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Biomedical subjects

S V Parikh

Publications and source records attributed to S V Parikh.

At least 19 recordsLinked to original sources
PubMed2003

Evidence that the N-methyl-D-aspartate subunit 1 receptor gene (GRIN1) confers susceptibility to bipolar disorder.

There is evidence for the involvement of glutamatergic transmission in the pathogenesis of major psychoses. The two most commonly used mood stabilizers (ie lithium and valproate) have been found to act via the N-methyl-D-aspartate receptor (NMDAR), suggesting a specific role of NMDAR in the pathogenesis of bipolar disorder (BP). The key subunit of the NMDAR, named NMDA-1 receptor, is coded by a gene located on chromosome 9q34.3 (GRIN1). We tested for the presence of linkage disequilibrium between the GRIN1 (1001-G/C, 1970-A/G, and 6608-G/C polymorphisms) and BP. A total of 288 DSM-IV Bipolar I, Bipolar II, or schizoaffective disorder, manic type, probands with their living parents were studied. In all, 73 triads had heterozygous parents for the 1001-G/C polymorphism, 174 for the 1970-A/G, and 48 for the 6608-G/C. These triads were suitable for the final analyses, that is, the transmission disequilibrium test (TDT) and the haplotype-TDT. For the 1001-G/C and the 6608-G/C polymorphisms, we found a preferential transmission of the G allele to the affected individuals (chi(2)=4.765, df=1, P=0.030 and chi(2)= 8.395, df=1, P=0.004, respectively). The 1001G-1970A-6608A and the 1001G-1970A-6608G haplotypes showed the strongest association with BP (global chi(2)=14.12, df=4, P=0.007). If these results are replicated there could be important implications for the involvement of the GRIN1 in the pathogenesis of BP. The role of the gene variants in predicting the response to mood stabilizers in BP should also be investigated.

Adult↗
PubMed2001

Altered TRPC7 gene expression in bipolar-I disorder.

BACKGROUND: As altered storage-operated calcium (Ca(2+)) entry (SOCE) may affect Ca(2+) homeostasis in bipolar disorder (BD), we determined whether changes occur in the expression of TRPC7 and SERCA2s, proteins implicated or known to be involved in SOCE, in B lymphoblast cell lines (BLCLs) from BD-I patients and comparison subjects. METHODS: mRNA levels were determined in BLCL lysates from BD-I, BD-II, and major depressive disorder patients, and healthy subjects by comparative reverse transcriptase-polymerase chain reaction, and BLCL basal intracellular Ca(2+) concentration ([Ca(2+)]B) was determined by ratiometric spectrophotometry using Fura-2, in aliquots of the same cell lines, at 13-16 passages in culture. RESULTS: TRPC7 mRNA levels were significantly lower in BLCLs from BD-I patients with high BLCL [Ca(2+)]B compared with those showing normal [Ca(2+)]B (-33%, p =.017) and with BD-II patients (-48%, p =.003), major depressive disorder patients (-47%, p =.049) and healthy subjects (-33%, p =.038). [Ca(2+)]B also correlated inversely with TRPC7 mRNA levels in BLCLs from the BD-I group as a whole (r = -.35, p =.027). CONCLUSIONS: Reduced TRPC7 gene expression may be a trait associated with pathophysiological disturbances of Ca(2+) homeostasis in a subgroup of BD-I patients.

Adult↗
PubMed2001

The 5HT1Dbeta receptor gene in bipolar disorder: a family-based association study.

The serotonin (5HT) receptor genes are considered good candidates for Major Depression (MD), Bipolar Disorder (BP), and Obsessive-Compulsive Disorder (OCD). The 5HT1Dbeta receptor gene has at least three polymorphisms known: G861C, T-261G, and the functional T371G (Phe-124-Cys). The aim of this study was to investigate for the presence of linkage disequilibrium between the 5HT1Dbeta receptor gene and BP. Two hundred and ninety probands with DSM-IV BPI, BPII, or Schizoaffective Disorder (Bipolar type) with their living parents were recruited. Genotyping data for the G861C and T371G polymorphisms were analyzed using the Transmission Disequilibrium Test (TDT). One hundred and sixty triads were informative for the TDT on the G861C polymorphism, which showed no preferential transmission of either allele (chi-square = 0.438, df = 1, p =.508). Only four triads were suitable for the analysis on the T371G variant, with the T allele transmitted once and the G allele transmitted four times to the affected. These findings validate further the results of pharmacological studies excluding a direct involvement of the 5HT1Dbeta receptor in the pathogenesis of BP. Further investigations combining genetic and pharmacological strategies are warranted.

