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Objective: Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts.Method: Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated.Results: The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not.Conclusions: The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses. [ABSTRACT FROM AUTHOR]

Objective: The authors sought to identify factors that moderate outcome in late-life major depression and that identify patients for whom antidepressants have clinically meaningful effects. Method: A previous systematic review identified 10 placebo-controlled trials of second-generation antidepressants in outpatients with major depressive disorder who were age 60 or older. For the present study, the authors obtained from the sponsors of the 10 trials individual patient data, including age, sex, duration of illness (current age minus age at onset), course (single episode or recurrent depression), baseline depression severity, treatment assignment, and outcomes. Logistic regression models were estimated and tested to examine the association of potential moderator variables with treatment response and the treatment group-response interaction. Results: All moderator variables were collected and documented for seven of the 10 trials (N=2,283). Univariate and multivariate analyses were restricted to these seven trials. Illness duration was the only variable significantly associated with drug-placebo differences in the multivariate model. In patients with an illness duration >10 years, baseline depression severity was also significantly associated with drug-placebo differences. In those with an illness duration >10 years and a Hamilton Depression Rating Scale score ≥21, the drug-placebo difference in response rates was relatively robust (number needed to treat=4). In the remaining patients, the drug-placebo difference in response rates was small (46.3% compared with 41.5%). Conclusions: Older patients with a long illness duration and moderate to severe depression appear to benefit from antidepressants as compared with placebo. Antidepressants do not appear to be effective for older patients with short illness duration. [ABSTRACT FROM AUTHOR]