Lack of association between schizophrenia and a CAG repeat polymorphism of the hSKCa3 gene in a north eastern US sample.
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Ethnicity↗
Biomedical subjects
R Ganguli
Publications and source records attributed to R Ganguli.
Family planning and parenthood needs of women with severe mental illness: clinicians' perspective.
Family planning and parenthood are important issues for women with severe and persistent mental illness (SPMI). The role of adult mental health clinicians with regard to these issues has been under investigated. Clinicians treating patients with SPMI at a large community health center completed survey forms on 419 women. Clinicians reported that a large fraction of sexually active women were not thought to be using birth control. Despite this, many clinicians had not discussed birth control with these patients. Clinicians had concerns about childcare in 72% of cases where the patient with SPMI was the primary custodian of a younger child; however, the majority of these families were not receiving child or family services. Further consideration of the role of the adult mental health clinician in addressing issues of family planning and parenting is required.
Adult↗
Lack of association between schizophrenia and a pancreatic phospholipase A-2 gene (PLA2G1B) polymorphism.
Patients with schizophrenia (DSM IV, n = 149) and controls (n = 180) participated in a case-control association study in which a trinucleotide repeat polymorphism of pancreatic phospholipase A2 group 1B (PLA2G1B) was examined. Both African-American and Caucasian populations were included in this USA sample. There were no significant case-control differences, therefore his study does not support an association between schizophrenia and a PLA2G1B polymorphism on chromosome 12.
Adult↗
Weight gain associated with antipsychotic drugs.
Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). Weight gain occurs no matter what the patient's age, sex, or race and is seen with both oral and depot drug formulations. Numerous studies have found that patients gain weight when treated with a conventional antipsychotic, such as chlorpromazine, fluphenazine, and haloperidol. The newer, novel antipsychotics offer advantages over conventional antipsychotics, especially a relative lack of extrapyramidal symptoms, but some still have the disadvantage of causing weight gain. Clozapine and olanzapine in particular appear to cause substantial weight gain, much more so than do most conventional neuroleptics and novel agents such as risperidone. Given the risks to health and treatment compliance associated with weight gain and obesity, clinicians should monitor weight during the course of antipsychotic therapy and consider switching agents if excessive weight gain occurs.
Administration, Oral↗
Mini-Mental State Examination (MMSE) performance of partially remitted community-dwelling patients with schizophrenia.
Patients with schizophrenia perform worse than healthy controls on many neuro-psychological tests. However, previous studies of neuro-cognitive function have mostly been carried out on acutely ill or institutionalized patients. The objective of this study was to generate norms for performance of partially remitted community-dwelling patients with schizophrenia on the Mini-Mental State Examination (MMSE). Partially remitted outpatients attending a depot antipsychotic clinic or a clozapine clinic (n = 272) were tested using the MMSE. Demographic and clinical characteristics associated with MMSE performance, as well as the performance of specific items, were examined. MMSE score was significantly associated with educational status and race. Patients in our sample performed approximately 2-3 points below the population norms at all ages, but the mean score for the group was not in the impaired range. There was no apparent widening of this gap with advancing age. Patients who did poorly most frequently had difficulty with memory, attention and construction tasks. The MMSE is easy to administer to outpatients with schizophrenia and most patients score in the un-impaired range. The MMSE may be used to identify a subgroup of patients who score in the impaired range, for further investigations.
Acute Disease↗
Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?
Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats. The second CAG repeat in hSKCa3 is highly polymorphic in control individuals, with alleles ranging in size from 12 to 28 repeats. The overall allele frequency distribution is significantly different in patients with schizophrenia compared to ethnically matched controls (Wilcoxon Rank Sum test, P=0.024), with CAG repeats longer than the modal value being over-represented in patients (Fisher Exact test, P=0.0035). A similar, non-significant, trend is seen for patients with bipolar disorder. These results provide evidence for a possible association between longer alleles in the hSKCa3 gene and both of these neuropsychiatric diseases, and emphasize the need for more extensive studies of this new gene. Small conductance calcium-activated K+ channels play a critical role in determining the firing pattern of neurons. These polyglutamine repeats may modulate hSKCa3 channel function and neuronal excitability, and thereby increase disease risk when combined with other genetic and environmental effects.
Alleles↗
Schizophrenia and the serotonin transporter gene.
A case control study was conducted among cases with schizophrenia (DSM IV criteria) and screened adult controls from three cohorts. Bi-allelic polymorphisms in the promoter region of the serotonin transporter gene (5-HTT) were examined in conjunction with those of the serotonin 5-HT2a receptor (HTR2). No significant association with 5-HTT was detected among US Caucasians (n = 207), African-Americans (n = 84) or Caucasians from Sweden (n = 221). However, survival analysis suggested an association with the age at onset among the Swedish cases. The association should be considered tentative as it was not evident in the smaller US samples. The following exploratory analyses among the US samples were also not significant: associations with subgroups of patients based on familiality or response to medications, or altered risk due to the joint effects of 5-HTT and HTR2 genotypes.