Adult↗
PubMed2001

Altered IMPA2 gene expression and calcium homeostasis in bipolar disorder.

Reduced inositol monophosphatase (IMPase) activity and elevated basal intracellular calcium levels ([Ca(2+)](B)) have been reported in B lymphoblast cell lines (BLCLs) from bipolar I affective disorder (BD-I) patients, which may reflect cellular endophenotypes of this disorder. As the PI cycle couples to intracellular Ca(2+) mobilization, these two putative endophenotypes may be related. Using an RT-PCR assay, mRNA levels were estimated for IMPA1 and 2 genes encoding human IMPase 1 and 2, respectively, in BLCLs phenotyped on [Ca(2+)](B), from patients with a DSM-IV diagnosis of BD-I (n = 12 per phenotype) and from age- and sex-matched healthy subjects (n = 12). IMPA2 mRNA levels were significantly lower in BLCLs from male BD-I patients with high [Ca(2+)](B) (n = 6) compared with healthy male subjects (n = 5) (-52%, P = 0.013), male BD-I patients with normal BLCL [Ca(2+)](B) (n = 8) (-42%, P = 0.003) and female BD-I patients with high [Ca(2+)](B) (n = 6) (-59%, P = 0.0004). A significant negative correlation was observed between IMPA2 mRNA levels and [Ca(2+)](B) in BLCLs from male (P = 0.046), but not female BD-I patients. Sex-dependent differences were also evident in postmortem temporal cortex IMPA2 mRNA levels which, in contrast to BLCLs, were significantly higher in male BD-I subjects compared with male controls (P = 0.025, n = 4/group). Collectively, these observations suggest a potential sex-dependent link between abnormalities in IMPA2 expression and calcium homeostasis in the pathophysiology of BD.

Adult↗
PubMed2001

Applying Prochaska's model of change to needs assessment, programme planning and outcome measurement.

A major goal of continuing medical education (CME) is to enhance the performance of the learner. In order to accomplish this goal, careful consideration and expertise must be applied to the three primary ingredients of CME planning: assessing learner needs, programme design and outcome measurement. Traditional methods used to address these three components seldom result in CME initiatives that change performance, even in the presence of sophisticated CME formats and capable learners. In part, performance may not change because the learner is not 'ready to change'. Planners of CME are aware of this concept but have been unable to measure 'readiness to change' or employ it in assessing learner needs, and planning and evaluating CME. One theory that focuses on an individual's readiness to change is Prochaska's model, which postulates that change is a gradual process proceeding through specific stages, each of which has key characteristics. This paper examines the applicability of this model to all components of CME planning. To illustrate the importance of this model, this paper provides examples of these three components conducted both with and without implementation of this model.

Behavior↗
PubMed2001

Clinical guidelines for the treatment of depressive disorders, I. Definitions, prevalence, and health burden.

BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments partnered to produce clinical guidelines for psychiatrists for the treatment of depressive disorders. METHODS: A standard guidelines development process was followed. Relevant literature was identified using a computerized Medline search supplemented by review of bibliographies. Operational criteria were used to rate the quality of scientific evidence, and the line of treatment recommendations included consensus clinical opinion. This section on "Definitions, Prevalence, and Health Burden" was 1 of 7 articles drafted and reviewed by clinicians. Revised drafts underwent national and international expert peer review. RESULTS: The 1-year prevalence rate of major depressive disorder (MDD) in Canada is 3.2% to 4.6%, similar to the rates in other countries. MDD frequently runs a chronic or recurrent course and carries high risks for mortality and morbidity. The significant economic costs and disability associated with depressive illness are reduced by effective treatment. CONCLUSIONS: MDD is a prevalent medical condition that results in a significant health burden in the world. Vigorous efforts to improve diagnosis, treatment, and prevention are indicated to reduce the societal and personal costs of depressive disorders.

