The SMILES Trial: what’s the real takeaway?

Prior to 2017, dozens of observational and epidemiological studies reported that there may be some kind of relationship between diet quality and one’s mental health. Studies that have yielded a positive association between diet quality and mental health state that the kind of dietary pattern that may improve mental health outcomes includes a pattern that focuses on a whole foods nutrient dense diet inclusive of fruits and vegetables, whole grains, nuts and seeds, fatty fish, and lean meats, and decreased intake of ultra-processed and sugary foods. These observational studies allowed for possible correlations to be determined and until the development of randomized controlled trials, the field was lacking in it’s confidence to say that dietary interventions caused mental health outcomes to improve.  Probably the most noted of dietary intervention trials, the SMILES trial, was the first randomized control trial (RCT) conducted in 2017 to assess if a dietary intervention compared to a social or “befriending” group, could produce positive mental health outcomes in a population of adults who were clinically depressed. Here’s their stated hypothesis: “we hypothesised that structured dietary support, focusing on improving diet quality using a modified Mediterranean diet model, would be superior to a social support control condition (befriending) in reducing the severity of depressive symptomatology.”

Method

Participants included in the study were diagnosed with moderate to severe depression via the Diagnostic and Statistical Manual of Mental Disorders (DSM) and screened for poor dietary intake at the time of recruitment. Poor dietary intake was characterized by having a low intake of fruits, vegetables, other plant foods and quality proteins and a high intake of processed or sugary foods. Researchers also used a dietary score to assess compliance to the diet throughout the study. There has been some recent criticism of the specific recruitment strategies since this paper has been published, mostly because of the way they had advertised to seek out their participants. For example, there were advertisements stating: ‘We are trialling the effect of an educational and counselling program focusing on diet that may help improve the symptoms of depression’. If you are curious about the critique, make sure you read this paper. It specifically highlights how expectancy bias is likely a factor with respect to these results which is important to consider when we are thinking about the clinical takeaways of this particular study.

In total, 67 participants were included in the study and were randomly allocated to two groups. The dietary intervention group received personalized dietary recommendations based on a modified Mediterranean diet during 7 60 minute one on one sessions with a clinical dietician. Participants in the social support group received social support via a befriending protocol which consisted of regular meetings to discuss topics of interest or playing games. Here’s a description of the details with regards to both groups: “The dietary intervention comprised personalised dietary advice and nutritional counselling support, including motivational interviewing, goal setting and mindful eating, from a clinical dietician in order to support optimal adherence to the recommended diet.” Both groups met at the same frequency and duration throughout the study.  Depression measures were assessed at baseline and at the conclusion of the study using a variety of self report measures including the Montgomery Asburg Depression Rating Scale (MADRS), which was the primary outcome of interest.

Results

After 12 weeks, results indicated that the dietary intervention group showed significantly greater improvements in mental health as compared to the social support group. “The dietary support group demonstrated significantly greater improvement in MADRS scores between baseline and 12 weeks than the social support control group, t(60.7) = 4.38, p < .001 (Fig. 2). The effect size for this difference was a Cohen’s d of –1.16 (95% CI –1.73, –0.59) and represented an estimated average between group difference, in terms of change from baseline to 12 weeks, of 7.1 points on the MADRS (SE = 1.6).” If you are familiar with nutrition research or in psychology, you would know that an effect size of -1.16 is absolutely huge. Typically, an effect size is considered small to moderate (d = 0.2 - .4), medium (d = 0.5 - .07), and large (d = 0.8 and greater) and it’s unusual to see an intervention with that large of an effect size.

It is important to note that beyond getting one on one counseling with a clinical dietician, participants in the dietary intervention group were given hampers of food, incorporating the main components of the diet, along with recipes and meal plans after each dietician session. This significantly increases adherence to the diet when one has the foods available to them in their home along with an understanding of the diet itself and how to cook specific recipes that adhere to the dietary guidelines. Meeting with a clinical dietician for 7 60 minute sessions created a guided individualized support system for the participants who were changing their dietary patterns and habits, something that can significantly increase one’s success with regards to behavior change. These are all independent interventions outside of diet that likely have created these extraordinary results.

Additional Thoughts

They conclude at the end of the study that modifying one’s diet to fit a modified Mediterranean diet, is a useful and effective intervention to help decrease symptoms of depression. In fact, here is what they state in the Discussion section of the paper: In summary, this is the first RCT to explicitly seek to answer the question: If I improve my diet, will my mental health improve? But I want to introduce the major confounding variables that I think, don’t allow us to simply come to the conclusion that diet indeed was the sole factor that caused these significant results. The “structured dietary support” which included meeting with a registered dietician on a regular basis, encouraged participation in a positive adaptive behavior (cooking for oneself). And we know that increasing one’s engagement in positive adaptive behaviors is a very effective behavioral treatment to assist with depression, called Behavioral Activation. It’s effectively, a behavioral strategy that increases a person’s engagement in positive and pleasant activities, thus helping to increase reinforcement, while decreasing punishing behaviors like social isolation, which tends to worsen depression. Behavioral activation independently has really strong effect sizes when we look at this as an independent intervention for depression. This, I would argue, is one of the main interventions used in this study (beyond modifying one’s diet). Meaning, the behavioral intervention within itself (cooking healthy meals for oneself consistently) allows the individual to not only engage in the adaptive behavior of cooking and preparing healthy meals, but it also inherently decreases the person’s engagement in any behavior that may exacerbate or worsen a person’s depression symptoms, simply because the person is now spending time engaged in this adaptive behavior. Additionally, tertiary interventions used like goal setting and motivational interviewing increased the person’s engagement in this goal directed behavior, which are hugely positive when it comes to treating clinical depression.

These are the confounds that exist in this particular intervention study and I think really highlights the need for us to be critical when it comes to interpreting these results. I think the more appropriate question here to ask is: If I improve my diet with the structured guidance and support of a nutrition professional, will my mental health improve?

With regards to the particular takeaways and conclusions we can potentially make from this study, I think it’s crucial to think about these above factors. If anything, the use of personalized sessions with a trained dietician or nutritionist to support dietary changes can be helpful in getting a mild or moderately depressed person to change their diet and that providing resources including handouts of recipes, as well as hampers of foods, increases a depressed person’s ability to adhere to these behavioral instructions.

Is it possible that diet helps to improve symptoms of depression? Maybe. But I think that it’s important to contextualize when diet is able to produce positive mental health outcomes based on the current evidence as well as these important factors of influence. Part of helping us understand this potential relationship, is also looking at other evidence for this relationship in prospective cohort studies. The benefit of the design of these kinds studies is that it allows us to determine over a longer period of time, typically in a healthy population (free of depression), if there is a relationship between one’s diet quality and the risk for developing depression over time. One particular review analyzing results of many prospective cohort studies assessing this relationship, reports that adherenece to a “high-quality diet,” regardless of type (i.e., healthy/prudent or Mediterranean, Tuscan, or vegetarian), was associated with a lower risk of depressive symptoms over time. But what is interesting is that they analyzed the results more comprehensively by accounting for studies that controlled for certain variables at baseline as well as looking at the difference in measures of outcome to see if that made a difference in this potential relationship. They found that studies that controlled for depression severity at baseline or that used a formal diagnosis as outcome did not yield any statistically significant findings. This is critical to understand as this means that a perons’s baseline status regarding depression severity mediates this relationship between diet quality and risk for developing depression long term. It also means that using a formal diagnosis vs. self report measures, are more sensitive to picking up on the diagnostic criteria for depression. Again, these are considerable factors that we need to think about when trying to answer the question if diet is really able to improve depressive symptomology in clinically depressed persons.

