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Archive of ‘depression’ category

Neuropsychiatric Burden of Disease


Years of Life Lost due to Death: World

Heart disease is well-known as the leading cause of death in the United States as in other developed countries of the western world.   The impact of this might be best understood by examining the years of life lost (YLL) to this disease.

YLL due to premature mortality is calculated by multiplying the number of deaths at each age by a reference life expectancy at that age. The table below indicates a total of about two billion years of life lost globally to disease states. The diseases and injuries with the largest number of YLLs in 2015 were cardiovascular disease, lower respiratory infections, stroke, preterm birth complications, and diarrheal disease, shown in the following table[1].


Rank Cause Global 2015 YLLs (000s)
0 All Causes 1,948,759
1 Cardiovascular disease 184,787
2 Lower respiratory infections 141,844
3 Stroke 133,424
4 Preterm birth complications  97,212
5 Diarrheal diseases  79,201

Years of Life Lost due to Death: United States

In the United States, by far the leading cause of YLL is cardiovascular disease, followed by lung cancer, stroke, chronic obstructive pulmonary disease (COPD), road injury, and self-harm, as shown in the following table[2].  The reason why road injury and self-harm (suicide)  are so high on the list is that the cause of death occurs across the age spectrum – not just in older age.

Rank Cause United States 2010 YLLs (000s)
1 Cardiovascular disease 7,164
2 Lung cancer 2,987
3 Stroke 1,945
4 COPD 1,913
5 Road Injury 1,873
6 Self-harm 1,457

Despite declines over the past ten years, 15.9% of YLLs were related to cardiovascular disease and 4.3% were related to stroke – cerebrovascular – highlighting the continued dominance of vascular diseases in premature death.

Years of Life Lost to Disability: World

While the goal is to increase years in our lives, an associated need is to have life in our years.

Non-fatal health outcomes from diseases are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level[3]. This information has raised awareness about a range of disorders that primarily cause ill health but not death, such as unipolar major depression, bipolar disorder, asthma, and osteoarthritis.

A measure of this is “years lost to disability” (YLD) calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; “disability” refers to any significant short- or long-term loss of health and function.

The following shows the leading global YLD[4].

Rank Cause Global 2010 YLDs (000s)
0 All Causes 777,401
1 Mental disorders 176,626,
2 Musculoskeletal disorders 165,955
3 Neurological disorders 42,943
4 Cardiovascular disease 8,795
5 Cancers 4,483
6 Cerebrovascular disease 4,346

Note that over three-quarters of a billion years are lost annually due to disabilities. Of these, mental disorders are the major cause of disability in the world, accounting for 22·7% of all YLDs. YLDs for this category as a whole have increased by 37% from 1990 to 2010. If one includes neurological and cerebrovascular diseases, directly related to mental, cognitive, and behavioral disorders – psychoneurological disorders – the importance of this category is further magnified.

Cardiovascular diseases did not contribute more than 5% of global YLDs, mental disorders being 20 times as important and neurological disorders about 5 times as important when considering years lost to disability.

Years of Life Lost to Disability: United States

YLD in the United States is similar to the global trend except COPD and diabetes outranks cancer and cardiovascular disease., as indicated in the following table[5]  Again mental or neuropsychiatric disorders, most prominently clinical depression, are the largest cause of years lost to disability.

Rank Cause United States 2010 YLD (000s)
1 Neuropsychiatric disorders
Major Depressive Disorder 3049
Anxiety Disorders 1866
Drug use disorders 1296
Alzheimer’s disease 830
Alcohol use disorders 836
Schizophrenia 825
Stroke 629
Bipolar disorder 578
Dysthymia 546
   Total Neuropsychiatric 10455
2 Muscular skeletal disorders
low back pain 3181
other 2602
neck pain 2134
osteoarthritis 994
Rheumatoid arthritis 403
 Total Musculoskeletal disorders  9314
3 COPD 1745
4 Diabetes 1165
8 Cardiovascular disease 685


[1] Global Health Estimates 2015: Disease burden by Cause, Age, Sex, by Country and by Region, 2000-2015. Geneva, World Health Organization; 2016.

