Depression
A persistent, whole-person state of physical, psychological, and spiritual dysfunction marked by loss (interest, energy, meaning, motivation, sleep, appetite, focus, and emotional variability) that impairs one’s capacity to engage with life processes.
“It’s like walking through a thick fog with weights on your legs. You can’t see where you’re going, and every step takes effort.”
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Signs and Symptoms of Depression.
The loss infuses several domains:
Interest (“anhedonia”)
Energy (“anergia”)
Meaning
Motivation (“amotivation or avolition”)
Sleep (quality and quantity)
Appetite & dietary balance
Focus/concentration
Thought processes (slow, stuck, ruminating)
Experiencing emotional variability (“alexithymia and affective flattening”)
Screening and Diagnosis of Depression.
The most widespread tool used for screening depression symptoms is the PHQ-9. This 9-item questionnaire explores the major symptoms of depression and allows for the generation of a score to rate the severity of depression. The score is interpreted as follows:
5-9, Mild
10-14, Moderate
15-19, Moderately Severe
20-27, Severe
If the score is greater than 10, it may be beneficial to explore further investigation and treatment.
The presence of depression symptoms can be used to diagnose the form of depression using the Diagnostic and Statistical Manual of Mental Disorders (DSM). Some diagnostic labels for depression include Major Depressive Disorder, Bipolar Depression, Post-Partum Depressive Disorder, and Persistent Depressive Disorder, among others.
While the diagnosis provides us with a descriptive label for your experiences, psychiatric diagnoses do not explain your symptoms. Unfortunately, this is a trap that many fall into. There are 227 combinations of symptoms that satisfy the criteria for major depressive disorder. In this context, two patients could share zero overlapping symptoms and still receive the same diagnosis. To explain your symptoms, we must explore the underlying causes and contributing factors.
Causes and Contributing Factors.
Depression is a complex experience that likely includes a combination of underlying causes and contributing factors. Some of these include the following:
Biological Factors:
Brain & Neurotransmission. While up to 80% of the population (clinicians included) believe that depression is caused by a chemical imbalance, focusing especially on serotonin, the overwhelming majority of research suggests that depression is NOT due to a neurochemical imbalance in the brain (Moncrieff et al., 2022). Medications help with depression symptoms but do not correct the underlying cause (think Tylenol for a fever, but the underlying cause of the fever is an infection). What has been consistently identified is changes in central and peripheral nervous system networking, which contributes to the symptoms of depression.
Hypothalamic-Pituitary-Adrenal Axis. This captures the stress response and activity of cortisol (the primary stress hormone in the body). Imbalances of cortisol and related adrenal impairment contribute to the symptoms of depression. This can be hallmarked by signs of stress, including burnout, fatigue, early morning awakening, and overall circadian imbalance.
Hypothalamic-Pituitary-Gonadal Axis. This captures the remainder of the hormonal environment (e.g., estrogen, progesterone, testosterone, etc.). Imbalances change the activity of neurotransmission and neural networking. Perimenstrual, postpartum, and perimenopausal correlations with symptoms may hallmark this.
Gut-Brain Axis. The enteric nervous system can be referred to as a “second brain,” mirroring the structure and functionality of the central nervous system in several ways. The gut manufactures the same neurochemistry as the brain, and there is a bidirectional relationship between the gut's function and that of the brain. Gut-brain axis anomalies may be characterized by irritable bowel syndrome features or gut symptoms that are provoked in the context of psychological symptom worsening, but in depression, it is often a little more subtle.
Hypothalamic-Pituitary-Thyroid Axis. The thyroid is the master regulator of metabolism and controls the energetic activities of the entire body. Oftentimes, subtle (“subclinical”) thyroid anomalies contribute to depressive symptoms. By extension, investigating glycemic (blood glucose) and lipid (cholesterol) regulation are key considerations for depression. Coincidentally, too high and too low cholesterol has been linked with suicidality and worsening depression.
Immune-Brain Axis. The immune system has been consistently linked to depression. Inflammation and autoimmune conditions have been shown to cause and contribute to depressive symptoms. In addition to this, chronic and even low-level inflammation interferes with the effectiveness of antidepressant treatment.
Micronutrient Environment. An imbalance of cofactors or nutrients required for neurochemical synthesis and brain rewiring (neuroplasticity) can contribute to depression. Some key vitamins and minerals implicated in depression include B complex, vitamin D, and iron, among others.
Epigenetics. Epi-genetics means “on top of” genes. In other words, it is an area that captures the influence of the environment on genetic activity. While there are several genes associated with depression, there is not a genetic cause of depression. However, genetic abnormalities in genes such as methylenetetrahydrofolate reductase and catechol-o-methyltransferase significantly contribute to depression. These genes, alongside others, can be modified to produce a more balanced environment.
Other. Other factors that contribute to depression include substance-induced dysregulation (e.g., downers such as alcohol, benzodiazepines, and opioids as well as withdrawal from uppers such as cocaine and methamphetamine). Certain medications can contribute to depression as well, such as steroids, contraceptives, and beta blockers.
Lifestyle/Environmental Factors:
Relationships. Impaired or dysfunctional relationships (to persons, places, and things), separation or loss.