Serotonin in the gut vs. Serotonin in the brain

Nutritional psychology as a field has been gaining increasingly more attention. If you look at social media and blogs online, one of the biggest reasons why some people are promoting the importance of the diet-mental health relationship is because of this fact: “95% of the bodies’s serotonin is produced in the gut.” And while that is true, that’s also suggesting that this gut serotonin is the same as the serotonin in our brain that is responsible for our mood and behavior. Let’s take a look at the current research to understand the difference between serotonin produced in the gut and serotonin that is produced in the brain to understand why this difference is important.

Serotonin

Serotonin is a neurotransmitter. A neurotransmitter is a molecule that neurons use to communicate at synapses. Serotonin is a complex molecule and exerts a variety of biological functions including regulating mood, cognition, learning, memory, even appetite and vomiting.

Altered serotonergic activity has been associated with many mood disorders including depression, anxiety and schizophrenia. MDD is one of the most important mental disorders associated with altered serotonergic activity. This discovery eventually lead to the development of SSRI’s (Selective Serotonin Reuptake Inhibitors) which allows for more serotonin to be available for the brain to use.

In the gut, serotonin is made and secreted by specialized cells called enterochromaffin cells that line the wall of the gut. Here, serotonin plays a major role in controlling peristalsis, which is the wave-like contractions of the gut walls that move food along the digestive tract, allowing for the digestion and absorption of nutrients. Serotonin mediates various functions in the gut by acting on a diverse range of receptors present on smooth muscle, enteric neurons, enterocytes, and immune cells. Some of these other functions include nausea, vomiting, and intestinal secretion. The serotonin produced in the gut is called peripheral serotonin. Altered levels of this peripheral serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis.

The rest of the serotonin that gets produced in the body is made in the brain and is called brain derived serotonin (BDS). In the brain, serotonin is produced in the raphe nucleus of the brain stem and hypothalamus. Here is where it functions as a neurotransmitter, responsible for influencing our mood, thoughts, and appetite. The serotonin produced in the gut and in the brain is the same molecule from a structural perspective, but as you can see functionally, it is different.

Does Peripheral Serotonin affect our mood?

Neural pathways connect the brain and the stomach via the enteric nervous system which means that serotonin in the gut can potentially send signals and communicate to the brain. The vagus nerve is one of the ways that the gut and the brain communicate with each other. It is also hypothesized that gut microbiota are able to significantly influence the production of peripheral serotonin and may also have an influence on brain derived serotonin.

There are very limited studies using humans which makes it difficult to generalize findings from animal studies because of our inherent differences in biology. Nevertheless, animal studies are used as guides to help us understand this phenomen. Elaine Hsiao and her research group published findings in the Journal Cell in 2015 that stated that in mice, a specific mixture of bacteria in the gut microbiota, produces molecules that signal to gut cells to increase production of serotonin. When their team raised germ free mice, known as mice without the bacteria, more than 50% of their gut serotonin was missing. This demonstrates that specific bacteria promote serotonin levels in the gut, at least in mice. More research is needed in order to understand the complexities related to the ways in which human gut microbiota can influence our mental and brain health, particularly if it offers new ways of treating mental health conditions like MDD.

Conclusion

The bottom line is that brain-derived serotonin (BDS) acts as a neurotransmitter, while gut-derived serotonin (GDS) acts as a hormone. In fact, the serotonin produced in the gut is not able to cross the blood brain barrier (BBB), a picky vascular barrier that helps regulate substances that enter and leave the brain. This means that the gut serotonin never enters the brain, and is instead used for other gut motility functions. It is the brain derived serotonin that is responsible for influencing our mood, thoughts, and appetite.

Clearly, there is an important connection that exists between the gut and the brain, as there are many ways in which they are able to communicate with each other. What is fundamental is that, we are still understanding this communication system and the myriad of ways this pathway influences our mental and brain health. But it’s not as straightforward as other people on the internet are making it seem. There are many reasons why its important to care about the diet-mental health relationship. But this known fact is not necessarily one of them.

References

Banskota, S., Ghia, J. E., & Khan, W. I. (2019). Serotonin in the gut: Blessing or a curse. Biochimie, 161, 56–64. https://doi.org/10.1016/j.biochi.2018.06.008

Namkung, J., Kim, H., & Park, S. (2015). Peripheral Serotonin: a New Player in Systemic Energy Homeostasis. Molecules and cells, 38(12), 1023–1028. https://doi.org/10.14348/molcells.2015.0258

Lin, S. H., Lee, L. T., & Yang, Y. K. (2014). Serotonin and mental disorders: a concise review on molecular neuroimaging evidence. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 12(3), 196–202. https://doi.org/10.9758/cpn.2014.12.3.196

Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161(2), 264–276. https://doi.org/10.1016/j.cell.2015.02.047

The Social Determinants of Mental Health

Mental health is the combination of complexities between your genes and your environment. As a field and to better help individuals we work with, it is integral to evaluate the role that non genetic social and environmental factors play in contributing to poor mental health and in causing and worsening mental illnesses.

The biopsychosocial model has served as a structure, primarily for clinicians to help them formulate a course and treatment plan for individual patients. The model essentially recognizes the interplay and interactions between biological, psychological, and social factors and how these factors contribute and influence the onset and course of mental (and physical) illnesses. The role of each of these factors is incredibly significant. Let’s take a look at the social determinants of mental health and why this is important and so influential.

What are Social Determinants of Mental Health?

The World Health Organization (WHO) defines the social determinants of health as the conditions in which people “are born, grow, live, work, and age and the wider set of forces and systems shaping the conditions of daily life.”

Michael T. Compton, M.D., M.P.H., and Ruth S. Shim, M.D., M.P.H in their book The Social Determinants of Mental Health write that the major social determinants of mental health are effectively the same as for physical health and that the “ “core” social determinants of mental health are: racial discrimination and social exclusion; adverse early life experiences; poor education; unemployment, underemployment, and job insecurity; poverty, income inequality, and neighborhood deprivation; poor access to sufficient healthy food; poor housing quality and housing instability; adverse features of the built environment; and poor access to health care.” They further state, “there are other social determinants of mental health that could be articulated, including inadequate or unequal access to transportation, exposure to violence, conflict, and war in childhood or adulthood, mass incarceration and poor relations between law enforcement and communities, environmental air, water, or land pollution, climate change, sexism and other forms of non–race-based discrimination; and adverse or unsupportive features of the workplace.”

These determinants suggest that mental health is deeply influenced by policies made at the government level and affecting change within these systems require change through policy and programs, as well as, collective and individual decisions within society.