[2] Murray, C. J. (2013). The State of US Health, 1990-2010. Jama, 310(6), 591. doi:10.1001/jama.2013.13805.

[3] Murray CJ, Ezzati M, Flaxman AD, et al. GBD 2010: design, definitions, and metrics. Lancet. 2012;380(9859):2063-2066.

[4] Voss, T. et al.,  Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010

[5] Murray ibid

Flaxseeds: single most important food for mental health?


by R. Aiken MD PhD @rcaiken

Flaxseed helps lower cholesterol, lowers blood pressure, is anti-inflammatory, has good anti-oxidants, and fiber.  It is the single most neuroprotective food; oh yes, then there is the omega-3 content.

There is no doubt that this food is an excellent source of essential omega-3 fats in the form of alpha-linolenic acid, the basic building block to other omega-3s – eicosapentaenoic acid and docosahexaenoic acid. Omega-3, and a proper omega-3 to omega-6 ratio, is important in mental wellness and recovery from psychiatric disorders.

But flaxseed offers more than just the ideal omega-3 source; it contains many polyphenolic compounds such as phenolic acids[1], flavonoids and lignans along with vitamins C and E[2].  One study found that flaxseed significantly decreased chronic stress (cortisol) levels, indicating a possible synergistic effect between omega-3 fatty acid and polyphenols[3].  Other components such as a flaxseed lignan (a phytoestrogen compound called secoisolariciresinol) has been shown to have possible applications in post-menopausal depression[4].

Studies of flaxseed oil supplementation have indicated a good tolerance even in the pediatric population where one study indicated its effectiveness in child bipolar disorder[5].

I recommend a daily intake of one to three tablespoons of ground flax, each tablespoon of which contains about 30 calories, 2.5 grams fat, 2 grams fiber, and 1.5 grams protein[6]. Be sure to grind the flaxseeds as the fine seeds with their hard shell will likely just pass on through the gut otherwise. Flaxseeds can be ground in a coffee bean grinder and the ground powder added to grains, salads, beans – practically any dish for a little texture.

Note that the shelf life of the oily seeds is limited unless kept in an airtight container in the fridge or freezer.  Ground flaxseeds or flax meal should be kept in the freezer; at room temperature and exposed to air, use the ground seeds within one week. Smell the flax – if it has a strong odor such as fishy smell, it may be rancid.  A taste test should reveal a mild nutty flavor – if bitter or sour that also may be a signal that it is rancid.

For these reasons, chia seeds, rich in antioxidants and omega-3 PUFAs may be preferable to some.


[1] Oomah, B. D., Kenaschuk, E. O., & Mazza, G. (1995). Phenolic Acids in Flaxseed. J. Agric. Food Chem. Journal of Agricultural and Food Chemistry, 43(8), 2016-2019. doi:10.1021/jf00056a011.

[2] Bidlack, W. W. (1999). Functional Foods: Biochemical and Processing Aspects, G. Mazza, ed. Lancaster, PA: Technomic Publishing Co., Inc., 437 pp, 1998. Journal of the American College of Nutrition, 18(6), 640-641. doi:10.1080/07315724.1999.10718899.

[3] Naveen, S., Siddalingaswamy, M., Singsit, D., & Khanum, F. (2013). Anti-depressive effect of polyphenols and omega-3 fatty acid from pomegranate peel and flax seed in mice exposed to chronic mild stress. Psychiatry Clin Neurosci Psychiatry and Clinical Neurosciences, 67(7), 501-508. doi:10.1111/pcn.12100.

[4] Wang, Y., Xu, Z., Yang, D., Yao, H., Ku, B., Ma, X., . . . Cai, S. (2012). The antidepressant effect of secoisolariciresinol, a lignan-type phytoestrogen constituent of flaxseed, on ovariectomized mice. Journal of Natural Medicines,67(1), 222-227. doi:10.1007/s11418-012-0655-x.

