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Biomedical subjects

M A Roy

Publications and source records attributed to M A Roy.

At least 19 recordsLinked to original sources
PubMed2001

Male gender is associated with deficit schizophrenia: a meta-analysis.

An association between deficit schizophrenia and male gender could be expected, since male schizophrenic subjects have been repeatedly found more severe than females on several dimensions of severity. Surprisingly, very few studies have confirmed such an association. We performed a more definitive test of this association using a meta-analysis. A pooled odds ratio was computed based on the 23 studies that reported the gender ratio in deficit vs. non-deficit schizophrenia. We tested for the heterogeneity of the association and examined the potential impact of the sampling method, the method used to assess the deficit syndrome, the breadth of diagnoses included and the mean duration of illness. A highly significant association between male gender and deficit schizophrenia was observed (pooled odds ratio=1.75). There was no definitive evidence that differences across studies in sampling methods, breadth of diagnoses included, mean duration of illness and methods to assess the deficit syndrome affected the strength of the association. However, the studies using the "Proxy Deficit Syndrome" method to assess the deficit syndrome yielded qualitatively weaker evidence. This significant association between male gender and deficit schizophrenia may reflect the influence of a gender related factor (e.g. sexual hormones) or gender differences in the liability to different etiologies of schizophrenia. The role of gender as a potential confounder must be closely examined in studies comparing deficit and non-deficit SZ.

Female↗
PubMed2001

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes.

We report the first stage of a genome scan of schizophrenia (SZ) and bipolar disorder (BP) covering 18 candidate chromosomal areas. In addition to testing susceptibility loci that are specific to each disorder, we tested the hypothesis that some susceptibility loci might be common to both disorders. A total of 480 individuals from 21 multigenerational pedigrees of Eastern Québec were evaluated by means of a consensus best-estimate diagnosis made blind to diagnoses in relatives and were genotyped with 220 microsatellite markers. Two-point and multipoint model-based linkage analyses were performed and mod scores (Z, for max Z(max)) are reported. The strongest linkage signals were detected at D18S1145 (in 18q12; Z = 4.03) for BP, and at D6S334 (in 6p 22-24; Z(het) = 3.47; alpha = 0.66) for SZ. Three other chromosomal areas (3q, 10p, and 21q) yielded linkage signals. Chromosomes 3p, 4p, 5p, 5q, 6q, 8p, 9q, 11q, 11p, 12q, 13q, 18p and 22q showed no evidence of linkage. The 18q12 results met the Lander and Kruglyak (1995) criterion for a genome-wide significant linkage and suggested that this susceptibility region may be shared by SZ and BP. The 6p finding provided confirmatory evidence of linkage for SZ. Our results suggest that both specific and common susceptibility loci must be searched for SZ and BP.

Adult↗
PubMed2001

Subtyping schizophrenia according to outcome or severity: a search for homogeneous subgroups.

There is a growing consensus that current definitions of schizophrenia (SZ) include different disorders, or else different dimensions underlain by different pathophysiologies. This article reviews the evidence for the validity of three novel strategies to subtype SZ according to outcome or severity (deficit vs. nondeficit, Kraepelinian vs. non-Kraepelinian, congenital vs. adult-onset). Medline and bibliographies were used to locate articles. The methodology of the studies was reviewed, and their results were grouped according to seven validating criteria. Several differences were found between subtypes, particularly for the deficit/nondeficit subtypes. However, for most of these differences, replications have yet to be undertaken. Important indicators of etiology from the environmental risk factors and genetic domains have received very little attention. These three subtyping strategies represent promising attempts to address the etiologic heterogeneity of SZ. However, one cannot conclude whether these strategies identify etiologically distinct SZ subgroups. We propose ten methodological and conceptual recommendations for future studies aimed at the identification of valid SZ subtypes according to outcome or severity.

Humans↗
PubMed2001

[Introduction to genetic psychiatry: progress in uncovering genetic susceptibility to psychiatric disorders].

The recent progress in human genetics suggests major benefits in clinical practice, including psychiatry. This article introduces the research methodology used in psychiatric genetics and explains how it is applied, for a better understanding of the challenges facing psychiatric genetics and the strategies being used to overcome them. We will review the evidence of genetic factors in psychiatric disorder etiology as well as the specificity or non-specificity of their expression. We will discuss problems associated with the approximate nature of diagnostic methods, the incomplete penetrance and the genetic heterogeneity of psychiatric disorders, the presence of phenocopies and our uncertainty concerning the mode of inheritance of psychiatric disorders. Finally, we will provide an overview of the most promising results and set out priorities for future studies.

