regions had decreased perfusion (lateral, orbital, medial), as well as regions in inferior temporal and parietal cortex that are known to be anatomically connected. Regions with increased perfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and subcortical circuits. INTERPRETATION: These distributed dysfunctional circuits may form the neural basis of schizophrenia through cognitive impairment of the brain, which prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as hallucinations, delusions, and loss of volition.

Adult↗
PubMed1997

Cavum septi pellucidi in normals and patients with schizophrenia as detected by magnetic resonance imaging.

Cavum septi pellucidi (CSP) is a cavity between the two leaflets of the septum pellucidum. CSP is a developmental anomaly, yet the pathologic implications, if any, of an abnormally large CSP remain unclear. The reported incidence of CSP among normal populations varies greatly from 0.15% to 85%. Several studies have suggested that there is a higher incidence of CSP in patients with schizophrenia. We conducted a thin-slice magnetic resonance imaging study to evaluate the prevalence of CSP in a sample of 75 controls and 55 patients. There was a high incidence of small CSP among both groups: 58.8% in the controls and 58.2% in the patients, suggesting that a small cavum could be considered a normal variant; however, the patient group had significantly higher incidence of large CSP (20.7%) compared to the normal group (3%). The patients with large CSP were all male.

Adult↗
PubMed1997

The Iowa Longitudinal Study of Recent Onset Psychosis: one-year follow-up of first episode patients.

The natural history of schizophrenia remains unclear. One strategy to further inform this area is to prospectively evaluate individuals early in the course of the disorder, both in terms of symptomatic and psychosocial/occupational functioning. Subjects were recruited into the study if they were in the midst of their first psychiatric hospitalization for a non-'organic' psychotic disorder. Subjects were extensively evaluated at index with semi-structured interviews including the Comprehensive Assessment of Symptoms and History (CASH), and followed at 6-month intervals. Data are presented on 35 subjects who were followed through 1 year. There was a significant improvement in overall symptomatology during index hospitalization, but this was accounted for primarily by improvement of positive symptoms, with negative symptoms remaining prominent. No further improvement was noted between discharge and 1-year follow-up in any of the symptom measures. Employment, interpersonal relationships, and sexual activity remained markedly impaired throughout the follow-up period. These data demonstrate that; (1) negative symptoms are prominent and stable early in the course of the disorder; (2) symptom severity at discharge from index hospitalization is predictive of symptom severity at 1 year; and (3) despite substantial overall symptomatic improvement during the first hospitalization, psychosocial and occupational functioning were found to be markedly impaired at 1-year follow-up.

Adult↗
PubMed1997

The life course of schizophrenia: age and symptom dimensions.

The life course of schizophrenia has eluded description for several reasons, including fluctuations in diagnostic criteria over the past century, and dramatic changes in treatment and expectations of the mentally ill. This study compared symptoms within a group of patients spanning ages 14 through 73. The three symptom dimensions (psychotic, disorganized and negative) were examined separately in relation to age. Using a multivariate analysis, the effects of age, sex and institutional status were found to have main effects for symptom severity with no interaction effects. The effect of age was significant in the negative direction for positive and disorganized symptoms. Age was specifically associated with decreased hallucinations, delusions, bizarre behavior and inappropriate affect. There was no age effect for formal thought disorder, nor was there an age effect for negative symptoms. Institutionalization was associated with greater symptom severity in all dimensions. Male gender was associated with greater severity of negative symptoms. We conclude that psychotic and disorganized symptoms are likely to be of lesser severity in older patients with schizophrenia, while negative symptoms tend to persist. Clinically, these findings suggest that medications targeting negative symptoms may confer the greatest benefit in treating the older patient with schizophrenia.

Adolescent↗
PubMed1997

Sex differences in brain morphology in schizophrenia.

OBJECTIVE: The current literature on sex differences in schizophrenia with regard to structural brain abnormalities is inconsistent. Several studies have suggested that male and female patients may differ in severity of brain abnormalities. Efforts to explore this issue have been hindered by small study groups, unbalanced groups (i.e., those with many more men than women), or both. The relatively smaller number of female schizophrenic patients in most studies may have made it more difficult to detect differences between patients and comparison subjects. This study was designed to evaluate brain morphology in a carefully selected group of patients with schizophrenia and healthy comparison subjects who were balanced by sex. METHOD: Eighty patients (40 male and 40 female) and 80 healthy volunteers matched by sex and age were studied. Magnetic resonance imaging scans were analyzed with the use of an automated method that yields volumes of major brain regions. RESULTS: There was a significant sex-by-diagnosis interaction for ventricular volume, with male patients having significantly larger ventricles than male comparison subjects but female patients showing no significant enlargement in comparison with healthy female subjects. Although the overall distribution of structural brain differences was very similar in the male and female patients, the male patients had a greater number of significant abnormalities than the female patients. CONCLUSIONS: These findings indicate that male and female patients with schizophrenia have the same pattern of structural brain abnormalities, but male patients appear to manifest greater severity, especially with regard to ventricular enlargement.

Adult↗
PubMed1997

Dependence on public financial support early in the course of schizophrenia.

Although most patients with schizophrenia rely on public financial support, little is known about how soon after the onset of illness such dependence occurs. Forty-eight patients with schizophrenia were followed for a mean of five years after their first hospitalization to examine their reliance on public support. At one year after their first hospitalization, 27 subjects (56 percent) were primarily supported by social service agencies. Once such support was initiated, it was maintained throughout the entire follow-up period for all patients except two. The findings indicate that dependence on public financial assistance begins very early in the course of illness for most hospitalized patients with schizophrenia.

Adult↗
PubMed1996

Making sense of schizophrenia.

The syndrome affects 1% of the population, and is probably not a single disease. Clinical observation has identified symptom "dimensions," perhaps related to differing pathophysiologic processes. Meanwhile, pharmacologic investigation implies that schizophrenia cannot be pinned to any single neurotransmitter system. Techniques of brain imaging are now providing glimpses of cognitive dysfunction.

Brain↗