Biomedical subjects

D Malaspina

Publications and source records attributed to D Malaspina.

At least 37 records · Page 2Linked to original sources

PubMed2000

Depression, psychomotor retardation, negative symptoms, and memory in schizophrenia.

OBJECTIVE: The purpose of this study was to examine the relations between depression, psychomotor retardation, and negative symptoms in schizophrenia as well as the specific contribution of each of these factors to memory impairment. BACKGROUND: It has been suggested that depression overlaps with negative symptomatology in schizophrenia. The relation between psychomotor retardation and negative symptomatology has been unclear. METHOD: The Hamilton Depression Rating Scale, The Positive and Negative Symptom Scale for Schizophrenia, and Scale for the Assessment of Negative Symptoms were used to assess depressive and negative symptomatology in a sample of patients with schizophrenia. Verbal memory performance was assessed by a free recall test. Two indices of processing speed were measured. Correlations among variables were computed. RESULTS: Depression score was correlated with the avolition item from the Scale for the Assessment of Negative Symptoms and with both measures of processing speed. Negative symptomatology was unrelated to processing speed. Memory performance was correlated with depression score, slowing of processing speed, and avolition. Its correlation with depression score and processing speed remained significant when the other factors were partialled out. CONCLUSIONS: Memory performance in schizophrenia may be affected by lack of motivation, psychomotor retardation, and depression. It is suggested that negative symptoms could be split between a volitional component linked to depression and cognitive efficiency and an emotional component unrelated to them.

Adult↗

PubMed2000

[Left atrium rupture after non-penetrating injury to the back].

Survival after cardiac rupture associated with blunt thoracic trauma is very uncommon. In these patients successful management demands a high index of suspicion of cardiac injury. A case of a 24-year-old woman who presented unconscious and shocked in the emergency room after motorcycle trauma strictly limited to her back is reported. Rib and sternal fractures were absent; the typical signs of cardiac tamponade were not found. Therefore the suspicion of cardiac chamber rupture was not immediate and the cardiologist was consulted after several diagnostic exams. Transthoracic echocardiography showed a pericardial effusion with clots and initial cardiac tamponade. The patient was transferred to the operating room and a large hemopericardium was disclosed. Two lacerations were noticed: the first pericardial, near the inferior vena cava, and the second one in the posterior wall of the left atrium. It is possible that the associated pericardial tear and pericardial clots could have contributed to survival. After surgical repair, carried out during cardiopulmonary bypass, the recovery was quick and complete. This case report confirms the possibility of heart chamber rupture after blunt chest trauma even in the absence of obvious thoracic lesion and it shows that the presentation could be very insidious without a "classic" clinical picture of cardiac tamponade. In front of an unexplained shock after nonpenetrating thoracic trauma, a rupture of the heart chambers should be suspected and echocardiography is mandatory. In the emergency room environment pericardiocentesis should be performed only with a quickly available cardiac surgery or in the presence of overwhelming hemodynamic failure.

Adult↗

PubMed1999

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion.

The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

Chromosomes, Human, Pair 10↗

PubMed1999

Opposite links of positive and negative symptomatology with memory errors in schizophrenia.

We wished to confirm and extend a previous correlational study of our group, suggesting that positive symptoms in schizophrenia were linked to an increase in certain types of memory errors, and negative symptoms to a decrease in other types of errors. A post-hoc analysis was conducted in 33 schizophrenic patients and 40 normal control subjects on memory errors collected in a free recall task and two types of recognition tasks. The memory errors were intrusions and list errors in free recall, and decision bias towards false alarms in recognition, all assumed to reflect a source-monitoring failure. In a first analysis, the patient sample was split along the median for positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS). In a second analysis, it was split along the median for negative symptoms as rated by the Scale for the Assessment of Negative Symptoms (SANS). Patients with high ratings of positive symptoms made more memory errors (intrusions, list errors, false alarms) than those with low ratings, supporting the hypothesis of a link between positive symptomatology and source-monitoring failure. On the other hand, patients with high ratings of negative symptoms made fewer of these errors than the other patients. Fewer errors were specifically associated with more affective flattening, alogia and anhedonia, whereas avolition was entirely unrelated to them.

Adult↗

PubMed1999

Amphetamine disrupts P50 suppression in normal subjects.