This is an incredibly layered and complex topic. I want to highlight and emphasize the reason for this post which is that I think these factors are not as discussed as much as they should be in the context of mental health. We are living in a time when the responsibility of taking care of ourselves is being solely put on the individual. That if we have poor health and poor mental health, we aren’t taking the time to take care of ourselves. Indeed, this misses the greater environmental and social context in which we all live and are affected by both consciously and unconsciously. In order to have a real conversation about what we can do to take care of our mental health as individuals, we have to consider these factors and the roles they play in our individual and collective lives.

Why this is important for our Mental Health

These social determinants predispose individuals and populations to poor health outcomes. For example, at the individual level, being affected by one or more social determinants can lead to “poor” choices. If you don’t make enough money to be able to purchase enough grocery items at the store for your family, one of the only other options you may have is access to fast food restaurants due to it’s affordability. This decision and other decisions that may negatively affect mental health, could occur simply because of a lack of healthy and affordable options, which in turn leads to known risk factors (e.g., poor diet, substance misuse) for poor physical and mental health. On top of which, exposure to adverse social conditions like inadequate housing or unemployment, leads to stress and known psychological and physiological stress responses that biologically create more vulnerability like increased HPA-axis activation (stress) and inflammation, both of which increase the risk of mental illness.

In this context, there are limited options for people to engage with with regards to taking care of their mental health. These are systemic issues that lead to poor mental health outcomes and to advise people on an individual level to modify their diet or to practice pop psychology “self care” by taking bubble baths and meditating when they are faced with such circumstances that dramatically affect their mental health, is unhelpful at best and offensive at worst. For example, to recommend someone to purchase organic “non-processed” foods when they work 50 hours a week to afford rent, have a sick family member to take care of, and have children of their own, is again, both dangerous and oblivious to the larger context that affects us as individuals.

In order to actually take care of our mental health, we need to have our basic needs met. We also need our stress levels to be manageable. Living in a pandemic has made that incredibly difficult for most people. We also need public health recommendations that make sense, are accurate and rooted in scientific practice and literature, and we need change at a societal and individual level.

What can you do?

Are there any lifestyle and behavioral factors that are in your control even if it is very little? Are you able to move your body for 15 minutes a couple of times a week? Are you able to connect to some kind of social support system? Do you have access to processed foods? Because processed foods are great. I’m sure you never read that in an article discussing mental health and nutrition, but it’s true. Packaged foods like oatmeal, oats, lentils, wholegrain pasta, canned vegetables and fruits, canned beans, canned seafood, frozen fruit and vegetables, pasta sauce, ready to heat microwaved rice, spices, are all excellent options that help support your mental health.

Practice real self care by taking care of your personal hygiene as best as you can. Are you able to get some help from a friend, neighbor, or family member to help make you a meal or give you an hour to rest? Budget your money and time. Try and prioritize your sleep. Do what you can when you can. And know that you are doing the best you are able to for you and your family. There are greater changes that need to be made at the societal level in order for public mental health outcomes to change at a large scale. You can’t eat your way our of depression and anxiety with the best Mediterranean style diet when you are living with the constant stress of being able to pay your bills, living with a partner who has chronic mental illness, or are experiencing racial discrimination and sexual harassment in the workplace. If the only thing you can afford to eat right now is McDonalds twice a week because it ensures that you are able to eat enough calories, please do it. Anyone shaming you for making those choices is ignorant to your life context and is speaking from a place of privilege which they likely are unaware of.

References

https://focus.psychiatryonline.org/doi/pdf/10.1176/appi.focus.20150017#:~:text=the%20main%20%E2%80%9Ccore%E2%80%9D%20social%20determinants,healthy%20food%3B%20poor%20housing%20quality

https://www.paho.org/en/topics/social-determinants-health

Inflammation: What the current research says about it's role in mental health

Inflammation is defined as the immune system’s response to contact with harmful stimuli including physical injury and pathogens, and involves the amazing communication of immune cells and blood vessels. Inflammation is necessary in order for us to survive and is not a harmful process unless it becomes chronic.

Chronic inflammation can be caused by a variety of things including chronic infections, unrepaired tissue damage, allergens, or indigestible foreign particles. Chronic inflammation contributes to many chronic inflammatory diseases including diabetes, cardiovascular, bowel diseases, and more recently, brain and mental health disorders. It can also be caused by medical conditions, exposure to chemicals or pathogens, as well as lifestyle behaviors including a sedentary lifestyle, poor dietary patterns, and alcohol intake.

Recently, inflammation is thought to be one of the major mechanisms that influence the diet mental health relationship, with several studies concluding strong associations between inflammatory biomarkers (health markers that can be measured in a lab that indicates inflammation in the body) and specific mental health disorders including depression and schizophrenia. But these findings are not always consistent. This article will review the current literature to date elucidating the relationship between inflammation and depression as well as highlight some important nuance and context to help us understand this relationship.

How Inflammation is Measured

Specific molecules called cytokines are classified as type of “biomarker” which can be measured in blood tests that show alterations in the body or tissue fluids. There are both pro-inflammatory cytokines that promote inflammation as well as anti-inflammatory cytokines which help inhibit or stop inflammation. These pro-inflammatory cytokines are used in clinical applications to indicate normal and abnormal biological processes, as well as to properly assess a person’s responses to therapeutic interventions. This helps researchers and clinicians decide if an intervention helped to lower or promote inflammation in the body. Some common pro-inflammatory cytokines used in research include IL-6, CR-P and TNF alpha.

Diet and Inflammation: Current Research

The majority of the current research related to diet and inflammation mostly comes from observational and epidemiological research studies. These kind of studies allow us to see if one factor correlates or has a relationship with another. It is difficult to determine if one nutrient or food itself is inflammatory or anti-inflammatory for multiple reasons. One is simply because of how we eat. We do not eat foods or nutrients in isolation (i.e. only eating avocados every day). We need to eat a variety of foods which themselves include a variety of nutrients (vitamins and minerals). The other is that there is a lot of inter individual differences with regards to how people respond to certain foods. For me, tomatoes and peppers don’t cause any sort of digestive distress, but for others, tomatoes and peppers may cause them a lot of digestive issues, which may indeed affect peripheral measures of inflammation. In this way, labeling a food as “anti inflammatory” or “inflammatory” is futile. Beyond these reasons, one food or nutrient is not “inflammatory” or anti inflammatory” on it’s own. What is more constructive and practical with regards to attempting to make determinations for the public and nutrition recommendations, is looking at overall dietary patterns to assess if that alone affects inflammation. Broadly speaking, ​​dietary factors that have been associated with decreased levels of inflammation are fiber, antioxidants, omega-3 fatty acids and fermented foods, as compared to other nutrients like saturated fat and sodium which have been associated with increased levels of inflammation. 

Some of the best research we have on humans is from large epidemiological research studies like the Nurses Health Study. The Nurses Health Study is one of the longest and largest investigations into risk factors for chronic disease in women. One analysis from this long term study includes a more recent look at diet and inflammation in over 40,000 women who were clinically depressed at the start of the study. The purpose of the analysis was to see if consuming a kind of dietary pattern associated with higher levels of inflammatory markers increased the future risk of depression. The participants were followed up for 12 years and during that time there were over 9,000 incident cases of depression. The authors report that an inflammatory dietary pattern was associated with a higher risk of developing depression. Here’s what we can take away from this analysis in particular: there is an association in middle aged women between consuming an inflammatory dietary pattern and developing depression over a period of 12 years. A more obvious limitation with regards to generalizing these results to a broader population is the limited demographic of the population in this analysis as it was mostly Caucasian women working in healthcare age 55-77. More studies like these in more diverse and varied populations would help clarify if these associations occur in most people. This would help benefit more people across the world with the goal of really helping improve public health.

