Posts tagged depression

Chronic stress, neurogenesis and depression

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Diagram of hippocampal regions in a rat brain....
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Chronically stressful life events have been shown to lead to depression. Chronic stress leads to hyperactivity of HPA axis leading to more glucocorticoids (cortisol) in the human body. This excess cortisol in term is proposed to underlie the affective symptoms of depression. Also, depressive people have been found to have up to 20% smaller hippocampal volume, and a recent theory is gaining ground that depression is due to reduced neurogenesis. Even if the entire spectrum of depressive symptoms is not due to reduced neurogenesis and atrophied or smaller hippocampus, at least the cognitive symptoms of depression are largely due to this.

I stumbled upon a commentary by Robert Sapolsky that although is 10 years old, but I still found interesting and worth bringing to notice of my dear readers. In it Sapolsky looks at a study by Czeh et al that found evidence linking reduced proliferation in dentate gyrus and a shrunken hippocampus to depressive stress as modeled by psycho-social stress paradigm in tree shrew. Also, they found that an antidepressant, tianeptine, reversed the effects of stress by restoring proliferation and hippocampus size and thus reversing symptoms of depression. However the level of glucorticiods were still higher, after anti-depressant treatment, and thus it is apparent that anti-depressants work downstream of stress induced increase in glucorticoids.

Sapolsky believes that the data support either of models presented in figure 1A or figure 1B i.e. the increased glucocrticoids can lead to shrinkage of hippocampus directly or through their effect on affective symptoms. I believe figure 1C is also possible and its not necessarily incompatible with 1A or 1B and that increased stress may lead to increased cortisol- may lead to reduced neurogenesis may lead to shrinkage of hippocampus and which may in turn lead to affective and cognitive symptoms.

An alternative to reduced neurogenesis/ proliferation theory is the dendritic atrophy/ neurotoxicity theory that posits that shrinkage of hippocampus is due to cell death/ white matter loss. This again is a possibility but the evidence in favor of reduced neurogenesis is growing and becoming strong by the day.

Overall the new paradigms in depression research that look beyond serotonin or mono amine imbalance is a welcome trend and hopefully would lead to better interventions and prevention strategies and not just better pharmaceutical innovations. Its time one realized the rile chronic stress play sin depression and how that can be easily prevented to reduce the mental health burden.

Sapolsky, R. (2001). Depression, antidepressants, and the shrinking hippocampus Proceedings of the National Academy of Sciences, 98 (22), 12320-12322 DOI: 10.1073/pnas.231475998
Czeh, B. (2001). Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine Proceedings of the National Academy of Sciences, 98 (22), 12796-12801 DOI: 10.1073/pnas.211427898

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Happiness opposed to despair/ennui; sadness to anger/irritability

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We normally view happiness and sadness to be opposites on a single continuum, but I propose that it is time to change the textbooks and view happiness as opposed to ennui/despair and sadness as opposed to anger/irritability when it comes to basic opponent affects.

But before we go down that path first a detour.

I recently read Flourishing: edited by Keyes & Haidt , and the last article by Keyes caught my attention. I looked up a few more articles by Keyes and found this one that again elaborates on the theory put forward in the book chapter.

The point Keyes wants to make is that mental illness and mental health are two different things and are relatively independent of each other. Traditionally mental health has been conceptualized as the absence of mental illness, but Keyes says that our intuitions are incorrect here and mental health is another, parallel continuum on which people can differ.

Throughout human history, there have been three conceptions of health.The pathogenic approach is the first, most historically dominant vision, derived from the Greek word pathos, meaning suffering or an emotion evoking sympathy. The pathogenic approach views health as the absence of disability, disease, and premature death. The second approach is the salutogenic approach, which can be found in early Greek writings and was popularized by Antonovsky (1979) and humanistic scholarship (e.g., Carl Rogers and Abraham Maslow). Derived from the word salus, meaning health, the salutogenic approach views health as the presence of positive states of human capacities and functioning in thinking, feeling, and behavior (Stru¨mpfer, 1995). The third approach is the complete state model, which derives from the ancient word for health as being hale, meaning whole and strong. This approach is exemplified in the World Health Organization’s (1948) definition of overall health as a complete state, consisting of the presence of a positive state of human capacities and functioning as well as the absence of disease or infirmity. By subsuming the pathogenic and salutogenic paradigms, the whole states approach is, in my opinion, the only paradigm that can achieve true population health.

