Marc-André Roy

How Prevalent Are Anxiety Disorders in Schizophrenia? A Meta-Analysis and Critical Review on a Significant Association

OBJECTIVE The presence of anxiety disorders (AD) in schizophrenia (SZ) is attracting increasing interest. However, published studies have yielded very broad variations in prevalence rates across studies. The current meta-analysis sought to (1) investigate the prevalence of co-occurring AD in SZ by reporting pooled prevalence rates and (2) identify potential sources of variations in reported rates that could guide our efforts to identify and treat these co-occurring disorders in patients with SZ. METHODS We performed a systematic search of studies reporting prevalence of AD in SZ and related psychotic disorders. Mean prevalence rates and 95% confidence intervals (CIs) were first computed for each disorder. We then examined the impact of potential moderators related to patient sampling or to AD assessment methods on these rates. RESULTS Fifty-two eligible studies were identified. Pooled prevalence rates and CIs were 12.1% (7.0%-17.1%) for obsessive-compulsive disorders, 14.9% (8.1%-21.8%) for social phobia, 10.9% (2.9%-18.8%) for generalized AD, 9.8% (4.3%-15.4%) for panic disorders, and 12.4% (4.0%-20.8%) for post-traumatic stress disorders. For all disorders, we found significant heterogeneity in rates across studies. This heterogeneity could at least partially be explained by the effect of moderator variables related to patient characteristics or assessment methods. CONCLUSIONS AD are highly prevalent in SZ, but important variations in rates are observed between studies. This meta-analysis highlights several factors that affect risk for, or detection of AD in SZ, and could, thus, have an important impact on treatment and outcome of SZ patients.

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.

Quantifying Dimensions in Autism: A Factor-Analytic Study

OBJECTIVE The objective of this study was to determine whether the phenotypic variation in autism and the related pervasive developmental disorders (PDDs) is a unitary construct or whether it is composed of distinct dimensions of autistic symptoms and measures of level of functioning. METHOD One hundred twenty-nine children with autism and other forms of PDD from two samples with different inclusion criteria were assessed with the Vineland Adaptive Behavior Scales to measure level of functioning and the Autism Diagnostic Interview to measure severity of autistic behaviors. A factor analysis with varimax rotation was performed on each sample, separately and combined. RESULTS Two factors emerged; one representing autistic symptoms and another representing level of functioning. The factor structure was remarkably similar and robust to variations in ascertainment and inclusion criteria between the samples. The validity of the distinction was supported by differences between males and females on the symptom factor, but not on the level of functioning factor. IQ was modestly correlated with level of functioning, but not with symptoms. CONCLUSIONS The phenotypic variation seen in autism/PDD is composed of at least two different dimensions of autistic symptoms and level of functioning. The implications of this dimensional heterogeneity for research, classification, and clinical practice are discussed.

6p24–22 Region and Major Psychoses in the Eastern Quebec Population

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.

Assessment of empathy in first-episode psychosis and meta-analytic comparison with previous studies in schizophrenia

Empathy is a multidimensional construct that relies on affective and cognitive component processes. A few studies have reported impairments of both cognitive and affective empathy components in patients with schizophrenia. It is, however, not known whether these difficulties are already present at psychosis onset. The affective and cognitive components of empathy were thus assessed in 31 patients with first-episode psychosis (FEP) and 31 matched healthy controls using the Interpersonal Reactivity Index (IRI). Our results were then compared to previous studies of empathy in patients with more chronic schizophrenia via a meta-analysis. In addition, we also assessed the relationship between empathy ratings, Mentalizing performance and clinical symptoms. Contrary to what has been reported in people with more chronic schizophrenia, the IRI ratings did not significantly differ between FEP and controls in our study, though a trend was observed for the Personal distress scale. For the Perspective taking scale, our meta-analysis revealed a significantly lower effect size in this study with FEP patients relative to previous schizophrenia studies. In the FEP group, the IRI ratings were not related to positive, negative or general psychopathology symptoms, but a significant relationship emerged between the Liebowitz Social Anxiety Scale and Perspective taking (negative correlation). In addition, a significant positive correlation was observed between the Empathic concern subscale and our theory of mind task. This study supports the idea that the cognitive component of empathy is less affected in patients with first-episode psychosis relative to patients with more chronic schizophrenia, and the impairments reported in previous reports with more chronic populations should be interpreted in light of a possible deterioration of this cognitive skill. The findings also provide some insight into the relationship between empathy and clinical symptoms such as social anxiety.

