Marc Pelletier

Cognitive and clinical moderators of recognition memory in schizophrenia: a meta-analysis

Recognition memory performance in schizophrenia has been shown to vary greatly across studies. To identify the conditions under which recognition memory is significantly impaired, we used a meta-analytic strategy to quantify the moderating effects of several cognitive and clinical variables. Eighty-four studies (from 1965 to July 2003) provided recognition memory data for both a schizophrenia and control group. The overall group comparison for recognition memory yielded a significant mean weighted effect size of d=0.76. Material specificity was the most significant cognitive variable found, with patients exhibiting greater impairment for figural than verbal recognition. A yes-no recognition format and auditory encoding also led to significantly greater effect sizes for recognition memory relative to forced-choice recognition tests and visual encoding, respectively. Furthermore, the effect size for recognition memory as measured by false alarm was smaller than the effect size as measured by hit rate or by d-prime and its related measures. Among clinical variables that were associated with higher effect sizes, chronicity was the most significant, but different trends linking poor performance to negative symptoms and general symptomatology were also observed. Thus, a recognition memory deficit moderated by both cognitive and clinical variables is clearly present in schizophrenia.

Angiogenesis and growth factor expression in a model of transmyocardial revascularization.

BACKGROUND The mechanism by which transmyocardial revascularization (TMR) exerts a beneficial effect remains unknown. We hypothesize that the myocardial punctures of TMR cause a myocardial injury, leading to an angiogenic response mediated by a number of growth factors. METHODS Fifty-three rats underwent ligation of the left coronary artery. Group I (n = 25) served as controls, whereas group II (n = 28) underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic zone. Surviving animals in both groups were sacrificed at intervals of 1, 2, 4, and 8 weeks (n = 5 in each subgroup). Immunohistochemistry in the infarct areas was performed for factor VIII to assess vascular density. Immunohistochemistry using specific antibodies was also performed for transforming growth factor-beta, basic-fibroblast growth factor, and vasoendothelial growth factor. Growth factor expression was quantitated by comparing areas of staining (in mm2) with computerized morphometric analysis. RESULTS Mortality was similar in both groups (5/25 versus 8/28; not significant). Group II had significantly greater vascular density than group I (5.65 versus 4.06 vessels/high-power field; p < 0.001), with a peak at 1 week postoperatively (9.12 versus 5.56 vessels/high-power field; p < 0.0001) in both groups. Overall, levels of both transforming growth factor-beta and basic-fibroblast growth factor were significantly higher in the TMR group compared with the control group (0.207 versus 0.141 mm2/mm2, p < 0.05; and 0.125 versus 0.099 mm2/ mm2, p < 0.05). CONCLUSIONS This model of TMR is associated with a significant angiogenic response, which appears to be mediated by the release of certain angiogenic growth factors such as transforming growth factor-beta and basic-fibroblast growth factor. With the long-term patency of laser-created myocardial channels in clinical TMR increasingly in doubt, its mechanism of myocardial revascularization may be similar to that observed in our model.

Episodic memory impairment in Huntington's disease : A meta-analysis

Memory dysfunction is an important feature in the clinical presentation of Huntingtons disease (HD) and may precede the onset of motor symptoms. Although several studies have contributed to the quantitative and qualitative description of memory impairments in HD, the characterization of episodic memory impairments has varied considerably. Whereas most studies report significant impairments on free recall tests, performance on recognition tests has been considerably more variable, ranging from normal to markedly deficient. This absence of a well-established recognition memory deficit has led some investigators to attribute the memory deficits in HD to a retrieval-based episodic memory impairment. We felt that a quantitative review of the literature was needed to better characterize these episodic memory impairments. We conducted a meta-analysis to assess the magnitude of the recognition memory deficit in HD and to examine it in relation to the known deficit in recall. Memory data were provided by 544 symptomatic HD patients, 224 presymptomatic gene-carriers, and 963 control subjects. The overall group comparison between symptomatic patients and controls yielded effect sizes of d=1.95 for free recall and d=1.73 for recognition. We split the symptomatic group into two subgroups based on their mental status (mild and moderate/severe dementia) and both showed significant deficits in recall and recognition memory, though recall was more impaired than recognition in the mild dementia subgroup. Only slight memory impairment was observed in the presymptomatic subjects. The results show that deficits in recognition memory must be accounted for in future models of memory impairment in HD.

Associative Memory Encoding and Recognition in Schizophrenia: An Event-Related fMRI Study

BACKGROUND We used an event-related functional Magnetic Resonance Imaging (fMRI) approach to examine the neural basis of the selective associative memory deficit in schizophrenia. METHODS Fifteen people with schizophrenia and 18 controls were scanned during a pair and item memory encoding and recognition task. During encoding, subjects studied items and pairs of visual objects. In a subsequent retrieval task, participants performed an item recognition memory test (old/new decisions) and an associative recognition test (intact/rearranged decisions). The fMRI analysis of the recognition data was restricted to correct items only and a random effects model was used. RESULTS At the behavioral level, both groups performed equally well on item recognition, whereas people with schizophrenia demonstrated lower performance on associative recognition relative to the control group. At the brain level, the comparison between associative and item encoding revealed greater activity in the control group in the left prefrontal cortex and cingulate gyrus relative to the schizophrenia group. During recognition, greater left dorsolateral prefrontal and right inferior prefrontal activations were observed in the control group relative to the schizophrenia group. CONCLUSION This fMRI study implicates the prefrontal cortex among other brain regions as the basis for the selective associative memory encoding and recognition deficit seen in schizophrenia.

Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures

BACKGROUND Transmyocardial laser revascularization (TMLR), which has been shown to reduce angina in clinical trials, was originally based on the belief that laser channels are unique and can remain patent. An increasing body of evidence indicates otherwise, and transmyocardial revascularization (TMR) angiogenesis is currently thought to be induced by nonspecific inflammatory response to tissue injuries. We tested the hypothesis that mechanical transmyocardial revascularization (TMMR) may induce angiogenic responses similar to that seen with lasers. METHODS Ameroid constrictors were implanted around proximal circumflex arteries of porcine hearts. Six weeks later, they were randomly assigned (n = 5 each) to receive 10 transmural channels in the ischemic zone by a carbon dioxide laser (group I) or by a needle (group II). A third group (group III) had 30 needle channels in the same area, while a control group (group IV) received no TMR. The hearts were harvested 1 week later, and, using immunohistochemistry, vascular endothelial growth factor (VEGF) expression was studied and quantified by computerized morphometric analysis. Densities of vascular structures positively stained for VEGF per high-power field (HPF) were also compared. RESULTS Virtually no TMR channels remained patent histologically. Group III had a significant higher level of total VEGF expression (14.18+/-0.78 mm2) compared with group I (7.07+/-2.06 mm2, p < 0.001) and group II (4.74+/-3.35 mm2, p < 0.001). Vascular density was significantly elevated in all treatment groups compared with the control (group I, 7.7+/-0.8/HPF vs group II, 4.5+/-2.3/HPF vs group III, 8.1+/-0.6/HPF vs group IV, 1.1+/-0.5/HPF). CONCLUSIONS In view of the significant cost implications, our findings that needle punctures may also induce angiogenic response comparable with that with laser suggest that it is justifiable and desirable to include a TMMR arm for comparison with TMLR in future clinical trials.

Successful treatment of acquired Factor VIII inhibitors with cyclosporin

The treatment of Factor VIII inhibitors remains controversial and no standard therapy exists. We describe in this report two consecutive patients with this inhibitor that responded to cyclosporin. Clinical improvement of the bleeding diathesis, a return to normal of the PTT, a decrease in the level of the inhibitor, and a return to normal of the factor VIII level followed use of this drug. We believe that cyclosporin is effective in the treatment of factor VIII inhibitors and deserves further investigation. Am. J. Hematol. 57:87–88, 1998.

Episodic Memory Bias and the Symptoms of Schizophrenia

Much of the research on episodic memory in schizophrenia spectrum disorders has focused on memory deficits and how they relate to clinical measures such as outcome. Memory bias refers to the modulatory influence that state or trait psychopathology may exert on memory performance for specific categories of stimuli, often emotional in nature. For example, subjects suffering from depression frequently have better memory for negative stimuli than for neutral or positive ones. This dimension of memory function has received only scant attention in schizophrenia research but could provide fresh new insights into the relation between symptoms and neurocognition. This paper reviews the studies that have explored memory biases in individuals with schizophrenia. With respect to positive symptoms, we examine studies that have explored the link between persecutory delusions and memory bias for threatening information and between psychosis and a memory bias toward external source memory. Although relatively few studies have examined negative symptoms, we also review preliminary evidence indicating that flat affect and anhedonia may lead to some specific emotional memory biases. Finally, we present recent findings from our group delineating the relation between emotional valence for faces and memory bias toward novelty and familiarity, both in schizophrenia patients and in healthy control subjects. A better understanding of the biasing effects of psychopathology on memory in schizophrenia (but also on other cognitive functions, such as attention, attribution, and so forth) may provide a stronger association between positive and negative symptoms and memory function. Memory measures sensitive to such biases may turn out to be stronger predictors of clinical and functional outcome.

Nitric oxide system in needle-induced transmyocardial revascularization

BACKGROUND Nitric oxide (NO) promotes endothelial proliferation and migration, essential for angiogenesis. The purpose of this study was to determine the cellular expression of inducible and endothelial nitric oxide synthases (iNOS and eNOS) in an ischemic cardiomyopathy animal model of needle-induced transmyocardial revascularization (TMR). METHODS Myocardial infarction was created in rats by ligating the left coronary artery, and animals were divided into two groups: no-TMR group (served as control) and TMR group (underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic area). Rats were sacrificed at intervals of 1, 2, 4, and 8 weeks. Immunohistochemistry using specific antisera was performed for iNOS, eNOS, and endothelial cell marker factor VIII. Vascular density and positive staining area with either iNOS or eNOS were assessed in the infarcted myocardium. RESULTS Vascular density in the infarcted myocardium was significantly increased in the TMR group (p < 0.001). The positive staining area for iNOS and the intensity of iNOS immunoreactivity in cardiomyocytes, vascular endothelium, and macrophages were significantly greater in the TMR group (p < 0.05). However, these differences were seen only in the first 2 weeks after TMR. There was no significant difference in the expression of eNOS between groups. CONCLUSIONS A mechanical injury using needle puncture in an ischemic myocardium increased vascular density and is associated with increased expression of myocardial iNOS. Increased production of NO derived from iNOS may contribute to the angiogenic response of TMR.