Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies

OBJECTIVE: Voxel-based morphometry is a method for detecting group differences in the density or volume of brain matter. The authors reviewed the literature on use of voxel-based morphometry in schizophrenia imaging research to examine the capabilities of this method for clearly identifying specific structural differences in patients with schizophrenia, compared with healthy subjects. The authors looked for consistently reported results of relative deficits in gray and white matter in schizophrenia and evaluated voxel-based morphometry methods in order to propose a future strategy for using voxel-based morphometry in schizophrenia research. METHOD: The authors reviewed all voxel-based morphometry studies of schizophrenia that were published to May 2004 (15 studies). The studies included a total of 390 patients with a diagnosis of schizophrenia and 364 healthy volunteers. RESULTS: Gray and white matter deficits in patients with schizophrenia, relative to healthy comparison subjects, were reported in a total of 50 brain regions. Deficits were reported in two of the 50 regions in more than 50% of the studies and in nine of the 50 regions in one study only. The most consistent findings were of relative deficits in the left superior temporal gyrus and the left medial temporal lobe. Use of a smaller smoothing kernel (4-8 mm) led to detection of a greater number of regions implicated in schizophrenia. CONCLUSIONS: This review implicates the left superior temporal gyrus and the left medial temporal lobe as key regions of structural difference in patients with schizophrenia, compared to healthy subjects. The diversity of regions reported in voxel-based morphometry studies is in part related to the choice of variables in the automated process, such as smoothing kernel size and linear versus affine transformation, as well as to differences in patient groups. Voxel-based morphometry can be used as an exploratory whole-brain approach to identify abnormal brain regions in schizophrenia, which should then be validated by using region-of-interest analyses.     

Predictors of treatment acceptance and completion in anorexia nervosa: implications for future study designs

CONTEXT: There have been very few randomized controlled treatment studies of anorexia nervosa. OBJECTIVE: To evaluate factors leading to nonacceptance and noncompletion of treatment for 2 specific therapies and their combination in the treatment of anorexia nervosa. DESIGN: Randomized prospective study. SETTING: Weill-Cornell Medical Center, White Plains, NY; University of Minnesota, Minneapolis; and Stanford University, Stanford, Calif.Patients One hundred twenty-two patients meeting DSM-IV criteria for anorexia nervosa. INTERVENTIONS: Treatment with cognitive-behavioral therapy, fluoxetine hydrochloride, or their combination for 1 year. MAIN OUTCOME MEASURES: Dropout rate and acceptance of treatment (defined as staying in treatment at least 5 weeks). RESULTS: Of the 122 randomized cases, 21 (17%) were withdrawn; the overall dropout rate was 46% (56/122) in the remaining patients. Treatment acceptance occurred in 89 (73%) of the 122 randomized cases. Of the 41 assigned to medication alone, acceptance occurred in 23 (56%). In the other 2 groups, acceptance rate was differentiated by high and low obsessive preoccupation scores (rates of 91% and 60%, respectively). The only predictor of treatment completion was high self-esteem, which was associated with a 51% rate of treatment acceptance. CONCLUSION: Acceptance of treatment and relatively high dropout rates pose a major problem for research in the treatment of anorexia nervosa. Differing characteristics predict dropout rates and acceptance, which need to be carefully studied before comparative treatment trials are conducted.     

Developing benchmark inventories to assess the content of telephone consultations in accident and emergency departments: use of the Delphi technique

The provision of telephone advice to members of the general public from staff based in accident and emergency departments is common practice. However, it is largely conducted on an ad hoc basis without the use of formal guidelines or decision support. The evidence base from which to derive guidelines for the telephone assessment and advice of many common conditions is lacking. This study, using the Delphi technique, was undertaken to develop a number of benchmarks for use as objective measures against which the comprehensiveness of telephone assessments could be tested. Consensus views on the essential and desirable items to be considered for each of 10 presenting complaints was achieved. It is argued that establishing consensus views on clinical topics provides an effective means of developing an evidence base where other sources of evidence are lacking.     

A prescription for the rogue doctor: part I--begin with diagnosis

Among the most serious problems a doctor can have may be those which are the result of a defect of character or a flaw in ethics. Under these circumstances, unacceptable behavior patterns may arise. Examples of unacceptable patterns of behavior include dishonesty, intentionally harming a patient, sexual harassment, and substance abuse. For years, doctors who have these patterns have been handled with kid gloves by those who educate, train, and supervise professionals in the healthcare industry. Counseling, coaching, training, supervising, transfers to less critical disciplines, disciplinary warnings, and offering opportunities to resign have been the typical protocols. Traditionally, outright firing of residents and doctors has been relatively taboo and too radical for the medical profession. Why has this been the case? Reasons may include unwillingness to get involved or to deal with the stress of disciplining a colleague, an unwillingness which often is grounded in fears of retaliation. In a litigious society, fears of slander lawsuits, for example, may be all-too-real. However, the implied paternalism and the practice of protecting doctors' careers by preserving their professional status as practicing doctors have become increasingly problematic. Aside from the fact that it is unethical, allowing problem doctors to continue to practice medicine may have an adverse impact on the well-being of patients and therefore may represent an enormous legal liability for organizations that employ them. In this first of a two-part series, problems that now exist and implementation of a performance management system as a starting point for removing rogues from the system are discussed. A subsequent paper will detail how such a system operates.     

The effect of the bovine hemoglobin oxygen therapeutic HBOC-201 on human neutrophil activation in vitro

BACKGROUND: We previously demonstrated that HBOC-201 is an efficient resuscitation fluid. However, little is known about its immunomodulatory effects. The goal of this study was to investigate human neutrophil activation after exposure to HBOC-201 and other low-volume resuscitation fluids. METHODS: Whole blood from 10 healthy volunteers was serially diluted with HBOC-201, 7.5% hypertonic saline (HTS), 7.5% hypertonic saline-6% dextran 70 (HSD), Hextend, or PentaLyte. After an incubation period, samples were analyzed for oxidative burst and CD11b expression using flow cytometry. RESULTS: Increases in both CD11b and oxidative burst activity were noted in samples diluted with HBOC-201, Hextend, PentaLyte, and lactated Ringer's solution. Samples maximally diluted with HBOC-201 demonstrated increased CD11b expression when compared with lactated Ringer's solution and Hextend (196.11% vs. 22.68% and 33.97%; p = 0.018 and p = 0.033). CONCLUSION: Although differences were noted only at the highest dilutions, further studies investigating the effects of HBOC-201 are warranted.     

A postmortem study of the mediodorsal nucleus of the thalamus in schizophrenia

Four studies have reported that the mediodorsal nucleus of the thalamus (MD) is smaller and contains fewer neurons in schizophrenia. The MD is a key node in a circuit proposed to be dysfunctional in the disorder. However, one study did not find a MD volume loss in schizophrenia, and all the studies to date are relatively small. Given the importance of establishing unequivocally the presence of MD pathology, we have carried out a study of the volume and number of neurons in the left and right MD in 21 patients with schizophrenia and 27 healthy comparison subjects. We also measured the size of MD neurons, and estimated total thalamic volume. We found no difference in the volume of the MD, the number of MD neurons, or the size of MD neurons in either hemisphere in schizophrenia. Neither was total thalamic volume altered. There are no obvious methodological or clinical factors to explain our failure to replicate the finding of MD involvement in schizophrenia. Hence our negative observations, in the largest sample yet investigated, cast doubt on the robustness and/or the generalisability of MD neuropathology in schizophrenia.