The Mediterranean Diet

I’m sure at this point you have heard and read about the Mediterranean Diet. Full of vegetables, fruits, whole grains, nuts, seeds, legumes, olive oil, seafood and limited dairy and lean meats, this diet has been studied extensively for it’s various health benefits including for brain health.

A recent review looking at over 60 observational studies reports that adherence to a Mediterranean and “anti-inflammatory diet” (as measured by dietary indices such as the Empirical Dietary Inflammatory Index as well as measurements of biomarkers such as C-Reactive Protein) is associated with lower levels of inflammation. The majority of analyses in the review report a positive association between a healthier diet and lower pro-inflammatory marker CRP, indicating less inflammation. These results again means that there seems to be an association between closer adherence to a Mediterranean diet in an adult population and lower levels of a pro-inflammatory cytokine (CRP). One of the limitations in this review and among all of the studies included was that only one inflammatory biomarker (CRP) was assessed and at only one time-point. Future research needs to focus on examining multiple inflammatory markers in order to better understand these complex biological inflammatory mechanisms and how diet influences this. Also, the studies included in the review were mostly cross-sectional, which only allows us to say that there is an association between diet and inflammation, not that diet necessarily causes inflammatory markers to increase. Additionally, there are many different disease states and variables that influence inflammation and hence, measures of inflammatory markers and mediators in the blood. These factors (like chronic medical diseases including Type 2 diabetes and rheumatoid arthritis) were not controlled for in the data analysis. This is important because trying to control for these variables will allow us to better understand the relationship between inflammation and diet alone. Future research needs to focus on longitudinal methods as well as methodological designs that get us closer to seeing if diet alone is enough to cause and maintain chronic inflammation in particular.

Recent Research on Inflammation and Depression

One recent hypothesis is that diet mediates chronic inflammation and that poor diet in some people, may lead to both inflammation as well as contribute to the development of depression. Meaning, that diet directly influences chronic inflammation.

Interestingly, there is some newer research that suggests that certain depressive symptoms may be associated with specific inflammatory biomarkers. For example, one review reports that there is an association between the neurovegetative symptoms of depression and inflammation, such as fatigue, disturbed appetite, sleep problems (specifically hypersomnia), and depressed mood. This review is also interesting because it analyzed data from a very large sample of people. The data was retrospectively analyzed with over100,000 individuals from the UK Biobank and NESDA cohort. The researchers report that CRP and IL-6 levels (two inflammatory cytokines) were associated with specific symptoms of depression including fatigue, sleeping problems, changes in appetite, and depressed mood. This study adds new information to the existing literature and if this is found repeatedly in depressive populations, this may be able to help clinicians tailor treatment based on these assessments. But I think these results need to be interpreted with caution as there is a ton of difficulty involved in helping to determine if certain subtypes of depression are related to inflammation status. There are also some limitations to consider as well in that although this study used elevated CRP as the criteria, a one time measurement of CRP may not be sufficient to identify patients with persistent inflammation.

A recent study from 2020 assessed and measured absolute numbers of 14 immune cell subsets from peripheral blood samples in 206 participants with depression and 77 healthy controls (as defined by not having any history of MDD or other psychiatric illness). Researchers tested the hypothesis that a subgroup of depressed cases would have peripheral inflammation using what’s called a top down analysis, dividing the cases into 2 subgroups based on their immune cell profiles. They then tested for significant differences between the groups in terms of inflammatory proteins and clinical variables. In terms of the characteristics of the participants in the MDD group: 114 had moderate to severe depressive symptoms, of whom 61% were taking an antidepressant medication, 50 with mild depressive symptoms of whom 90% were currently taking medication and 42 with minimal depressive symptoms of whom 100% were currently taking medication.

Results showed that CRP and IL-6 concentrations as well as absolute counts of neutrophils, intermediate monocytes, and CD4+ T cells (various immune cells) were significantly increased in the depressed group. They further defined 4 different subggroups within the MDD patients: an uninflamed group which had low levels of immune cells measured, and 3 other subgroups with elevated levels of different immune cells. The subgroup of cases with increased immune cell counts also had significantly increased inflammatory protein concentrations compared with the second subgroup with decreased immune cell counts. The researchers called this group the inflamed depression group. Cases of inflamed depression had significantly higher severity of observer related depressive symptoms as measured on the Ham-D and self reported depressive symptoms from the BDI, compared with the uninflamed depression cases. Inflamed vs. uninflamed cases had twice the rate of unemployment, were slightly older, and were more likely to be smokers. They still did not differ significantly on other variables like sex, current antidepressant use, alcohol use, and BMI.

Some limitations to consider are the methodological design in that case control designs are vulnerable to the effects of uncontrolled confounding variables, and there are many factors that could have effects on peripheral immune biomarkers. But these results are interesting and help us understand that not all cases of MDD are necessarily driven or are associated with increased levels of inflammation.

Another study published earlier this year that included older adults with late life depression MDD, sought to disassociate the links among depression, medical illness, and inflammation by carefully screening out patients with known inflammatory-associated illness. This approach allowed the researchers to determine, in the absence of known comorbid illness, whether depression was associated with higher rates of inflammation when compared to healthy adults without a diagnosis of MDD. They found that there were very low levels of circulating cytokines and inflammatory mediators in individuals with MDD and in healthy controls, when study participants in both groups were carefully screened to exclude medical causes of inflammation. The researchers report that there was no observable difference in inflammatory markers between patients with MDD and controls, which included levels of 29 different circulating cytokines and chemokines. The authors also note that a large number of patients had to be excluded which highlights the high rates of physical illness in most patients with MDD. In fact, one review estimates that the prevalence of MDD in those with chronic medical diseases is at least twice as high and often more than four times higher than the prevalence in the general population. This is extremely important as other medical conditions that are inflammatory driven (like IBS and rhemutoid arthritis) significantly increase the risk for depression and also will affect the number of plasma inflammatory proteins.

These two recent studies in tandem tell us that inflammation is not necessarily a central component when it comes to the pathophysiology of depression, but that it may be for some individuals. It provides further support that depression is a heterogenous disorder in that there is a lot of variability with regards to how depression develops, it’s time course, as well as ways in which people respond to treatments. Hopefully more research can done to replicate the findings that there may be subgroups of patients with depression where inflammation may be the primary driver. In this way, treatment potentially can be tailored to focus on ways to help lowers these levels of inflammation.

Takeaways

While most of the research on diet and inflammation in humans are from correlational studies, there is growing evidence that dietary patterns influence inflammation. More research needs to be done with more diverse populations as well as with more diverse dietary patterns to help understand the complexity of this relationship and what to relay to the public. Indeed the Mediterranean diet isn’t the only dietary pattern that helps to support our mental health. It’s just that is has been the dietary pattern that has been most studied thus far and therefore has been recommended to promote health more than other dietary patterns.