Shared Neurocognitive Dysfunctions in Young Offspring at Extreme Risk for Schizophrenia or Bipolar Disorder in Eastern Quebec Multigenerational Families

BACKGROUND Adult patients having schizophrenia (SZ) or bipolar disorder (BP) may have in common neurocognitive deficits. Former evidence suggests impairments in several neuropsychological functions in young offspring at genetic risk for SZ or BP. Moreover, a dose-response relation may exist between the degree of familial loading and cognitive impairments. This study examines the cognitive functioning of high-risk (HR) offspring of parents having schizophrenia (HRSZ) and high-risk offspring of parents having bipolar disorder (HRBP) descending from densely affected kindreds. METHODS The sample consisted of 45 young offspring (mean age of 17.3 years) born to a parent having SZ or BP descending from large multigenerational families of Eastern Québec that are densely affected by SZ or BP and followed up since 1989. The offspring were administered a lifetime best-estimate diagnostic procedure (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) and an extensive standard neuropsychological battery. Raw scores were compared with age- and gender-matched controls. RESULTS The offspring displayed differences in memory and executive functions when compared with controls. Moderate to large effect sizes (Cohen d) ranging from 0.65 to 1.25 (for IQ and memory) were observed. Several of the cognitive dysfunctions were present in both HRSZ and HRBP, even when considering DSM-IV clinical status. CONCLUSIONS HRSZ and HRBP shared several aspects of their cognitive impairment. Our data suggest that the extremely high genetic and familial loading of these HRs may have contributed to a quantitatively increased magnitude of the cognitive impairments in both HR subgroups, especially in memory. These offspring at heightened risk present difficulties in processing information that warrant preventive research.

Opioid medications and longitudinal risk of delirium in hospitalized cancer patients

Delirium is an important problem in hospitalized cancer patients. The objective of this study was to determine whether exposure to corticosteroids, benzodiazepines, or opioids predicted delirium.

Quetiapine in patients with comorbid schizophrenia-spectrum and substance use disorders: an open-label trial.

ABSTRACT Background: Preliminary evidence suggests that clozapine relieves the craving for psychoactive substances in schizophrenia patients. Quetiapine shares crucial pharmacological properties with clozapine. Promising results have been described with quetiapine therapy in patients with psychosis and substance use disorder. Methods: Based on Diagnostic and Statistical Manual of Mental Disorders – fourth edition (DSM‐IV) criteria, patients were diagnosed with comorbid schizophrenia-spectrum and substance use disorders. Patients were switched to quetiapine for a 12‐week open-label trial. Craving, quantities used, days of consumption, and severity of substance abuse were assessed every 3 weeks. Alcohol and Drug Use Scales were administered on baseline and end-point. Psychiatric symptoms, depressive symptoms, extrapyramidal symptoms, and cognition were also assessed at baseline, week 6 and week 12. Results: Twenty-four schizophrenia-spectrum patients were included in the last observation carried forward (LOCF) analyses, responding to one or more of the following substance use disorders: cannabis (15 patients), alcohol (10 patients), and other psychoactive substances (nine patients). Overall, severity of substance abuse improved during the study. Less weekly days were spent on drugs of abuse. A decrease in the weekly Canadian dollars spent on psychoactive substances was also observed. Cognition, psychiatric, depressive, and extrapyramidal symptoms also significantly improved ( p < 0.05). Conclusions: In this open-label, uncontrolled trial, significant improvements were noted in substance abuse, psychiatric symptoms, extrapyramidal symptoms, and cognition during quetiapine therapy. The study suffered from three main limitations: (1) the open-label design of the study; (2) the patients’ poor compliance; and (3) the small sample size involved. Controlled studies on the use of quetiapine in dual diagnosis schizophrenia are warranted to confirm that the effects are drug-related.

Adiposity and eating behaviors in patients under second generation antipsychotics.

Background: Second generation antipsychotics (SGA) induce substantial weight gain but the mechanisms responsible for this phenomenon remain speculative.

Cognitive restructuring in the treatment of psychotic symptoms in schizophrenia: A critical analysis**

This article reviews the 15 empirical studies that have used cognitive restructuring in the treatment of schizophrenia, more specifically for psychotic symptoms (delusions and hallucinations). Three elements are considered before investigating its effectiveness: (a) if subjects are reliably diagnosed with schizophrenia with chronic course and severe impairment; (b) if psychotic symptoms are adequately measured; and (c) if designs are methodologically sound. Our investigation revealed that schizophrenia is not reliably diagnosed and severity is low to moderate. Assessment of psychotic symptoms is satisfactory, but assessment of generalization to other areas is limited. Only five studies possess reliable design and are performed with schizophrenia subjects. These studies suggest that cognitive restructuring is effective to reduce or eliminate hallucinations or delusions in schizophrenia patients.