About 17% of humanity goes through an episode of major depression at some point in their lifetime. Despite the enormous societal costs of this incapacitating disorder, it is largely unknown how the likelihood of falling into a depressive episode can be assessed. Here, we show for a large group of healthy individuals and patients that the probability of an upcoming shift between a depressed and a normal state is related to elevated temporal autocorrelation, variance, and correlation between emotions in fluctuations of autorecorded emotions. These are indicators of the general phenomenon of critical slowing down, which is expected to occur when a system approaches a tipping point. Our results support the hypothesis that mood may have alternative stable states separated by tipping points, and suggest an approach for assessing the likelihood of transitions into and out of depression. D epression is one of the main mental health hazards of our time. It can be viewed as a continuum with an absence of depressive symptoms at the low endpoint and severe and debilitating complaints at the high end (1). (Throughout this manuscript, the term "depression" refers to this continuum of depressive symptoms.) The diagnosis major depressive disorder (MDD) defines individuals at the high end of this continuum. Approximately 10-20% (2) of the general population will experience at least one episode of MDD during their lives, but even subclinical levels of depression may considerably reduce quality of life and work productivity (3). Depressive symptoms are therefore associated with substantial personal and societal costs (4,5). The onset of MDD in an individual can be quite abrupt, and similarly rapid shifts from depression into a remitted state, so-called sudden gains, are common (6). However, despite the high prevalence and associated societal costs of depression, we have little insight into how such critical transitions from health to depression (and vice versa) in individuals might be foreseen. Traditionally, the broad array of correlated symptoms found in depressed people (e.g., depressed mood, insomnia, fatigue, concentration problems, loss of interest, suicidal ideation, etc.) was thought to stem from some common cause, much as a lung tumor is the common cause of symptoms such as shortness of breath, chest pain, and coughing up blood. Recently, however, this common-cause view has been challenged (7-9). The alternative view is that the correlated symptoms should be regarded as the result of interactions of components of a complex dynamical system (7,(10)(11)(12). Consequently, new models of the etiology of depression involve a network of interactions between components, such as emotions, cognitions, and behaviors (8,9). This implies, for instance, that a person may become depressed through a causal chain of feelings and experiences, such as the following: stress → negative emotions → sleep problems → anhedonia (9, 13-15). However, the network view also implies that there can be positive feedback mechanisms between symptoms, such...

The human gastrointestinal (GI) tract microbiota acts like a virtual organ and is suggested to be of great importance in human energy balance and weight control. This study included 40 monozygotic (MZ) twin pairs to investigate the influence of the human genotype on GI microbiota structure as well as microbial signatures for differences in body mass index (BMI). Phylogenetic microarraying based on 16S rRNA genes demonstrated that MZ twins have more similar microbiotas compared with unrelated subjects (Po0.001), which allowed the identification of 35 genus-like microbial groups that are more conserved between MZ twins. Half of the twin pairs were selected on discordance in terms of BMI, which revealed an inverse correlation between Clostridium cluster IV diversity and BMI. Furthermore, relatives of Eubacterium ventriosum and Roseburia intestinalis were positively correlated to BMI differences, and relatives of Oscillospira guillermondii were negatively correlated to BMI differences. Lower BMI was associated with a more abundant network of primary fiber degraders, while a network of butyrate producers was more prominent in subjects with higher BMI. Combined with higher butyrate and valerate contents in the fecal matter of higher BMI subjects, the difference in microbial networks suggests a shift in fermentation patterns at the end of the colon, which could affect human energy homeostasis.

Genetic liability to depression is in part expressed as the tendency to display negative affect in response to minor stressors in daily life. This trait may represent a true depression endophenotype.

The study supports a causal effect of physical activity on PA. However, people with past experience of clinical depression may benefit less from the PA-inducing effect of physical activity. These findings have implications for the use of physical exercise in clinical practice.