Food is more than just nutrients, it’s pleasurable, comforting, social, cultural, and emotional. The most consistent finding shown thus far is that it is your dietary pattern that is what seems to matter most when it comes to diet and overall health. Which means it’s not about finding magic brain healthy nutrients, it’s about eating a spectrum of food that both satisfies the soul as well as nourishes our brain. Sticking with sustainable basics like increasing your fruits, vegetables, fiber, and water intake, ensures you are feeding and supporting your mental health as best as you can. And remember, inflammation has not been shown to be a central component when it comes to the pathophysiology of complex mental health disorders, which means you do not need to be obsessive about focusing on lowering inflammation if you have a mental illness. It’s a lot more complicated than that :)

References

Colditz, G. A., Manson, J. E., & Hankinson, S. E. (1997). The Nurses' Health Study: 20-year contribution to the understanding of health among women. Journal of women's health, 6(1), 49–62. https://doi.org/10.1089/jwh.1997.6.49

Hart, M.J., Torres, S.J., McNaughton, S.A. et al. Dietary patterns and associations with biomarkers of inflammation in adults: a systematic review of observational studies. Nutr J 20, 24 (2021). https://doi.org/10.1186/s12937-021-00674-9

Melo, H. M., Santos, L. E., & Ferreira, S. T. (2019). Diet-Derived Fatty Acids, Brain Inflammation, and Mental Health. Frontiers in neuroscience, 13, 265. https://doi.org/10.3389/fnins.2019.00265

Salari-Moghaddam, A., Keshteli, A. H., Afshar, H., Esmaillzadeh, A., & Adibi, P. (2019). Association between dietary inflammatory index and psychological profile in adults. Clinical nutrition (Edinburgh, Scotland), 38(5), 2360–2368.

Zhao, H., Wu, L., Yan, G. et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Sig Transduct Target Ther 6, 263 (2021). https://doi.org/10.1038/s41392-021-00658-5

Omega6 fats vs. Omega3's, does the ratio matter for your Mental Health?

One of the potential mechanisms in which mental disorders and challenges manifest is via inflammation. Inflammation is your bodies’ response to injury and is essential for our survival. Inflammation becomes a problem when it becomes chronic.  Omega3 fats DHA and EPA are especially important for our mental health and while they help to decrease inflammation, they also contribute to the structural integrity and fluidity for every one of our cell membranes. In fact, DHA makes up about 90% of the omega3 fats in your brain!

Observational studies report deficiencies of Omega3’s in many clinical mental health disorders including depression and anxiety. The current western diet is devoid of many essential nutrients and is thus incredibly deficient in these important brain healthy fats. In fact, consumption of a Western dietary pattern is associated with increased levels of inflammation as well as increased levels of Omega 6 fat arachadonic acid (AA). More recent evidence suggests that the ratio and balance of Omega6:Omega3 in one’s diet may be relevant to disease states including one’s poor mental health. In fact, case controlled studies suggest that individuals with depression have lower levels of omega 3’s and higher omega6:omega3 ratio levels compared to healthy controls. But if you take a closer look at the research, the culprit may not be AA afterall, but instead a lack of enough Omega 3 fats EPA and DHA in the diet.

Both Omega 3 fats and Omega 6 fats are important because they help to provide the structural components of cell membranes and as well as a source of energy and fuel. While Omega 3 fats seem to have been getting more of the positive attention they deserve, Omega 6 fats are instead getting blamed as the cause for poor health outcomes. It is commonly believed that consuming foods with high levels of Omega 6 fats, like vegetable oils including canola oil, will increase levels of inflammation. But studies in humans suggest otherwise in that an increase in the consumption of ARA or LA (Linoleic Acid) does not increase inflammatory biomarkers and instead help to decrease inflammation. In fact, one meta-analyses of over 30 randomized controlled trials reports that increasing consumption of Omega 6 fat LA did not increase any inflammatory biomarkers including interleukin-6 and tumor necrosis factor, two commonly used markers measuring levels of inflammation in the body. And yet another review of 15 human intervention trials investigating the effects of LA on inflammatory biomarkers concluded that “virtually no data are available from randomized controlled intervention studies among healthy, non-infant human beings to show that the addition of LA to diets increases markers of inflammation.”

Let’s take a look at what EPA and AA influences to help us discern whether paying attention this ratio is important.

EPA and AA both act as precursors for cell signaling pathways. Increasing EPA by supplementing helps to reduce the EPA:AA ratio, which is important because they both compete for the same enzymatic conversion pathways. By increasing EPA, it results in the increase of resolvins and other substrates that help signal anti-inflammatory pathways, which help to improve the regulation of neuroinflammation (inflammation that occurs in the brain). This is one proposed mechanism by which EPA helps to reduce depression (future blog post soon). But this is just one proposed mechanism and way EPA has an influence on depression.

We need to be careful about interpreting findings about associations of higher ratios of Omega6:Omega3’s and mental health conditions and immediately relating that to inflammation and dietary recommendations. Omega6 fats are also crucial for brain health and we need them in balance with our Omega3’s to help our mental functioning thrive. Yes a Western style dietary pattern is associated with increased biomarkers of inflammation and levels of AA, but maybe that’s more because there is a lack of beneficial dietary omega3 fats DHA and EPA present in this dietary pattern. Perhaps it’s the deficiency of EPA, fruits and vegetables, nuts, and legumes, that lend itself to promoting further inflammation instead of the consumption of Omega 6 fats. The Western dietary pattern is characterized by a high content of saturated fats, refined grains, sugar, alcohol, and salt. Consuming these foods doesn’t leave much room for the consumption of more beneficial nutrients and foods that help to lower levels of inflammation, like we have seen with the Mediterranean style diet so far. The issue isn’t that you can’t ever consume processed foods because they have Omega 6 fats. It’s that in order to help promote anti-inflammatory mechanisms in the body, you want to focus on limiting your consumption of those foods while also consuming other foods with more brain supporting nutrients (seafood, fruits, veggies, wholegrains, etc.).

That being said, it is important to consume both Omega 6 and Omega 3 fats as both contribute to lowering levels of inflammation. For mental health specifically, omega 3 fats EPA and DHA seem to be particularly significant.

How Inflammation Affects our Brain 

There are several proposed mechanisms as to why inflammation may be a major contributor to mental health disorders, particularly for depression. One of the hypotheses is that elevated inflammatory markers activate the HPA axis, which result in the increased release of cortisol. Cortisol receptors become desensitized which increases the activity of proinflammatory immune mediators and leads to  disturbances in the transmission of neurotransmitters. Another hypothesis is that inflammatory cytokines and cortisol may lower serotonin precursor availability and can instead lead to serotonin depletion. This is important because serotonin is central to the development of depression. You need to have enough of it in the synapse between cells in order to experience stability in mood. Individuals with Major Depressive Disorder (MDD) have been shown to have increased levels of proinflammatory cytokines, leading to believe that inflammation is a major contributor to this clinical disorder.

