The Neurobiology of Appetite

Metabolic set point 

People alter the quantity and frequency of food consumption daily and yet the brain seems to have a regulatory process that allows people to maintain a relatively stable body weight. 

Isn’t that crazy? 

Anyone who has ever tried to diet knows all too well about this metabolic set point. There are staggeringly low rates of success with diet programs. A systematic review of studies published between 1931 and 1999 found that only 15% of patients achieved dietary success after 5 years. Most people who diet will slowly return to their preexisting weight within 1 year.

This metabolic set point appears to be controlled by our genetics. There is a strong correlation between the body mass of biological parents and adoptees in adoption-based studies. In the case of weight, genetics has far more influence than environmental factors. 

Despite all this obesity rates in the United States as well as other developed countries continues to rise, so what gives? 

Our genes have difficulty responding to the modern environment. 3000 years ago, when food sources were scarce, it was advantageous to consume and store as many calories as possible. However, in the modern world where there is no shortage of opportunity to consume calorie dense foods, our genetics are working against us. The weight issue is genetic but also influenced by availability of high-calorie delicious food. 

When it comes to weight, energy in (food) must equal energy out (heat and work). The energy out is made up of the resting metabolic rate (calories burned when the body is stationary) and physical activity. The brain has a unique mechanism for managing the RMR. When more calories are consumed the RMR increases and when we diet the RMR is turned down. 

To solidify the point, we can look no further than The Biggest Loser competition. Investigators assessed 14 of the 16 contestants before the competition, after completion of the 30-week program, and 6 years after the show. 13 of the 14 study participants regained weight and 4 were heavier than when they started the competition 6 years ago. The real downer was they all burned less calories at rest 6 years after the show ended. Despite exercising more and theoretically being much healthier their RMR decreased. 

What are the important signals used by the body that indicate when to eat and when to stop eating?

Short-Term signels include: 

Glucose: This is the primary nutrient that mediates satiety. Hypoglycemia will stimulate hunger and increase eating, while glucose infusions will decrease food intake. 

Mechanoreceptors in the gut: The physical presence of food in the stomach activates these receptors due to stretching, the vagus nerve transmits signals of gastric stretch to the hindbrain to decrease eating. 

Gut Hormones: The most well understood is cholecystokinin (CCK) which is released by endocrine cells in the small intestine. This will inhibit further food intake by stimulating the vagus nerve and decreasing gastric emptying. People have tried using CCK as a weight loss measure but all it does is decrease the size of meals but increases the frequency of eating thus producing a net zero effect on weight loss.

Ghrelin is the only gut hormone that stimulates hunger. Some suggest that decreased ghrelin produced by the stomach is the reason gastric bypass surgery is effective for weight loss. 

It’s now known that adipose tissue releases a hormone that conveys information about energy stores. Leptin is produced by fat cells and increases or decreases based on the total amount of fat. Leptin is a hormone that tells the body to stop eating. In the case of obesity leptin levels are high and energy expenditure increases while food intake decreases. When someone goes on a diet and fat stores decrease leptin decreases resulting in decreased energy expenditure and increased food intake. 

Two groups of neurons in the arcuate nucleus of the hypothalamus mediate the leptin signal, proopiomelanocortin (POMC) and neuropeptide Y (NPY). POMC stops eating and NPY increases food intake and decreases energy expenditure. In obesity there is increased leptin which inhibits NPY and activates POMC resulting in increased energy expenditure and decreased food intake. The opposite is true for the lean individual. 

Eating and Pleasure

It’s well established that eating can result in pleasure, we have all had this experience after a stressful week a good meal can instantly change our mindset. The pleasure from food is likely an adaptation that enhanced survival when food sources were scarce. Increased dopamine in the nucleus accumbens and release of endogenous opioids appears to be more active when we are eating a meal we enjoy. 

Omega-3 Fatty Acids and Mental Health

Omega-3 fatty acids are reported to help with several physical and mental health conditions. 

They are termed essential because they cannot be produced by the body and must come from the diet. 

In fact, I use 1000 mg of omega-3 fish oil daily as part of my own supplement routine.

How Do Omega-3s Work:

Omega-3’s coat neurons, increase cell membrane fluidity, have neuroprotective properties, and the most well-established mechanism is an anti-inflammatory action. They directly affect arachidonic acid metabolism because they displace arachidonic acid from membranes and compete with it for the enzyme that catalyzes the biosynthesis of thromboxanes, prostaglandins, and leukotrienes involved in the inflammatory process thus reducing the formation of these products. 