Canada↗
PubMed2000

Associated disturbances in calcium homeostasis and G protein-mediated cAMP signaling in bipolar I disorder.

BACKGROUND: Evidence of extensive cross-talk between calcium (Ca(2+))- and cAMP-mediated signaling systems suggests that previously reported abnormalities in Ca(2+) homeostasis in bipolar I (BP-I) patients may be linked to disturbances in the function of G proteins that mediate cAMP signaling. METHODS: To test this hypothesis, the beta-adrenergic agonist, isoproterenol, and the G protein activator, sodium fluoride (NaF), were used to stimulate cAMP production in B lymphoblasts from healthy and BP-I subjects phenotyped on basal intracellular calcium concentration ([Ca(2+)](B)). cAMP was measured by radioimmunoassay and [Ca(2+)](B) by ratiometric fluorometry with fura-2. RESULTS: Isoproterenol- (10 microM) stimulated cAMP formation was lower in intact B lymphoblasts from BP-I patients with high [Ca(2+)](B) (>/= 2 SD above the mean concentration of healthy subjects) compared with patients having normal B lymphoblast [Ca(2+)](B) and with healthy subjects. Although basal and NaF-stimulated cAMP production was greater in B lymphoblast membranes from male BP-I patients with high versus normal [Ca(2+)](B), there were no differences in the percent stimulation. This suggests the differences in NaF response resulted from higher basal adenylyl cyclase activity. CONCLUSIONS: These findings suggest that trait-dependent disturbances in processes regulating beta-adrenergic receptor sensitivity and G protein-mediated cAMP signaling occur in conjunction with altered Ca(2+) homeostasis in those BP-I patients with high B lymphoblast [Ca(2+)](B).

Adult↗
PubMed2000

An unstable trinucleotide-repeat region on chromosome 13 implicated in spinocerebellar ataxia: a common expansion locus.

Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long ( approximately 1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1. 25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.

Adult↗
PubMed2000

Use of antidepressants among elderly subjects: trends and contributing factors.

OBJECTIVE: The authors assessed changes over time in antidepressant utilization among elderly subjects regarding the prevalence of antidepressant users, shifts in prescription patterns, and related financial implications. METHOD: The authors conducted a population-based study of more than 1.4 million Ontario residents aged 65 years or older. Cross-sectional data regarding annual antidepressant utilization were obtained from administrative databases for 1993 to 1997. Time series analysis was used to assess trends over time and to make future projections. RESULTS: The proportion of antidepressant users increased from 9.3% of the elderly population in 1993 to 11.5% in 1997. Prescriptions for selective serotonin reuptake inhibitors (SSRIs) accounted for 9.6% of antidepressant prescriptions dispensed in the first 30 days of 1993 and 45.1% of those dispensed by the last 30 days of 1997 and were projected to increase to approximately 56% by the end of 2000. Prescriptions for tricyclic antidepressants fell from 79.0% in the first 30 days of 1993 to 43.1% by the last 30 days of 1997 and were projected to decline to approximately 28% by the end of 2000. Annual antidepressant costs (in Canadian dollars) increased by 150%, from $10.8 million in 1993 to $27.0 million in 1997. Population shifts and an increase in the prevalence of antidepressant users accounted for at least 20% of this increase, whereas the prescribing transition from tricyclic antidepressants to SSRIs accounted for at least 61% of the increase. CONCLUSIONS: The introduction of SSRIs has had a substantial financial impact at the drug utilization level. Future research should address the appropriate balancing of the cost of newer agents versus their ostensible advantages.

Aged↗
PubMed2000

Effectiveness of psychosocial treatments in bipolar disorder: state of the evidence.