[5] Gracious, B. L., Chirieac, M. C., Costescu, S., Finucane, T. L., Youngstrom, E. A., & Hibbeln, J. R. (2010). Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder. Bipolar Disorders, 12(2), 142-154. doi:10.1111/j.1399-5618.2010.00799.x.

[6] A very convenient way to have ground flax ready to serve is provided by Carrington Farms Organic Ground Milled Flax Seeds, two tablespoon packets sealed and lasting without refrigeration about one year.

Nutritional yeast for mood, stress, and immune function


Nutritional yeast natural source of vitamin B. Saccharomyces cerevisiae.

by R Aiken MD PhD @rcaiken

Nutritional yeast has a nutty, cheesy flavor and is often used to emulate cheese, thicken sauces and dressings, and to provide an additional boost of nutrients, particularly B vitamins, folates, thiamine, riboflavin, niacin, selenium and zinc. It is a complete source of essential amino acids.

Impressive research exists that supports a positive effect of nutritional yeast on stress and related immune function resulting, for example, in a decrease for the susceptibility to the common cold[1]. Beta glucan fiber, found in baker’s, brewer’s and nutritional yeast, helps to maintain our body’s defense against pathogens. And this is extended to improvement in mood states, related to immune vitality and emotional vitality[2].

For endurance athletes who place significant stress on their bodies, regular ingestion of this substance is recommended.

Keep a container of nutritional yeast on your countertop and regularly, even daily, use about one heaping tablespoon (4 grams) on a variety of foods.


[1] Auinger, A., Riede, L., Bothe, G., Busch, R., & Gruenwald, J. (2013). Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: A double-blind, randomized, placebo-controlled, multicentric study in healthy subjects. European Journal of Nutrition, 52(8), 1913-1918. doi:10.1007/s00394-013-0492-z.

[2] Talbott, S. M., & Talbott, J. A. (2012). Baker’s Yeast Beta-Glucan Supplement Reduces Upper Respiratory Symptoms and Improves Mood State in Stressed Women. Journal of the American College of Nutrition, 31(4), 295-300. doi:10.1080/07315724.2012.10720441.

Turmeric for mood, inflammation, and stress


by R. Aiken MD PhD @rcaiken

Turmeric is a spice with perhaps the highest antioxidant and anti-inflammatory properties of any culinary spice – or herb. One active component of turmeric is curcumin (the pigment responsible for the bright yellow color of the spice), which may have natural antidepressant qualities and has been shown to protect neurons from the damaging effects of chronic stress.

The beneficial effects of curcumin in the pathophysiology of major depression are probably related to its anti-inflammatory and antioxidant properties, inhibition of monoamine oxidase[1], and modulation of neurotrophic factors and hippocampal neurogenesis and neuroplasticity[2].

In a randomized controlled trial[3] , a comparable efficacy was obtained after curcumin monotherapy (1000 mg/day) compared to fluoxetine monotherapy.  Supplementation of conventional antidepressants with curcumin (1000 mg/ day) has shown to be an effective and safe enhancement[4].

Meta-analysis of data from the six clinical trials[5] revealed a significant reduction in major depressive symptoms following the administration of curcumin in combination with piperdine (see below).  These studies all used the 1000 mg/ day and the anti-depressant effect was best after a duration of six weeks.

Turmeric suppresses pain and inflammation similar to non-steroidal anti-inflammatories but without the potential side effects. The health benefits derive, as for Rhodiola and Maca, from “xenohormesis” – a biological principle that explains why environmentally stressed plants produce bioactive compounds that can confer stress resistance and survival benefits to animals that consume them (see Chapter 6).

Turmeric contains about 2% by weight curcumin, so a tablespoon of turmeric (6.8 grams) contains about 136 mg of curcumin. To get 1000 mg/ day curcumin from raw turmeric would then require more than seven tablespoons.  Supplements that purport to contain 500 mg curcumin are commercially available.

One tablespoon of turmeric (1000 mg) per day with a pinch or two of ground pepper (see below) is recommended. If you grate the turmeric root yourself, be prepared to wear gloves as the color is so intense you will have yellow finger tips otherwise.


