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“I’ve got everything someone could ask for. Why do I feel like this?” has escaped the lips of more than one patient. True, some may not seem to have anything to be depressed “about,” although they nonetheless suffer. It’s important to remember that depression isn’t necessarily “about” anything and that there are many avenues to depression.

If you’ve googled “depression,” you’ve probably encountered those canned statements that “scientists aren’t sure what causes depression…” It’s as if the world is waiting for some researcher to stumble upon a yet-unmapped cortical region with a switch labeled “depression mode” that can be flicked on and off.

Further, it implies that depression is a homogenous experience. The truth is, depression has many faces and disguises, as detailed in "The Many Faces of Depression." Further, there is no one route to depression. Different types of depression present strong evidence of different contributors. These include physiological, environmental, and psychosocial components, and the various presentations spurring from these require their own unique clinical considerations.

Forget the deceptively-simplistic popular concept of mere "serotonin imbalance," which has lately been challenged scientifically (i.e., Montcrieff, et al., 2022). And forget the more sinister idea that someone is "psychologically weak." The reality is, the following 10 items, whether individually or in combination, are what we know to be strong contributors to depression.

1. Bipolar disorders

Bipolar disorder is not simply a moody person, as pop culture may dictate. There are significant, sustained mood alterations, and depression is the "South Pole," or low, of the condition. As written about in "Can Bipolar Disorder Be Detected Early?" major depressive episodes that seem spontaneous, intense, and long-lasting, especially in teens and young adults, are not unusually the initial mood episode of a bipolar disorder.

2. Circadian rhythm disruption

Sleep disturbance has always been a notable characteristic of depression. Now, modern researchers are uncovering a complicated relationship between our synchronicity with natural rhythms and depression. In 2009, Kalman and Kalman released a paper called "Depression as Chronobiological Illness" and since then, the topic has gained a lot of interest. Researchers Vadnie and McClung (2017), and Lamont et al., (2022) noted it seems that disruption in circadian rhythm engenders significant sleep disturbance and/or other hormonal imbalances, the downstream effect being mood complications. If depression seems treatment resistant, especially if the person has worked third shift, a referral for chronobiology study is ideal.

3. General medical conditions

Underlying medical conditions should be ruled out as cause of mental illness symptoms, as they can encourage mimicry of psychogenic pathology. Medical mimicry is especially suspect if the person has no personal/family history of symptoms, they come on quickly, and there's no triggering event. Common culprits are thyroid disease, especially hypothyroidism (APA, 2022); low iron, Lyme disease, and Cushing's Disease. Clearly, a physician specialist, not psychotherapy or an antidepressant, would be the first-line intervention.

4. Genetics

Modern researchers have discovered that depression has a 30 to 50 percent heritability rate. Further, over 100 specific gene locations have been implicated in major depressive disorder (Kendall et al., 2021), clearly indicating genetic influence.

However, it's likely that the sprouting of depression is often a matter of nature and nurture. Researchers like Park et al. (2019), for instance, note, "Growing evidence suggests that epigenetic [how experience alters genes] changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behavior."

Depression can also be a response to inflammation, vulnerability to which may also be influenced by genetics (Beurel et al., 2020). Interested readers are directed to Dr. Edward Bullmore's The Inflamed Mind (2018) for an easily-digested, expansive understanding of inflammation and depression.

5. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction

HPA complications have long been known to influence depression (e.g., Fink & Taylor, 2007; Parker, et al., 2010; Juruena et al., 2018). This is particularly true regarding melancholic major depressive disorder, as written about in an earlier post, "The Darkest Mood."

Melancholic depression is marked by a palpable darkness/heaviness to the sufferer's mood, severe feelings of guilt, loss of appetite/weight loss, early morning awakening and psychomotor agitation or retardation. Clearly, more biological interventions are necessary, and, as written in the aforementioned post, tricyclic antidepressants, electroconvulsive therapy, and transcranial magnetic stimulation are often successful.

6. Life events

It's no secret that less-than-desirable life events can take the wind from our sails. For some, especially if there is genetic proneness to depression, a hard time can become a shipwreck. Adverse life events are highly correlated to depression onset (e.g., Shrout et al., 1999; Kendler et al., 1999; APA, 2022) even in the absence of obvious genetic influence. I've worked with many people who, midlife, had major changes like divorce, and, despite no other personal or family history of depression, met criteria for major depressive episodes.

7. Perinatal matters

This is an expansive topic, involving the intersection of genetic proneness to depression, natal-related hormonal changes, and parenting anxieties.

8. Psychiatric comorbidities

Depression is not unusually a downstream effect of another psychiatric condition. For example, people with social anxiety disorder want relationships but are debilitating fearful of scrutiny. Thus, they can become very lonely and just watch life go by, a fertile breeding ground for depression.

Those with personality disorders (PDO's) tend to have tumultuous interpersonal relationships, make poor decisions, and/or have ingrained self-images of ineptness and undesirability. If this is one's baseline of existence, it's easy to see how depression can settle in. Major depressive disorder is a well-documented comorbidity of PDO's (e.g. Millon, 2011; APA, 2022). Given it is encouraged by another condition, resolving the in this case, social anxiety or PDO, will likely have the most lasting effects on managing the depression.

9. Seasonal changes

Seasonal depression is most often associated with decreased sunlight, but it can also occur as daylight increases. As noted in "3 Seasonal Depression Myths," seasonal depression is more prevalent in females and is highly correlated to significant vitamin D sensitivities disrupting healthy neurotransmitter transporters. Light therapy, dietary supplements, and pharmacology and therapy during the problematic season are successful interventions.

 

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10. Substances

Like general medical conditions, providers should consider if psychological symptoms are influenced by drug/alcohol abuse, prescriptions, or environmental toxin exposure. Substance-induced depression may be considered if onset or worsening of depression symptoms coincides with a change in medication(s), initiation of or decreased/increased use of alcohol/illicit substances, or perhaps working in an environment where there is regular exposure to neurotoxins (APA, 2022), like a chemical factory. If suspected, immediate pharmacological re-assessment or pointed substance abuse or toxicity treatment must be considered.

Disclaimer: The material provided in this post is for informational purposes only and is not intended to diagnose, treat, or prevent any illness in readers or people they know. The information should not replace personalized care or intervention from an individual’s provider or formal supervision if you’re a practitioner or student.