Indications For Omega-3 Use In Psychiatry:

In mental health the most well-established use of Omega-3s is for the treatment of depression. It’s been looked at as a primary treatment as well as augmentation. The results aren’t that great when Omega-3s are used as stand-alone therapy. As augmentation they have an effect size of 0.5 to 0.6.

Given our previous talks about inflammation and depression, people with high inflammatory biomarkers may respond better to Omega-3 treatment. 

Omega-3s And Schizophrenia:

Maybe the most interesting data comes from studies of Omega-3 use in schizophrenia. It seems to work best when started early in the illness when the first signs or symptoms appear. There also seems to be a reduction in white matter changes on imaging studies. 

This raised the important question; can we prevent schizophrenia? 

Vienna Study:

There was a study published in nature communications that looked at outcomes in the prevention of psychotic disorders in Vienna. 

They started with 12-week trial with omega-3s which proved to reduce the risk of progression to a psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared to placebo. 

They then completed a long term follow up of the study to show that brief intervention with Omega-3s reduced the risk of progression to a psychotic disorder and psychiatric morbidity. 

A year after the Omega-3 treatment only 5% converted to schizophrenia, compared to 28% in the control arm. Seven years later the rates of conversion to schizophrenia were 10% Vs 40% with most of the patients being retained in the study. 

Side Effects of Using Omega-3:

There are very few risks to adding omega-3 fatty acids to existing psychiatric treatments. Fish burps are a common occurrence and can be mitigated with enteric coated capsules or refrigerating the capsules. Omega-3 can increase bleeding time and require careful monitoring if the person is scheduled for surgery or taking anticoagulants. Keeping doses at 1000 mg/day is advised for this population. 

Sources of Omega-3:

You can use a supplement, or you can consume fish like salmon, herring, or anchovies two times per week to get an adequate dose. 

Ensuring the EPA to DHA ratio is 2:1 (EPA: DHA) or pure EPA is essential when selecting a product. Consumerlabs.com to help ensure the purity and potency of the product is accurate. 

The cost of adding an Omega-3 supplement to your treatment is $8 to $30 per month depending on the specific product. 

There is very little downside to increasing your consumption of Omega-3 fatty acids either from whole food sources or as a high-quality supplement. 

How to Sleep Better: Prescriptions From Your Psychiatrist

I will talk about sedative and hypnotic medications in future videos, but I want to start a discussion on sleep with sleep hygiene. I recommend all my patients start here and follow this process at least 90% of the time prior to talking about medication. I find most patients are not doing these things and if they are it’s not consistent enough to see a noticeable improvement. 

  1. Stick to a routine by waking up at approximately the same time each day. Do this for seven days, and do not alter the time on weekends. This will help you gradually set your internal clock. You have more control over your wake times than your sleep time as you may not feel tired. Try to avoid taking a nap during the day even on nights where you do not get much sleep.
  2. Avoid all caffeine after 12 PM, the effects of caffeine are long lasting and can interrupt sleep. If you can completely stop caffeine that would be best, but at the very least minimize consumption before 12 PM. 
  3. Try to exercise daily (seven days per week), preferably early in the day and not too close to bedtime. Start with 15 minutes per day and gradually work your way up. A combination of resistance training and cardiovascular training is best.
  4. Stop doing active mental work at least one hour before bed. 
  5. Avoid watching TV, using a phone, laptop, or tablet before bed. The blue light from screens has been shown to worsen sleep. The bed should be used for sleep and sex only. 
  6. Create a bedtime ritual to follow every night before bed, warm bath, mindfulness exercise, gratitude journal, reading, or listening to music. 
  7. Do not use alcohol as a way to promote sleep. Alcohol negatively impacts sleep architecture and the sleep you do get will be unsatisfying. 
  8. The bedroom should be dark, quiet, and the temperature should be cool but not cold around 65 degrees is ideal. Consider blackout curtains, a fan to cool the room, and ear plugs to facilitate these conditions. 
  9. Restrict Food and drink 2-3 hours prior to bedtime. This will reduce the chances of sleep being interrupted to use the bathroom.
  10. If you have any pain, take appropriate pain medications prior to bed. 

