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Cochrane Database of Systematic Reviews of cognitive rehabilitation, on a measure of self-esteem (Rosenberg Self-Esteem Scale, MD 6.3 CI 1.07-11.53) is worthy of replication in any future trials.

Major depression (MD) is a common mental disorder and a leading cause of disability worldwide. We conducted a GWAS meta-analysis of more than 1.3 million individuals, including 371,184 with MD, identifying 243 risk loci. Sixty-four loci are novel, including glutamate and GABA receptors that are targets for antidepressant drugs. Several biological pathways and components were enriched for genetic MD risk, implicating neuronal development and function. Intersection with functional genomics data prioritized likely causal genes and revealed novel enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages. We found MD to be highly polygenic, with around 11,700 variants explaining 90% of the SNP heritability. Bivariate Gaussian mixture modeling estimated that > 97% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar disorder and ADHD) are influencing MD risk when both concordant and discordant variants are considered, and nearly all MD risk variants influence educational attainment. Additionally, we demonstrated that MD genetic risk is associated with impaired complex cognition, including verbal reasoning, attention, abstraction and mental flexibility. Analyzing Danish nation-wide longitudinal data, we dissected the genetic and clinical heterogeneity, revealing distinct polygenic architectures across case subgroups of MD recurrency and psychiatric comorbidity and demonstrating two- to six-fold increases in absolute risks for developing comorbid psychiatric disorders among MD cases with the highest versus the lowest polygenic burden. The results deepen the understanding of the biology underlying MD and its progression and inform precision medicine approaches in MD.

Heritage tourism is a growing field, both from a visitation perspective and in terms of research efforts. This article adds value by reporting results of a study that estimated the economic contributions of heritage tourism in a major state in the U.S. Patterns of visitor behavior and spending detailed within these data could be used by future researchers as a benchmark for estimating the economic contribution of heritage tourism in other regions. Survey data were collected at dozens of diverse heritage-related attractions across hundreds of miles of geography in Pennsylvania using traditional printed questionnaire instruments as well as a mobile/online questionnaire instrument. A total of 3,524 completed questionnaires were collected and analyzed. The study estimated that tourists spent 7.5 million days/nights visiting survey sites, purchasing US$2 billion worth of goods and services attributable to heritage tourism. Limitations of the study are discussed along with implications for future research.