[1] Kulkarni, S. K., Bhutani, M. K., & Bishnoi, M. (2008). Antidepressant activity of curcumin: Involvement of serotonin and dopamine system. Psychopharmacology, 201(3), 435-442. doi:10.1007/s00213-008-1300-y.

[2] Liu, D., Wang, Z., Gao, Z., Xie, K., Zhang, Q., Jiang, H., & Pang, Q. (2014). Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress. Behavioural Brain Research, 271, 116-121. doi:10.1016/ j.bbr.2014.05.068.

[3] Sanmukhani, J., Satodia, V., Trivedi, J., Patel, T., Tiwari, D., Panchal, B., . . . Tripathi, C. B. (2013). Efficacy and Safety of Curcumin in Major Depressive Disorder: A Randomized Controlled Trial. Phytother. Res. Phytotherapy Research, 28(4), 579-585. doi:10.1002/ptr.5025.

[4] Yu, J., Pei, L., Zhang, Y., Wen, Z., & Yang, J. (2015). Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder. Journal of Clinical Psychopharmacology, 1. doi:10.1097/jcp.0000000000000352.

[5] Al-Karawi, D., Mamoori, D. A., & Tayyar, Y. (2015). The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials. Phytother. Res. Phytotherapy Research, 30(2), 175-183. doi:10.1002/ptr.5524.

Ground peppercorns for cognitive function, mood, and bioavailability.


by Aiken MD PhD @rcaiken

Black pepper has an ancient history of being a highly desirable but expensive spice.  It has even been used as a currency.

Piperine is a simple and pungent alkaloid found in the seeds of black pepper. Piperine is commonly known as a bioavailability enhancer for a number of nutraceuticals, including antioxidants[1] and anti-inflammatories[2], as well as for its neuroprotective activity[3]. The Journal of Food and Chemical Toxicology reported that the compound piperine in black pepper increases the cognitive function of the brain and helps mood disorder.

Piperine helps the body absorb curcumin and therefore enhances curcumin’s antidepressant effect long-term. There may be similar absorption assistance given to selenium, vitamin B12, and beta-carotene.

Piperine has shown multiple mechanisms of action, including inhibition of MAO enzymes, elevation of brain serotonin (5-HT) brain derived neurotropic factor (BDNF) levels, and modulation of HPA axis[4].

Because of its intense taste in small quantities, it is typically used as just a few “pinches” into turmeric recipes.

Typically 2.5 mg/ kg is used so for a 70 kg person that would equal 175 mg; a teaspoon of black pepper weighs about 2000 mg, so this is less than 10% of a teaspoon – otherwise known as a “pinch” or two.


[1] Johnson, J. J., Nihal, M., Siddiqui, I. A., Scarlett, C. O., Bailey, H. H., Mukhtar, H., & Ahmad, N. (2011). Enhancing the bioavailability of resveratrol by combining it with piperine. Molecular Nutrition & Food Research Mol. Nutr. Food Res., 55(8), 1169-1176. doi:10.1002/mnfr.201100117.

[2] Ying, X., Yu, K., Chen, X., Chen, H., Hong, J., Cheng, S., & Peng, L. (2013). Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells. Cellular Immunology, 285(1-2), 49-54. doi:10.1016/j.cellimm.2013.09.001.

[3] Shrivastava, P., Vaibhav, K., Tabassum, R., Khan, A., Ishrat, T., Khan, M. M., . . . Islam, F. (2013). Anti-apoptotic and Anti-inflammatory effect of Piperine on 6-OHDA induced Parkinson’s Rat model. The Journal of Nutritional Biochemistry,24(4), 680-687. doi:10.1016/ j.jnutbio.2012.03.018

[4] Mao, Q.Q., Xian, Y.F., Ip, S.P., and Che, C.T. (2011). Involvement of serotonergic system in the antidepressant-like effect of piperine. Prog. Neuropsychopharmacol. Biol. Psychiatry 35, 1144–1147