Storm Clouds Hover Over a Village

Stress and Depression

How much is too much of anything? We often judge poorly. A youngster fails to finish a banana split and an old (or not so old) person tries to lift suitcases that the arms can hoist but the vertebrae can’t support.

Psychological stress is even harder to judge. We confuse stressors at work with our response to them. We grow up unaware of the long-term effects of childhood trauma. We are resilient until suddenly we aren’t, and it shows up in many ways.

Most of us have heard that stress can become overwhelming, perhaps leading to emotional problems.

The brain mediates the emotional effects of stress, and so chronic stress becomes visible in behavioral disorders such as depression. As the post on resilience outlined, chronic stress also triggers chronic inflammation that can occur in any part of the body, including the brain. Chronic inflammation is one cause of mental illness. Is this cause and effect?

Obviously stress, inflammation and depression are common conditions in our society, so positive correlations among them might arise for many reasons. This discussion is intended to open up the links and make them more specific, without intending to suggest that all depression arises from inflammation or that inflammation inevitably leads to depression.

Physicians can test for chronic inflammation; we can’t. So, while remembering that a little stress is good, it’s worth monitoring our stress to tell when it’s getting over the limit. Man or woman, chronic stress is not good.

I will emphasize that I am neither a physician nor a clinical psychologist. My Ph.D. is in the area of psychology that is now labeled behavioral neuroscience. Though I am not a disease specialist, we can’t escape questions about the psychological effects of SARS-CoV-2 virus and the COVID-19 disease that it causes as we address this topic.

Some salient facts are that COVID-19 is often followed by psychological disorders, including depression. This has been true of other large-scale disasters. You may wish to visit this meaty article (also available here) and a lighter discussion of it there. You can explore the physical effects at this interactive website.

Not only the patients but the health professionals who care for them, as well as relatives and  bystanders, may also be affected.

And yet it is not yet clear how these outcomes occur. The disease itself is not the only traumatizing event. An intensive-care unit can drive extreme anxiety. Hospitalization will leave uninsured patients in financial distress.

The pandemic is a serious stressor for patients and many others. However, as we will see, the brain inflammation that often brings about depression does not necessarily require a virus. It can occur without a responsible pathogen

(Diligent reading may turn up questions about cytokine storms triggered by inflammation. This description and that one will bring clarity, I hope.)

Broken Doll Head with Other Doll Pieces

BIO: Although the whole body is affected by the stress response, it’s the brain that organizes behavior to cope with it. If only by forcing a response, chronic stress changes the brain, targeting particularly the amygdala, hippocampus and prefrontal cortex.

In the amygdala, the stress response is associated with hyperactivity, which may be responsible for the itchiness some folks feel when they’re under pressure. More seriously, heightened amygdaloid activity is positively correlated with a variety of functional neurological symptom disorder called a conversion disorder.

Chronic stress may cause abnormalities in the hippocampus and prefrontal cortex as well, and trigger excessive production of myelin. (While myelin loss is harmful and moderate increases are helpful in learning, dysregulation can impair normal brain activity.)

How does stress change the brain so menacingly? Prominent changes have been seen in dendrites, including a loss of dendritic spines and abnormal development, with chronic stress. Consider that dendrites are the sites of connection for synapses with other neurons and that the smallest glia, called microglia, actively maintain normal dendritic growth.

However, chronic stress disturbs the normal pattern of support. Instead, stress provokes inflammation that can spread into the brain via mechanisms that are probably not necessary here.

Brain scientists are rethinking microglia. In short-term or acute stress, microglia can  multiply to increase inflammation. They have an initially healthy effect. They maintain our synapses and prune away unused synapses. They regulate neurogenesis.

But when chronic stress affects the brain, the work of the microglia turns harmful. They “turn rogue” and destroy  synaptic connections. Chronic inflammation causes a number of diseases. Perhaps not coincidentally, excessive pruning is one of the contributors to schizophrenia. Destructive microglia are increasingly linked to depression.

PSYCHO: To review briefly, acute stress and acute inflammation are helpful, while chronic stress and inflammation are not helpful, contributing to mental illness even decades after trauma. As this occurs, microglia that normally support healthy synaptic organization in the brain become disruptive.

If this is the whole story, it follows that mental health professionals should focus treatments for mental illness on counteracting inflammation.

Two reasons for caution are that anti-inflammatory drugs have not been panaceas, and brain inflammation seems not to be the whole story about mental illness. It omits an interesting explanatory loop through the intestines, the enteric nervous system, the vagus nerve, and back to the brain to change our moods.

Activation of microglia in the brain may recruit bacteria* residing in the gut to depress hippocampal activity and contribute to depression. Alternatively, it may be the absence of some bacterial species in the intestines that brings on depression. Or perhaps either may occur.