Genetic Markers↗
PubMed2001

Intensive surveillance and treatment of dyslipidemia in the postinfarct patient: evaluation of a nurse-oriented management approach.

BACKGROUND: Lowering plasma low density lipoprotein (LDL) cholesterol concentrations in patients with established coronary artery disease is essential if recurrent cardiac events and mortality are to be prevented; however, a large proportion of patients with myocardial infarction (MI) are not screened and treated appropriately in the months immediately following hospital discharge. OBJECTIVES AND METHODS: The CHOlesterol Post-INfarct (CHOPIN) project is a nurse-centred program initiated to close the large gap between nationally centred recognized guidelines for LDL lowering and current actual practice in the secondary prevention of coronary artery disease. RESULTS: The authors report findings in 151 consecutive patients (70 years of age or less) followed for an average of 5.5+/-3.3 months. Three months after an index MI and at a time when patients started being followed in CHOPIN, 46% of patients had LDL in excess of 2.5 mmol/L and 36% had LDL greater than 3.20 mmol/L. LDL-lowering interventions undertaken comprised either consultation with a dietitian (35%) or initiation or modification of lipid-lowering medication (58%). Mean LDL on discharge from CHOPIN was 2.58+/-0.49 mmol/L, and 97% of the patients had LDL cholesterol less than 3.20 mmol/L at discharge. CONCLUSIONS: This experience shows that a nurse-based case management strategy can achieve good control of dyslipidemia in a large proportion of post-MI patients. Because intervention to lower LDL has been prospectively shown to reduce the need for coronary artery bypass and angioplasty, these results suggest that projects configured in the manner of CHOPIN should reduce hospital costs associated with cardiovascular disease.

Aged↗
PubMed2000

Significant linkage for Tourette syndrome in a large French Canadian family.

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS.

Adult↗
PubMed2000

Anticipation in schizophrenia and bipolar disorder controlling for an information bias.

Anticipation was investigated in schizophrenia (SZ) and bipolar disorder (BP) while addressing several biases in 18 large families (154 subjects) from Eastern Québec densely affected by SZ, BP, or both over three generations. In particular, we controlled for an information bias using a measure of quality and quantity of clinical information (QOI) concerning the subjects' illness. Otherwise, spurious anticipation could have arisen because we found that QOI varied with the generations as well as with the severity of illness. Although anticipation was investigated separately for SZ and BP, both disorders were also included in one analysis that tested anticipation under the unitary hypothesis that the SZ and the BP spectrums represent a continuum of severity of the same disease. Age of onset (AOO) and five indices of severity were tested for anticipation. Two statistics were used: the difference in the mean AOO or severity between two successive generations, and the mean difference in parent-offspring pairs (POP). The study led to four main findings: 1) the choice of the statistics greatly influenced the results, POP yielding systematically greater biased estimates; 2) for SZ and BP, the evidence for anticipation with the five severity indices vanished after controlling for QOI; 3) as regards AOO a decrease of 8.6 years, p = 0.0001, and 5.3 years, p = 0.009 in AOO was found for SZ between Generations 1-2, and 2-3, respectively, despite controlling for QOI and addressing all biases; and 4) conversely for BP, anticipation with AOO may be due to censoring. Findings suggest that future anticipation studies should also control for QOI. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:61-68, 2000.

Adult↗
PubMed2000

Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives.

BACKGROUND: Brain function, as indexed by brain electrical activity, is heritable in humans, and it may be impaired in autism. Autism also has strong genetic determinants, and like all major psychiatric disorders, its complex clinical phenotype renders genetic studies difficult. Innovative strategies focused on alternative biological phenotypes are needed. METHODS: The early brain auditory-evoked response was assessed in 73 autistic probands and 251 relatives who were compared with 521 normal controls. RESULTS: We first confirmed in the autistic probands the presence of a slowing in nerve conduction in the auditory system as expressed by the prolongation of early brain auditory-evoked response under the form of I-III interpeak latencies (IPLs). Furthermore, we observed the same I-III IPL prolongation in the unaffected first degree relatives of the autistic probands compared with controls. Despite clear evidence of a coaggregation of autism and I-III IPL prolongation in families, the IPLs did not seem to be the sole liability factor for autism as suggested by the observation of 52% of families in which the autistic proband and relatives showed normal IPLs. CONCLUSION: A prolongation of the early brain auditory-evoked response IPLs may be a marker for one of several deficits underlying autism and deserves further analysis as a potential alternative phenotype for the disorder.