Thus when we talk of whole states mental health we are basically talking about two related things- a mental illness or disability dimension and a flourishing or mental health dimension. Keyes et al have performed confirmatory factor analysis on measure used to measure mental health and illness and found that the data is best explained by two latent factors-one related to flourishing and the other to illness.

This is how they define mental health or flourishing dimension.

Until recently, mental health remained undefined, unmeasured, and therefore unrecognized at the level of governments and nongovernmental organizations. In 1999, the Surgeon General, then David Satcher, conceived of mental health as “a state of successful performance of mental function, resulting in productive activities, fulfilling relationships with people, and the ability to adapt to change and to cope with adversity” (U.S. Public Health Service, 1999, p. 4). In 2004, the World Health Organization published a historic first report on mental health promotion, conceptualizing mental health as not merely the absence of mental illness but the presence of “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community” (World Health Organization, 2004, p. 12).

Keyes comes up with 13 symptoms of mental health and these include Positive emotions (i.e., emotional well-being) including positive affect and avowed quality of life; Positive psychological functioning (i.e., psychological well-being) consisting of self-acceptance, positive relations with others, personal growth, purpose in life, environmental mastery, and autonomy (see Keyes & Ryff, 1999); and Positive social functioning (i.e., social well-being) consisting of social coherence, social actualization, social integration, social acceptance, and social contribution. In DSM style they propose that individuals exhibit some minimum symptoms to classify as flourishing and those with very low scores be classified as languishing.

To be diagnosed as flourishing in life, individuals must exhibit high levels on at least one measure of hedonic well-being and high levels on at least six measures of positive functioning. Individuals who exhibit low levels on at least one measure of hedonic well-being and low levels on at least six measures of positive functioning are diagnosed as languishing in life. Adults who are moderately mentally healthy do not fit the criteria for either flourishing or languishing in life.

Keyes then goes on to show the costs of languishing and not focusing on mental health and why a narrow focus on cure/prevention of mental illness is detrimental, but that is beside the point as to today’s topic. what is most important take way for today is that there are two separate factors of mental health and mental illness.

This brings us back to the affects- happiness, sadness, ennui/despair and anger/irritability. Consider for a moment depression. It is an illness characterized by sad mood and anhedonia etc. Consider its counterpart on the illness spectrum. while a normal person not having depression may seem the counterpart, the real counterpart is mania which often has a angry/irritable mood (alongside euphoria) associated with it. Also depression is characterized as a reaction to losses/continuous exposure to stresses that makes goals out of reach/unachievable. Here the focus is preventive in nature- the state does not deteriorate further and goals do not remain unmet. However, depression or sad mood is also an avoidance reaction. One becomes withdrawn from the situation and does not fight the stress, but flights from the stress by withdrawing in a cocoon. The loss of appetite and more sleep can be seen as behavioral counterparts of withdrawing or exhibiting a flight response to stress.

As opposed to this, mania can be seen behaviorally as an active approach state in which one works actively towards the things required to overcome the loss of valued entity/life goal. Again, I propose that mania is a reaction to a situation similar to depression – when something is lost/ is under threat of losing- but this time , under stress, one fights and not flights- thus one becomes energized to right the wrong and may become angry/ irritable if the efforts to retain goals/ valued entities are frustrated by external world. It is important that both mania and depression are on the illness scale of functioning/ mental health and are a result of life trauma/ stress/ perceived/ real/ threat of loss of loved object/person. Thus the focus is preventive and the state is of scarcity.

Contrast this to a state of abundance when ones (life) goals have been met/ are within reach.// This apparent positive state of affairs may again give rise to different emotions/ behavioral manifestations depending on whether one has approach or avoidance dominant reaction. If one approaches the more free time available after goal accomplishment as a boon that can be used to home ones hobbies/find other meaning in life/ build relationships etc and not as a threat ( free time can be a threat) then one experiences positive emotion of happiness and behaviorally flourishes.

In contrast consider a similar person who has achieved everything in life – (a good job, wife, kids etc ) , but given the fact that one is living in abundance is frightened or flights from the free time that has been made available. that person will be listless, will exhibit ennui or boredom and may even exhibit despair as he finds life meaningless. Thus behaviorally he would languish.

