Neurochemistry is just one factor among many.
Readership: All
Theme: Charisma and Chemistry
Length: 2,200 words
Reading Time: 12 minutes
The Ongoing Controversy Regarding the “Cause” of Depression
The fields of psychiatry and psychopharmacology have failed to adequately identify and treat depression and anxiety.
Dr. Scott once stated that after 20 years and 50,000 clinical contact hours dealing with patients suffering from depression, he still has no idea what causes it. He tends to think people are born with a predisposition inherited from their parents. In his conception, one’s biological nature and temperament is inborn, and environmental factors either bring out or suppress whatever is in there. Knowing one’s self is half the battle.* GOOD therapy can help patients work through their nature and nurture and hopefully gain insight into the behaviors that are most troubling to them. But they will ALWAYS have those core personality traits to fight against.*
What “causes” depression is debatable, and that debate has been going on for a really long time. All of this debate revolves around the various conceptualizations that different medical and behavioral health providers have of these disorders. Is depression just a list of symptoms that hang together in factorial analysis? Or is there something deeper to it?
This post reports several new concepts of depression that have emerged over the past year or two.
Chemical Imbalance?
Since the late 1980s, the most popular explanation for depression has been attributed to a “chemical imbalance” in the brain. This concept was supported by the fact that many symptoms of depression have been successfully treated with drugs that affect neurochemical imbalances (e.g. dopamine and serotonin reuptake), such as Prozac, selective serotonin reuptake inhibitors (SSRIs), and tricyclics.
Although it was never decisively proven that depression is “caused” by a chemical imbalance, the view that depression is NOT the function of a chemical imbalance was never contested and remained uncontroversial…
Until just last year, when a comprehensive research study by Moncrieff, et al. determined that the main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. There was even some evidence that long-term antidepressant use reduces serotonin concentration. Several papers have been written over the past year challenging Moncrieff’s claims, and as of the time of this writing, the conclusions remain undecided as to whether serotonin is a base factor in depression.
Meanwhile, scientists have been discovering other factors related to depression, such as zinc deficiency, neuroplasticity, immune activation, inflammation, stress related hormonal dysregulation, and conditions within the digestive tract. I’ll briefly go over each of these (except for zinc which I covered before).
Neuroplasticity
A process called “neuroplasticity” is increasingly thought to play a role in mood disorders like depression. The basic idea is that in depression, there may be issues with the quality, number, and type of connections our neurons make, and this may help explain the symptoms of depression. Importantly, research is showing that we may be able to positively affect neuroplasticity through lifestyle choices like exercise, learning new things, and certain dietary modifications. There is also data showing that conventional antidepressants, as well as psychedelics (yeah, ‘shrooms), may positively influence neuroplasticity.
Immune Activity
Immune activation, and especially inflammation, is thought to be a risk factor for the development of conditions like depression. Excess, chronic, or higher levels of inflammation in the blood and/or the brain blocks healthy neuroplasticity, impairs the healthy function of neurons by physically damaging them, and leads to the breakdown of molecules thereby generating toxins that further damage neuron health and contribute to depressive pathology. This concept may also partly explain the link between alcoholism and depression. The good news is that inflammatory status can be regulated by a nutritious diet, regular sleep and exercise, stress-lowering interventions, and… spending time in nature.
The Digestive System
A wide range of research now suggests that the digestive system and the brain are in constant communication, and it’s been proposed that this data exchange may have an effect on everything from our attitude towards life, to our cognitive state, to our mood. In fact, alterations in the bacteria that live in the gut microbiome have been linked to depression. It’s thought that these bacteria may influence brain function through their effects on the vagus nerve (which runs from the gut to the brain), their impact on the immune system (e.g., by affecting levels of inflammation), and through tiny molecules they create (e.g., short-chain fatty acids), which may reach the brain by way of the bloodstream. Researchers have proposed that the state of our gut health (e.g., the porosity of our gut lining, AKA “leakiness”, the immune cells in the gut, and the biodiversity of the microbes that live in the gut) plays a major role in our mental health and may significantly influence depression symptomatology. In fact, one study showed that the type and quality of microbial culture in the digestive system was even more important than diet for maintaining good health. Probiotics and eating fiber rich foods may help regulate and replenish a healthy digestive microbiome, and thereby improve mood and energy.