Adult↗
Functional hypofrontality and working memory dysfunction in schizophrenia.
OBJECTIVE: Hypofrontality is a common but not invariable finding in schizophrenia. Inconsistencies in the literature may reflect, in part, the fact that abnormal physiological responses in the prefrontal cortex are best identified under conditions that place well-specified functional demands on this region. METHOD: The authors studied eight patients with schizophrenia and eight matched comparison subjects using [(15)O]H2O positron emission tomography and the "N-back" task, which activates the prefrontal cortex as a function of working memory load in normal subjects. RESULTS: Under low-working-memory-load conditions, the accuracy of both groups in the N-back task was equal, but when the memory load increased, the patients' performance deteriorated more than did that of the comparison subjects. The regional cerebral blood flow response to increased working memory load was significantly reduced in the patients' right dorsolateral prefrontal cortex. CONCLUSIONS: These results confirm the importance of using tasks that tap specific cognitive functions, linked to specific neural systems, in studies of brain-behavior relationships in schizophrenia. Hypofrontality is reliably demonstrated in schizophrenia during tasks that engage working memory functions of the prefrontal cortex.
Functional Laterality↗
The effects of risperidone and olanzapine on the indications for clozapine.
The effects of the availability of risperidone and olanzapine on the indications for which clozapine is prescribed (treatment-resistance, treatment-intolerance, and/or negative symptoms) were examined for 252 patients with schizophrenia who began treatment at our hospital between June 1990 and June 1997. There were no statistical differences in the indications for clozapine treatment before and after the availability of either risperidone or olanzapine. Furthermore, there were no significant differences in the frequencies of the indications in subgroups of patients who had previously received a trial with risperidone or olanzapine, as compared with the remaining patients. The indications for clozapine appear to have been unaffected by the advent of risperidone and olanzapine; however, we noted a decrease in the absolute number of patients starting clozapine after risperidone became available. More recently, the majority of patients referred for treatment with clozapine had received previous trials with risperidone or olanzapine.
Antipsychotic Agents↗
Negative association of schizophrenia with HLA DQB1*0602: evidence from a second African-American cohort.
The authors attempted a replication of an earlier study of African-Americans, in which they detected a negative association of schizophrenia with HLA DQB1*0602. Patients with schizophrenia (n = 75, DSM-III-R criteria) and screened adult controls of African-American ethnicity (n = 66) were genotyped with respect to HLA DQB1*0602 using a combination of two polymerase chain reaction (PCR) based assays: amplification with sequence specific primers and a dot blot assay. A significant negative association with HLA DQB1 was not noted overall, but was present among women (female patients vs. female controls: odds ratio, OR = 0.42, 95% confidence intervals, CI = 0.32, 0.55). Reanalysis of the earlier study also revealed a gender related association. When the present and earlier samples from both genders were combined, the association persisted (OR 0.48; 95% CI: 0.12, 0.52). The present findings support and association between schizophrenia and the HLA DQB1 gene locus among African-Americans.
Adult↗
PET brain mapping study of auditory verbal supraspan memory versus visual fixation in schizophrenia.
Changes in regional cerebral blood flow (rCBF), associated with performance of an auditory verbal supraspan memory task, were studied in eight remitted DSM-III-R schizophrenic patients and eight pair-wise matched normal controls. Four positron emission tomography (PET) scans, using the [15O]-H2O technique, were acquired: two while subjects fixated a cross hair and two while performing a verbal free-recall supraspan memory task. Task performance showed typical patterns of recency and primacy effects in both groups; however, patients performed more poorly than controls on the primary (working) memory aspect of the task. Regions showing rCBF changes overlapped in both groups and were similar to those seen in previous studies of normals; however, patients had smaller increases in rCBF than controls in frontal and superior temporal cortical regions bilaterally. Our results suggest that remitted patients with schizophrenia demonstrate impairments of capacity-limited information processing, which may be related to metabolic dysfunction within a distributed network of brain structures, including the prefrontal and temporal cortical regions; however, dysfunction limited to the frontal cortex cannot be ruled out by the results of this experiment.
Adult↗
The effects of clozapine on negative symptoms in patients with schizophrenia with minimal positive symptoms.
The effectiveness of clozapine in the treatment of the negative symptoms of schizophrenia remains controversial, as improvements in negative symptoms are invariably accompanied by improvements in positive symptoms and neurological side effects. We examined the effectiveness of treatment with clozapine on negative symptoms in a cohort of patients with minimal positive symptoms. Improvements in positive and negative symptoms were measured by BPRS ratings in a subgroup of schizophrenic patients (n=17, from a state hospital cohort of 75) with minimal positive symptoms, who had received clozapine for 6 months. In this subgroup, significant improvements were noted by a composite score on the three negative symptom items of emotional withdrawal, blunted affect, and motor retardation. Positive and depressive symptoms remained unchanged. The remaining cohort (n=58) showed improvements in overall psychopathology including positive, negative, and depressive symptoms. Interestingly, nearly 50% of each group were discharged from the hospital. These findings suggest that clozapine may be beneficial in the treatment of core negative symptoms, even in the absence of other improvements in psychopathology. This effect of clozapine may be a function of its unique pharmacological profile.