Thus, I rest my case that happiness is opposed to ennui/despair while sadness is opposed to anger/irritability and while happiness is a measure of flourishing; sadness is a measure of illness. One can definitely conduct experiments , perform factor analysis to confirm, that indeed happiness and sadness is not a unitary construct, but are two separate but related dimensions. I would love to hear your comments.

Keyes, C. (2007). Promoting and protecting mental health as flourishing: A complementary strategy for improving national mental health. American Psychologist, 62 (2), 95-108 DOI: 10.1037/0003-066X.62.2.95

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Am happy, will seek novelty; am sad, will stick with familiar

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NEW YORK - SEPTEMBER 07:  A man exercises on t...
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I have earlier written about the entrepreneurial roller-coaster and how when entrepreneurs are in a happy mood, they focus on long-term vision related creativity; while when they are in negative mood they focus on the task at hand. I had also tried to relate this to prevention and promotion focus and weave it in the narrative of preventive focus as depressive and promotion focus as being manic in nature.

Another bit of research extends the thesis and adds to our knowledge base. This new article by Winkielman et al suggest that people in sad mood tend to value familiarity whereas those in a happy mood are more open and welcoming of novelty.

Here is the abstract of the study:

People often prefer familiar stimuli, presumably because familiarity signals safety. This preference can occur with merely repeated old stimuli, but it is most robust with new but highly familiar rototypes of a known category (beauty-in-averageness effect). However, is familiarity always warm? Tuning accounts of mood hold that positive mood signals a safe environment, whereas negative mood signals an unsafe environment. Thus, the value of familiarity should depend on mood. We show that compared with a sad mood, a happy mood eliminates the preference for familiar stimuli, as shown in measures of self-reported liking and physiological measures of affect (electromyographic indicator of spontaneous smiling). The basic effect of exposure on preference and its modulation by mood were most robust for prototypes (category averages). All this occurs even though prototypes might be more familiar in a happy mood. We conclude that mood changes the hedonic implications of familiarity cues.

The authors reasoning is as follows:

Happy or sad mood signal the safety of the environment.

Much psychological research points out that one signal of environmental safety or danger is an individual’s mood (e.g., Clore, Schwarz, & Conway, 1994; Schwarz, 2002). Bad mood signals a problem, tuning individuals toward safety concerns, whereas good mood signals that an environment is benign. Tuning accounts assume that mood adjusts cognitive and affective reactions so that they best serve the individual in the specific context.

In a safe environment, one can experiment or value novelty. In an unsafe environmental it makes sense to stick to tried and proven things.

After all, familiarity is only a heuristic cue to safety. Thus, as with any heuristic cue, its validity and hedonic meaning vary by context (Hertwig, Herzog, Schooler, & Reimer, 2008). Specifically, the familiarity-positivity link should depend on whether individuals are tuned toward safety concerns. Familiarity should be valued in an unsafe environment, but less so in a benign environment (e.g., Bornstein, 1989). Analogously, in a strange city a familiar face elicits a warm glow, whereas locally the same face prompts a yawn. Numerous studies (and parents) have observed that in unsafe environments infants are neophobic, but in safe settings, they are less so (Shore, 1994). Similarly, in multiple species, stress increases neophobia, whereas comfort reduces it.

Thus they hypothesize that sad mood should lead to mare liking for familiarity while happy mood should lead to novelty preference. They do some clever experimentation and get exactly the same result.

To me this is extension of promotion focus is expansive, is happy, is creative and long-term, and is novelty preferring versus prevention focus is restrictive, is sad, is focused on the task at hand, and is familiarity preferring. In other words people in safe environments having promotion focus are manic while those in unsafe environments and having prevention focus are depressive.

Another finding that struck out from the current paper was that the (false) memory for prototype was increased in positive mood condition. This is congruent with the fact that the promotion focus / mania condition has a more narrative focus that tries to weave a narrative around things and remembers a gist rather than is accuracy based and tries to recall the exact events. thus, I believe the risk of delusions and hallucinations magnifies as one goes deep into promotion focus / mania and starts weaving narratives and having false prototypical memories of events/happenings.

de Vries, M., Holland, R., Chenier, T., Starr, M., & Winkielman, P. (2010). Happiness Cools the Warm Glow of Familiarity: Psychophysiological Evidence That Mood Modulates the Familiarity-Affect Link Psychological Science DOI: 10.1177/0956797609359878

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