Lifestyle Psychiatry and the Gut Microbiome

  • The gut microbiome consists mostly of bacteria and that is largely the portion of the microbiome we are focusing on (fungi and viruses exist but their function is largely unknown) 
  • Communication pathways exist between the microbiota-gut-and brain. 
  • Multiple mechanisms exist that allow gut microbiota to signal to the brain and control physiological processes. 
  • These include release of gut peptides from enteroendocrine cells which activate receptors of the immune system and vagus terminals in the gut. 
  • Studies indicate that these bacteria can manufacture and secrete essential neurochemicals including serotonin, dopamine, NE, GABA, and acetylcholine 
  • Depression and anxiety have been linked to a less well diversified gut microbiome.
  • What can help diversify the gut microbiome? Diet, processed food, sugar, saturated fats, and red meat. Medication can also alter the gut microbiome, a good example is oral antibiotics used to treat an acute infection, sleep, exercise. Sounds a lot like a healthy lifestyle will get you the microbiome you need for optimal mental health. 
  • However, if you want a treatment there have been several studies that looked at fecal transplant to treat psychiatric disorders. Fecal transplants are much easier these days and now there is a capsule version that you take orally. There is not enough data to recommend this as a practical treatment and if the patient goes back to eating a poor diet, sleeping poorly, not exercising then the gut microbiome will revert after the transplant. 
  • What are the practical things you can do? Stop eating processed food, sugar, and red meat. Increase your fiber intake and select a diet like the Mediterranean diet or a plant based whole food diet that will provide those prebiotics. You could supplement with a probiotic but most of what you need can be had from a good diet alone and I think it’s far better to change the diet then to try using supplements to treat a poor diet. Fermented products like kimchi, kombucha and sauerkraut are good sources of live bacteria.
  • If you choose to take a probiotic make sure it’s a quality, 3rd party tested product. 
  • Increase aerobic activity, I think if you goal is overall general health and you have limitted time, I think aerobic activity is a better bang for your buck. 
  • The way I believe you get and keep a healthy gut microbiome is through lifestyle modification. Improving your diet, exercise, and sleep is a good place to start. If you want to supplement with food products like kimchi or kombucha, go for it. I do not believe there is enough evidence to support a probiotic supplement for psychiatric disorders at this point, but if you want to spend $30 or more per month on a product if it’s a quality one that’s fine. Remember you cannot supplement away a bad diet. 

Lifestyle Medicine for Psychiatry: Lessons in Being Resilient

In this video I focus the discussion on the exercise/physical activity portion of lifestyle medicine for psychiatry. Exercise is an underrated and underutilized tool for fighting depression. It can have a profound impact on mood, and helps people learn to be more resilient.

Key Findings Include: 

  • For resistance training, higher intensity and shorter duration provides improvement in mood symptoms 
  • For aerobic exercise, durations of 45-60 minutes appear to provide the most improvement in mood symptoms. Longer and shorter durations showed less benefit. 
  • Keep it simple and just get started. There are a million different programs, and you can easily find yourself worrying to much about getting all the information and not enough time worrying about exercising.
  • The simplest way to start is with a daily walking routine. Spend six months consistently walking for 45-60 minutes. That’s it, no special equipment or significant out of pocket expenses required. 
  • A walking routine will set the foundation for adding additional forms of exercise including resistance training

Why Psychiatrists Don’t Use Lifestyle Medicine to Treat Psychiatric disorders

My clinical experience indicates that most psychiatric disorders would benefit from the use of lifestyle medicine. As a member of the American College of Lifestyle Medicine, I’ve used lifestyle interventions to treat many of my patients. It’s an underutilized and undervalued part of health care in general and these are my thoughts about why that is the case. 

Grounding Technique For Anxiety

Anxiety is something most of us have experienced. This five-step exercise can be helpful during periods of anxiety by helping to ground you in the present moment. 

Start the exercise by drawing attention to your breathing. Slow, deep, breaths can help you induce a feeling of relaxation. Once you feel relaxed, go through the following steps to ground yourself: 

One: Note ONE thing you can taste

Examples may include: gum, sugar free candy, coffee, sparkling water (anything you can taste in the moment). 

Two: Note TWO things you can smell 

Examples may include: fresh air, scented candle, flowers, food cooking (anything around you that you can smell)

Three: Note THREE things you can hear 

Examples may Include: people talking, cars driving, wind blowing, rain falling (anything in the environment you can hear) 

Four: Note FOUR things you can touch 

Examples may Include: desk, chair, pen, phone (anything around you that you can touch) 

Five: Note FIVE things you can see 

Examples may include: door, computer screen, car, tree, house (anything you see around you)

Introducing Shrinks In Sneakers on YouTube

I’ve done a soft rollout of the Shrinks In Sneakers YouTube channel over the past several months. I think I’m finally comfortable introducing it on the blog. I made the decision to start making videos because I can create content at a more rapid rate, and I can connect with the viewer in a more personal and intimate way. Please subscribe to the channel for updates. If you have specific topics you want covered, or have questions about existing content please comment. I will try to answer all questions and continue creating engaging content based on your interests. 