Adult↗
Fertility in schizophrenia: results from a contemporary US cohort.
To investigate procreation in schizophrenia, as well as gender-related differences, female patients with schizophrenia (n = 79, DSM-III-R criteria) were compared with screened female controls (n = 124) and subsequently with male patients (n = 86). Two outcomes were investigated: (i) the proportion of subjects with one or more children (an index of fertility) and (ii) the number of children per subject among those with one or more children (an index of fecundity). Multivariate analysis was used to control for confounding variables. No significant differences in fertility between female patients and controls were detected, but reduced fecundity was noted among female patients past the reproductive period. Male patients showed a significant reduction in both fertility and fecundity compared to female patients. These results suggest that there is a relatively small impairment of fecundity among female patients compared with controls, but that there are more significant gender-related differences in both fertility and fecundity. The latter have important implications for the genetics of schizophrenia.
Adolescent↗
Association study of schizophrenia and the dopamine D3 receptor gene locus in two independent samples.
Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (D3RG) locus was investigated. Initial analysis of pooled results from published studies revealed a significant excess of individuals homozygous for either allele among the patients. The association was next tested in two cohorts ascertained independently at Pittsburgh, Pennsylvania and at Houston, Texas. The Pittsburgh sample was comprised of patients with schizophrenia (DSM-III-R) (n = 130). The controls belonged to two groups: adults screened for the absence of substance abuse or major psychiatric illness (n = 128), and neonates (n = 160). Multivariate analysis suggested an association with allele 1 of the biallelic D3RG polymorphism in comparison with the adult, but not the neonatal, controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.69, confidence intervals 1.80, 104.30). Survival analysis suggested an earlier age of onset among male patients homozygous for allele 2. The Houston cohort included Caucasian patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria, n = 50), and normal controls matched for gender (n = 51). In this group, no significant associations were noted among all the patients or among subgroups of patients based on family history or age of onset. Possible reasons for the discordant results are discussed.
Adult↗
5-HT2 receptor gene locus: association with schizophrenia or treatment response not detected.
In view of a reported association between schizophrenia and the 5-HT2 receptor gene locus, as well as an association with treatment refractoriness at this locus, a case-control association study was conducted using a biallelic polymorphism. The distribution of the polymorphism was investigated among patients with schizophrenia (DSM-III-R, n = 174) and unaffected controls (n = 239). No significant differences in genotype distributions or allele frequencies were noted between the two groups. In support of the earlier report, a significant excess of individuals homozygous for allele C2 was noted among patients who responded unsatisfactorily to antipsychotic medication in comparison with the controls (odds ratio 1.78; 95% confidence intervals 1.06, 2.97). However, this difference was not significant following multivariate analysis. This study does not support an association between the 5-HT2 receptor gene locus and schizophrenia or subgroups based on treatment response.
Adult↗
Association study of schizophrenia and the IL-2 receptor beta chain gene.
A case-control association study was conducted in Caucasian patients with schizophrenia (DSM-III-R, n = 42) and unaffected controls (n = 47) matched for ethnicity and area of residence. Serum interleukin-2 receptor (IL-2R) concentrations, as well as a dinucleotide repeat polymorphism in the IL-2R beta chain gene, were examined in both groups. No significant differences in IL-2R concentrations or in the distribution of the polymorphism were noted. This study does not support an association between schizophrenia and the IL-2R beta gene locus, contrary to the suggestive evidence from linkage analysis in multicase families.
Adult↗
Impaired mitogen (PHA) responsiveness and increased autoantibodies in Caucasian schizophrenic patients with the HLA B8/DR3 phenotype.
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Adult↗
Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients. The influence of age at onset and negative symptoms.
BACKGROUND: Decreased interleukin-2 (IL-2) production is characteristic of active autoimmune diseases and has previously been reported in patients with schizophrenia. We attempted to replicate this finding in never-medicated schizophrenic patients and examine the possible correlation between IL-2 production and clinical variables. METHODS: The production of IL-2 was measured in equal numbers (N = 33) of DSM-III-R-diagnosed schizophrenic patients and controls who were matched for age, race, and gender. Patients were also assessed for positive, negative, and depressive symptoms. RESULTS: The production of IL-2 was significantly lower in patients than in controls. There was a significant positive correlation between IL-2 production and age at onset, and significant negative correlation between IL-2 production and negative symptom scores. In multivariate analyses, the predictive power was stronger for age at onset than for negative symptoms. Positive or depressive symptoms were unrelated to IL-2 production. CONCLUSIONS: Our finding of low IL-2 production in neuroleptic-native schizophrenic patients confirms that this finding is not confounded by medications. The correlation of low IL-2 production with younger age at onset suggests that this may be a marker for a subtype of the illness or for severity.
Acute Disease↗