Global structural brain abnormalities in mood disorders: evidence from a meta-analysis versus a traditional review.
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Biomedical subjects
Publications and source records attributed to L Friedman.
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It has been hypothesized that a deficit in serotonin may be a crucial determinant in the pathophysiology of major depression. Serotonin-1A receptors are located on serotonin cell bodies in the midbrain dorsal raphe (DR) nucleus, and the activation of these receptors inhibits the firing of serotonin neurons and diminishes the release of this neurotransmitter in the prefrontal cortex. Repeated treatment with some antidepressant medications desensitizes serotonin-1A receptors in the rat midbrain. The present study determined whether the binding of [3H]8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotonin-1A receptors, is altered in the midbrain of suicide victims with major depression. Radiolabeling of the serotonin-1A receptor in the DR varied significantly along the rostral-to-caudal extent of the human midbrain. The binding of [3H]8-OH-DPAT to serotonin-1A receptors was increased significantly in the midbrain DR of suicide victims with major depression as compared with psychiatrically normal control subjects. In suicide victims with major depression, the increase in the binding of [3H]8-OH-DPAT to serotonin-1A receptors was detected in the entire DR and specifically localized to the dorsal and ventrolateral subnuclei. Enhanced radioligand binding of an agonist to inhibitory serotonin-1A autoreceptors in the human DR provides pharmacological evidence to support the hypothesis of diminished activity of serotonin neurons in suicide victims with major depression.
This is a study of word generation during functional MRI (fMRI). Eleven normal healthy subjects were instructed to generate words covertly, (i.e., silently) that began with particular letters. Images were acquired on a conventional 1.5T scanner at three contiguous axial planes encompassing language-related areas of the temporal and frontal lobe. The data were analyzed at the level of a Talairach box, after individually fitting the proportional Talairach grid system to each slice. The main variable of interest was the number of activated pixels within a Talairach box. Boxes with a significant increase in the proportion of activated pixels were located in three regions of the left neocortex: (1) Brodmann areas 44 and 45 in the dorsolateral frontal cortex (Broca's area), (2) areas 21 and 37 in the temporal cortex, (3) and the striate/extrastriate cortex (areas 17 & 18). The results are discussed in terms of a cognitive model of word generation and are compared, in detail, with the results of prior relevant imaging studies.
We report a case of a 32-year-old woman who presented with parosteal osteosarcoma of the distal femur with simultaneous dedifferentiation to a high-grade osteoclast-rich osteogenic sarcoma. This pattern of dedifferentiation is rare, particularly at the time of presentation. We are aware of three other somewhat comparable cases in the literature; however, none is quite similar to our case.
This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years. Many of these agents will be used by pediatricians and child psychiatrists for treatment of depression in children, and although much further research is needed, the future for alternative antidepressants and augmenting strategies is extremely promising.
Until only very recently, the occurrence of schizophrenia in childhood and early adolescence had been largely neglected. Improved diagnostic formulations have resulted in clarification of the boundaries between childhood schizophrenia, other psychotic disorders, and pervasive developmental disorder. The study of schizophrenia in childhood or adolescence provides a unique opportunity to examine illness characteristics in the absence of the confounds of substance abuse illness, chronicity, and medication effects. Additionally, current etiopathologic models of schizophrenia can be tested in this patient subgroup.
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PURPOSE: Adults have frequently been concerned about the adverse influence that music may have on teenagers. This study was designed to examine the relationship between the intensity of emotional response to music and health risk-taking behavior in adolescents. METHODS: Consecutive participants from the University of California, San Diego, Adolescent Medicine Clinics completed a written survey about music preference, emotional response to music using the Positive Affect Negative Affect Schedule (PANAS), and a variety of health-risk behaviors. For each participant, the PANAS scores were summed to give a positive, negative, and total affect score, and health-risk behaviors were assigned a point value based on the level of risk and then summed to give a risk score. RESULTS: Health-risk behavior was found to be correlated with increasing emotional response to music (r = 0.23), whether those emotions were positive (r = 0.19) or negative (r = 0.24). Strong negative emotional response to music in particular was correlated with a history of greater risk behavior, particularly among whites (risk score = 14.0). CONCLUSIONS: Our study indicates that subjects who experience strong negative emotions to music are at an increased risk of participating in a variety of risk-taking behaviors. Further evaluation of the link between emotional response to music and health-risk behaviors will be useful in clarifying the nature of this relationship.
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This article reports cross-sectional and follow-up data with actigraphic measures of nocturnal sleep and rest/activity in 61 Alzheimer's disease (AD) patients as well as the relation of actigraphic measures to levels of behavioral disturbance across different stages of the disease. Over the course of approximately 1.5 years' follow-up, patients showed significant deterioration of nocturnal sleep parameters, but no significant change in rest/activity circadian rhythm parameters. There were also significant correlations among nocturnal sleep, rest/activity circadian rhythm, and behavioral disturbance measures, but only in relatively early stages of AD. It is argued that study of nocturnal sleep and circadian rhythm in relation to behavioral disturbance in AD requires longitudinal data and analyses that take into account the stage of disease at which patients are assessed.