On an interesting side note, C. S. Lewis once identified “good digestion” as a necessary precursor to vital physical health. He wrote,
“Most of the man’s psychological makeup is probably due to his body: when his body dies all that will fall off him, and the real central man, the thing that chose, that made the best or worst out of this material, will stand naked. All sorts of nice things which we thought our own, but which were really due to a good digestion, will fall off some of us: all sorts of nasty things which were due to complexes or bad health will fall off others. We shall then, for the first time, see every one as he really was. There will be surprises.”
C. S. Lewis, in Mere Christianity
Hormone Dysregulation
Although married men have known this about their wives for millenia, ¡ScIeNcE! is only now discovering that the endocrine system and hormones play an important role in mood regulation. There are at least four hormones especially that are under growing suspicion of being linked to depression — cortisol, insulin, estrogen, and testosterone.
Adverse and traumatic life events cause stress, which burdens the neurochemical pathways, increasing inflammation, damaging neuroplasticity, and even killing off neurons. Extended periods of increased cortisol, AKA the stress hormone, leads to anxiety, depression, irritability, and weight gain, and has been shown to exacerbate wear and tear on both the endocrine and neurological systems and accelerate aging.
Insulin is a key metabolic hormone that facilitates the uptake of glucose by cells throughout the body. In the brain, insulin is thought to regulate blood sugar as well as influence memory and behavior. Insulin resistance is an increasingly common condition of metabolic dysfunction, where the body has trouble sensing insulin and using glucose. In addition to diabetes, insulin has now been linked to a substantially higher risk of developing depression.
Scientists are discovering that estrogen (i.e. estradiol) plays a major role in depression. Estrogen has a number of brain-protective, mood enhancing, and neuroplasticity improving roles. It has been proposed that declining levels of estrogen, progesterone, and other related hormones during menstruation and after menopause may explain the higher rates of depression and moodiness seen by women during this period. Conversely, higher levels of estrogen in men is linked to depression in younger men and obesity in older men.
One might suppose that testosterone would exacerbate stress since it induces aggressiveness and vigilance, but scientists are discovering the opposite. Low testosterone in men is associated with numerous maladaptive symptoms including anxiety and depression (Khera, 2013; Alkamel et al., 2014). Testosterone modulates serotoninergic transmission which plays a crucial role in the development of depression (Jovanovic et al., 2015). Standard antidepressants tend to normalize testosterone levels (Pope et al., 2003). Testosterone replacement therapy has been shown to greatly improve mood, alleviate anxiety, and mitigate symptoms of depression (Kanayama et al., 2007; Zarrouf et al., 2009). These findings suggest a strong and also reciprocal relationship between testosterone and depression; not only that lower testosterone can lead to depression but also that depression can lower testosterone. Overall, the evidence shows that testosterone improves mood and quality of life for men.
A Note on Antidepressant Medications
¡ScIeNcE! has no idea how or why antidepressants work.
When psychiatrists prescribe medications for treating depression and anxiety, they are only addressing the symptoms. If the symptoms of depression can be alleviated, then this can help a person suffering from a depressive episode to get back up and running, which helps speed up the recovery time. Medications are never expected or intended to “fix” brain chemistry. Some people have good results from taking antidepressants, while others do not. Side effects are always an issue.
Prozac and tricyclics are now outdated and have been replaced by newer medications. OTOH, SSRIs do a pretty good job of treating the physiological symptoms of depression, for example, the appetite disturbances, low energy, psychomotor agitation, sleepiness, slowing, etc. But they are not so good with the purely psychological symptoms like anhedonia, guilt, low mood, poor affect, etc. Patients on SSRIs can SOMETIMES get some relief from the symptoms that make it difficult to even get up in the morning while they actually work on the issue that is the underlying driver of their depression (or anxiety). The patient has to decide if they can tolerate whatever side effects it comes with.
