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Biomedical subjects

M Flaum

Publications and source records attributed to M Flaum.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Racial differences in the diagnosis of psychosis.

In clinical populations, it has been reported that African-American patients are more likely to receive a diagnosis of schizophrenia than similar Caucasian patients. Factors contributing to this racial discrepancy are poorly defined. The authors examined the hypothesis that racial differences in severity of first-rank symptoms of schizophrenia contribute to this diagnostic difference. Patients were recruited as part of the DSM-IV Field Trial for Schizophrenia and Other Psychotic Disorders, and evaluated using a structured rating instrument. Symptom and diagnostic comparisons were performed between black and white patients. Black patients were significantly more likely than white patients to be diagnosed with schizophrenia and less likely with psychotic depression. Racial differences in symptom profiles were observed with black patients demonstrating more severe psychotic symptoms, in general, and first-rank symptoms, specifically. There were no racial differences in rates of affective syndromes or severity of affective symptoms. Racial disparity in diagnosis of psychotic patients may be in part secondary to more severe first-rank symptoms in black patients, causing clinicians to stray from DSM-III-R criteria.

Adult↗

The deficit syndrome in the DSM-IV Field Trial: I. Alcohol and other drug abuse.

Drug abuse is common in schizophrenia. Previous studies suggested patients with the deficit syndrome have a lower risk of drug abuse than do patients without deficit features. We distinguished deficit and nondeficit groups in the DSM-IV Field Trial dataset, and compared the two groups relative to current and lifetime (worst ever) severity of alcohol, cannabis, and other drugs of abuse. Deficit syndrome patients had a lower severity of current use of alcohol and other drugs, but the two groups did not differ significantly relative to cannabis use. Deficit patients also had less severe lifetime use of all three classes of drugs. These findings could not be attributed to differences between the deficit and nondeficit groups in demographics, severity of psychotic symptoms, chronicity of illness, or the quality of information available for the two groups. Deficit categorization and drug abuse were independently associated with poor level of function. Negative symptoms broadly defined were weaker predictors of drug abuse than was the deficit/nondeficit categorization. These findings further support the validity of the deficit syndrome of schizophrenia. Within schizophrenia, groups with relatively high or low risk for substance abuse can be identified.

Adult↗

Soft signs and neuropsychological performance in schizophrenia.

OBJECTIVE: Both neuropsychological impairment and neurological soft signs have been documented in at least a subset of patients with schizophrenia. The purpose of the present study was to examine the relationship between soft signs and neuropsychological performance in patients with schizophrenia in order to address the issue of whether soft signs are related to global or more selective cognitive impairment. METHOD: Patients with a DSM-III-R diagnosis of schizophrenia (N=176) were given a standardized neuropsychological battery and underwent a neurological examination. The study group was dichotomized on the basis of presence or absence of neurological soft signs. RESULTS: Patients with neurological soft signs (N=68) demonstrated significantly poorer performance on neuropsychological tasks that assessed timed motor speed and motor coordination (e.g., finger tapping, the Purdue Pegboard task, and part B of the Trail Making Test). These findings continued to be significant even after lifetime medication exposure, extrapyramidal symptoms, and abnormal involuntary movements were used as covariates. CONCLUSIONS: These findings support the notion that soft signs are a manifestation of a localizable behavioral deficit of the systems that are involved in motor speed, coordination, and sequencing and are not indicative of global cognitive impairment. The specific deficit in motor abilities is consistent with the types of neurological soft signs that are most frequently reported and suggests involvement of frontal/subcortical circuitry in schizophrenia.

Adolescent↗

Suicidal behavior in schizophrenia and its relationship to awareness of illness.

OBJECTIVE: Suicidal behavior is prevalent in individuals with schizophrenia. Although a relationship between greater awareness of illness and suicidal behavior has been posited, the question has not been systematically studied. The purpose of this study was to examine the relationship between suicidal behavior and various aspects of insight in 218 patients with schizophrenia. METHOD: Patients who were participating in the DSM-IV field trial for schizophrenia were assessed with the Scale to Assess Unawareness of Mental Disorder and an instrument that was developed for the field trial study that measured multiple aspects of psychopathology, including suicidal behavior. RESULTS: The prevalence of suicidal thoughts and behavior found in this study was consistent with previous published reports. Schizophrenia patients with recurrent suicidal thoughts and behavior were generally more aware of their negative symptoms and delusions than were nonsuicidal patients. Contrary to expectations, general awareness of having a mental disorder did not predict suicidal behavior. CONCLUSIONS: The notion that insight may be associated with greater suicidality was partially supported.

Adult↗

The core symptoms of schizophrenia.

The diagnosis of schizophrenia is made on the basis of a diverse set of characteristic signs and symptoms. These include disturbances in perception and inference, abnormalities in communication, behaviour and motor activity, and deficits in emotional expressivity, hedonic capacity and drive. No single symptom or set of symptoms is pathognomonic, and the question of which symptoms are indeed at the 'core' of schizophrenia has been an issue of much debate, opinion and study since the disorder was first described a century ago. In this review, the symptoms emphasized in current diagnostic criteria for schizophrenia are described and the relative importance of these symptoms in the evolution of the schizophrenia construct is discussed.

Delusions↗

Premorbid adjustment as a predictor of phenomenological and neurobiological indices in schizophrenia.

Previous studies have demonstrated relationships between poor premorbid adjustment and a variety of phenomenological and neurobiological indices in schizophrenic patients. Using the Modified Premorbid Adjustment Scale we re-examined these relationships in a large sample (n = 131) of schizophrenic patients. Subjects were evaluated with the Comprehensive Assessment of Symptoms and History (CASH) and magnetic resonance imaging. Multiple correlation indicated that poor premorbid adjustment was significantly associated with prominence of negative symptoms, early age of onset, educational problems, chronicity, and neurological soft signs, but not with any MRI measures. These results confirm poor premorbid adjustment as an important predictor of a malignant form of schizophrenia as evidenced by an earlier age of onset, poorer educational performance, prominent negative symptoms, presence of soft signs, and chronicity of course.

Brain↗

Gray matter heterotopias in schizophrenia.

Gray matter heterotopias (GMHs) are a type of neuronal migration anomaly in which collections of normal neurons are abnormally located secondary to an arrest of radial migration. They are often manifested clinically by seizures and cognitive, motor, and language deficits. Through magnetic resonance imaging, we have observed two cases in patients presenting with symptoms of schizophrenia, but no neurological abnormalities, and otherwise normal scans. While the incidence of GMH among normal individuals is unknown, it is possible that this particular anomaly may occur in schizophrenic patients at a higher rate than in the normal population. Furthermore, neuronal migration abnormalities may be involved in the pathogenesis of the disorder among a small subset of patients with schizophrenia.

Adult↗

Symptoms of schizophrenia. Methods, meanings, and mechanisms.

BACKGROUND: 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 of which is a subdivision into positive and negative symptoms. METHODS: This study examined the positive vs negative distinction in a sample of 243 patients with schizophrenia or schizophreniform disorder who were evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. A two-stage factor analysis was applied, beginning with a principal components analysis applying varimax rotation, followed by an extension analysis. The purpose of these analyses was to evaluate the correlational relationships of the various symptoms of schizophrenia. RESULTS: The results confirmed previous reports by our group and others suggesting that the symptoms of schizophrenia fall into three natural dimensions, as assessed by the correlational interrelationships: positive symptoms subdivide into psychotic and disorganized dimensions, while a third negative dimension also emerges. CONCLUSION: Because 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.

Age of Onset↗