Cheers,

Dr. G

Link to YouTube Channel

https://www.youtube.com/channel/UCaaywi6nWB4zzpqBCMvxbsA

Election Anxiety Solutions

Anxiety is a part of life; we all experience it. The amount of anxiety a person experiences is to some degree related to how important a particular outcome is to that person. It seems like everything these days is high stakes and anxiety provoking. There is a global pandemic that continues to create chaos around the world, economic uncertainty, gender and racial inequality, and now a presidential election.

People are more anxious than ever about this presidential election. According to a recent article by the American Psychological Association 68% of U.S. adults say the 2020 U.S. presidential election is a significant source of stress. This is compared to the 2016 election where 52% of U.S. adults found the election stressful. It might just be a symptom of the times, but it remains a significant concern. If you are having election anxiety here are some simple ways to reduce stress and anxiety during this election cycle. 

  1. Make sure you are getting enough sleep. Set a regular sleep time and wake time. Make sure the room you sleep in is as conducive to sleep as possible (e.g. dark room with no ambient light). Limit the bed to sleep and sex only, do not play games on your phone or read in bed. If you can’t sleep get out of the bed and do a mildly strenuous activity. A good example is a crossword puzzle, then come back to bed when you feel tired. If you are not sleeping well it can cause problems in other areas of life such as mood and cognitive function. 
  2. Get outside or stay inside whichever you prefer, but make sure to move. Exercise is a great way to cope with stress and anxiety. There are countless free guided exercise routines on sites like YouTube that require little or no equipment to perform. If you do not like that option, take a walk in your favorite park, take a bike ride, or go for a hike on your favorite trail. 
  3. Limit your consumption of news throughout the day. Set aside one or two times per day to check the news and see what is going on with the election. Resist the urge to continually check in and get play by play updates. This simple, but difficult to follow advice will save you a lot of stress and anxiety. 
  4. Avoid talking to people in your life about the election who are unable to keep their emotions under control while discussing the topic. You should have a good idea of who these people are in your life. This will save you a lot of stress and anxiety by simply choosing to talk about other topics with those individuals.
  5. The last thing I recommend for people who want an activity they can perform to reduce stress is a thought journal . This can be as simple as a piece of paper that you record the thoughts on. There are printable versions of this online. I will provide a link to one such example here. This is a common technique used in cognitive behavioral therapy (CBT) all the time.

What Can We Do to Help Prevent Alzheimer’s disease (AD)

Introduction

The other day I had a conversation with a friend, and the topic of Alzheimer’s disease (AD) came up. My friend’s opinion was basically why would I want to know I have a disease that results in steady decline in function, and lacks any disease modifying treatments? This is in large part true, there have been multiple clinical trials of both symptomatic and disease modifying drugs that failed to produce adequate results. However, this is a very limitted view and neglects the benefits of focusing on modifiable risk factors and primary prevention. We know approximately 1/3rd of AD cases are due to modifiable risk factors, and the implementation of lifestyle modification early may prevent or delay the onset of AD. 

Modifiable Risk Factors

Common modifiable risk factors for AD include hypertension, hyperlipidemia, diabetes, obesity and smoking. Management of these risk factors as early as possible may offer a preventative approach for AD. Equally important are lifestyle modifications such as physical exercise, diet, mediation/mindfulness, and social activity.

Physical Activity

Physical inactivity has a significant influence on the development of AD. Twenty-one percent of AD cases are attributable to physical inactivity. There is a significant number of studies in the literature that indicate physical activity is neuroprotective. We know one of the areas in the brain affected by physical activity is the hippocampus which is involved in memory. Exercise leads to increased neurogenesis and neuroplasticity in the hippocampus. Other benefits of exercise on the brain include increased blood flow, modulation of inflammatory markers, and increased brain-derived neurotrophic factor (BDNF). The exact definition of adequate exercise varies in the literature. Any activity that is sufficient to increase heart rate and can be sustained for 30-60 minutes is my definition. A basic example would be brisk walking for 30-60 minutes. Physical activity two times a week beginning in middle age is associated with reduced risk of AD. Aerobic exercise is associated with additional cognitive benefits including improved processing speed, attention, and memory in adults with mild cognitive impairment. This recommendation is especially important for ApoE4 carriers, as exercise is associated with reduced amyloid deposits. 