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The pharmacologic treatment and assessment of outcomes in adolescents with schizophrenia have been inadequately addressed. Structural brain imaging and brain function studies both point to a continuity between adolescent and adult stages of schizophrenia. Because the teenage population seems to be less tolerant of physical side effects, the advent of atypical antipsychotic medications may offer increased safety and efficacy. Studies support the notion that adolescent illness is associated with a more severe form of schizophrenia and that length of illness before treatment is correlated with long-term outcome. As a consequence, the authors recommend assertive pharmacologic intervention in adolescents with schizophrenia and future research focused on the issues of treatment and outcome in teenagers suffering a psychotic disorder.
OBJECTIVE: To compare the sensitivity of traditional motion studies, bone scintigraphy and radiocarpal arthrography to a "carpal stretch test," for evaluation of dynamic dissociative carpal instability. DESIGN: Experimental study comparing the results of the tests to the findings of arthroscopy, the "gold standard." SETTING: A university hospital-based upper extremity practice. PATIENTS: Six patients with chronic wrist pain, arthroscopically confirmed proximal row ligamentous disruption and radiographs not suggestive of proximal row instability. INTERVENTIONS: The carpal stretch test: both affected and unaffected wrists were subjected to the same testing, wherein the wrist was suspended from finger traps for 10 minutes by a 4.5-kg weight. Standardized posteroanterior radiographs were taken of the suspended wrists. MAIN OUTCOME MEASURES: Disruption of Gilula's arcs I and II, and sensitivity of the carpal stretch test compared with other investigations. MAIN RESULTS: Step deformities ranging from 2.5 to 6 mm (average 3.7 mm) were recorded in the affected wrists and 0 to 4 mm (average 1.5 mm) in the "unaffected" wrists. The test was more sensitive than traditional radiography, arthrography and scintigraphy in defining both presence and site of proximal carpal row ligamentous tears and was almost as sensitive as arthroscopy. CONCLUSION: In patients with chronic wrist pain and dynamic dissociative wrist instability, the carpal stretch test may prove to be a valuable screening tool for detecting ligamentous tears of the proximal carpal row.
BACKGROUND: Trials of drug therapy for hypertension have shown that such therapy has a clear overall benefit in preventing cardiovascular disease. Although these trials have included slightly more women than men, it is still not clear whether treatment benefit is similar for both sexes. OBJECTIVE: To quantify the average treatment effect in both sexes and to determine whether available data show significant differences in treatment effect between women and men. DESIGN: Subgroup meta-analysis of individual patient data according to sex. Analysis was based on seven trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) database and was adjusted for possible confounders. PATIENTS: 20,802 women and 19,975 men recruited between 1972 and 1990. INTERVENTIONS: Primarily beta-blockers and thiazide diuretics. RESULTS: In women, treatment effect was statistically significant for stroke (fatal strokes and all strokes) and for major cardiovascular events. In men, it was statistically significant for all categories of events (total and specific mortality, all coronary events, all strokes, and major cardiovascular events). The odds ratios for any category of event did not differ significantly between men and women. In absolute terms, the benefit in women was seen primarily for strokes; in men, treatment prevented as many coronary events as strokes. Graphical analyses suggest that these results could be completely explained by the difference in untreated risk. CONCLUSIONS: In terms of relative risk, treatment benefit did not differ between women and men. The absolute risk reduction attributable to treatment seemed to depend on untreated risk. These findings underline the need to predict accurately the untreated cardiovascular risk of an individual person in order to rationalize and individualize antihypertensive treatment.
The purpose of the present study was to evaluate the differential activation of the motor cortex during finger tapping in patients with schizophrenia using the newly available imaging method of functional magnetic resonance imaging (fMRI). Nine patients with DSMIII-R schizophrenia and 9 well-matched healthy volunteer subjects underwent fMRI examination on a conventional MR unit; activation of the primary motor cortex was evaluated during performance of a finger motion task. Localized activation of the motor cortex was observed in 17 of 18 subjects during fMRI. Patients and controls were, however, indistinguishable with respect to signal intensity or area thereof within the motor cortex. fMRI did not reveal motor cortical dysfunction in schizophrenia. Despite its infancy, fMRI holds considerable promise to advance understanding of the neurodynamics of psychiatric disorders, particularly schizophrenia.
BACKGROUND: Biological relatives of patients with schizophrenia demonstrate an increased prevalence of schizotypal personality disorder symptoms, eye tracking deficits, and attentional disturbances. We investigated whether these hypothesized components of a schizophrenia-related phenotype are associated with one another or are independent in nonpsychotic relatives of patients with schizophrenia. METHODS: Eighty-three nonpsychotic first-degree relatives of 38 patients with schizophrenia and 45 control subjects without a psychiatric diagnosis underwent clinical evaluation, eye tracking evaluation, and the Continuous Performance Test (CPT) of visual attention. RESULTS: Eye tracking qualitative rating was more powerful than quantitative eye tracking measures or CPT measures in discriminating relatives of patients with schizophrenia from control subjects. Correlations between neurocognitive variables and DSM-III-R schizotypal personality disorder symptom clusters suggested that CPT errors of omission are associated with positive schizotypal symptoms. Eye tracking measures were not significantly correlated with schizotypal symptoms or CPT errors in relatives of patients with schizophrenia. CONCLUSIONS: Eye tracking deficits in the relatives of patients with schizophrenia are unrelated to CPT deficits and schizotypal symptoms. Eye tracking deficits and disturbances in visual attention may be separate components of a schizophrenia-related phenotype and should be considered as independent factors in genetic studies of schizophrenia.