Cost-effective psychotherapeutic interventions can enhance pharmacotherapy and improve outcomes in major depression and schizophrenia, but they are rarely studied in bipolar disorder, despite its often unsatisfactory response to medication alone. Following a literature search, we compiled and evaluated research reports on psychotherapeutic interventions in bipolar disorder patients. We found 32 peer-reviewed reports involving 1052 patients-14 studies on group therapy, 13 on couples or family therapy, and five on individual psychotherapy-all supplementing standard pharmacotherapy. Methodological limitations were common in these investigations. Nevertheless, important gains were often seen, as determined by objective measures of increased clinical stability and reduced rehospitalization, as well as other functional and psychosocial benefits. The results should further encourage rising international interest in testing the clinical and cost-effectiveness of psychosocial interventions in these common, often severe and disabling disorders.

Bipolar Disorder↗
PubMed1999

Sociodemographic, clinical, and attitudinal characteristics of the untreated depressed in Ontario.

BACKGROUND: Epidemiologic surveys consistently document high rates of untreated depression, yet why this unmet need exists is only partially understood. METHODS: We compared untreated depressed, treated depressed and "healthy" subjects on sociodemographic characteristics, need for treatment, and help-seeking attitudes using household survey data from Ontario, Canada (n = 9953). DSM-III R Major Depression was assessed by structured interview (UM-CIDI), and treatment was defined as seeking formal mental health care. Need for treatment was assessed using a broad array of clinical, disability, and risk measures. RESULTS: Depressed (treated and untreated) and "healthy" respondents differed significantly on nearly all comparative measures. However, the two depressed groups showed few sociodemographic or "need for treatment" differences. Notably, there were no significant clinical differences although the untreated did report less physical comorbidity (33.9% vs 60.0% treated depressed). There were, however, several attitudinal differences. Compared to the treated depressed, untreated respondents were less likely to feel they had a mental health problem (51.6% vs. 78.8%), to say they would seek help for a serious problem (36.6% vs 64.7%) or to feel comfortable consulting a professional (19.0% vs. 43.2%). LIMITATIONS: Because the data are cross-sectional, temporal relationships cannot be directly addressed. CONCLUSIONS: Despite appreciable morbidity, access to care by the untreated depressed may be hindered by their self-perceptions and greater discomfort with help-seeking. Lower physical comorbidity may also contribute through decreased health care contact and thus fewer opportunities for disclosing or detecting their illness.

Adolescent↗
PubMed1999

Clinical characteristics of bipolar disorder subjects with large CAG/CTG repeat DNA.

BACKGROUND: Unstable DNA has been implicated in a variety of neuropsychiatric disorders, with increasing severity of disease associated with larger DNA repeats. We examined the unstable DNA hypothesis for bipolar disorder by looking for increased severity of symptoms and earlier age of onset amongst bipolar individuals with large CAG/CTG repeats. METHODS: From a sample of 91 bipolar subjects, eight with large CAG/CTG (> or = 270bp) trinucleotide repeats were matched to eight bipolar individuals with small repeats (< or = 150bp). Medical charts were reviewed for age of onset and a number of severity indicators. Candidate CAG/CTG expansions on chromosomes 17 and 18 were also genotyped. RESULTS: No obvious differences were noted for the clinical indices, however seven out of eight individuals with large Repeat Expansion Detection (RED) products had expansions at the CTG18.1 locus, while four out of eight had large repeats at ERDA1. Both of these sites are unlikely to be related to disease. LIMITATIONS: Our total sample size is small and less than 9% have large repeats. CONCLUSIONS: The lack of increased severity or earlier age of onset amongst bipolar subjects with large CAG/CTG repeats suggests these repeats are unlikely to have a major etiological role in bipolar disorder.

Adult↗
PubMed1999

Analysis of genome-wide CAG/CTG repeats, and at SEF2-1B and ERDA1 in schizophrenia and bipolar affective disorder.

