Genetics of recurrent early-onset major depression (GenRED): final genome scan report.

OBJECTIVE: The authors carried out a genomewide linkage scan to identify chromosomal regions likely to contain genes that contribute to susceptibility to recurrent early-onset major depressive disorder, the form of the disorder with the greatest reported risk to relatives of index cases. METHOD: Microsatellite DNA markers were studied in 656 families with two or more such cases (onset before age 31 in probands and age 41 in other relatives), including 1,494 informative "all possible" affected relative pairs (there were 894 independent affected sibling pairs). Analyses included a primary multipoint allele-sharing analysis (with ALLEGRO) and a secondary logistic regression analysis taking the sex of each relative pair into account (male-male, male-female, female-female). RESULTS: Genomewide suggestive evidence for linkage was observed on chromosome 15q25-q26 (at 105.4 centimorgans [cM]). The authors previously reported genomewide significant linkage in this region in the first 297 families. In the secondary analysis, after empirical genomewide correction for multiple testing, suggestive linkage results were observed on chromosome 17p12 (28.0 cM, excess sharing in male-male and male-female pairs) and on chromosome 8p22-p21.3 (25.1 cM, excess sharing in male-male pairs). CONCLUSIONS: These regions of chromosomes 15q, 17p, and 8p might contain genes that contribute to susceptibility to major depression and related disorders. Evidence for linkage has been reported independently in the same regions of chromosome 15q for major depression and of chromosome 8p for related personality traits.

Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.

OBJECTIVE: The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. METHOD: In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. RESULTS: The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (Z(LR))=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum Z(LR) for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases. CONCLUSIONS: This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.

Cognitive therapy vs medications in the treatment of moderate to severe depression.

BACKGROUND: There is substantial evidence that antidepressant medications treat moderate to severe depression effectively, but there is less data on cognitive therapy's effects in this population. OBJECTIVE: To compare the efficacy in moderate to severe depression of antidepressant medications with cognitive therapy in a placebo-controlled trial. DESIGN: Random assignment to one of the following: 16 weeks of medications (n = 120), 16 weeks of cognitive therapy (n = 60), or 8 weeks of pill placebo (n = 60). SETTING: Research clinics at the University of Pennsylvania, Philadelphia, and Vanderbilt University, Nashville, Tenn. PATIENTS: Two hundred forty outpatients, aged 18 to 70 years, with moderate to severe major depressive disorder. INTERVENTIONS: Some study subjects received paroxetine, up to 50 mg daily, augmented by lithium carbonate or desipramine hydrochloride if necessary; others received individual cognitive therapy. MAIN OUTCOME MEASURE: The Hamilton Depression Rating Scale provided continuous severity scores and allowed for designations of response and remission. RESULTS: At 8 weeks, response rates in medications (50%) and cognitive therapy (43%) groups were both superior to the placebo (25%) group. Analyses based on continuous scores at 8 weeks indicated an advantage for each of the active treatments over placebo, each with a medium effect size. The advantage was significant for medication relative to placebo, and at the level of a nonsignificant trend for cognitive therapy relative to placebo. At 16 weeks, response rates were 58% in each of the active conditions; remission rates were 46% for medication, 40% for cognitive therapy. Follow-up tests of a site x treatment interaction indicated a significant difference only at Vanderbilt University, where medications were superior to cognitive therapy. Site differences in patient characteristics and in the relative experience levels of the cognitive therapists each appear to have contributed to this interaction. CONCLUSION: Cognitive therapy can be as effective as medications for the initial treatment of moderate to severe major depression, but this degree of effectiveness may depend on a high level of therapist experience or expertise.

Dieting and the development of eating disorders in obese women: results of a randomized controlled trial.

BACKGROUND: Some investigators fear that dieting may precipitate binge eating and other adverse behavioral consequences. OBJECTIVE: The objective of the study was to examine whether dieting would elicit binge eating and mood disturbance in individuals free of these complications before treatment. DESIGN: A total of 123 obese women were randomly assigned to 1) a 1000 kcal/d diet that included 4 servings/d of a liquid meal replacement (MR); 2) a 1200-1500 kcal/d balanced deficit diet (BDD) of conventional foods; or 3) a nondieting (ND) approach that discouraged energy restriction. All women attended weekly group sessions for 20 wk and biweekly sessions from week 20 to week 40. RESULTS: At week 20, participants in the MR, BDD, and ND groups lost 12.1 +/- 6.7%, 7.8 +/- 6.0%, and 0.1 +/- 2.4% of initial weight, respectively (P < 0.001). During the first 20 wk, there were no significant differences among groups in the number of persons who had objective binge episodes or in reports of hunger or dietary disinhibition. Symptoms of depression decreased significantly more (P < 0.001) in the MR and BDD groups than in ND participants. At week 28, significantly more (P < 0.003) cases of binge eating were observed in MR participants than in the 2 other groups. No differences, however, were observed between groups at weeks 40 or 65 (a follow-up visit). At no time did any participant meet criteria for binge-eating disorder. CONCLUSION: Concerns about possible adverse behavioral consequences of dieting should not dissuade primary care providers from recommending modest energy restriction to obese individuals.

Therapist interventions in the interpersonal and cognitive therapy sessions of the Treatment of Depression Collaborative Research Program.

This report provides a descriptive evaluation of the therapist interventions implemented in the cognitive and interpersonal sessions of the Treatment of Depression Collaborative Research Program. 135,552 therapist statements drawn from 548 treatment sessions were coded for response mode category, time frame, and person. Therapists in both treatments were quite active, using predominantly clarifications, questions, and facilitative comments focused on the present time frame. The treatments also revealed important differences: cognitive therapists used more questions, restatements, and information/directional statements. Variance component analyses further revealed that differences between patients and between therapists explained a significant amount of variance in therapist response modes, indicating that manual-guided treatments can still reveal flexibility to address unique patient needs.

Retention in psychosocial treatment of cocaine dependence: predictors and impact on outcome.

This report describes retention in treatment in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (CCTS), a multi-site trial of four psychosocial treatments for 487 cocaine dependent patients. Younger, African-American, and unemployed patients were retained in treatment for fewer days than their counterparts. African-American patients who lived with a partner were retained in treatment for less time than if they lived alone. Higher psychiatric severity kept men in treatment longer but put women at risk for dropping out sooner. Patients who completed the full treatment used drugs less often than patients who dropped out, but outcome did not differ at each month. Patients in the drug counseling condition stayed in treatment for fewer days than patients in psychotherapy, but they were more likely to be abstinent after dropout. Patients with higher psychiatric severity were more at risk for continuing to use drugs after dropout.