Leisure. An imbalance between restorative/rejuvenating activities and laborious activities (tends to contribute to stress and adrenal dysfunction).
Labor. Occupational strain and stressors in addition to high health maintenance needs and socioeconomic demand. Where there’s high demand, there’s a risk of imbalance that leads to stress. Stressful events (accumulation of small stressors and/or large stressors) contributes to depression.
Nutrition. Nutritional imbalances and food intolerances and sensitivities contribute to depression. This is especially true of the Standard American Diet (the “SAD” diet).
Exercise. Sedentary lifestyle or impaired ability to exercise. Lack of exercise has significant neuroendocrine impacts and is worth exploring as a contributing factor in depression. Nature deficit is a common factor contributing to depression as well (Remes et al., 2021).
Sleep. Inadequate or impaired sleep. A circadian imbalance is a common factor contributing to depression.
Substance use et al. addictions. Addiction is often a solution to a deeper problem worth exploring but the use of substances can contribute to depression.
Spirituality. A deficit in practices that enhance your sense of meaning, purpose, and connectedness contributes to depression. This may include but is not necessarily religious practices.
Trauma. Traumatic experiences (single incident, multiple incidents, developmental, or transgenerational), adverse childhood experiences (presence of events in childhood that should not be there), and disconnection, especially at an early age (absence of what should be there) and the wound that is sustained (trauma) are significant contributing factors in depression. Read more about Trauma here.
Psychological Factors: coping skills and resources, stress responsivity, perception of self (including a mismatch between ability and performance), sensitivity to rejection, interpretation bias, rumination, negative emotionality, attachment style, and personality structure (including personality disorder) (Remes et al., 2021).
The Integrative (Holistic) Psychiatry Approach.
Through an Integrative Psychiatry lens, we conduct a thorough examination of underlying causes and contributing factors. As these underlying causes and contributing factors are identified, we guide you through personalized treatment considerations that will meet your specific needs. We want to help you get to the root of your experiences. Below, you’ll find some of the treatment considerations for depression.
Treatments for Depression.
Medications. Common medications used in the treatment of depression include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), bupropion (Wellbutrin), tricyclic antidepressants (TCAs), second-generation antipsychotics (SGAs), and several adjunctive treatments.
Nutraceuticals. There are several nutraceutical options that will help with depression. Unlike pharmacologic approaches, nutraceutical approaches are a little more differentiated in terms of subtypes of depression. Some nutraceutical products are better for endocrine-related (stress-related) depression, anxious depression, agitated depression, inflammatory depression, etc. Common nutraceuticals used for depression include Rhodiola, Saffron, Curcumin, SAMe, 5HTP, L-methyl folate, and Saint John's Wort, among others.
The Body. The brain and body are not separate entities. In Integrative Psychiatry, we explore and treat causes and contributing factors such as the adrenal glands, gut, thyroid, immune system, metabolism, mitochondrial functioning, epigenetic factors, B complex levels, iron, and vitamin D. These considerations are based on a comprehensive evaluation of these systems through laboratory and diagnostic testing.
Lifestyle. Several lifestyle modifications can help improve depressive symptoms:
Habits: Reducing and eliminating substance use and other addictions. Although easier said than done, this often involves multimodal treatment and exploration of root causes.
Sleep: Stabilization of sleep routines and patterns (e.g., reducing blue light exposure from screens 4 hours prior to bed, avoiding stimulating activity prior to bed, etc.) with a goal of 6-7 hours per night (sometimes medication or nutraceutical options are helpful here).
Exercise: Moderate intensity exercise (e.g., walking) with a goal of 3-4 times per week has the best evidence basis for improving upon depression, though any activity is better than none. It’s recommended to start with something you enjoy and build upon a routine and habit from there.
Nutrition: Dietary adjustments such as sugar reduction (<10% added sugar in products) and a goal of a Mediterranean diet with healthy fats and high fiber have been shown to improve depressive symptoms.
Therapy. Therapy approaches help to develop strategies and techniques to influence your experiences AND/OR involve depth-oriented work to get to the root causes of symptoms. Common therapy modalities used in the treatment of depression include cognitive-behavioral therapy (CBT), dialectical behavioral therapy (DBT), psychodynamic psychotherapy (PDT), positive psychotherapy (PPT), and solution-focused or problem-solving therapy (SFT/PST), among others. While there are several psychotherapy modalities used for depression, at the core is the relationship between the individual and therapist.
Additional Treatments. Transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) have also been used in depression. A more novel treatment in psychedelic-assisted and psychedelic integration therapy for depression. Several studies out of Johns Hopkins surrounding the use of psilocybin for depression have been promising.
Our clinicians can help you navigate these options safely and effectively to determine the best course of action for you.
Get to the Roots of Depression!
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Li, B., Friston, K., Mody, M., Wang, H., Lu, H., & Hu, D. (2018). A brain network model for depression: From symptom understanding to disease intervention. CNS Neuroscience and Therapeutics, 24(11), 1004-1019.
Remes, O., Mendes, J. F., & Templeton, P. (2021). Biological, psychological, and social determinants of depression: A review of recent literature. Brain Science, 11(12), 1633.
Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2023). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry, 28(8), 3243-3256. https://doi.org/10.1038/s41380-022-01661-0