Focusing on increasing your consumption of Omega3 fats EPA and DHA with foods like fatty fish will help benefit your mental health, especially if you have clinical depression. Following a whole foods nutrient dense diet like the Mediterranean diet complete with lots of vegetables, fruit, seafood, nuts, beans, legumes, seeds, olive oil, and some red meat will help lower levels of inflammation, helping to promote mental health.

 References

 Berger, M. E., Smesny, S., Kim, S. W., Davey, C. G., Rice, S., Sarnyai, Z., Schlögelhofer, M., Schäfer, M. R., Berk, M., McGorry, P. D., & Amminger, G. P. (2017). Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study. Translational psychiatry, 7(8), e1220. https://doi.org/10.1038/tp.2017.190

Johnson, G. H., & Fritsche, K. (2012). Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. Journal of the Academy of Nutrition and Dietetics, 112(7), 1029–1041.e10415. https://doi.org/10.1016/j.jand.2012.03.029

Lin PY, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry 2010; 68: 140–147.

Su, H., Liu, R., Chang, M., Huang, J., & Wang, X. (2017). Dietary linoleic acid intake and blood inflammatory markers: a systematic review and meta-analysis of randomized controlled trials. Food & function, 8(9), 3091–3103. https://doi.org/10.1039/c7fo00433h

Tułowiecka, N., Kotlęga, D., Prowans, P., & Szczuko, M. (2020). The Role of Resolvins: EPA and DHA Derivatives Can Be Useful in the Prevention and Treatment of Ischemic Stroke. International Journal of Molecular Sciences, 21(20), 7628. MDPI AG. Retrieved from http://dx.doi.org/10.3390/ijms21207628

https://institute.progress.im/en/content/hypothalamic-pituitary-adrenal-hpa-axis-depression

Pregnancy in the Age of COVID-19

March 29th 2020. Since January, there are over 100,000 COVID-19 cases and over 2,000 deaths from this illness in the U.S. and New York is now officially the epicenter of the disease with over 50,000 cases reported since March 26th 2020. I’m 16.5 weeks pregnant and I’m also a clinical psychologist. To say this is a unique period in my life would be an understatement.

 Collectively, this is a unique period of time in everyone’s life across the globe as this virus has uprooted society in almost all countries across the world. Non-essential businesses have been closed for just over a week now in N.Y. and I have been at home and have not left my house in 18 days unless to take a walk around our neighborhood. Since the insidious and quick spread of the disease in N.Y., I have been working exclusively from home, seeing patients virtually through phone and video telehealth sessions. I work part time at Northwell Health, a major hospital in N.Y. at an outpatient clinic located in Queens, N.Y. I have patients there who are from the community as well as the health system that include medical assistants, nurses and medical residents, all currently working on the front lines of this disease. I also work part time at a local practice in Westchester and I have my own small private practice consisting of patients with a ranging scale of anxiety disorders.  During the first week of the lockdown here in N.Y., every one of my sessions that week consisted of a discussion around COVID-19 and how their individual lives were being affected and changed by this epidemic. The amount of fear and anxiety they were currently experiencing, as well as the level of uncertainty that remains prevalent in everyone’s thoughts and feelings was unbelievably tangible. Uncertainty and fear are generally part of feelings of anxiety, but this epidemic has since highlighted either existing fears or exacerbated ones that may have been dormant, coped with by the ability to distract ourselves with activities outside of our homes. We are all practicing social distancing, not attending regular functions like birthday parties or weddings, trying to figure out the best time to grocery shop and purchase goods we need for the week, making sure we have enough soap and disinfectant to wipe down any item we receive from the outside world. While others have to still go to work, in hospitals and clinics that are directly in contact with individuals who are sick and positive from this disease, all wearing masks and gloves and washing their hands um-teen times a day to ensure essential hygiene principles and reduce the spread of the disease.

 To say that being a psychologist during this time is difficult would also be an understatement. Medical professionals and our own government still do not have answers as to how long this disease and outbreak will last, what the health consequences are for individuals who get sick, if this disease will only occur once or instead occur 2-3 times a year as long as we don’t have a vaccination, and what I have been most concerned with, the long term consequences of getting this disease while pregnant or if your newborn gets contracted with it. Data is incredibly limited at this stage and there are no definitive answers to any of these questions.

 Uncertainty is difficult for many reasons and for most people. It is uncomfortable and can make us feel powerless and hopeless in a time when we are longing for direction. In my clinical experience, many of my patients who experience anxiety disorders tend to cope with thoughts and feelings of uncertainty with distraction, or by engaging in negative behaviors that temporarily alleviate the feelings of uncertainty or anxiety. It’s not to say that those of us who aren’t clinically diagnosed with an anxiety disorder are any better at coping with these feelings either. Human nature is to want and seek answers. We feel lost without an anchor, leaving us with little to hold on to, easily spiraling into negative thought patterns and feelings that feel like they will never dissipate or settle. So, what’s the solution in a time of extreme uncertainty and anxiety?

 If you notice, the title of this article is ‘Pregnancy in the age of COVID-19’ and yet what I have been speaking of is the collective and communal experience of anxiety and uncertainty during this outbreak. This is my first pregnancy and to be brutally honest, I have been fearful of being pregnant for most of my adult life and I only realized why after I became pregnant. It all had to do with uncertainty and lack of control. The unbelievable lesson I have experienced while being pregnant, with or without COVID-19 is this: surrender to what is and learn to trust the process because that is how you get through it and remain grounded. It is essentially the same process that is described in the serenity prayer, “grant me the serenity to accept the things I cannot change and the courage to change the things I can.” We must learn to tolerate and accept the uncertainty in our lives and focus on the aspects that we are able to modify. What does this look like in practice during the COVID-19 outbreak? Here are some examples. As we listen to the directives and stay home, adapt and create spaces in your home to help you develop a routine. I advise to stay physically active by taking walks around your neighborhood or working out at home using various Apps you can download to your phone or computer. It doesn’t require much but spending 30 minutes a few times a week allows us to stay physically and mentally healthy. Start a meditation practice. Stillness is the ultimate teacher in how to learn how to create distance between your thoughts and your feelings. It is important that we are not constantly consuming the news, engaging in work at all hours of the day or mindlessly scrolling on our phones. Times away from ‘doing’ and learning how to be with yourself will give you gift of learning how to tolerate difficult feelings and thoughts and learn that you don’t have to do anything with them except give them the space to exist. Talk to your friends and family via phone and video. It is important we stay connected to our community, it is what helps us stay calm and thrive. Spend time playing. You can read, dance, paint, cook, play some board games, spend more time with your kids or your dog, the point is to focus on activities you may have not “had time for” in the past. Let’s learn how to be present and happy in our own homes with ourselves and our loved ones around us. And finally, if you feel yourself undoubtedly worried and anxious during periods of your day and week, create space for that to exist as well. You can mourn things that you aren’t able to engage in right now. I’m mourning the loss of having to spend any “real time” with my family and close friends as I grow into and experience my own pregnancy. It’s ok to be sad if you had to cancel a trip or reschedule your wedding. There’s going to be loss during this time, don’t push it away and keep distracting from it.