BACKGROUND: P50 suppression is viewed as an operational measure of sensory "gating" that is reduced in patients with schizophrenia and their family members. Previous reports have demonstrated that neural gating is regulated by monoaminergic tone in rodent models of P50 suppression. METHODS: In this study, 11 healthy subjects participated in P50 event-related potential recordings at baseline and after either oral administration of dextroamphetamine (.3 mg/kg) or placebo, to determine if the administration of a monoaminergic agonist produces P50 suppression deficits similar to those observed in patients with schizophrenia. RESULTS: As hypothesized, amphetamine disrupted the suppression of the P50 event-related potential. There was a statistically significant decrement in P50 suppression during the amphetamine challenge condition (t10 = 3.15, p < .01, mean difference = -44.1%, d = -2.5) relative to the baseline P50 condition. A comparison of P50 suppression in the placebo and amphetamine conditions (both after a baseline recording session) revealed a significant amphetamine-induced disruption of P50 suppression (t6 = 3.71, p < .01, mean difference = -54.4%, d = -3.14). CONCLUSIONS: The biochemical alterations associated with an amphetamine-induced disruption of P50 suppression in this study may be related to the pathophysiology of P50 suppression deficits in schizophrenia. The findings are consistent with several careful examinations of suppression deficits in rodent models that have identified the monoaminergic regulation of P50 suppression. These data indicate that amphetamine induces a disruption of P50 suppression in normal subjects.

Adrenergic Agents↗

PubMed1999

SPECT study of visual fixation in schizophrenia and comparison subjects.

BACKGROUND: The consistent association of impaired eye movements and schizophrenia suggests a relationship between the neurobiology of the illness and visual pursuit systems. Visual fixation (VF), an eye "movement" task at zero velocity, is the simplest such abnormality in schizophrenia patients and their relatives. METHODS: We used a VF task for a functional imaging study. Six neuroleptic-free schizophrenia patients and eight gender and mean age matched comparison subjects had SPECT scans with 20 mCi of Tc99-HMPAO, during VF on a simple blue line intersection. MEDX data saved in ANALYZE format for SPM 95 was used to generate paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. RESULTS: Patients, compared to controls, had increased rCBF in both the parahippocampal gyrus (bilaterally) and in the right fusiform gyrus. They had decreased rCBF in the left frontal cortex, including medial and superior frontal gyri and anterior cingulate. Overall, compared to controls, patients had medial temporal lobe hyperperfusion along with left prefrontal hypoperfusion. CONCLUSIONS: These findings are consistent with the hypothesized imbalance between the medial temporal and frontal lobes that is postulated for schizophrenia. It was of interest that the relative rCBF differences between schizophrenia patients and controls in this small sample were observable with this cognitively non-demanding visual fixation task.

Adult↗

PubMed1999

Elevation of CD5+ B lymphocytes in schizophrenia.

BACKGROUND: A variety of immunologic alterations have been observed in patients with schizophrenia. These findings have lent support to theories that autoimmune mechanisms may be important in some patients with the illness. The CD5+ B lymphocyte, a B-cell subset associated with autoimmune disease, has been the subject of two previously published studies yielding disparate results. METHODS: In this study, we used immunofluorescent flow cytometry to measure CD5+ B cells, total B and T cells, and CD4 and CD8 subsets in patients with schizophrenia and in normal control subjects. RESULTS: A significantly higher percentage of patients with schizophrenia, relative to normal control subjects, exhibited an elevated level of CD5+ B cells (27.6% vs 6.7%). Antipsychotic withdrawal had no effect on CD5+ B-cell levels, suggesting that medication effects were not the cause of this difference. No other studied lymphocyte subsets differed between the two groups. CONCLUSIONS: A subset of patients with schizophrenia have elevated levels of CD5+ B cells. This finding replicates an earlier study by another group and provides further evidence suggestive of autoimmune manifestations in schizophrenia.

Adult↗

PubMed1999

Brain event-related potentials (ERPs) in schizophrenia during a word recognition memory task.