Physical activity should be a recommendation for all patients without major health concerns preventing physical activity. The earlier in life a patient begins an exercise routine the better. Some of these studies have looked specifically at starting exercise routines in middle age, but there is no reason to wait. The physical and cognitive benefits of exercise are beneficial regardless of age. It’s much easier to begin training when you are young and healthy. If you build healthy lifestyle habits earlier in life, they are likely to last as you age. Guidelines for regular exercise can be found on the American Heart Association or American College of Sports Medicine websites. 

Meditation

Meditation or mindfulness is a topic that is beginning to get more attention in the medical literature. Chronic stress is believed to effect brain structures involved in memory and may contribute to AD. Psychological stress increases oxidative stress and telomere shortening which could contribute to the neuronal loss seen in AD. Meditation has emerged as a possible way to reduce the stress associated with daily life. The techniques of mindfulness involve directing one’s attention to the present moment to reduce the stress associated with constant thinking and worrying. Randomized controlled trials (RCTs) have shown significant improvements in overall well-being and attention. Improved executive function and reduced inflammatory processes implicated in AD. Additional research and larger RCTs are needed to improve the evidence base. Given the data we currently have there is no reason to not begin mindfulness practices. The techniques are relatively simple and can be learned from a variety of sources. If you are looking for low cost options for learning mindfulness, YouTube has a variety of guided mediations available. I personally like Headspace for beginners because it provides a solid foundation, has a variety of meditation courses, and allows you to track your progress. There is a fee for access to all the courses, but the first 10 sessions are free. Whichever route you choose, spending 10-15 minutes per day practicing mindfulness will lead to a happier and healthier brain. 

Diet

A great deal of research has been conducted over the last several years on the role of diet with respect to cognition. People with high calorie diets, specifically those high in fat are at higher risk for AD. Traditional western diets high in processed carbohydrates, simple sugars, and saturated fatty acids can impact the hippocampus and memory. When Japan transitioned to western diet the incidence of AD increased. Lower calorie diets with lower saturated fat content are linked to lower oxidative stress, decreased Beta amyloid burden, and decreased inflammation. One diet with proven benefits for preventing AD is the Mediterranean diet. This diet is rich in fruits, vegetables, whole grains, olive oil, and fish. There is moderate intake of low-fat dairy products and low intake of red meat, saturated fats, and sugar. Most of the data supporting the reduce risk of AD with this diet comes from epidemiological studies. Studies have shown combining this diet with exercise further reduces the risk of AD. The Mediterranean diet is associated with better cognitive function and reduced cognitive decline. This is one specific example, but the basic principles can be applied without the need to adhere to one specific named diet. 

Some specific foods you may want to add to your diet to prevent AD include fresh berries which have the highest amounts of antioxidants among the fruits. They are also low in calories and work well in diets where weight loss is a goal. Green leafy vegetables and tomatoes have the highest nutritional value when it comes to brain health amongst the vegetables. Foods high in omega-3 fatty acids are considered to be helpful in supporting brain function. The omega-3 fatty acid most important in brain function is docosahexaenoic acid (DHA), which is mostly found in fish. The anti-inflammatory and antioxidant properties of DHA are thought to be responsible for its role in preventing AD. Patients with diagnosed AD are known to have low levels of DHA. Omega-3 fatty acids recommendations from the American Heart association for adults is to eat fish rich in omega-3s two or more times per week. If using a supplement 1-3 grams per day is an adequate dose. Over 3 grams per day, you should consult with your doctor before moving above 3 grams per day. 

Finally, curcumin which is derived from turmeric has anti-inflammatory, antioxidant, and anti-amyloid properties. There is low bioavailability of the curcumin lead to mixed results in the initial trials. A new more bioavailable form called Theracumin demonstrated positive results in a randomized double-blind placebo-controlled study on memory, attention, and amyloid plaques in older adults without dementia. 

Conclusion

While there is no guarantee that lifestyle modification alone will prevent AD, there are some promising studies indicating it plays a role in the development of this disorder. Most of these interventions are things patients can implement in their lives immediately. They will not only improve cognitive function and lower the risk of developing AD, but it will improve and potential reverse other diseases of lifestyle. 

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