Adult↗
PubMed2000

Longitudinal comparative study of risperidone and conventional neuroleptics for treating patients with schizophrenia. The Quebec Schizophrenia Study Group.

This study compared the long-term (12 months) effectiveness of risperidone (RP) with that of conventional neuroleptics (CNs) in a population with chronic schizophrenia who had shown suboptimal response to CNs. A randomized, open, parallel, multicenter design was used. One hundred eighty-four subjects meeting DSM-IV criteria for schizophrenia were randomly assigned to receive either RP or a CN, and 165 of them completed the follow-up. Outcome measures were taken at 3, 6, and 12 months and included the Positive and Negative Syndrome Scale (PANSS) and the Extrapyramidal Symptom Rating Scale. Within this 12-month follow-up, RP was found to be superior to CNs in terms of both the average change in score from baseline on the PANSS (p = 0.006) and the proportion of good responders (as defined by a 20% decrease in total PANSS scores;p = 0.03). For positive symptoms, the effectiveness of the RP treatment tended to increase over time. At 12 months, the percentage of good responders in the RP group was twice as large as that in the CN group (30% vs. 15%;p = 0.03). The superiority of RP over CNs was constant over the three dose categories. In both the RP and the CN groups, the maximum decrease in psychopathology was achieved with the lowest dose range. A worsening of akathisia was less frequent in subjects receiving RP than in those receiving CNs (p = 0.02). In conclusion, this study showed that, compared with CNs, RP is beneficial in the treatment of patients with chronic schizophrenia and that some of these benefits may appear only after longer-term treatment.

Adult↗
PubMed1999

Evidence of linkage in subtypes of alcoholism.

We believed that subtyping alcoholism might be an efficient strategy for mapping susceptibility genes. Cluster analysis is one of the possible statistical techniques for such a purpose. We required that, ideally, the variables to be used in cluster analysis should be: 1) related to alcoholism, 2) related to the severity of alcoholism, and 3) familial, i.e., correlated within families. Only three variables met all three conditions. Those included age of onset of ALDX1, smoking, and TPQ-HA. A global score of symptoms of alcoholism was systematically introduced as one of the variables composing a subset for cluster analysis, although this score did not show any familial aggregation. Our strategy led to a strong evidence of linkage at D15S230 in only 20 families whose members are mainly characterized by heavy smoking.

Age of Onset↗
PubMed1998

WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors.

Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1-8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12-20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis.

Amino Acid Sequence↗
PubMed1997

Selecting a control group in studies of the familial coaggregation of two disorders: a quantitative genetics perspective.

We sought to compare four different definitions of control groups in studies of the coaggregation between two disorders (A and B) on: 1) their ability to detect valid familial coaggregation; 2) their liability to artifactual evidence for familial coaggregation; and 3) their robustness to the overselection of comorbid cases. Using a quantitative genetic model of transmission, we simulated sibling pairs with familial and nonfamilial sources of comorbidity. Four different definitions of controls were tested to predict disorder B in siblings of cases vs. controls: 1) unscreened controls included subjects with A or B as well as subjects with either A or B; 2) in the symmetrical selection method, controls included only subjects without A; 3) supernormal controls included only subjects without A or B; and 4) in the pure proband method, cases included subjects with A only, and controls included only subjects without A or B. In the absence of selection bias, 1) the unscreened control and the symmetrical selection methods did not yield spurious evidence for familial coaggregation and could detect familial coaggregation; 2) the supernormal controls yielded spurious evidence of familial coaggregation; and 3) the pure proband method sometimes yielded spurious evidence for negative familial coaggregation, and had limited power to detect familial coaggregation. However, the pure proband method was the only one unaffected by overselection of comorbid cases. In the absence of selection bias, both the unscreened control and the symmetrical selection methods are appropriate, and the robustness of the pure proband method to overselection of comorbid cases may be an interesting feature in studies using clinical samples. Moreover, quantitative genetics methods may offer important advantages in the study of familial coaggregation.

Anxiety Disorders↗
PubMed1997

6p24-22 region and major psychoses in the Eastern Quebec population. Le Groupe IREP.

