Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer ’s disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin - a peptide hormone that increases markedly during sleep - is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD. Sleep deprivation increases plaque formation and AD, which itself disrupts sleep, potentially creating a positive feedback cycle. These and other physiological benefits of sleep may be compromised by short sleep durations. Our hypothesis highlights possible long-term side effects of medications that reduce sleep, and may lead to potential new strategies for preventing and treating AD.

Previous studies have established that scores on Major Depressive Disorder scales are correlated with measures of impairment of psychosocial functioning. It remains unclear, however, whether individual depressive symptoms vary in their effect on impairment, and if so, what the magnitude of these differences might be. We analyzed data from 3,703 depressed outpatients in the first treatment stage of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Participants reported on the severity of 14 depressive symptoms, and stated to what degree their depression impaired psychosocial functioning (in general, and in the five domains work, home management, social activities, private activities, and close relationships). We tested whether symptoms differed in their associations with impairment, estimated unique shared variances of each symptom with impairment to assess the degree of difference, and examined whether symptoms had variable impacts across impairment domains. Our results show that symptoms varied substantially in their associations with impairment, and contributed to the total explained variance in a range from 0.7% (hypersomnia) to 20.9% (sad mood). Furthermore, symptoms had significantly different impacts on the five impairment domains. Overall, sad mood and concentration problems had the highest unique associations with impairment and were among the most debilitating symptoms in all five domains. Our findings are in line with a growing chorus of voices suggesting that symptom sum-scores obfuscate relevant differences between depressed patients and that substantial rewards will come from close attention to individual depression symptoms.

Background: Medical and public health scientists are using evolution to devise new strategies to solve major health problems. But based on a 2003 survey, medical curricula may not adequately prepare physicians to evaluate and extend these advances. This study assessed the change in coverage of evolution in North American medical schools since 2003 and identified opportunities for enriching medical education.

Methods: In 2013, curriculum deans for all North American medical schools were invited to rate curricular coverage and perceived importance of 12 core principles, the extent of anticipated controversy from adding evolution, and the usefulness of 13 teaching resources. Differences between schools were assessed by Pearson’s chi-square test, Student’s t-test, and Spearman’s correlation. Open-ended questions sought insight into perceived barriers and benefits.

Results: Despite repeated follow-up, 60 schools (39%) responded to the survey. There was no evidence of sample bias. The three evolutionary principles rated most important were antibiotic resistance, environmental mismatch, and somatic selection in cancer. While importance and coverage of principles were correlated (r = 0.76, P < 0.01), coverage (at least moderate) lagged behind importance (at least moderate) by an average of 21% (SD = 6%). Compared to 2003, a range of evolutionary principles were covered by 4 to 74% more schools. Nearly half (48%) of responders anticipated igniting controversy at their medical school if they added evolution to their curriculum. The teaching resources ranked most useful were model test questions and answers, case studies, and model curricula for existing courses/rotations. Limited resources (faculty expertise) were cited as the major barrier to adding more evolution, but benefits included a deeper understanding and improved patient care.

Conclusion: North American medical schools have increased the evolution content in their curricula over the past decade. However, coverage is not commensurate with importance. At a few medical schools, anticipated controversy impedes teaching more evolution. Efforts to improve evolution education in medical schools should be directed toward boosting faculty expertise and crafting resources that can be easily integrated into existing curricula.

Most measures of depression severity are based on the number of reported symptoms, and threshold scores are often used to classify individuals as healthy or depressed. This method – and research results based on it – are valid if depression is a single condition, and all symptoms are equally good severity indicators. Here, we review a host of studies documenting that specific depressive symptoms like sad mood, insomnia, concentration problems, and suicidal ideation are distinct phenomena that differ from each other in important dimensions such as underlying biology, impact on impairment, and risk factors. Furthermore, specific life events predict increases in particular depression symptoms, and there is evidence for direct causal links among symptoms. We suggest that the pervasive use of sum-scores to estimate depression severity has obfuscated crucial insights and contributed to the lack of progress in key research areas such as identifying biomarkers and more efficacious antidepressants. The analysis of individual symptoms and their causal associations offers a way forward. We offer specific suggestions with practical implications for future research.