Impairments of recognition memory for words and attenuation of the ERP 'old-new' effect have been found in patients with left medial temporal lobe damage. If left temporal lobe dysfunction in schizophrenia involves medial structures (e.g. hippocampus), then schizophrenic patients might show similar abnormalities of verbal recognition memory. This study recorded ERPs from 30 electrode sites while subjects were engaged in a continuous word recognition memory task. Results are reported for 24 patients having a diagnosis of schizophrenia (n = 16) or schizoaffective disorder (n = 8) and 19 age-matched healthy controls. Both patients and controls showed the expected 'old-new' effect, with greater late positivity to correctly recognized old words at posterior sites, and there was also no significant difference between groups in P3 amplitude. However, accuracy of word recognition memory was poorer in patients than controls, and patients showed markedly smaller N2 amplitude. Reduced amplitudes of N2 and N2-P3 were associated with poorer performance, with highest correlations over the left inferior parietal (N2) and left medial parietal (N2-P3) region. Moreover, patients failed to show significantly greater left than right hemisphere amplitude of N2-P3 at posterior sites, which was seen for healthy controls. These findings suggest that impaired word recognition in schizophrenia may arise from a left lateralized deficit at an early stage of processing, beginning at 200-300 ms after word onset.

Adult↗

PubMed1999

Clinical and neurobiological correlates of cytogenetic abnormalities in childhood-onset schizophrenia.

OBJECTIVE: Cytogenetic abnormalities are increased in schizophrenia, suggesting a possible etiologic contribution. However, their clinical and pathophysiologic roles in the disorder are unknown. To investigate this, a group of children and adolescents participating in a comprehensive study of childhood-onset schizophrenia were screened for chromosomal abnormalities, and their clinical and neurobiological correlates were examined. METHOD: Cytogenetic screening with the use of high-resolution banding, fluorescent in situ hybridization for chromosome 22q11 deletions, and molecular fragile X testing was undertaken in a group of 47 children and adolescents with very early onset of schizophrenia. Clinical, neurobiological (including brain morphometry), and risk factor measures of the subjects with cytogenetic abnormalities were compared with those of the remaining patients without cytogenetic anomalies. RESULTS: Five patients had previously undiagnosed cytogenetic abnormalities. Lower performance IQ and more pronounced premorbid developmental impairments were seen in this subgroup. Rates of obstetric complications, familial schizophrenia spectrum disorders, and familial eye tracking dysfunction were similar for the patients with and without cytogenetic abnormalities. CONCLUSIONS: Cytogenetic abnormalities appear to be increased in childhood-onset schizophrenia, suggesting an association with a very early age at onset. The data from the subgroup of patients with cytogenetic anomalies are consistent with a model in which a childhood onset of schizophrenia is due to a greater impairment of neurodevelopment secondary to the interaction of a number of factors, particularly genetic ones.

Adolescent↗

PubMed1999

Obstetrical complications and childhood-onset schizophrenia.

OBJECTIVE: Increased obstetrical complications have been reported in individuals with adult-onset schizophrenia, with several studies finding an association between such complications and an earlier age at onset. Consequently, obstetrical records were examined for individuals with childhood-onset schizophrenia to determine if birth complications were more prevalent. METHOD: The birth records of 36 patients with childhood-onset schizophrenia and 35 sibling comparison subjects were rated for birth complications by two psychiatrists who were unaware of group membership. RESULTS: There were no significant differences between the groups in rates of obstetrical complications. Patients with such complications did not have a relatively earlier age at onset of schizophrenia. CONCLUSIONS: A very early age at onset of schizophrenia is probably not due to birth complications.

Age of Onset↗

PubMed1999

Suicidal behavior in schizophrenia: characteristics of individuals who had and had not attempted suicide.

OBJECTIVE: This study compares demographic and clinical characteristics of 52 individuals with schizophrenia or schizoaffective disorder who had attempted suicide with those of 104 individuals with schizophrenia or schizoaffective disorder who had not made a suicide attempt. METHOD: Participants were interviewed with the Diagnostic Interview for Genetic Studies. RESULTS: Most suicide attempts were of moderate to severe lethality, required medical attention, and involved significant suicidal intent. Individuals who had and had not attempted suicide did not differ with respect to demographic variables, duration of illness, rate of depression, or substance abuse. The two groups are affected differentially when depressed. CONCLUSIONS: Biopsychosocial assessments and interventions are essential for reducing the risk for suicidal behavior in individuals with schizophrenia.

Adult↗

PubMed1998

Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative.

Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the alpha7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia.

Chromosomes, Human, Pair 15↗

PubMed1998

Genome-wide search for schizophrenia susceptibility loci: the NIMH Genetics Initiative and Millennium Consortium.

Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment.

Adolescent↗

PubMed1998

NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees.

The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere.

Adolescent↗

PubMed1998

Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.

The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs. Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241-247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241-247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P = .0004) and its neighbor, D10S582 (NPL Z = 3.2, P = .0006).

Adolescent↗

PubMed1998

SPECT imaging of odor identification in schizophrenia.

Deficits in olfactory identification, despite normal odor perception, are found in some neuropsychiatric disorders, including schizophrenia. We examined if regional cerebral blood flow (rCBF) differed between schizophrenia patients and controls during odor identification, hypothesizing that these brain regions could be relevant to odor identification impairments. Eight schizophrenia and eight comparison subjects provided a baseline (picture identity matching) and activation (odor identification) SPECT scan, obtained using 99mTc-HMPAO in a low dose/high dose design. Six patients and seven controls had analyzable data. MEDX data saved in ANALYZE format for SPM 95 generated paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. There was no schizophrenia vs. control group difference in rCBF for the baseline picture-matching test. For odor identification, schizophrenia patients had a hypometabolic right-sided cortical region that included the frontal lobe Broca's area, superior temporal lobe, and supramarginal and angular gyri. Post hoc within-group contrasts of picture-matching vs. odor identification showed that the controls significantly increased rCBF in the right-sided inferior temporal fusiform gyrus, and bilateral hippocampi and visual association areas for the odor test. The schizophrenia group showed no rCBF differences for picture-matching compared to odor identification. Patients showed significant hypometabolism in right-sided cortical areas for odor identification. They also failed to show increased rCBF in the hippocampus and visual association area, as seen in controls for odor identification compared to picture-matching. These regions may be unique to schizophrenia or have broader implications for olfactory memory retrieval.

Adult↗

PubMed1998

Psychobiological heterogeneity of familial and sporadic schizophrenia.

BACKGROUND: Although schizophrenia is presumed to be heterogeneous, there has been limited success distinguishing familial from sporadic cases. We used psychobiological measures to examine heterogeneity, as they may be closer to neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and dichotic listening (DL) tests to tones and words were used to assess hemispheric laterality asymmetry. METHODS: Forty-six research unit patients participated in assessments of family history (FH) and physiological measures. FH was categorized by three exclusive groups: FH-1 patients had a chronic schizophrenia-related psychosis in a first-degree relative, FH-2 had it in second-degree relative, and FH-3 had no family member with a reoccurrence. RESULTS: Analysis of variance showed a significant group difference for SPEM and DL tones. SPEM was significantly worse in all three schizophrenia groups than for the normal comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3) had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric lateralization for tones, whereas familials did not, and FH-2 again had intermediate values. The lateralization quotient for DL words did not significantly differ among the groups. CONCLUSIONS: SPEM was affected most in sporadic, not familial schizophrenia, whereas dichotic listening was most affected in familial schizophrenia. This double dissociation supports the utility of the familial/sporadic distinction and suggests that etiological factors in different forms of schizophrenia may impact principally on distinct neurobiological substrates, despite similar patient phenomenology.

Adult↗

PubMed1998

A simple method of preparation for [123I]-(S)-(-)-IBZM.

Sterile, apyrogenic [123I]IBZM was prepared in a sealed, capped 'V' vial, followed by SEP-PAK C-18 cartridge purification, and then was placed under sealed vial condensation. The quantity of BZM present in the final product ranged from 3.3-5.9 micrograms, as measured by a UV spectrophotometer at 254 and 308 nm. Animal biodistribution studies revealed that the [123I]IBZM prepared by this method which contained 5.9 micrograms of BZM, compared to the standard preparation method containing 0 microgram of BZM, resulted in identical brain uptakes at 15, 30, 60, and 120 min post-injection. The in vitro and in vivo studies demonstrated that a small amount of BZM presence in the final product did not affect the radiochemical purity, nor the D2 receptor binding capacity in the rat brain of [123I]IBZM. The preparation time can be shortened to 1.5 h compared with at least 2-4 h needed for the standard method of preparation. This factor may be important in routine clinical application.

Animals↗