Depression ranks as the primary emotional problem for which help is sought. Depressed people often have severe, complex problems, and rumination is a common feature. Depressed people often believe that their ruminations give them insight into their problems, but clinicians often view depressive rumination as pathological because it is difficult to disrupt and interferes with the ability to concentrate on other things. Abundant evidence indicates that depressive rumination involves the analysis of episode-related problems. Because analysis is time consuming and requires sustained processing, disruption would interfere with problem-solving. The analytical rumination (AR) hypothesis proposes that depression is an adaptation that evolved as a response to complex problems and whose function is to minimize disruption of rumination and sustain analysis of complex problems. It accomplishes this by giving episode-related problems priority access to limited processing resources, by reducing the desire to engage in distracting activities (anhedonia), and by producing psychomotor changes that reduce exposure to distracting stimuli. Because processing resources are limited, the inability to concentrate on other things is a tradeoff that must be made to sustain analysis of the triggering problem. The AR hypothesis is supported by evidence from many levels, including genes, neurotransmitters and their receptors, neurophysiology, neuroanatomy, neuroenergetics, pharmacology, cognition and behavior, and the efficacy of treatments. In addition, we address and provide explanations for puzzling findings in the cognitive and behavioral genetics literatures on depression. In the process, we challenge the belief that serotonin transmission is low in depression. Finally, we discuss implications of the hypothesis for understanding and treating depression.

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Background: Antidepressants (ADs) are commonly prescribed medications, but their long-term health effects are debated. ADs disrupt multiple adaptive processes regulated by evolutionarily ancient biochemicals, potentially increasing mortality. However, many ADs also have anticlotting properties that can be efficacious in treating cardiovascular disease. We conducted a meta-analysis assessing the effects of ADs on all-cause mortality and cardiovascular events in general-population and cardiovascular-patient samples. Methods: Two reviewers independently assessed articles from PubMed, EMBASE, and Google Scholar for AD-related mortality controlling for depression and other comorbidities. From these articles, we extracted information about cardiovascular events, cardiovascular risk status, and AD class. We conducted mixed-effect meta-analyses testing sample type and AD class as moderators of all-cause mortality and new cardiovascular events. Results: Seventeen studies met our search criteria. Sample type consistently moderated health risks. In general-population samples, AD use increased the risks of mortality (HR = 1.33, 95% CI: 1.14-1.55) and new cardiovascular events (HR = 1.14, 95% CI: 1.08-1.21). In cardiovascular patients, AD use did not significantly affect risks. AD class also moderated mortality, but the serotonin reuptake inhibitors were not significantly different from tricyclic ADs (TCAs) (HR = 1.10, 95% CI: 0.93-1.31, p = 0.27). Only “other ADs” were differentiable from TCAs (HR = 1.35, 95% CI: 1.08-1.69). Mortality risk estimates increased when we analyzed the subset of studies controlling for premedication depression, suggesting the absence of confounding by indication. Conclusions: The results support the hypothesis that ADs are harmful in the general population but less harmful in cardiovascular patients.

Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.

1317handwashing studies show that chlorhexidine hand cleanser is an easy, practical method of removing such organisms from the hands of staff, and these findings agree with those of Lowbury et all" who studied alcoholic solutions for the preoperative disinfection of surgeon's hands.The reduction in klebsiella colonisation or infection of newlyadmitted patients that coincided with increased staff handwashing, and which was sustained over two-years, provides perhaps the most convincing evidence that hands are a major, but correctable, route of transmission for Klebsiella spp.Transmission of klebsiellae from hands explains several epidemiological features of klebsiella infection we have previously observed in this ward. It explains how the serotypes contaminating food may be transmitted from the bowel of a colonised patient to clinical lesions in others, and why food types relate to patient-isolates on this ward as a whole while individual patients do not always acquire the strain that they have themselves ingested. Furthermore, such a route of transmission would contribute, via cross-infection, to the "clusters" of clinical infection and colonisation with the same serotype that we observed between 1969 and 1973. Hands may also be an important route of transmission in types of hospital-acquired klebsiella infection of obscure epidemiology, such as the spread of gentamicin-resistant klebsiella strains. Medical_Journal, 1977, 2, 1317-1319 Summary A double-blind controlled study of the effect of piperazine oestrone sulphate on sleep, depression, anxiety, and hot flushes was performed in 34 perimenopausal women. Half of the patients were given six weeks' placebo followed by eight weeks' oestrogen, and half remained on placebo throughout. Sleep was recorded electrophysiologically every week, and mood and anxiety were rated daily by means of visual analogue scales. Hot flushes were counted daily. Observer rating scales of anxiety and depression were completed at intervals.During the first month of active treatment the amount of intervening wakefulness in the first six hours of sleep decreased significantly more in the oestrone group than in those on placebo. Between the baseline period and the second treatment month the oestrone group showed a significantly greater decrease in the total amount of intervening wakefulness and in the frequency of awakenings. Their total amount of rapid eye movement sleep increased. Mood and anxiety improved and the number of hot flushes decreased to a similar degree in both groups.Although oestrogen did reduce the number of episodes of wakefulness in perimenopausal women complaining of insomnia, its effects on their psychological symptoms were little different to those of placebo.