A shift towards larger CAG/CTG triplet repeats and schizophrenia (SCZ) and bipolar affective disorder (BPAD) has been detected by several recent studies, using the Repeat Expansion Detection (RED) technique, however no specific loci have been shown to be responsible for this shift. Further analyses by our group of RED (CTG)10 ligation products amongst an extended sample of patients and comparison with controls matched for age, sex and ethnicity show no significant differences in distribution (P= 0.23, n=95; P=0.93, n=91, for SCZ and BPAD respectively). Alleles at two recently discovered unstable trinucleotide repeat loci at 18q21.1 (SEF2-1B) and 17q21.3 (ERDA1) have also been analysed in affecteds and matched controls. We observed no increase in frequency of larger alleles (>37 repeats) in affected individuals at SEF2-1B (BPAD: P=0.95, n= 100; SCZ: P=0.61, n=97) or at ERDA1 (BPAD: P= 0.4, n = 101; SCZ: P= 0.05, n = 151, with larger alleles more frequent in controls). Our findings suggest that larger CAG/CTG repeats at these loci are neither major contributory factors to the etiology of psychosis, nor in linkage disequilibrium with a gene that is. Furthermore, when the RED results were compared to allele sizes at SEF2-1B and ERDA1, it was observed that a majority of SCZ, BPAD and control individuals with large RED products had a large allele at either or both sites (78% for RED products > or =270 bp; 62% for RED products > or =180 bp).

Adult↗
PubMed1999

Genetic association analysis of serotonin system genes in bipolar affective disorder.

OBJECTIVE: This study examined the putative role of serotonin genes in the etiology of bipolar affective disorder. METHOD: Genetic association analysis was performed for individuals with bipolar affective disorder and unaffected subjects closely matched in age, sex, and ethnic background (N=103 in each group). The allele and genotype frequencies of polymorphisms at the genes for serotonin receptors HTR1A, HTR1Dalpha, HTR1Dbeta, HTR2A, HTR2C, HTR7, tryptophan hydroxylase (TPH), and the serotonin transporter (hSERT) were compared in the two groups of subjects. RESULTS: Statistically significant positive associations were found for HTR2A and hSERT polymorphisms. However, results from an independent replication group of over 100 patients with bipolar affective disorder and their matched comparison subjects failed to confirm these associations. CONCLUSIONS: These results suggest that the serotonin genes studied are not associated with bipolar affective disorder, although transmission disequilibrium studies are required in order to confirm this conclusion.

Adult↗
PubMed1998

Major depression in individuals with a history of childhood physical or sexual abuse: relationship to neurovegetative features, mania, and gender.

OBJECTIVE: Numerous studies have linked childhood trauma with depressive symptoms over the life span. However, it is not known whether particular neurovegetative symptom clusters or affective disorders are more closely linked with early abuse than are others. In a large community sample from Ontario, the authors examined whether a history of physical or sexual abuse in childhood was associated with particular neurovegetative symptom clusters of depression, with mania, or with both. METHOD: The World Health Organization Composite International Diagnostic Interview was used to assess 8,116 individuals aged 15-64 years. Each subject was asked about early physical and sexual abuse experiences on a structured supplement to the interview. Six hundred fifty-three cases of major depression were identified. Rates of physical and sexual abuse in depressive subgroups defined by typical and reversed neurovegetative symptom clusters (i.e., decreased appetite, weight loss, and insomnia versus increased appetite, weight gain, and hypersomnia, respectively) and by the presence or absence of lifetime mania were compared by gender. RESULTS: A history of physical or sexual abuse in childhood was associated with major depression with reversed neurovegetative features, whether or not manic subjects were included in the analysis. A strong relationship between mania and childhood physical abuse was found. Across analyses there was a significant main effect of female gender on risk of early sexual abuse; however, none of the group-by-gender interactions predicted early abuse. CONCLUSIONS: These results suggest an association between early traumatic experiences and particular symptom clusters of depression, mania, or both in adults.

Adult↗
PubMed1998

Propofol anesthesia, seizure duration, and ECT: a case report and literature review.

Propofol is a nonbarbiturate anesthetic induction agent known to have anti-convulsant properties. When used as an anesthetic for electroconvulsive therapy (ECT), it can reduce seizure duration to a significant degree, which may not be fully appreciated. A case is presented in which propofol caused a 63.1% reduction in mean seizure duration compared with preceding and subsequent treatments with thiopental anesthesia. The literature on the use of propofol for ECT was reviewed with specific reference to its effect on seizure duration and any evidence of superiority to the barbiturate induction agents. It is concluded that propofol may have only very circumscribed indications as an anesthetic for ECT. If used, psychiatrists and anesthetists must be aware of its potency as an anticonvulsant.

Adult↗