Recent reports of a linkage trend in 6p24-22 for schizophrenia (SZ), in different samples, were tempered by the concurrent evidence of negative reports in other samples. In the studies showing positive results, different definitions of affection and a wide spectrum of diagnoses were used. Our objectives were not only to test for linkage at 6p24-22 in the Eastern Quebec population, but also to test whether this putative vulnerability locus was either selectively linked to schizophrenia (SZ), or to bipolar disorder (BP), or to both major psychoses. Parametric and nonparametric linkage analyses with 12 microsatellite markers in 6p24-p22 were performed on a sample of 18 large multigenerational pedigrees (N = 354) either affected by SZ, or by BP, or equally affected by both major psychoses (i.e., mixed pedigrees). Three affection definitions were usually tested in our program: one on schizophrenia (SZ), one on bipolar disorder (BP), and one that comprised SZ and BP under the hypothesis of a susceptibility locus common to both in major psychoses (common locus, CL). The results of parametric analyses did not support a major gene hypothesis. However, in one large mixed pedigree (#151), we observed with the common locus phenotype (CL) lod scores of 2.49 and 2.15, respectively, at the D6S296 and D6S277 loci under a dominant model. Our data suggest the presence of a potential vulnerability locus at 6p24-22 that could be related to both schizophrenia and bipolar affective disorder. These results may be seen as congruent with former studies that used schizoaffective as well as schizophrenia diagnoses as entry criteria for the affected families, and used an affection definition that comprised affective psychoses as well as schizophrenia.

Bipolar Disorder↗
PubMed1997

Inflammatory bowel disease.

The vast majority of patients with inflammatory bowel disease experience chronic symptoms punctuated by periodic exacerbations requiring adjustments in medical therapy or surgery. True emergencies are fortunately uncommon but have been associated with high rates of morbidity and mortality. Patients presenting with fulminant colitis, toxic megacolon, or perforation require prompt identification as well as intensive medical therapy and monitoring by physicians and surgeons experienced in the care of such patients. Recent advances in the evaluation and treatment of these complicated patients are reviewed.

Abdomen, Acute↗
PubMed1997

Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure.

OBJECTIVE: The reliability and accuracy of the best-estimate diagnostic procedure were examined, and factors associated with reliability were determined. METHOD: The subjects were 134 members of large multigenerational pedigrees densely affected by bipolar disorders or schizophrenia. Three best-estimate diagnoses were derived: first, by a research psychiatrist and research assistant unblind to the relatives' diagnoses; second, by two blind independent psychiatrists; third, by a panel of four blind psychiatrists. The subjects were characterized on several clinical and methodological variables, which were used to compare the agreements of two types of best-estimate diagnoses with the disagreements. RESULTS: There was satisfactory agreement between the unblind and blind consensus best-estimate diagnoses and between the two blind independent psychiatrists. Latent class analyses revealed that limited sensitivity was the main source of imperfect reliability. Confusability analyses revealed that the most problematic diagnostic distinctions involved schizoaffective disorder, which was confused with schizophrenia, bipolar I disorder, and schizophreniform disorder. Blindness significantly affected diagnostic outcome in latent class analyses. Moreover, for diagnostic disagreements, unblind diagnoses had greater continuity with the most predominant diagnosis in the pedigree than did blind diagnoses. Diagnostic disagreements were associated with the presence of mixed affective and psychotic symptoms, less diagnostic certainty, and shorter duration of illness. CONCLUSIONS: These results suggest that it is possible to identify cases that are more likely to lead to diagnostic disagreements in family and epidemiological studies and that blind diagnoses may help to prevent false positive diagnoses, which may be particularly detrimental to genetic linkage analyses.

Adult↗
PubMed1997

Childhood/early adolescence-onset and adult-onset schizophrenia. Heterogeneity at the dopamine D3 receptor gene.

BACKGROUND: The dopamine D3 receptor gene (DRD3) is a meaningful candidate gene because it unifies the dopamine and the limbic hypotheses for schizophrenia. We tested for an allelic association between schizophrenia and the DRD3 Mscl alleles, hypothesising heterogeneity between childhood/early adolescence-onset schizophrenia (CO-SZ) and adult-onset schizophrenia (A-SZ). METHOD: The frequencies of the DRD3 alleles were compared between 70 DSM-III-R schizophrenics (35 CO-SZ and 35 A-SZ) and 79 controls. RESULTS: Compared with the controls, the subsample of A-SZ, but not CO-SZ, showed an over-proportion (P = 0.025) of allele 1. The association was not found in the total sample, combining the two subsamples. CONCLUSIONS: Consistently with former studies, our data suggest an aetiological heterogeneity between CO-SZ and A-SZ and a possible specificity of the excess of allele 1 to the familial form of schizophrenia and to schizophrenia with a better outcome.

Adolescent↗