Chantal Mérette

Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial.

CONTEXT Cognitive behavioral therapy (CBT) and hypnotic medications are efficacious for short-term treatment of insomnia, but few patients achieve complete remission with any single treatment. It is unclear whether combined or maintenance therapies would enhance outcome. OBJECTIVES To evaluate the added value of medication over CBT alone for acute treatment of insomnia and the effects of maintenance therapies on long-term outcome. DESIGN, SETTING, AND PATIENTS Prospective, randomized controlled trial involving 2-stage therapy for 160 adults with persistent insomnia treated at a university hospital sleep center in Canada between January 2002 and April 2005. INTERVENTIONS Participants received CBT alone or CBT plus 10 mg/d (taken at bedtime) of zolpidem for an initial 6-week therapy, followed by extended 6-month therapy. Patients initially treated with CBT attended monthly maintenance CBT for 6 months or received no additional treatment and those initially treated with combined therapy (CBT plus 10 mg/d of zolpidem) continued with CBT plus intermittent use of zolpidem or CBT only. MAIN OUTCOME MEASURES Sleep onset latency, time awake after sleep onset, total sleep time, and sleep efficiency derived from daily diaries (primary outcomes); treatment response and remission rates derived from the Insomnia Severity Index (secondary outcomes). RESULTS Cognitive behavioral therapy used singly or in combination with zolpidem produced significant improvements in sleep latency, time awake after sleep onset, and sleep efficiency during initial therapy (all P<.001); a larger increase of sleep time was obtained with the combined approach (P = .04). Both CBT alone and CBT plus zolpidem produced similar rates of treatment responders (60% [45/75] vs 61% [45/74], respectively; P = .84) and treatment remissions (39% [29/75] vs 44% [33/74], respectively; P = .52) with the 6-week acute treatment, but combined therapy produced a higher remission rate compared with CBT alone during the 6-month extended therapy phase and the 6-month follow-up period (56% [43/74 and 32/59] vs 43% [34/75 and 28/68]; P = .05). The best long-term outcome was obtained with patients treated with combined therapy initially, followed by CBT alone, as evidenced by higher remission rates at the 6-month follow-up compared with patients who continued to take zolpidem during extended therapy (68% [20/30] vs 42% [12/29]; P = .04). CONCLUSION In patients with persistent insomnia, the addition of medication to CBT produced added benefits during acute therapy, but long-term outcome was optimized when medication is discontinued during maintenance CBT. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00042146.

The natural history of insomnia: a population-based 3-year longitudinal study.

BACKGROUND Despite its high prevalence, little information is available about the natural history of insomnia. The extent to which episodes of insomnia will persist or remit over time is difficult to predict. We examined the natural history of insomnia and describe the most common trajectories over 3 years. METHODS Three hundred eighty-eight adults (mean [SD] age, 44.8 [13.9] years; 61% women) were selected from a larger population-based sample on the basis of the presence of insomnia at baseline. They completed standardized sleep/insomnia questionnaires at 3 annual follow-up assessments. For each follow-up assessment, participants were classified into 1 of 3 groups (individuals with an insomnia syndrome, individuals with insomnia symptoms, and individuals with good sleep) on the basis of algorithms using standard diagnostic criteria for insomnia. Rates of persistent insomnia, remission, and relapse were computed for each group. RESULTS Of the study sample, 74% reported insomnia for at least 1 year (2 consecutive assessments) and 46% reported insomnia persisting over the entire 3-year study. The course of insomnia was more likely to be persistent in those with more severe insomnia at baseline (ie, insomnia syndrome) and in women and older adults. Remission rate was 54%; however, 27% of those with remission of insomnia eventually experienced relapse. Individuals with subsyndromal insomnia at baseline were 3 times more likely to remit than worsen to syndrome status, although persistence was the most frequent course in that group as well. CONCLUSION These findings indicate that insomnia is often a persistent condition, in particular when it reaches the diagnostic threshold for an insomnia disorder.

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.

Meta-analysis of 32 genome-wide linkage studies of schizophrenia

A genome scan meta-a nalysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (PSR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142–168 Mb) and 2q (103–134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119–152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for ‘aggregate’ genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16–33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.

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 Zmax) are reported. The strongest linkage signals were detected at D18S1145 (in 18q12; Z = 4.03) for BP, and at D6S334 (in 6p 22–24; Zhet = 3.47; α = 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.

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.

Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial

BACKGROUND Psychological distress (PD) and depressive symptoms are commonly observed during menopausal transition. Studies suggest that omega-3 (n-3) fatty acids may help alleviate depression. OBJECTIVE The objective was to compare enriched ethyl-eicosapentaenoic acid (E-EPA) supplementation with placebo for the treatment of PD and depressive symptoms in middle-aged women. DESIGN Women with moderate-to-severe PD (n = 120) were randomly assigned to receive 1.05 g E-EPA/d plus 0.15 g ethyl-docosahexaenoic acid/d (n = 59) or placebo (n = 61) for 8 wk. The main outcomes were 8-wk changes in PD scores [Psychological General Well-Being Schedule (PGWB)] and depressive scales [20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the 21-item Hamilton Depression Rating Scale (HAM-D-21)]. RESULTS At baseline, women with PD were mildly to moderately depressed, and 24% met the major depressive episode (MDE) criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. After 8 wk, outcomes improved in both groups, but no significant differences were noted between them. Stratification analyses for MDE diagnosis at baseline indicated that differences in adjusted 8-wk changes between the E-EPA group without MDE (n = 46) and the placebo group (n = 45) were 8.0 (95% CI: 0.6, 15.3; P = 0.034) for the PGWB, -0.2 (95% CI: -0.01, -0.4; P = 0.040) for the HSCL-D-20, and -2.7 (95% CI: -0.3, -5.1; P = 0.030) for the HAM-D-21. Differences in adjusted 8-wk changes between the E-EPA group with MDE (n = 13) and the placebo group (n = 16) were not significant. CONCLUSIONS To our knowledge, this is the first trial of n-3 supplementation in the treatment of PD and depressive symptoms in middle-aged women. In women with PD without MDE at baseline, the 8-wk changes in PD and depressive scales improved significantly more with E-EPA than with placebo. This trial was registered at http://www.controlled-trials.com as ISRCTN69617477.

Prevalence of Insomnia and its Treatment in Canada

Objectives: To estimate the prevalence of insomnia and examine its correlates (for example, demographics and physical and mental health) and treatments. Methods: A sample of 2000 Canadians aged 18 years and older responded to a telephone survey about sleep, health, and the use of sleep-promoting products. Respondents with insomnia were identified using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and the International Classification of Diseases, Tenth Edition, criteria. Results: Among the sample, 40.2% presented at least 1 symptom of insomnia (that is, trouble falling or staying asleep, or early morning awakening) for a minimum of 3 nights per week in the previous month, 19.8% were dissatisfied with their sleep, and 13.4% met all criteria for insomnia (that is, presence of 1 insomnia symptom 3 nights or more per week for at least 1 month, accompanied by distress or daytime impairment). Insomnia was associated with female sex, older age, and poorer self-rated physical and mental health. Thirteen per cent of respondents had consulted a health care provider for sleep difficulties once in their lifetime. Moreover, 10% had used prescribed medications for sleep in the previous year, 9.0% used natural products, 5.7% used over-the-counter products, and 4.6% used alcohol. There were differences between French- and English-speaking adults, with the former group presenting lower rates of insomnia (9.5%, compared with 14.3%) and consultation (8.7%, compared with 14.4%), but higher rates of prescribed medications (12.9%, compared with 9.3%) and the use of natural products (15.6%, compared with 7.4%). Conclusions: Insomnia is a prevalent condition, although few people seek professional consultation for this condition. Despite regional differences in the prevalence and treatments used to manage insomnia, prescribed medications remain the most widely used therapeutic option.

Informative phenotypes for genetic studies of psychiatric disorders.

Despite its initial promise, there has been both progress and some set backs in genetic studies of the major psychiatric disorders of childhood and adulthood. Finding true susceptibility genes may be delayed because the most genetically informative phenotypes are not being used on a regular basis in linkage analysis and association studies. It is highly likely that using alternative phenotypes instead of DSM diagnostic categories will lead more rapid success in the search for these susceptibility genes. The objective of this paper is to describe the different types of informative phenotypes that can be employed in psychiatric genetic studies, to clarify their uses, to identify several methodologic issues the design and conduct of linkage and association studies that use alternative phenotypes and finally to suggest possible solutions to those difficulties. This is a conceptual review with a focus on methodological issues that may arise in psychiatric genetics and examples are taken from the literature on autism, schizophrenia, bipolar disorder, and alcoholism.

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.