Chapter 6: Depression Flashcards
True or False: pharmaceuticals are most effectvive (compared to CAM therapies) in SEVERE forms of depression.
True. But many alternative therapies are effective in mild-moderate cases.
What US and worldwide prevalence of adult depression? What about in chronic disease?
1 in 10 (10%) in US adults.
25% in people with chronic diseases (unclear if US or worldwide)
What is the stress-diathesis model of illnes and how does it apply to pathophysiology of depression?
- Significant emotional, social, and environmental antecedents such as the loss of a family member or a romantic or professional disappointment, as well as genetic and acquired vulnerabilities, are clearly involved in development.
- significant stressors more involved in initial episodes
- vulnerability increases in recurrent episodes
- over time, recurrence becomes more autonomous (kindling)
PHQ2 screens and PHQ9 can diagnose.
What are the physiologic changes that occur with kindling in depression?
Central nervous system dysfunction increases, as manifested by:
1. hypercortisolemia
2. decreased slow-wave (restful) sleep
3. increased rapid eye movement (arousing) sleep
4. disruption of neuroplasticity.
Kindling is the autonomous process leading to repeat episodes of illness
How does inflammation play a role in the pathophysiology of depression?
- High levels of inflammatory biomarkers are found in depressed patients and improve as symptoms resolve.
- There is a particularly strong association between inflammatory processes and recurrent major depressive disorder (MDD).
- The biochemical impact of depression may be stored in neurons through changes in the activity of gene transcription factors and neuronal growth factors.
How does inflammation and kindling affect neurotransmitters / biogenic amines in depression?
It leads to the biochemical imbalance of biogenic amines or neurotransmitters (e.g., serotonin, norepinephrine, gamma-aminobutyric acid [GABA], and dopamine), via:
1. impaired synthesis,
2. increased breakdown, and
3. increased pump uptake, with
4. consequent alterations in neurotransmitter levels.
How does exercise affect depression?
- More than 1000 trials, most show a benefit of exercise
- Exericse is protective against onset of depression in all ages across continents
- Regular exercise is as effective as psychotherapy / meds
- Exercise + meds is more effective than either alone
- Both aerobic and anaerobic are effective
- Total energy expenditure per week more important than number of times per week
- high energy exercises are more effective than low energy ones
- Effective even when naloxone given to block endorphins (so unclear why beneficial). It may increase nerve cell growth in area of brain that modulates mood
So one should write a movement prescription for all patients; tailor the type of movement to something the patient enjoys, whether aerobic or anaerobic.
What is the association between sugar intake and depression?
- Higher consumption of a high-sugar, high-fat dietary pattern (chocolate, pastries, red meat, added sugars, high-fat dairy, fried foods, cream sauces) was associated with higher depressive symptoms and depressed mood in a multiethnic population.
- high sugar–sweetened beverage intake is associated with increased risk for depression
- non-nutritive sweetener use was associated with increased likelihoods of having major depression in one study
Note: direction of causality can make understanding dietary impact on population health difficult to interpret.
What is the association between caffeine and depression?
- some studies show protection with 2-5 cups coffee/ day
- One large study in Canada showed detrimental effect of heavy coffee (4+ cups per day)
- Daily tea drinking appears to be associated with depression!
What is the association of overall dietary patterns and depression?
- WFPB or Mediterranean diet have a protective effect compared to a Western-style diet, across different populations.
- Small Australian RCT showed mediterranean diet effective as an adjunctive treatment of mod to severe depression
- Another australian RCT showed a Med diet supplemented with fish oil reduced depression
evolving understanding of inflammation in depression suggests a role for dietary manipulation in treatment
How is alcohol use associated with depression?
- alcohol-related problems are more common in depressed individuals than in the general population and are associated with worse outcomes.
- treatment for depression is effective even when thought to be independent but co-occurring with an alcohol use disorder
- alcohol transiently increases the turnover of serotonin, but the long-term result is diminished levels of serotonin and catecholamines
- Elimination of alcohol intake appeared to reduce depressive symptoms
What is the role of Omega-3 Fatty Acids in depression?
- deficiency of omega-3 fatty acids or an imbalance in the ratio of omega-6 and omega-3 fatty acids correlates positively with increased rates of depression.
- May be related to PUFAs and cholesterol’s role in synaptic membrane fluidity
- 2016 Cochrane review didnt show benefit in Omega3 consumption for treatmetn of MDD.
- 2019 meta-analysis did show benefit in Omega-3 forumlations containing 60% or more EPA had an antidepressant effect (dose 1g lor less per day)
- Consider 2-3 servings of cold water fish per week (herring, mackarel, wild salmon, sardine). Larger fish and farmed fish caution for heavy metals and polychlorinated biphenyls
- Vegetarian alternatives haven’t been studied in relation to depression
Pearl: DHA is generally more structural (important for brain and retina development), whereas EPA is generally more functional (improves communication across cell membranes).
How does EPA block proinflammatory cascades?
- EPA seems to block proinflammatory eicosanoid synthesis from arachidonic acid (e.g., prostaglandins, thromboxanes, and leukotrienes), prostaglandin E2 and thromboxane B2
- EPA binds = peroxisome proliferator–activated receptor gamma (PPARγ) nuclear transcription receptor that downregulates expression of nuclear factor-kappa B (NF-kB), inhibiting neuronal parainflammatory cascades.
What is the role of Vitanmin D in depression?
- vitamin D deficiency is associated with an 8% to 14% increase in depression.
- more studies are needed to make a more definitive statement on the effectiveness of vitamin D supplementation on depression.
What is the role of B-vitamins in depression?
- large trials lacking, but likely good to give a B-complex vitamin in older patients and those with suboptimal diets.
- Folic acid and vitamin B12 are linked with the synthesis of S-adenosylmethionine (SAMe), serve as methyl donors for neurotransmitters, and may play a role in immue response.
- B6 (pyridoxine) is necessary to make serotonin. B6 deficiency common in depression, especially premenoupausal women taking OCPs or estrogen.
- caution: B6 is neurotoxic at >200mcg/day (most B-complex vitamins are either B50 or B100)