 As difficult as this time is, let’s learn how to slow down, how to be present with ourselves and not continually distract ourselves to help make us “feel better.” Anxiety isn’t inherently bad. It’s a signal that states to us that something important and potentially threatening is happening. Our brains evolved to make us pay attention to it and see what we can do in order to manage it and make it better. Create the space to feel and experience whatever it is that you are experiencing and let’s help each other through these difficult experiences. We are never alone. It’s only our anxious thoughts that make us feel that way sometimes. There will be a day when we will no longer need to be on lockdown and quarantined, where we can hug our friends and our families again without the fear of contagion and the unknown, and that will be such a beautiful day. Such a beautiful day indeed.

Increase BDNF and Decrease Depression: Can food be used as a therapeutic tool?

Research has been demonstrating a clear link between a poor dietary pattern and negative implications in one’s cognitive health and function for the past decade. There are likely many mechanisms in which this occurs and one of those is through a neurotrophin called BDNF or Brain Derived Neurotrophic Factor.

BDNF allows for neurogenesis, or the production of new neurons, and neuronal plasticity (our brains ability to change), which affects our memory and contributes to our ability to learn. BDNF levels are subject to changes from our diet and other lifestyle habits. In fact, levels of BDNF are significantly lower in many neurodegenerative diseases that include Alzheimer’s, Multiple Sclerosis and Huntington’s Disease.

Animal studies suggest that a brain structure called the hippocampus is very much associated with diet and our mental and cognitive health. The hippocampus itself is associated with learning, memory and mood regulation and is also negatively affected by depression. In fact, research has demonstrated that there are structural alterations in brain regions in patients with Major Depressive Disorder (MDD) that include the hippocampus and the frontal cortex (responsible for planning, organizing, and more complex behaviors). Not only that, but studies further indicate that for individuals who experience moderate to severe depression, the volume of the hippocampus decreases significantly and has been shown to decrease as much as 19%. And, the longer the duration of the depression, the greater the loss in the hippocampus.

Since individuals who experience depression typically also experience stress, further loss of the hippocampus can ensue. Furthermore, because self care activity and motivation significantly decrease in depression, it is more likely that individuals with depression are eating a poor dietary pattern. Cognitive Behavior Therapy, an evidenced based therapy designed to help individuals challenge their unhealthy thought patterns and behaviors, leading to the development and maintenance of healthy ones, requires an ability to learn and recall information. The ability to do so is already diminished in depression due to the reduced hippocampal volume and decrease of BDNF. Throw in a poor diet, increased stress, and lack of exercise, all common symptoms for a person experiencing depression, and you have a perfect storm and cycle of ever depleting BDNF levels and a continued decrease in hippocampal volume, all of which will also worsen a person’s depression. To this point, it would make sense to help these individuals increase their BDNF levels, allowing for neurogenesis, plasticity, and the increased ability to learn, to memorize and to better regulate mood. CBT therapy is all intended to help increase BDNF levels theoretically by having the person practice engaging in activities they used to enjoy, by increasing their practice of self care, decreasing and managing stress, and by helping to strengthen rational thoughts and frontal cortex activity. This hasn’t been statistically significant in any studies as of yet but positive changes occur in the brain as a result of CBT therapy that enhance frontal cortex activity and emotion regulation centers. Interestingly, antidepressants have been found to help increase BDNF levels.

With regards to a therapeutic context and including the typical cognitive and behavioral treatment for individuals with depression, I further surmise that helping a person to eat a healthy dietary pattern that is right for them, will increase their BDNF levels (beyond giving them other mental health benefits, see other posts for details), consequently, increasing their ability to learn and retain the information that is being discussed in therapy, and further allowing them to engage in the behavioral tasks that are commonly given by CBT therapists simply because they are giving their body and brain nutrients to support them in these goals. It is already incredibly difficult for individuals who are depressed to start engaging in the tasks discussed in therapy and without the raw materials to help support these mental and behavioral changes, the person has to work at least twice as hard.

Foods such as omega-3 fats, antioxidant rich berries that contain polyphenols (plant chemicals to have health benefits) including flavanoids, help to stimulate neurogenesis, reduce free radical activity, and help to decrease pro-inflammatory processes in the body, all of which help support the brain health of an individual struggling with depression. While high saturated fat and high sugar foods reduce the growth of new neurons, contribute to free radical production and increase the activity of pro-inflammatory processes. These results have been consistently observed in a number of animal studies. There is only one human study that found hippocampal volume changes as a function of dietary patterns. In this study, it was found that in a community cohort study of older adults, lower intake of nutrient dense foods and higher intakes of unhealthy foods (such as processed meats, desserts and chips) was associated with smaller left hippocampal volumes. This reinforces what we already suspected about food and our cognitive health.

 Other ways to increase your BDNF levels include endurance exercise, meditation, deep sleep, and exposure to sunlight. All of these tools should be part of the conversation in therapy to help strengthen mental health and cognitive functioning. Even if you don’t experience depression, increasing BDNF levels will significantly change your brain function for the good by helping you learn more effectively, remember better, age slower, and regulate your mood. Who doesn’t want those benefits?

References

https://www.ncbi.nlm.nih.gov/pubmed/12088740

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/

https://server12.np.unimaas.nl/MHeNs_newsletters/Background%20papers%2012TTN/Sapolsky2000GCsHIP.pdf

http://downloads.hindawi.com/journals/np/2013/873278.pdf

https://www.psychiatrictimes.com/psychotherapy/how-psychotherapy-changes-brain

Omega 3's and your mental

Last week, I highlighted in my latest blog post that research within the last decade has shown that nutritional deficiencies exist in those with mental health disorders and that one of the most common nutritional deficiencies is Omega-3 fatty acids. There are now tons of supplements and headlines promoting the need for Omega-3 fatty acids, but do you know why? Why is this particular kind of fatty acid so important and how does it affect our mental?

Fats have gotten so demonized in our culture and unfortunately it has led many people to not have them in their diets. Fats are one of the three macronutrients (the others being proteins and carbohydrates) that we need to fuel our bodies and our mental. Fats are classified into a few different categories: saturated, unsaturated, monounsaturated, and polyunsaturated. Omega 3 fats are one type of Polyunsaturated Fatty acid (PUFAs). In terms of it’s chemical composition, this class of fats (PUFAs) consist of long chains of carbon atoms with a carboxyl group at one end of the chain and a methyl group at the other end. There are three main types of Omega-3s, Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and Alpha-linolenic acid (ALA). ALA is present in plant oils, such as flaxseed, soybean, and canola oils, while DHA and EPA are found most abundantly in fish, fish oils and krill oils. One of the most important roles in the body that fats play is being a major structural component of every cell in your body (Read that again: FATS ARE STRUCTURALLY PART OF EVERY SINGLE CELL IN YOUR BODY). All of our cell membranes in our bodies are made up of fats (phospholipids). They are important because they separate the cells in the body from their outside (their membrane) and they facilitate the exchange of nutrients between cells. This wouldn’t happen if not for fats.

