Depression.

More About Depression.

We understand that depression is a complex illness. Because depression of this, to isolate a "one specific cause" that causes depression would risk missing the bigger picture. Several biological, lifestyle and psychological factors are involved. In most cases there is a combination of causes. Depression can be best understood as disrupted brain networking between the areas of the brain responsible for motivation, energy, pleasure, and thoughts about the self, others, and the world.

Some key networks involved in depression include:

• Default mode network (DMN): Involved in self-narrative, self-concept, social evaluations, and narrative/life story comprehension. Includes the medial prefrontal cortex, posterior cingulate cortex, angular gyrus, and lateral parietal cortex.

• Emotional network: Involved in emotional thinking and affective bias. Includes the anterior cingulate cortex, orbitofrontal prefrontal cortex, amygdala, hippocampus, and insula.

• Reward network: Involved in interest, motivation, and pleasure. Includes the prefrontal cortex, caudate, and nucleus accumbens.

• Central executive or task positive network (CEN/TPN): Involved in goal-oriented tasks, reasoning, problem-solving, and top-down control of negative thoughts and emotions. Includes the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, and posterior parietal cortex.

The communication between these key networks accounts for several of the symptoms of depression (Li et al., 2018). Ideally, shifting activity over to the CEN/TPN and reward network while quieting the DMN and reducing overactivity of the emotional network is the goal.

Signs and Symptoms.

The syndrome of depression consists of a persistent low mood, low energy, low motivation, impaired sleep and appetite, negative views of self and others, anger, loss of interest, feelings of guilt or unworthiness, impaired concentration, and/or suicidal thoughts. These symptoms are well-captured by a commonly used acronym (SIGECAPS):

• S: Sleep disturbances

• I: Interest decreased, referred to as anhedonia

• G: Guilt and/or feelings of worthlessness

• E: Energy decreased

• C: Concentration problems

• A: Appetite and weight changes

• P: Psychomotor agitation or sluggishness, changes in activity/movement

• S: Suicidal ideation or death preoccupation

Causes.

As previously mentioned, depression is a complex illness that likely includes a combination of biological, lifestyle/environmental, and psychological factors. These factors contribute to the aforementioned networking abnormalities and include the following:

Biological Factors:

• Impaired genetic abnormalities (e.g., MTHFR or COMT abnormalities)

• Impaired immunity (i.e., inflammatory depression)

• Altered endocrine function (e.g., hypothyroid, hypercortisolemic/adrenal, and glycemic dysregulation depression)

• Post-partum and peri-menopausal changes

• An imbalance of key brain chemicals (serotonin, norepinephrine, and dopamine)

• An imbalance of brain growth and development hormone (e.g., neurotrophins such as brain-derived neurotrophic factor).

• Imbalanced cofactors, methylation, and nutritional factors (e.g., vitamins and minerals)

• Impaired receptor responsiveness (i.e., reception and response to brain chemicals)

• Impaired gut health (i.e., gut dysbiosis)

• Substance-induced dysregulation (e.g., downers such as alcohol, benzodiazepines and opioids as well as withdrawal from uppers such as cocaine and methamphetamine)

• Medication-induced depression (certain medications can cause depression such as steroids, contraceptives, and beta blockers)

Lifestyle/Environmental Factors: traumatic experiences (single incident, multiple incidents, developmental, or transgenerational), adverse childhood experiences, stressful events (accumulation of small stressors and/or large stressors), socioeconomic strain, impaired or dysfunctional relationships, separation or loss, sedentary lifestyle or impaired ability to exercise, nutritional imbalances and food intolerances/sensitivities, inadequate or impaired sleep, substance use at al. addictions, seasonal changes and nature deficit (Remes et al., 2021).

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).

Screening.

The most widespread tool for screening for depression 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. If the score is greater than 10 it may be beneficial to explore medication or nutraceutical treatments for depression. This is an excellent tool for monitoring and tracking symptoms over time with treatment interventions as well.

Here is the standardized interpretation of PHQ-9 scoring:

• 5 – 9, Mild

• 10 – 14, Moderate

• 15 – 19, Moderately Severe

• 20 – 27, Severe

Diagnosis.

Conventional Psychiatry tends to focus on the DSM-oriented construct of depression as a labeled syndrome of "Major Depressive Disorder", "Post-partum depressive disorder", and "persistent depressive disorder" among a few others. These constructs tend to focus more on who fits the syndrome. Unfortunately, discovering who fits the syndrome does a poor job of differentiating the nature and cause underlying the Depressive syndrome.

In the specialty of integrative psychiatry, we expand these syndromic labels to identify particular morphologies (subtypes) that are indicative of particular root causes. Then the focus becomes exploring the root causes of depression so that a more individualized plan of care can be developed for you.

Treatment.

Because depression is a complex illness, a combination of treatments is more likely to yield positive results and this combination depends on the individual’s experience.

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.

Nutraceutical.

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-methylfolate, and Saint John's Wort among others.

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 aims to re-establish top-down control and typically involves a bi-modal approach: interventions to help with cortical strengthening (e.g., cognitive restructuring, behavioral activation, goal-oriented activity, navigating through problems and stressful encounters et al.) and subcortical strengthening (e.g., emotion regulation, stress reduction, et al.). There may be an incorporation of other tools such as trauma-related work and existential therapy to alter the impact of trauma and build your sense of purpose and meaning.

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.

If I were to recommend one thing to start out with, I would encourage monitoring activities in some way tracking the mood that is associated with activities. This gives a tremendous amount of insight into how your daily activities impact your mood and where you could potentially make changes to improve your mood. Try this free downloadable Activity Monitoring Template. Feel free to use the instructions included, or adjust it based on your needs. This can be used broadly to monitor most activities, or you could focus on specific activities and track how it impacts your mood.

Additional Treatments.

Targeting biological derangements with treatments such as thyroid supplementation, B12/folate supplementation, iron, and vitamin D can reduce symptoms of depression. 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.

References

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.