Concerning su!c!dal!ty, SSRIs are a mixed bag. There have been some cases in which patients became more su!c!dal AFTER taking SSRIs. The prevailing theory about why su!c!de risk sometimes increases with SSRIs is because the person now has the energy and inclination to do something about it. IOW, they are activating the will.
Jack’s Personal Testimony
Jack suffered from depression after his parents divorced in 1994. He took some antidepressant medications at that time. The medicine did help him recover faster, but it also made him jittery, jumpy, and unable to sleep. Ever since then, he has had severe and recurring insomnia that has affected his work performance and has required other medications. (Melatonin is his personal favorite, as it is all natural and doesn’t lead to a dependency.) Jack cannot be certain, but he believes his insomnia is related to his past use of antidepressants. Looking back, he wishes he would have stayed away from antidepressant medication unless his depression became so severe that he couldn’t function or had recurring su!c!dal tendencies.
“Side effect” is an understatement.
Closing Statements
The scientific field of psychoneuralendocrinology is complicated and remains poorly understood. However, it is markedly different for men and women, and is strongly affected by age and BMI.
Concerning depression, overall, the body has a limit of how much anger, disappointment, frustration, and stress it can endure. Once the hypothalamic-pituitary-adrenal (HPA) axis (AKA the stress system) is exhausted, dysregulation sets in and the risk for depression is significantly increased. It has been found that a single high-stress event increases the risk for a depressive episode by 1.4 times, and episodes of major depression are 2.5 times more likely to come behind the heels of a stressful event than not.
A number of strategies have been shown to be successful in reducing stress and recovering from depression, such as…
- Avoiding excess smoking and alcohol consumption.
- Daily meditation (e.g. prayer).
- Deep breathing exercises, which reduce cortisol.
- Dietary modification, eating right, less sugar and more fiber.
- Eliminating or minimizing contact with stressful people and situations.
- Getting enough rest.
- Improving insulin resistance.
- Regular exercise.
- Regulating HPA function.
- Spending time in nature and the great outdoors.
- Taking essential vitamins, zinc, and probiotics.
Moreover, using the term “chemical imbalance” to explain the cause of depression is now naïve and outdated. There’s a lot more going on that is now being discovered and is not yet fully understood.
Aside from the physiological vectors, my faith tells me there is a spiritual component to depression. Unresolved anger, chronic bitterness, frustration, sinful habits, and a lack of faith may all contribute towards depression.
Ultimately, the only thing we can be sure of is that depression is a symptom of all the sin in the world. Good habits like those listed above can all keep the zephyrs of depression at bay or help fight them off. This post may remind us of how important these things are to our biological, emotional, and spiritual lives.
* Here at Σ Frame, we have condensed this concept into “knowing one’s self”, and “maturity” – striving for spiritual perfection which includes a whole bunch of introspection and recognizing your own limitations and boundaries, leading to growth, good health, and the glory of God.
H/T: Cameron232 and Scott.
References
- The Weary Christian: STUDY: Fixing your gut bacteria might really help your depression (2018/6/18)
- Moncrieff, J.; Cooper, R.E.; Stockmann, T.; Amendola, S.; Hengartner, M.P.; Horowitz, M.A. The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry (2022). https://doi.org/10.1038/s41380-022-01661-0
- Psychology Today: If Serotonin Doesn’t Cause Depression, Then What Does? (2022/7/22)
- Psychology Today: Depression Is Not Caused by Chemical Imbalance in the Brain (2022/7/24)
- The Weary Christian: Still a medical condition: About that study on serotonin and depression (2022/7/25)
Related
- Σ Frame: The Link between Zinc, Male Health, and Depression (2022/4/29)
- Σ Frame: Mopey Dopey (2022/5/6)
- Σ Frame: The 13 Harbingers of Masculine Doom (2022/9/7)
- Spawny’s Space: Male Depression (2023/8/7)