Following consumption of these fats, omega-3 fatty acids are incorporated into cell membranes in all tissues of the body. Whether the source of these omega-3 fatty acids is fish, fish-oil supplements or food products fortified with the appropriate omega-3 fatty acids, measurable changes in cellular membrane content occur within days of increasing the daily consumption of these fatty acids. Dietary changes that include healthful PUFAs have a significant impact on the cell’s function. These fats help important signaling and communication within and between cells. Specifically, DHA, being the most abundant Omega-3 found in the brain, has been shown to be crucial for maintaining nerve cell structure and function. Both EPA and DHA have been shown to help the brain support healthy memory, cognition and emotional well-being. EPA and DHA also promote healthy blood flow, which is essential for brain function and memory. EPA and DHA are being studied extensively to assess the wide range kind of effects these two Omega-3 fats have on the brain. For instance, a recent meta analysis found that although blood EPA, DHA and total Omega-3 PUFAs are significantly decreased in patients with dementia, only EPA was found to be significantly lower in patients with pre-dementia syndrome, leading the researchers to suggest that EPA may be a biomarker and a risk factor for age-related cognitive impairment. This suggests that your Omega-3 intake, specifically DHA, can help possibly prevent cognitive decline.

Let’s take a look at some studies to see what the research has to say about how Omega-3’s protect the brain. The Easton Center for Alzheimer’s Disease Research report examined levels of DHA in red blood cells in a group of over 1500 men and women aged 67 +/- 9 years who were dementia free. The study measured the size of their brains and evaluated the subjects using a variety of cognitive assessments. Results indicated that those individuals having the lowest DHA levels had significantly lower total brain volume and greater levels of small strokes in their brain compared to those with higher levels of DHA. Additionally, those individuals with lower levels of DHA performed worse on tests for visual memory and executive function.  This is more evidence that suggests that DHA protects our brain, allowing for optimal functioning despite the chronological aging process.

There is also evidence that Omega-3’s may be useful as a supplement for the treatment of bipolar disorder related depression and evidence that EPA-supplemented food is helpful in patients suffering depression. More research is needed to make this conclusive, since due to participant recall and diet-related systematic differences, there is complexity in interpreting the literature in order to make specific conclusions.

Although epidemiological research has shown that an increase in the symptoms of depression is correlated with lower intakes of dietary omega-3 fish oil, omega-3 fatty acids have not, so far, proved significant as a monotherapy for major depressive disorder. Individuals experiencing the symptoms of depression were also found to have lower serum concentrations of essential fatty acids, which was also revealed by several studies of EPA and DHA.

Besides treating depression, omega-3 fatty acids may also be useful in treating and preventing dementia. Nine epidemiological studies now support that increased dietary intake of fish is associated with reduced risk for cognitive decline or dementia with several of the studies showing a 40–50% reduced risk of dementia! DHA has also been shown to be specifically protective against Alzheimer’s Disease. One of the ways it does this is by limiting the production and accumulation of the amyloid β peptide toxin that is widely believed to drive the disease. Pretty amazing!

What happens when Omega-3 fats are used in conjunction with medication treatment for depression? Results of one study that evaluated Omega-3 fatty acids with and without SSRI fluvoxamine suggest that the patients treated with a combination of omega-3 fatty acids and fluvoxamine showed a significant difference compared with those treated with fluvoxamine alone in improving depression symptoms. Among women in the USA, depressed symptoms were examined in relation to intake of omega-3 fatty acids and omega-6 fatty acids. Higher intake of omega-3 fatty acids than omega-6 fatty acids was found to be associated with decreased risk of heightened symptoms of depression.

So does this mean that you can use foods rich in Omega-3 to help manage depression and mood disorders? The answer is yes, as a supplement to other forms of therapy that have been shown to be effective (i.e. Cognitive Behavioral Therapy, exercise, stress management techniques).  It is important to note that while these studies listed above all have promising and positive results, there are other studies that have been inconclusive or have shown that Omega-3s when compared to medication management for depression (i.e. an SSRI) have not demonstrated significant statistical effects. More research is needed to help clarify these results, specifically with regards to dosing, quality of the Omega-3s being used in studies, and severity of depression or said mood disorder. Other factors that may be responsible for these variable results are differences in sample size, biological and genetic differences among patients, environmental variability, and variability in response to Omega-3 fatty acids. It is also important to note that severity of the mental health diagnosis will dictate what will be necessary in order to manage the disorder. Someone with more chronic mood disorders that also have a strong familial component, might not benefit from the use of Omega-3 fatty acids as much as someone whose presentation isn’t as severe, or whose depression is more caused from environmental or stress related factors. Depression is a disorder that is caused by many different factors and depression due to insufficient Omega-3 fatty acids can be of one type. What this research does demonstrate is that eating nutrient dense whole foods that have a balanced macronutrient profile (fats/proteins/carbs) will have both short term and long term benefits for your mental. Disease accumulates in the body after months or years of “bad habits” i.e. poor diet, poor stress management, lack of exercise, etc. It is much more beneficial to act preventatively and feel the benefits that feeding your mental will have on your day-to-day life. At the very least, you will have improved energy, improved focus and attention, improved overall brain function, and increased satiety. Adding these healthful Omega-3s to your diet will only help protect your brain and other systems of the body (cardiovascular, immune).

The best sources of Omega-3 include fatty fish, such as salmon, mackerel, tuna, herring, and sardines. Other sources include grass fed meat, chia seeds, flax seeds, soybeans, and oysters. In terms of how much to eat? No Recommended Daily Allowance has been set for total fat or individual fatty acids, however, it is estimated that it is healthful to have these healthy fats be between 20-35% of total calories. It’s interesting to note that during hunter-gatherer times, our ancestors ate between 28-58% fat.

According to Dr. Janelle Sinclair, a biochemist and a registered natural medicine practitioner, in order to treat depression with Omega-3, you need to take a considerable amount. In fact, studies show that you need to take between 1000-2000mg EPA per day to treat depression. She further recommends that in order to treat depression, taking EPA over DHA is more effective and that the supplement is most effective when it has twice as much EPA as DHA.

I hope this helped to provide a general overview of how Omega-3’s can affect our mental and how incorporating this powerful nutrient can help provide long lasting benefits.

References

Appleton K.M., Hayward R.C., Gunnell D., Peters T.J., Rogers P.J., Kessler D. Effects of n-3 long chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Am J Clin Nutr. 2006;84:1308–1316.

Cole G.M., Ma Q.L., Frautschy S.A. Omega-3 fatty acids and dementia. Prostaglandins Leukot Essent Fatty Acids. 2009;81:213–221.

Hegarty B., Parker G. Fish oil as a management component for mood disorders—an evolving signal. Curr Opin Psychiatry. 2013;26:33–40.

Lin PY, Chiu CC, Huang SY, Su KPJ Clin Psychiatry. 2012 Sep; 73(9):1245-54.

Marangell L.B., Martinez J.M., Zboyan H.A., Kertz B., Kim H.F., Puryear L.J. A double- blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry. 2003;160:996–998.

Safa M., Fallah Tafti S., Ghassem Boroujerdi F., Talischi F. Clinical trial in the treatment of 80 Iranian patients with major depression disorder by the combination of omega 3fatty acid and a selective serotonin reuptake inhibitor. Ther. Adv Psychopharmacol. 2013;3:186–190.

Wani, A., Bhat, S., and Ara, A. Omega-3 fatty acids and the treatment of depression: a review of scientific evidence. Integr Med Res. 2015 Sep; 4(3): 132–141.