This is far from a settled area of research, fascinating though the microbiome is. Further introductions are available here, there, and yonder. The gut-brain axis is useful, too. The story about how our intestinal bacteria shape the mind via the gut-brain axis may have begun with the encapsulation of the stress response in the HPA axis, or HPAA, which is a top-down alarm system that unites the brain with the adrenal glands. The gut-brain axis is top-down and bottom-up; it both informs the brain and carries out the brain’s commands using the vagus nerve (cranial nerve X or 10). Despite large individual differences in behavior that influence the gut-brain axis, there is hope that it may open new avenues for treatment of psychological disorders.

Including our intestines in the explanation of mental illness brings us closer to understanding mental illness. There remain two reasons for caution: Gut bacteria vary for reasons that seem to have little to do with different psychological challenges, and people sharing the same disorder may differ a lot in their bacterial endowment.

*Most of the cells in the body are microbes, and most of these are bacteria in the intestines. Bacteria in the big intestine, the colon, are the ones that make gas that we expel as (flammable) farts.

SOCIAL: A psychological disorder might appear “social” because we exhibit it because of the social group we belong to.

Or it might be a social trait displayed by individuals as a result of evolution.

One of the problems is that we’re stuck with coping mechanisms that evolved millions of years ago in mammals who were not civilized. (Maybe there were treatments back then that we’ve overlooked?) 

So now we feel a killing rage when a driver cuts in front of us. The fight-or-flight response erupts in a job interview.

It’s no joke. Medical researchers have suggested that the change from caveman to commuter puts us in a mismatch that causes disease. Even the mismatch hypothesis is not enough for some to accept the possibility that genes for mental illness evolved because they gave us more adaptive traits.

Furthermore, it is an oversimplification to hope to find a gene “for” schizophrenia or depression or addiction. Many genes have multiple effects and most psychological disorders are multifactorial.

An alternative to a strict gene-trait evolutionary hypothesis is the diathesis-stress model of mental illness. This is the idea that some people inherit a vulnerability to stress that is a risk factor for mental illness. It’s what you labeled “cocking the gun and pulling the trigger”. In contrast to the simplified evolutionary model, the diathesis-stress model is more amenable to empirical testing.

A real-life example of the diathesis-stress model may be occurring during the COVID-19 pandemic, as people react with greater or lesser anxiety to the threat of a potentially fatal disease.

An alternative to both of these explanations is the differential-susceptibility hypothesis, which uncovered the orchid-dandelion polarity in stress resilience. (Personally, I think that the diathesis-stress and differential-susceptibility hypotheses may be consistent with an evolutionary explanation. Diatheses and differences in susceptibility could have evolved: It’s the old distinction between ultimate and proximate causes of behavior.)

Maybe the point of mental illness is that it gives warning of a failure to cope, so that others–family, tribe, society–can offer prompt aid to someone who faces problems greater than they can handle?

Points to consider:

  • Many forms of mental illness have a long prodrome that signals a breakdown. I suppose most of us are familiar with prodromes for more common afflictions: We know what it’s like to feel a cold or the flu or a migraine coming on. In fact, psychological changes can also be part of a physical prodrome in ways that belong very much to this discussion. And one of the negative symptoms of a psychological crisis can include wanting to be alone. You may have heard a friend say (s)he was glad to have “caught it in time” to prevent the flu from running its full course. Similarly, early psychological intervention may forestall hospitalization. Accounts of what it feels like are still sparse, but a prodrome for schizophrenia has been well studied.
  • Psychological disorders often appear in adolescence, when individuals are still subject to adult oversight and intervention.
  • It may be the prodrome that is adaptive rather than the psychosis. This hypothesis does not require an evolutionary mismatch, as it applies to early humans as well as to us. When a changing environment, common in adolescence, proves overwhelming, we step in to help and thereby strengthen our entire group.

What do you think? Unfortunately, the past hides from us. We paint our evolutionary backdrop with stereotypes: cavemen, volcanoes, leopard skin clothing, and the discovery of fire.

The reality is that our bodies reveal some questionable turns we took in our evolution. We have teeth that evolved in a decay-free environment. Here we are today in a sugar-filled culture, visiting the dentist.

The prehistoric world was different from ours. The mismatch theory says this explains why some ancient traits are no longer adaptive, like decay-prone teeth, the fight-or-flight response that sends us into a killing rage when someone sideswipes us in traffic, obesity, and maybe addiction. It’s also true that our view of what’s abnormal changes over time.

We’re living with age-old genes. Just as there are some words that no longer mean what they used to, so there are genes that no longer fit the modern world, and the prehistoric world turns out to be not quite what we expected.

All of our behavior results partly from heredity and partly from our experience, though rarely in equal proportions. For example, addiction shows cultural influences as well as genetic and epigenetic ones (harder but probably worth it). We probably did not inherit genes that were always harmful or they would have become extinct. It seems useful to try to understand why those genes are still with us. (One idea is neuronal recycling, to explain how we came up with brain circuits before their modern use appeared, as with reading.)

So it may be also with depression, schizophrenia, Alzheimer’s disease — and maybe other diseases as well, if they have strong hereditary influences.

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